EXHIBIT 10.4

MASTER COLLABORATION AGREEMENT

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

The Master Collaboration Agreement is not intended to provide any factual
information about Alnylam. The Master Collaboration Agreement contains
representations, warranties and covenants that Alnylam and Genzyme made to each
other as of specific dates. The assertions embodied in those representations,
warranties and covenants were made solely for purposes of the Master
Collaboration Agreement between Alnylam and Genzyme and may be subject to
important qualifications and limitations agreed to by Alnylam and Genzyme in
connection with negotiating its terms, including being qualified by confidential
disclosures exchanged between the parties in connection with the execution of
the Master Collaboration Agreement. Moreover, the representations and warranties
may be subject to a contractual standard of materiality that may be different
from what may be viewed as material to investors or security holders, or may
have been used for the purpose of allocating risk between Alnylam and Genzyme
rather than establishing matters as facts. Moreover, information concerning the
subject matter of the representations and warranties may change after the date
of the Master Collaboration Agreement, which subsequent information concerning
the subject matter of the representations and warranties may change after the
date of the Master Collaboration Agreement, which subsequent information may or
may not be fully reflected in Alnylam’s public disclosures. For the foregoing
reasons, no person should rely on the representations and warranties as
statements of factual information at the time they were made or otherwise.

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

TABLE OF CONTENTS

 

     Page  

1. OVERVIEW; DEFINITIONS

     2   

1.1. Overview of Transactions

     2   

1.2. Definitions

     4   

2. EFFECTIVENESS OF AGREEMENTS AND LICENSES

     27   

2.1. Effective Date

     27   

2.2. Effectiveness of Licenses to Collaboration Products

     31   

2.3. Cooperation

     32   

2.4. No Antitrust Undertakings

     32   

2.5. No Effect

     32   

3. GRANT AND EXERCISE OF OPTIONS

     33   

3.1. Alnylam Programs

     33   

3.2. Option Grants

     37   

3.3. Option Exercise Period

     41   

3.4. Exercise of an Option

     45   

3.5. Option Not Exercised

     48   

3.6. Exclusivity during Option Period

     49   

4. DEVELOPMENT AND PHARMACOVILIGANCE

     51   

4.1. Overview

     51   

4.2. Diligence

     51   

4.3. Scientific Records

     52   

4.4. Third Parties

     52   

4.5. Oversight

     52   

4.6. Pharmacovigilance

     52   

5. COLLABORATION MANAGEMENT

     52   

5.1. Alliance Joint Steering Committee

     52   

5.2. Pipeline Advisory Committee

     57   

5.3. IP Committee

     58   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

5.4. Manufacturing Committee

     59   

5.5. Product Joint Steering Committees

     61   

5.6. No Power to Amend

     61   

5.7. Confidentiality

     61   

5.8. Modifications

     61   

5.9. Other Governance Terms

     61   

6. MANUFACTURE AND SUPPLY OF THE COLLABORATION PRODUCTS

     61   

6.1. ALN-TTR02 Supply Agreements

     61   

6.2. Collaboration Product Supply Agreements

     62   

6.3. General Supply Agreement Requirements

     62   

6.4. Disputed Supply Agreement Terms

     62   

6.5. Transfer of Manufacturing Know-How

     63   

6.6. Establishment of Second Source and Back-Up Sources

     63   

6.7. Third Party Manufacturers and Subcontracting

     63   

6.8. Waivers

     64   

7. CONFIDENTIALITY AND PUBLICATION

     64   

7.1. Nondisclosure Obligation

     64   

7.2. Publication and Publicity

     66   

7.3. Press Release

     67   

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

     68   

8.1. Mutual Representations and Warranties as of the Execution Date

     68   

8.2. Representations and Warranties of Alnylam

     69   

8.3. Warranty Disclaimer

     71   

8.4. Certain Covenants

     72   

9. ROYALTY REPORTS; PAYMENTS; AUDIT

     74   

9.1. Reports; Payment of Royalty

     74   

9.2. Audits

     74   

9.3. Payment Exchange Rate

     75   

9.4. Late Payments

     75   

9.5. Blocked Payments

     75   

9.6. Taxes

     76   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

10. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE

     76   

10.1. General Indemnification by Genzyme

     76   

10.2. General Indemnification by Alnylam

     77   

10.3. Product Liability

     77   

10.4. Indemnification Procedure

     77   

10.5. Limitation of Liability

     78   

10.6. Insurance

     78   

11. INTELLECTUAL PROPERTY

     79   

11.1. Prosecution and Maintenance of Patent Rights

     79   

11.2. Patent Prosecution Information Sharing

     79   

11.3. In-Licenses

     79   

11.4. Common Interest

     82   

12. TERM AND TERMINATION

     83   

12.1. Term

     83   

12.2. Termination Rights

     83   

12.3. Effect of Termination

     84   

13. MISCELLANEOUS

     86   

13.1. Assignment

     86   

13.2. Governing Law

     86   

13.3. Jurisdiction

     86   

13.4. Venue

     86   

13.5. Entire Agreement; Amendments

     87   

13.6. Severability

     87   

13.7. Headings

     87   

13.8. Waiver of Rule of Construction

     87   

13.9. Interpretation

     87   

13.10. No Implied Waivers; Rights Cumulative

     88   

13.11. Notices

     88   

13.12. Compliance with Export Regulations

     89   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

13.13.

   Force Majeure      89   

13.14.

   Independent Parties      90   

13.15.

   Counterparts      90   

13.16.

   Performance by Affiliates      90   

13.17.

   Binding Effect; No Third Party Beneficiaries      90   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

SCHEDULES

 

Schedule 1.2.7    Additional Alnylam In-Licenses Schedule 1.2.21    ALN-AT3
Schedule 1.2.22    ALN-TTR Core Technology Patents Schedule 1.2.24    ALN-TTR
Product-Specific Patents Schedule 1.2.26    ALN-TTR02 Schedule 1.2.29   
ALN-TTRsc Schedule 1.2.34    [***] Schedule 1.2.71    Core Pipeline Program List
Schedule 1.2.80    Form of Exercise Notice Schedule 1.2.82    Existing Alnylam
In-Licenses Schedule 1.2.88    Final Option Data Package Schedule 1.2.116   
Human POP Proposed Studies Schedule 1.2.123    Initial Option Data Package
Schedule 1.2.134    Locked Core Pipeline Program List Schedule 1.2.135    Locked
Non-Core Pipeline Program List Schedule 1.2.146    Named Pipeline Programs
Schedule 1.2.149    Non-Core Pipeline Program List Schedule 1.2.159    Option
Product Core Technology Patents Schedule 1.2.162    Option Product-Specific
Patents Schedule 1.2.178    Potential Alnylam In-Licenses Schedule 2.1.3.3   
Exempted Third Party CNS Agreements

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Schedule 6.1    ALN-TTR02 Supply Agreement Terms Schedule 6.2    Supply
Agreement Terms Schedule 7.3    Press Release Schedule 8.2    Disclosure
Schedule Schedule 10.2    Identified Patent Rights

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

APPENDICES

 

Appendix A    Regional License Terms Appendix B    Global License Terms
Appendix C    Co-Co License Terms

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

MASTER COLLABORATION AGREEMENT

THIS MASTER COLLABORATION AGREEMENT (this “Master Agreement”), entered into as
of January 11, 2014 (the “Execution Date”), is entered into by and between
Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the
laws of the State of Delaware (“Alnylam”), and, Genzyme Corporation, a
corporation organized and existing under the laws of the Commonwealth of
Massachusetts (“Genzyme”).

RECITALS:

WHEREAS, Alnylam, among other things, conducts programs to discover, to
characterize and to develop siRNAs targeting human genes;

WHEREAS, the Parties have entered into that certain License and Collaboration
Agreement dated as of October 18, 2012 (the “Historical TTR Agreement”) pursuant
to which Alnylam granted Genzyme certain exclusive licenses and other rights
with respect to the siRNAs known as ALN-TTR02 and ALN-TTRsc (and certain back-up
and improvement products) in certain Asian countries;

WHEREAS, Alnylam and Genzyme desire to enter into the transactions contemplated
by this Master Agreement, which will supersede and replace the Historical TTR
Agreement and under which, among other things, (1) Genzyme shall have certain
exclusive licenses and other rights with respect to ALN-TTR02 and ALN-TTRsc,
including the exclusive right to Develop and Commercialize ALN-TTR02 and
ALN-TTRsc on a regional basis outside North America and western Europe and the
further right to co-Commercialize ALN-TTRsc with Alnylam in North America and
western Europe, and (2) Genzyme shall have certain Options to obtain from
Alnylam exclusive licenses and other rights to certain of Alnylam’s other siRNAs
targeting human genes as potential treatments for Orphan Diseases (a) on a
regional basis outside North America and western Europe, (b) with respect to
certain siRNAs, on a global basis, or (c) with respect to a certain other siRNA
on a regional basis outside North America and western Europe with the right to
co-Commercialize such siRNA in North America and western Europe, in each case on
terms and conditions set forth in this Master Agreement and the License Terms
attached to this Master Agreement as Appendix A (Regional License Terms),
Appendix B (Global License Terms) and Appendix C (Co-Co License Terms);

WHEREAS, Alnylam and Genzyme desire to enter into exclusive discussions and
negotiations to potentially enter into an agreement under which the Parties
would collaborate to advance new technology for the delivery of siRNA to the CNS
with the objective of enabling the discovery of siRNAs for the treatment of CNS
disorders, and Genzyme would obtain certain rights to the technology and
products discovered in such collaboration;

WHEREAS, as partial consideration for Alnylam’s grant of the Options, licenses
and other rights to Genzyme under the Collaboration Agreement, Genzyme desires
to subscribe for and purchase from Alnylam, and Alnylam desires to issue and
sell to Genzyme, certain shares of Common Stock pursuant to the terms and
subject to the conditions set forth in the Stock Purchase Agreement; and

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

 

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MASTER AGREEMENT

 

WHEREAS, a more detailed overview of the transactions contemplated by this
Master Agreement is set forth in Section 1.1 (Overview of Transactions) below.

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the Parties hereby agree as follows:

1. OVERVIEW; DEFINITIONS

1.1. Overview of Transactions. This Master Agreement is part of the
Collaboration Agreement between Genzyme and Alnylam under which the Parties are
Developing and Commercializing ALN-TTR02 and ALN-TTRsc and under which Alnylam
has granted Genzyme various Options to obtain licenses to Develop and
Commercialize siRNAs generated by Alnylam’s Core Pipeline Programs, subject to
the terms and conditions of this Master Agreement. As of the Effective Date, the
Collaboration Agreement shall supersede and replace the Historical TTR Agreement
pursuant to which Alnylam granted Genzyme certain exclusive licenses and other
rights with respect to ALN-TTR02 and ALN-TTRsc in certain Asian countries. The
Collaboration Agreement consists of: (a) this Master Agreement; (b) the Regional
License Terms, which are attached to this Master Agreement as Appendix A;
(c) the Co-Co License Terms, which are attached to this Master Agreement as
Appendix B; (d) the Global License Terms, which are attached to this Master
Agreement as Appendix C; and (e) the schedules and exhibits attached to each of
the foregoing. As of the Effective Date, ALN-TTR02 shall be a Regional Licensed
Product and, as such, shall be governed by this Master Agreement and the
Regional License Terms. As of the Effective Date, ALN-TTRsc shall be a Co-Co
Licensed Product and, as such, shall be governed by this Master Agreement and
the Co-Co License Terms.

This Master Agreement includes, among other things, the terms of the various
Options granted to Genzyme (i.e., the Regional Option, the 2019 Trailing
Regional Option, the 2021 Trailing Regional Option, the Co-Co/Global Option, the
Global Option, the Additional Global Option and the Trailing Global Option), and
the process for exercising such Options. The Master Agreement sets forth, among
other things, the Parties’ obligations to one another with respect to the Core
Pipeline Programs during the period when Genzyme may exercise such Options.

This Master Agreement also contains certain terms and conditions that are
applicable to all of the “Collaboration Products” (i.e., siRNAs with respect to
which Genzyme exercises one of its Options) after Genzyme exercises an Option
with respect to any such Collaboration Product. For example, the Master
Agreement describes portions of the overall governance structure for the
Collaboration and also includes manufacture and supply terms, payment terms,
confidentiality and publication provisions, indemnification, limitations of
liability, insurance requirements, provisions regarding intellectual property
and in-licenses, and miscellaneous provisions that are applicable to the
Collaboration Products, subject to the terms and conditions of this Master
Agreement and the applicable License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Following Genzyme’s exercise of an Option for an siRNA generated by an Alnylam
Core Pipeline Program (or, with respect to ALN-TTR02 and ALN-TTRsc, following
the Effective Date of the Collaboration Agreement), the Development and
Commercialization of the applicable siRNA will be governed by this Master
Agreement and one of the 3 Appendices attached to the Master Agreement as
follows:

(1) The Regional License Terms will govern the Parties’ joint Development and
Commercialization of ALN-TTR02 and any siRNA for which Genzyme exercises a
Regional Option, including the 2019 Trailing Regional Option or a 2021 Trailing
Regional Option. Any such siRNA is referred to as a “Regional Licensed Product.”
Under the Regional License Terms, Genzyme shall acquire a license to Develop and
Commercialize Regional Licensed Products in only the Genzyme Territory.

(2) The Co-Co License Terms will govern the Parties’ joint Development and
Commercialization of ALN-TTRsc, and will also govern the Parties’ joint
Development and Commercialization of ALN-AT3 if Genzyme exercises the
Co-Co/Global Option to acquire a license to Develop and Commercialize ALN-AT3 in
the Genzyme Territory and to co-Commercialize ALN-AT3 in the Alnylam Territory.
Each such siRNA is referred to as a “Co-Co Licensed Product.” Subject to the
specific terms in this Master Agreement and to the Co-Co License Terms, the
Co-Co License Terms are largely identical to the Regional License Terms with
respect to the Genzyme Territory, but provide for additional terms governing the
co-Commercialization of Co-Co Licensed Products in the Alnylam Territory.

(3) The Global License Terms will govern Genzyme’s Development and
Commercialization of ALN-AS1 if Genzyme exercises the Co-Co/Global Option for
ALN-AS1, and any siRNA for which Genzyme exercises the Global Option, the
Additional Global Option or the Trailing Global Option. Each such siRNA is
referred to as a “Global Licensed Product.” Under the Global License Terms,
Genzyme shall acquire the exclusive right to Develop and Commercialize Global
Licensed Products worldwide.

Unlike the Master Agreement, which contains terms that apply to all
Collaboration Products, the License Terms include only terms that apply to the
specific type of Collaboration Product to which the License Terms relate, such
as economic terms, license grants, product-specific governance provisions,
Development and Commercialization provisions, intellectual property provisions,
and provisions relating to term and termination, including termination on a
product-by-product basis, in each case subject to the specific terms of the
License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2. Definitions.

Unless specifically set forth to the contrary herein, the following terms,
whether used in the singular or plural, shall have the respective meanings set
forth below:

1.2.1. “2019 Trailing Regional Option” has the meaning set forth in
Section 3.2.1.2 (2019 Trailing Regional Option Grant).

1.2.2. “2021 Trailing Regional Option” has the meaning set forth in
Section 3.2.1.3 (2021 Trailing Regional Option Grant).

1.2.3. “Acquirer” has the meaning set forth in Section 13.16.2 (Future
Acquisition of a Party or its Business).

1.2.4. “Action” has the meaning set forth in Section 13.3 (Jurisdiction).

1.2.5. “Active Alnylam Program” means an Alnylam Program that has generated an
siRNA (i) that achieved Clinical Success, (ii) that was administered to a
patient in a Phase III Study, (iii) for which Development activities have not
been terminated and (iv) in which Alnylam has retained commercial rights
anywhere in the world.

1.2.6. “Additional Global Option” has the meaning set forth in Section 3.2.3.2
(Additional Global Option Grant).

1.2.7. “Additional Alnylam In-Licenses” means (a) with respect to ALN-TTR02,
ALN-TTRsc and each Co-Co/Global Option Product, the Third Party agreements set
forth on Schedule 1.2.7; and (b) with respect to each Option Product, the
additional Third Party agreements that are identified in the applicable Option
Data Package as “Additional Alnylam In-Licenses” for such Option Product (which,
for clarity, shall include any of the Third Party agreements described in clause
(a) if the Patent Rights licensed to Alnylam under such agreements, if issued,
could be infringed by the Development, Manufacture or Commercialization of such
Option Product in the Genzyme Territory).

1.2.8. “AF11 Lipid Nanoparticle Formulation” [***].

1.2.9. “Affiliate” means, with respect to a Person, any other Person which
controls, is controlled by, or is under common control with the applicable
Person. For purposes of this definition, “control” shall mean: (a) in the case
of corporate entities, direct or indirect ownership of at least fifty percent
(50%) of the stock or shares entitled to vote for the election of directors, or
otherwise having the power to control or direct the affairs of such Person; and
(b) in the case of non-corporate entities, direct or indirect ownership of at
least fifty percent (50%) of the equity interest or the power to direct the
management and policies of such non-corporate entities.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.10. “ALAS-1” means the human ALAS-1 gene (also known as ALAS, ALAS3, ALASH,
aminolevulinate delta-synthase, Delta-ALA synthase, Delta-Aminolevulinate
synthase 1, 5-aminolevulinic acid synthase 1, ALAS-H, 5-aminolevulinate
synthase, MIG4, aminolevulinate synthase-1). As of the Execution Date, an
example of an identifier for the ALAS-1 gene is NCBI RefSeq code NM_000688 and
an example of an identifier for the ALAS-1 protein product is NCBI RefSeq code
NP_000679.

1.2.11. “Alliance Joint Steering Committee” or “AJSC” means the Alliance Joint
Steering Committee as more fully described in Section 5.1(Alliance Joint
Steering Committee).

1.2.12. “Alliance Manager” has the meaning set forth in Section 5.1.3 (Alliance
Managers).

1.2.13. “Alnylam Indemnitees” has the meaning set forth in Section 10.1 (General
Indemnification by Genzyme).

1.2.14. “Alnylam In-Licenses” means any Existing Alnylam In-License or any
Collaboration In-License to which Alnylam is a party.

1.2.15. “Alnylam Manufacturing Know-How” means any Know-How related to the
Manufacture of Option Products or Collaboration Products (or oligonucleotides
generally) Controlled by Alnylam at any time during the Term, to the extent such
Know-How is disclosed or made available to Genzyme by or on behalf of Alnylam.

1.2.16. “Alnylam Program” means any Development program conducted by Alnylam or,
subject to Section 13.16.2 (Future Acquisition of a Party or its Business), any
of its Related Parties to Develop an siRNA targeting a human gene.

1.2.17. “Alnylam Supply Agreements” means the ALN-TTR02 Clinical Supply
Agreement, the ALN-TTR02 Commercial Supply Agreement, each Clinical Supply
Agreement and each Commercial Supply Agreement.

1.2.18. “Alnylam Territory” means with respect to any Regional Licensed Product
or Co-Co Licensed Product, the countries of the United States, Canada, Austria,
Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg,
the Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway,
Switzerland, Liechtenstein, Andorra, Iceland and Greenland.

1.2.19. “Alnylam Territory MMC” means [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.20. “ALN-AS1” means (i) the first siRNA that targets ALAS-1 that is
generated by a Core Pipeline Program that achieves Human POP Study Completion or
(ii) if the siRNA described in clause (i) fails to achieve Clinical Success, the
next siRNA that is generated by a Core Pipeline Program and that targets ALAS-1.

1.2.21. “ALN-AT3” means (i) an siRNA Controlled by Alnylam, comprising the siRNA
(#ALN-[***]) conjugated to a GalNAc Conjugate, as further described on Schedule
1.2.21 or (ii) if the siRNA described in clause (i) fails to achieve Clinical
Success, the next siRNA that is generated by a Core Pipeline Program and that
targets Antithrombin.

1.2.22. “ALN-TTR Core Technology Patents” means the Alnylam Core Technology
Patents for ALN-TTR02 and the Alnylam Core Technology Patents for ALN-TTRsc. The
TTR Core Technology Patents existing as of the Execution Date are those Patent
Rights identified on Schedule 1.2.22.

1.2.23. “ALN-TTR Patents” means the Alnylam Patents for ALN-TTR02 and the
Alnylam Patents for ALN-TTRsc.

1.2.24. “ALN-TTR Product-Specific Patents” means the Alnylam Product-Specific
Patents for ALN-TTR02 and the Alnylam Product-Specific Patents for ALN-TTRsc.
The TTR Product-Specific Patents existing as of the Execution Date are those
Patent Rights identified on Schedule 1.2.24.

1.2.25. “ALN-TTR Technology” means the Alnylam Technology for ALN-TTR02 and the
Alnylam Technology for ALN-TTRsc.

1.2.26. “ALN-TTR02” means an siRNA Controlled by Alnylam, comprising the siRNA
(#AD[***]) formulated in an AF11 Lipid Nanoparticle Formulation, as further
described on Schedule 1.2.26.

1.2.27. “ALN-TTR Clinical Supply Agreement” has the meaning set forth in
Section 6.1 (ALN-TTR02 Supply Agreements).

1.2.28. “ALN-TTR Commercial Supply Agreement” has the meaning set forth in
Section 6.1 (ALN-TTR02 Supply Agreements).

1.2.29. “ALN-TTRsc” means an siRNA Controlled by Alnylam, comprising the siRNA
(#AD[***]) conjugated to a Ga1NAc Conjugate, as further described on Schedule
1.2.29. For the sake of clarity (but not for purposes of interpretation of the
Collaboration Agreement), even though ALN-TTRsc will be a Co-Co Licensed Product
that is subject to the Co-Co License Terms as of the Effective Date, ALN-TTRsc
will be exclusively licensed to Genzyme in the Genzyme Territory in much the
same way that ALN-TTR02 will be exclusively licensed to Genzyme in the Genzyme
Territory under the Regional License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.30. “Antithrombin” means the human antithrombin gene and its protein
product, antithrombin (also known as SERPINC1, antithrombin3, AT3 and ATIII). As
of the Execution Date, an example of an identifier for the antithrombin gene is
NCBI RefSeq code NM_000488 and an example of an identifier for the antithrombin
protein product is NCBI RefSeq code NP_000479.

1.2.31. “Antitrust Laws” means any federal, state or foreign law, regulation or
decree, including the HSR Act, designed to prohibit, restrict or regulate
actions for the purpose or effect of monopolization or restraint of trade.

1.2.32. “Available Third Party Right” has the meaning set forth in Section 3.6.3
(ROFN for Available Third Party Rights).

1.2.33. “Back-Up Source” has the meaning set forth in Section 6.6 (Obligation to
Establish).

1.2.34. [***].

1.2.35. “Blocking Patent Right” means a Patent Right Controlled by a Third Party
that Covers a Collaboration Product.

1.2.36. “Bulk Drug Product” has the meaning set forth in Schedule 6.1 or
Schedule 6.2, as applicable.

1.2.37. “Bulk Drug Substance” has the meaning set forth in Schedule 6.1 or
Schedule 6.2, as applicable.

1.2.38. “Calendar Quarter” means the respective periods of three (3) consecutive
calendar months ending on March 31, June 30, September 30 and December 31 of
each calendar year.

1.2.39. “Carbohydrate Conjugate” means a carbohydrate ligand covalently linked
to the 3’ end of the sense strand of an siRNA via a linker.

1.2.40. “cGMP” or “current Good Manufacturing Practices” means the then-current
standards for manufacturing activities for pharmaceuticals, as set forth in the
United States Federal Food, Drug, and Cosmetic Act, as amended, and applicable
regulations promulgated thereunder, as amended from time to time, and such
standards of good manufacturing practice as are required by other Governmental
Authorities in countries in which Option Products or Collaboration Products are
intended to be manufactured or sold.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.41. “Clinical Study” means a Phase I Study, Phase II Study, Phase III Study,
Post-Marketing Study, Secondary Indication Study or other study (including a
non-interventional study) in humans to obtain information regarding the product,
including information relating to the safety, tolerability, pharmacological
activity, pharmacokinetics, dose ranging or efficacy of the product.

1.2.42. “Clinical Success” means [***].

1.2.43. “Clinical Supply Agreement” has the meaning set forth in Section 6.2
(Collaboration Product Supply Agreements).

1.2.44. “CNS” has the meaning set forth in Section 2.1.3.1 (CNS Exploration
Period).

1.2.45. “CNS Collaboration and License Agreement” has the meaning set forth in
Section 2.1.3.1 (CNS Exploration Period).

1.2.46. “CNS Exploration Period” has the meaning set forth in Section 2.1.3.1
(CNS Exploration Period).

1.2.47. “CNS ROFN Exercise Notice” has the meaning set forth in Section 2.1.3.4
(ROFN for CNS).

1.2.48. “CNS ROFN Negotiation Period” has the meaning set forth in
Section 2.1.3.4 (ROFN for CNS).

1.2.49. “CNS ROFN Non-Binding Offer” has the meaning set forth in
Section 2.1.3.4 (ROFN for CNS).

1.2.50. “CNS ROFN Offer Period” has the meaning set forth in Section 2.1.3.4
(ROFN for CNS).

1.2.51. “CNS ROFN Period” has the meaning set forth in Section 2.1.3.4 (ROFN for
CNS).

1.2.52. “Co-Co License Terms” means the Co-Commercialization License and
Collaboration Terms attached hereto as Appendix C, under which (i) Alnylam and
Genzyme shall amend, restate and supersede the Historical TTR Agreement in
respect of ALN-TTRsc effective as of the Effective Date, and (ii) Alnylam may
grant Genzyme a license to ALN-AT3 effective as of the applicable Option
Exercise Date. For the sake of clarity (but not for purposes of interpretation
of the Collaboration Agreement), each Co-Co Licensed Product that becomes
subject to the Co-Co License Terms will be exclusively licensed to Genzyme in
the Genzyme Territory in much the same way that each Regional Licensed Product
will be exclusively licensed to Genzyme in the Genzyme

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Territory under the Regional License Terms, and will be licensed to Genzyme in
the Alnylam Territory to the extent necessary to enable Genzyme to
co-Commercialize such Co-Co Licensed Product in the Alnylam Territory as
contemplated by the Co-Co License Terms.

1.2.53. “Co-Co Licensed Product” means (i) ALN-TTRsc as of the Effective Date
and (ii) if Genzyme exercises the Co-Co/Global Option for ALN-AT3, then ALN-AT3
as of the applicable Option Exercise Date, in each case, for as long as the
Co-Co License Terms apply to ALN-TTRsc or ALN-AT3. For the sake of clarity (but
not for purposes of interpretation of the Collaboration Agreement), each Co-Co
Licensed Product that becomes subject to the Co-Co License Terms will be
exclusively licensed to Genzyme in the Genzyme Territory in much the same way
that each Regional Licensed Product will be exclusively licensed to Genzyme in
the Genzyme Territory under the Regional License Terms, and will be licensed to
Genzyme in the Alnylam Territory to the extent necessary to enable Genzyme to
co-Commercialize such Co-Co Licensed Product in the Alnylam Territory as
contemplated by the Co-Co License Terms.

1.2.54. “Co-Co/Global Option” has the meaning set forth in Section 3.2.2
(Co-Co/Global Option Grant).

1.2.55. “Co-Co/Global Option Product” means either (i) ALN-AT3 or (ii) ALN-AS1.

1.2.56. “Co-Co/Global Option Trigger Notice” has the meaning set forth in
Section 3.2.2.4 (Discontinuation of Second Co-Co/Global Option Product).

1.2.57. “Collaboration” means the collaboration of the Parties under the
Collaboration Agreement.

1.2.58. “Collaboration Agreement” means this Master Agreement and each of the
License Terms.

1.2.59. “Collaboration In-License” has the meaning set forth in Section 11.3.3.1
(Proposed In-Licenses).

1.2.60. “Collaboration Product” means any Regional Licensed Product, Co-Co
Licensed Product or Global Licensed Product, after exercise of the applicable
Option by Genzyme and the occurrence of the applicable Option Exercise Date and
effectiveness of the applicable License Terms, following which any such Option
Product shall cease to be an Option Product.

1.2.61. “Collaboration Product-Specific Payment” has the meaning set forth in
Section 11.3.4.2 (Collaboration In-Licenses).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.62. “Commercial Indication” means [***].

1.2.63. “Commercial Supply Agreement” has the meaning set forth in Section 6.2
(Collaboration Product Supply Agreements).

1.2.64. “Commercialization” or “Commercialize” means any and all activities
directed to marketing, promoting, distributing, importing, exporting, using,
offering to sell and/or selling a product, and activities directed to obtaining
pricing and reimbursement approvals, as applicable.

1.2.65. “Commercialization Plan” means (i) with respect a Regional Licensed
Product, the Alnylam Territory Commercialization Plan and the Genzyme Territory
Commercialization Plan, as such terms are defined under the Regional License
Terms, and (ii) with respect to a Co-Co Licensed Product, the Co-Co Territory
Commercialization Plan and the Genzyme Territory Commercialization Plan, as such
terms are defined under the Co-Co License Terms.

1.2.66. “Common Stock” means shares of common stock, par value $.01 per share,
of Alnylam.

1.2.67. “Confidential Information” means any and all confidential or proprietary
information and data (including Option Product Technology, ALN-TTR Technology,
Alnylam Technology (as defined in the License Terms), Genzyme Technology (as
defined in the License Terms), Genzyme Manufacturing IP and Genzyme Disclosed
Manufacturing Know-How (each as defined in the License Terms), Alnylam
Manufacturing Know-How and Joint Collaboration IP (as defined in the License
Terms)) and all other scientific, pre-clinical, clinical, regulatory,
manufacturing, marketing, financial and commercial information or data, whether
communicated in writing or orally or by any other method, which is or has been
provided by one Party to the other Party in connection with the Collaboration
Agreement, Stock Purchase Agreement, Investor Agreement or the Historical TTR
Agreement. Option Product Technology, Alnylam Manufacturing Know-How and Alnylam
Technology are the Confidential Information of Alnylam. Genzyme Technology,
Genzyme Manufacturing IP and Genzyme Disclosed Manufacturing Know-How are the
Confidential Information of Genzyme. Joint Collaboration IP and the terms of the
Collaboration Agreement, Stock Purchase Agreement, Investor Agreement and the
Historical TTR Agreement are the Confidential Information of both Parties,
subject to Section 7.1 (Nondisclosure Obligation).

1.2.68. “Control”, “Controls” or “Controlled by” means, with respect to any
Know-How, Patent Rights or other intellectual property right, the possession of
(whether by ownership or license, other than pursuant to the Collaboration
Agreement), the ability of a Person or its Affiliates to assign, transfer, or
grant access to, or to grant a license or sublicense of, such item or right as
provided for herein without violating the terms of any

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

agreement or other arrangement with any Third Party existing at the time such
Person would be required hereunder to assign, transfer or grant another Person
such access or license or sublicense, provided that with respect to rights to
any Third Party Know-How, Patent Rights or other intellectual property right
that are licensed to, or otherwise obtained by, a Party pursuant to an agreement
entered into by such Party, such Third Party Know-How, Patent Rights or other
intellectual property right shall be deemed not to be under the Control of such
Party unless the agreement pursuant to which such rights are obtained is an
In-License.

1.2.69. “Core Pipeline Dispute” has the meaning set forth in Section 5.1.8.2
(Escalation).

1.2.70. “Core Pipeline Program” means an Alnylam Program, existing as of the
Execution Date or initiated thereafter during the Option Period, to Develop an
siRNA targeting a human gene, where [***]. Core Pipeline Programs include as of
the Execution Date, without limitation, the Alnylam Programs identified on the
Core Pipeline Program List.

1.2.71. “Core Pipeline Program List” means the non-limiting list of Core
Pipeline Programs, attached hereto as Schedule 1.2.71, as the same may be
updated from time to time in accordance with Section 3.1.1 (Program
Identification). The Core Pipeline Programs as of the Execution Date are listed
on Schedule 1.2.71.

1.2.72. “Cost of Goods” means, with respect to the supply of a Product:
(a) where Alnylam or its Affiliates Manufacture such Product, the reasonable
internal and external costs incurred by Alnylam and its Affiliates in
Manufacturing such Product, including the fully allocated cost of Manufacture of
such Product, consisting of direct material and direct labor costs (including
direct material and labor costs incurred for facility start-up), plus overhead
directly attributable to the Manufacture of such Product (including all directly
incurred Manufacturing variances and a reasonable allocation of related
Manufacturing administrative, facilities operations and facilities depreciation
costs for such Product, but in all cases excluding corporate administrative
overhead and/or costs associated with excess capacity), all calculated strictly
in accordance with GAAP, and (b) where such Product is Manufactured by a Third
Party manufacturer, the actual fees paid by Alnylam to the Third Party for the
Manufacture and supply of such Product. Any CMC costs that can be classified
under Costs of Goods pursuant to GAAP will be classified as such for the
purposes of calculation of R&D Costs (as defined in the License Terms).

1.2.73. “Cover,” “Covering” or “Covers” means, as to a product and Patent
Rights, that, in the absence of a license granted under, or ownership of, such
Patent Rights, the manufacture, use, offer for sale, sale or importation of such
product would infringe such Patent Rights or, as to a pending claim included in
such Patent Rights, the manufacture, use, offer for sale, sale or importation of
such product would infringe such Patent Rights if such pending claim were to
issue in an issued patent.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.74. “CRO” means a contract research organization.

1.2.75. “Development,” “Developing” or “Develop” means under the Collaboration
Agreement, with respect to Option Products, Collaboration Products and other
siRNA, the research and development activities related to the generation,
characterization, optimization, construction, use and production of Option
Products, Collaboration Products or other siRNA, any other non-clinical,
pre-clinical or clinical research and development activities related to the
testing and qualification of Option Products, Collaboration Products or other
siRNA, as applicable, including toxicology studies, statistical analysis and
report writing, pre-clinical testing, formulation development, CMC activities,
Clinical Studies, regulatory affairs and registration activities, and all other
activities necessary to prepare and file applications for Regulatory Approval
and to seek, obtain and maintain Regulatory Approval.

1.2.76. “Development Plan” means (i) with respect a Regional Licensed Product,
the Global Development Plan, Alnylam Territory Development Plan and the Genzyme
Territory Development Plan, as such terms are defined under the Regional License
Terms, and (ii) with respect to a Co-Co Licensed Product, the Global Development
Plan and the Genzyme Territory Development Plan, as such terms are defined under
the Co-Co License Terms.

1.2.77. “DOJ” means the U.S. Department of Justice.

1.2.78. “Effective Date” has the meaning set forth in Section 2.1.1
(Effectiveness of Collaboration Agreement).

1.2.79. “EMA” means the European Medicines Agency and any successor Governmental
Authority having substantially the same function.

1.2.80. “Exercise Notice” means the written notice Genzyme delivers to Alnylam
to exercise an Option with respect to an Option Product, in the form set forth
on Schedule 1.2.80, containing the information set forth in such form.

1.2.81. “Existing Core Option Products” means the Option Products of the
following Core Pipeline Programs existing as of the Execution Date and listed on
the following referenced Schedule as of the Execution Date: (i) the Named
Pipeline Programs listed on Schedule 1.2.146, (ii) the Core Pipeline Programs on
the Locked Core Pipeline Program List set forth on Schedule 1.2.134, and
(iii) the Core Pipeline Programs listed in Section A (but not Section B) of
Schedule 1.2.71.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.82. “Existing Alnylam In-Licenses” means (a) with respect to ALN-TTR02,
ALN-TTRsc and any Co-Co/Global Option Product for which Genzyme exercises an
Option, the Third Party agreements set forth on Schedule 1.2.82 as of the
Execution Date; (b) with respect to each Option Product, additional Third Party
agreements that are identified in the applicable Option Data Package as
“Existing Alnylam In-Licenses” for such Option Product (which, for clarity,
shall include any of the Third Party agreements described in clause (a) if the
Patent Rights and Know-How licensed to Alnylam under such agreements are
necessary or useful for the Development, Manufacture or Commercialization of
such Option Product in the Genzyme Territory); and (c) any Additional Alnylam
In-License which is deemed to be an Existing Alnylam In-License pursuant to
Section 11.3.1 (Additional Alnylam In-Licenses), in each case ((a), (b) and (c))
as such agreement may be amended or supplemented from time-to-time.

1.2.83. “Existing Genzyme In-License” means, with respect to a Collaboration
Product, any agreement between Genzyme and a Third Party entered into on or
prior to the Option Exercise Date for such Collaboration Product pursuant to
which Genzyme Controls Know-How or Patent Rights that are necessary or useful to
Develop, Manufacture or Commercialize such Collaboration Product in the Field
under the applicable License Terms.

1.2.84. “Execution Date” has the meaning set forth in the preamble.

1.2.85. “Expert” has the meaning set forth in Section 5.1.8.3 (Resolution of
Core Pipeline Disputes).

1.2.86. “FDA” means the United States Food and Drug Administration and any
successor Governmental Authority having substantially the same function.

1.2.87. “Field” means the treatment, diagnosis or prevention of all human
diseases.

1.2.88. “Final Option Data Package” means, with respect to an Option Product:

 

  (a) [***].

 

  (b) [***].

1.2.89. “Finished Product” has the meaning set forth in Schedule 6.1 or Schedule
6.2, as applicable.

1.2.90. “First Co-Co/Global Option Product” has the meaning set forth in
Section 3.2.2.1 (First Co-Co/Global Option Product).

1.2.91. “FTC” means the U.S. Federal Trade Commission.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.92. “GAAP” means generally accepted accounting principles as practiced in
the United States or IFRS (International Financial Reporting Standards), in each
case, consistently applied.

1.2.93. “GalNAc Conjugate” means a triantennary N-acetylgalactosamine ligand
(GalNAc3) covalently linked to the 3’ end of the sense strand of the siRNA via a
linker.

1.2.94. “Genzyme Indemnitees” has the meaning set forth in Section 10.2 (General
Indemnification by Alnylam).

1.2.95. “Genzyme Disclosed Manufacturing Know-How” means Know-How (a) Controlled
by Genzyme at any time during the Term that is useful in the Manufacture of a
Regional Licensed Product and (b) that Genzyme, in its sole discretion,
discloses in writing to Alnylam in the course of the Collaboration.

1.2.96. “Genzyme In-Licenses” means any Existing Genzyme In-License or any
Collaboration In-License to which Genzyme is a party.

1.2.97. “Genzyme Patent Jurisdictions” means [***].

1.2.98. “Genzyme Supply Agreement” has the meaning set forth in Section
6.6.2.1(Qualification).

1.2.99. “Genzyme Territory” means (i) with respect to any Regional Licensed
Product or Co-Co Licensed Product, all countries and territories of the world
other than the Alnylam Territory and (ii) with respect to any Global Licensed
Product, worldwide.

1.2.100. “Genzyme Territory MMC” means [***].

1.2.101. “Global Development Plan” has the meaning set forth in the applicable
License Terms.

1.2.102. “Global Development Strategy” has the meaning set forth in the
applicable License Terms.

1.2.103. “Global/Additional Global Option Forfeiture” has the meaning set forth
in Section 3.4.2.2 (Exercise of Preserved Option).

1.2.104. “Global License Terms” means the Global Product License and
Collaboration Terms attached hereto as Appendix B, under which Alnylam may grant
Genzyme a license to (i) ALN-AS1 and/or (ii) a Global Option Product, in each
case with such license to be effective as of the applicable Option Exercise
Date.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.105. “Global Licensed Product” means (i) if Genzyme exercises the
Co-Co/Global Option for ALN-AS1, then ALN-AS1 as of the applicable Option
Exercise Date, and (ii) if Genzyme exercises the Global Option for any Global
Option Product, then such Global Option Product as of the applicable Option
Exercise Date, in each case for as long as the Global License Terms apply to
such Co-Co/Global Option Product or such Global Option Product.

1.2.106. “Global Option” has the meaning set forth in Section 3.2.3.1 (Global
Option Grant).

1.2.107. “Global Option Outside Date” means [***].

1.2.108. “Global Option Period” means the period beginning on the Effective Date
and ending on the earlier of (i) the occurrence of the Option Exercise Date for
the exercise of the Global Option and, if exercisable, the Additional Global
Option and (ii) the Global Option Outside Date.

1.2.109. “Global Option Product” means any siRNA targeting a human gene that is
generated by a Core Pipeline Program, where such Core Pipeline Program is not a
Named Pipeline Program.

1.2.110. “Global R&D Costs” has the meaning ascribed thereto in each of the
applicable License Terms.

1.2.111. “Global Regulatory Costs” has the meaning ascribed thereto in the Co-Co
License Terms.

1.2.112. “GLP” or “Good Laboratory Practices” means, with respect to a
particular Development activity or non-clinical study conducted by a Party, that
such Development activity or non-clinical study (i) was conducted in accordance
with “good laboratory practices” as set forth in 21 C.F.R. Part 58, the United
States Animal Welfare Act, the International Conference on Harmonization’s
(“ICH”) Guideline on Nonclinical Safety Studies for the Conduct of Human
Clinical Trials for Pharmaceuticals or the ICH Guideline on Safety Pharmacology
Studies for Human Pharmaceuticals or (ii) involved experimental research
techniques that were performed for informational purposes only (whether or not
included in a regulatory filing) or could not be performed by a GLP-compliant
testing facility (with appropriate notice being given to the FDA in regulatory
filings), and such Party employed the procedures and controls generally used by
qualified experts in animal or preclinical studies of products comparable to
those being developed by such Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.113. “Governmental Authority” means any applicable government authority,
court, tribunal, arbitrator, agency, department, legislative body, commission or
other instrumentality of (a) any government of any country or territory, (b) any
nation, state, province, county, city or other political subdivision thereof or
(c) any supranational body.

1.2.114. “Historical TTR Agreement” has the meaning set forth in the recitals.

1.2.115. “HSR Act” means the Hart-Scott-Rodino Antitrust Improvements Act of
1976, as amended.

1.2.116. “Human POP Study” means [***].

1.2.117. “Human POP Study Completion” means, with respect to an Option Product
or other siRNA, the [***] day [***].

1.2.118. “IFRS” means International Financial Reporting Standards, as
consistently applied.

1.2.119. “Implementation Date,” with respect to a Collaboration Product, has the
meaning set forth in the License Terms applicable to such Collaboration Product.

1.2.120. “IND” means an Investigational New Drug application, Clinical Trial
Application or similar application or submission for approval to conduct human
clinical investigations filed with or submitted to a Regulatory Authority in
conformance with the requirement of such Regulatory Authority, and any
amendments thereto.

1.2.121. “Indemnitee” has the meaning set forth in Section 10.4 (Indemnification
Procedure).

1.2.122. “Initial Evaluation Period” means, with respect to Option Product, the
[***] day period beginning on the date that Genzyme acknowledges receipt of an
Initial Option Data Package, as such period may be extended pursuant to
Section 3.3.4.3 (Extension of Initial Evaluation Period and Option Exercise
Period).

1.2.123. “Initial Option Data Package” means, with respect to an Option Product,
the information set forth on Schedule 1.2.123.

1.2.124. “Initial Option Notice” has the meaning set forth in Section 3.3.1
(Initial Option Data Package).

1.2.125. “In-Licenses” means, collectively, all Existing Alnylam In-Licenses,
all Existing Genzyme In-Licenses and all Collaboration In-Licenses.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.126. “Investor Agreement” means that certain Investor Agreement between
Genzyme and Alnylam, executed as of the Effective Date, as the same may be
amended from time to time.

1.2.127. “IP Committee” means the intellectual property advisory committee as
more fully described in Section 5.3 (IP Committee).

1.2.128. “Know-How” means all chemical or biological materials and other
tangible materials, inventions, improvements, practices, discoveries,
developments, data, information, technology, methods, protocols, formulas,
knowledge, know-how, trade secrets, processes, assays, skills, experience,
techniques and results of experimentation and testing, including
pharmacological, toxicological and pre-clinical and clinical data and analytical
and quality control data; provided, however, excluding in any event any Patent
Right and Trademarks.

1.2.129. “KPIs” has the meaning set forth in Section 6.3 (General Supply
Agreement Requirements).

1.2.130. “Laws” means all applicable laws, statutes, rules, regulations, orders,
judgments, injunctions, ordinances or other pronouncements having the binding
effect of law of any Governmental Authority, including if either Party is or
becomes subject to a legal obligation to a Regulatory Authority or other
Governmental Authority (such as a corporate integrity agreement or settlement
agreement with a Governmental Authority).

1.2.131. “License Terms” means the Regional License Terms, the Co-Co License
Terms or the Global License Terms, as applicable.

1.2.132. “Licensed Target” means, for each Collaboration Product, the human gene
that is targeted by such Collaboration Product.

1.2.133. “Lipid Nanoparticle Formulation” means a lipid-based nanoparticle
comprising more than one lipid species designed to enable delivery of siRNAs to
mammalian cells.

1.2.134. “Locked Core Pipeline Program List” means the list of Core Pipeline
Programs, as the same may be updated from time to time in accordance with
Section 3.1.1 (Program Identification), identifying those Core Pipeline Programs
that shall remain Core Pipeline Programs for all purposes under the
Collaboration Agreement, except as the Parties, each acting in its sole
discretion, may later mutually agree in writing. The Core Pipeline Programs that
exist as of the Execution Date and shall be included on the Locked Core Pipeline
Program List are identified on Schedule 1.2.134.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.135. “Locked Non-Core Pipeline Program List” means the list of Non-Core
Pipeline Programs, as the same may be updated from time to time in accordance
with Section 3.1.1 (Program Identification), identifying those Non-Core Pipeline
Programs that shall remain Non-Core Pipeline Programs for all purposes under the
Collaboration Agreement, except as the Parties, each acting in its sole
discretion, may later mutually agree in writing. The Non-Core Pipeline Programs
that exist as of the Execution Date and shall be included on the Locked Non-Core
Pipeline Program List are identified on Schedule 1.2.135.

1.2.136. “Losses” has the meaning set forth in Section 10.1 (General
Indemnification by Genzyme).

1.2.137. “Manufacturing” or “Manufacture” means, as applicable, all activities
associated with the production, manufacture, process of formulating, processing,
filling, finishing, packaging, labeling, shipping, importing and storage of
Collaboration Products or Option Products (including Bulk Drug Product, Bulk
Drug Substance and Finished Product) including process development, process
validation, stability testing, manufacturing scale-up, pre-clinical, clinical
and commercial manufacture and analytical development, product characterization,
quality assurance and quality control development, testing and release.

1.2.138. “Manufacturing Committee” means the manufacturing advisory committee as
more fully described in Section 5.4 (Manufacturing Committee).

1.2.139. “Manufacturing FTE” means [***] hours of work per annum devoted to or
in support of the Development or Manufacture of a Collaboration Product that is
carried out by one or more qualified scientific or technical employees of a
Party or its Affiliates.

1.2.140. “Manufacturing FTE Rate” means [***] per Manufacturing FTE, increased
annually beginning, for the first time, on January 1, 2015 and thereafter on
January 1 of each succeeding year by the percentage increase in the CPI as of
December 31 of the then most recently ended calendar year over the level of the
CPI on December 31, 2013.

1.2.141. “Merger Control Authorities” means all relevant Governmental
Authorities under applicable Antitrust Laws, including the FTC and DOJ.

1.2.142. “MicroRNA” or “miRNA” means a structurally defined functional RNA
molecule usually between nineteen (19) and twenty-five (25) nucleotides in
length, which is derived from an endogenous, genetically-encoded non-coding RNA
which is predicted to be processed into a hairpin RNA structure that is a
substrate for the double-stranded RNA-specific ribonuclease Drosha and
subsequently is predicted to serve as a substrate for the enzyme Dicer, a member
of the RNase III enzyme family.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.143. “MicroRNA Mimic” means a single-stranded or double-stranded
oligonucleotide with the same or substantially similar-base composition and
sequence (including chemically modified bases) as a particular natural miRNA and
which is designed to mimic the activity of such miRNA. For clarity, miRNA Mimic
excludes a double-stranded oligonucleotide which functions or is designed to
function as an siRNA.

1.2.144. “Minimum Annual Investment” means [***],

1.2.145. “MMC” means any Alnylam Territory MMC or Genzyme Territory MMC.

1.2.146. “Named Pipeline Programs” means those Alnylam Programs listed on
Schedule 1.2.146.

1.2.147. “NDA” means a New Drug Application, Biologics License Application,
Marketing Authorization Application or similar application or submission filed
with a Regulatory Authority in a country or group of countries to obtain
Regulatory Approval to market a product in that country or in that group of
countries, and any amendments thereto.

1.2.148. “Negotiation Period” has the meaning set forth in Section 6.6.2.2
(Negotiating Period).

1.2.149. “New Information” has the meaning set forth in Section 3.4.2.3
(Exercise of Preserved Option).

1.2.150. “Non-Core Pipeline Program List” means the non-limiting list of
Non-Core Pipeline Programs, attached hereto as Schedule 1.2.149, as the same may
be updated from time to time by Alnylam in accordance with Section 3.1.1
(Program Identification). The Non-Core Pipeline Programs as of the Execution
Date are listed on Schedule 1.2.149.

1.2.151. “Non-Sales-Based Payment” means any Third Party License Payment that is
not a Sales-Based Payment.

1.2.152. “Option” means any Regional Option, the Co-Co/Global Option, the Global
Option, the Additional Global Option, the 2019 Trailing Regional Option, any
2021 Trailing Regional Option or any Trailing Global Option, as applicable.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.153. “Option Data Package” means, with respect to an Option Product, the
Initial Option Data Package or, if applicable, the Final Option Data Package for
such Option Product.

1.2.154. “Option Exercise Date” means the date on which an Exercise Notice is
deemed to have been given by Genzyme to Alnylam pursuant to Section 13.11
(Notices) or such later date as may be required pursuant to Section 2.2.2
(Effectiveness of Licenses to Collaboration Products).

1.2.155. “Option Exercise Period” means:

(a) with respect to any Regional Option Product or ALN-AT3, the period [***];

(b) with respect to ALN-AS1 or any Global Option Product, the period [***]; or

(c) if Alnylam delivers a Co-Co/Global Option Trigger Notice under
Section 3.2.2.4 (Discontinuation of Second Co-Co/Global Option Product) for the
First Co-Co/Global Option Product, the [***] day period following Genzyme’s
acknowledgement of receipt of such notice, as such period may be extended
pursuant to 3.3.4.3 (Extension of Initial Evaluation Period and Option Exercise
Period).

1.2.156. “Option Period” means the period beginning on the Effective Date and
ending on the date that no Option remains exercisable.

1.2.157. “Option Preservation Notice” has the meaning set forth in Section 3.3.2
(Initial Evaluation Period).

1.2.158. “Option Product” means any Regional Option Product (including any
Trailing Regional Option Product), Co-Co/Global Option Product or Global Option
Product (including any Trailing Global Option Product).

1.2.159. “Option Product Core Technology Patents” means Patent Rights Controlled
by Alnylam during the Option Period that are reasonably necessary or useful to
Develop, Commercialize, and/or Manufacture Option Products, other than Option
Product-Specific Patents. Option Product Core Technology Patents include Patent
Rights Controlled by Alnylam that claim [***]. The Option Product Core
Technology Patents existing as of the Execution Date, solely in respect of the
Existing Core Option Products, are those Patent Rights identified on Schedule
1.2.159.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.160. “Option Product Know-How” means Know-How Controlled by Alnylam during
the Term that is reasonably necessary or useful for Genzyme to Develop,
Manufacture and/or Commercialize Option Products in the Field.

1.2.161. “Option Product Patents” means Option Product Core Technology Patents
and Option Product-Specific Patents.

1.2.162. “Option Product-Specific Patents” means Patent Rights Controlled by
Alnylam during the Term that claim [***]. The Option Product-Specific Patents
existing as of the Execution Date, solely in respect of the Existing Core Option
Products, are those Patent Rights identified on Schedule 1.2.162.

1.2.163. “Option Product Technology” means, collectively, Option Product
Know-How and Option Product Patents.

1.2.164. “Optioned Target” means, for each Option Product, the human gene that
is intended to be targeted by the Option Product.

1.2.165. “Orphan Disease” means [***].

1.2.166. “Out-of-Pocket Costs” means, with respect to certain activities
hereunder, direct expenses paid or payable by either Party or its Affiliates to
Third Parties and specifically identifiable and incurred (and invoiced) to
conduct such activities for an Option Product or a Collaboration Product, as
applicable, including payments to contract personnel.

1.2.167. “Party” means Genzyme or Alnylam.

1.2.168. “Patent Challenge” has the meaning set forth in Section 12.2.4
(Challenges of Patent Rights).

1.2.169. “Patent Rights” means (a) all issued patents (including any extensions,
restorations by any existing or future extension or registration mechanism
(including patent term adjustments, patent term extensions, supplemental
protection certificates or the equivalent thereof), substitutions,
confirmations, re-registrations, re-examinations, and patents of addition);
(b) patent applications (including all provisional applications, substitutions,
requests for continuation, continuations, continuations-in-part, divisionals and
renewals); (c) inventor’s certificates; and (d) all equivalents of the foregoing
in any country of the world.

1.2.170. “Paying Party” has the meaning set forth in Section 9.6 (Taxes).

1.2.171. “Permitted Third Party Agreement” has the meaning set forth in
Section 3.6.3 (ROFN for Available Third Party Rights).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.172. “Person” means any natural person, corporation, unincorporated
organization, partnership, association, sole proprietorship, joint stock
company, joint venture, limited liability company, trust or government, or
Governmental Authority, or any other similar entity.

1.2.173. “Phase I Study” means a study in humans which provides for the
introduction into humans of a product, conducted in healthy volunteers or
patients, to obtain initial information on product safety, tolerability,
pharmacological activity or pharmacokinetics, as further defined in 21 C.F.R. §
312.21(a) (or the equivalent thereof outside the United States).

1.2.174. “Phase II Study” means a study in humans of the safety, dose ranging or
efficacy of a product, as further defined in 21 C.F.R. § 312.21(b) (or the
equivalent thereof outside the United States).

1.2.175. “Phase III Study” means a study in humans of the efficacy and safety of
a product, which is prospectively designed to demonstrate statistically whether
such product is effective and safe for use in a particular indication in a
manner sufficient (alone or together with one or more other such studies) to
file an application for Regulatory Approval for the product. For the avoidance
of doubt, the Parties acknowledge that, because of the nature of the diseases
which the Collaboration Products are anticipated to treat, a Phase III Study for
a Collaboration Product may not include all of the elements that a Phase III
Study for other kinds of drug products may include (e.g., a Phase III Study for
a Collaboration Product may be a single study and there may be no prospective
plan to run a second pivotal clinical trial independent of such Phase III
Study).

1.2.176. “Pipeline Advisory Committee” or “PAC” means the pipeline advisory
committee as more fully described in Section 5.2 (Pipeline Advisory Committee).

1.2.177. “Post-Marketing Study” means a non-human or human clinical study of a
Collaboration Product initiated after receipt of Regulatory Approval for such
Collaboration Product in a country or territory, that is required by the
Regulatory Authority in such country or territory to maintain the Regulatory
Approval for such Collaboration Product in such country or territory, but
excluding any Secondary Indication Study.

1.2.178. “Potential Alnylam In-Licenses” means, with respect to ALN-TTR02,
ALN-TTRsc and each Option Product, the potential future Third Party agreements
described on Schedule 1.2.178.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.179. “Product” means a given quantity of Collaboration Product in one of
Bulk Drug Substance, Bulk Drug Product or Finished Product form.

1.2.180. “Proposed CNS Terms” has the meaning set forth in Section 2.1.3.4 (ROFN
for CNS).

1.2.181. “Proposed In-License” has the meaning set forth in Section 11.3.3.1
(Proposed In-Licenses).

1.2.182. “Proposed In-License Notice” has the meaning set forth in
Section 11.3.3.1 (Proposed In-Licenses).

1.2.183. “Receiving Party” has the meaning set forth in Section 9.6 (Taxes).

1.2.184. “Regional License Terms” means those certain Regional Product License
and Collaboration Terms between Genzyme and Alnylam, in the form of Appendix A
attached hereto, under which (i) Alnylam and Genzyme shall amend, restate and
supersede the Historical TTR Agreement in respect of ALN-TTR02, effective as of
the Effective Date, and (ii) Alnylam may grant Genzyme a license to one or more
Regional Licensed Products, effective as of the applicable Option Exercise Date.

1.2.185. “Regional Licensed Product” means (i) ALN-TTR02 as of the Effective
Date, and (ii) if Genzyme exercises a Regional Option for any Regional Option
Product, then such Regional Option Product as of the applicable Option Exercise
Date, in each case for as long as the Regional License Terms applies to
ALN-TTR02 or any such Regional Option Product.

1.2.186. “Regional Option” has the meaning set forth in Section 3.2.1.1
(Regional Option Grants).

1.2.187. “Regional Option Outside Date” means [***].

1.2.188. “Regional Option Period” means the period beginning on the Effective
Date and ending on the Regional Option Outside Date.

1.2.189. “Regional Option Product” means an siRNA that is generated by a Core
Pipeline Program. For clarity, any such siRNA shall constitute a Regional Option
Product even if any such Regional Option Product is also a Co-Co/Global Option
Product or a Global Option Product.

1.2.190. “Regulatory Approval” means any and all approvals, licenses,
registrations or authorizations of any Regulatory Authority that are necessary
for the marketing and sale of a product in a country or group of countries.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.191. “Regulatory Authority” means any Governmental Authority involved in
granting approvals for the Development, Manufacturing, Commercialization,
reimbursement or pricing of Option Products or Collaboration Products, including
the FDA, the EMA, the Japanese Ministry of Health, Labour and Welfare (“MHLW”)
and the Pharmaceuticals and Medical Devices Agency in Japan (“PMDA”).

1.2.192. “Regulatory Briefing Document” has the meaning set forth in
Section 3.3.3.1 (Final Option Data Package).

1.2.193. “Related Party” means a Party’s Affiliates and permitted Sublicensees
(as defined in any of the License Terms).

1.2.194. “Residual Knowledge” means knowledge, techniques, experience and
Know-How that (a) are, or are based on any Confidential Information of the
disclosing Party and (b) are retained in the unaided memory of any authorized
representative of the receiving Party after having access to such Confidential
Information. An individual’s memory shall be considered to be unaided if the
individual has not intentionally memorized the Confidential Information for the
purpose of retaining and subsequently using or disclosing it. In no event,
however, shall Residual Knowledge include (i) any Genzyme Disclosed
Manufacturing Know-How, (ii) any Alnylam Manufacturing Know-How or (iii) any
Know-How to the extent (at any time, for such time) it is within the scope of
any issued, valid and enforceable Patent Right Controlled by the disclosing
Party under any License Terms.

1.2.195. “ROFN Exercise Notice” has the meaning set forth in Section 3.6.3 (ROFN
for Available Third Party Rights).

1.2.196. “ROFN Negotiation Period” has the meaning set forth in Section 3.6.3
(ROFN for Available Third Party Rights)

1.2.197. “ROFN Non-Binding Offer” has the meaning set forth in Section 3.6.3
(ROFN for Available Third Party Rights)

1.2.198. “ROFN Offer Notice” has the meaning set forth in Section 3.6.3 (ROFN
for Available Third Party Rights)

1.2.199. “Safety Concern” means (a) any safety concern required to be reported
under 21 C.F.R. § 312.32(c)(1)(iii) (“Findings from animal or in vitro testing”)
if an IND with respect to such Option Product was open at the time of the
observation or (b) a material toxicity or material drug safety issue or a
Serious Adverse Event reasonably related to an Option Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.200. “Sales-Based Payment” means any Third Party License Payment that is
calculated based on sales of a product (e.g., royalties and sales milestones).

1.2.201. “SDEA” has the meaning set forth in Section 4.6 (Pharmacovigilance).

1.2.202. “Second Co-Co/Global Option Product” has the meaning set forth in
Section 3.2.2.2 (Second Co-Co/Global Option Product).

1.2.203. “Second Source” has the meaning set forth in Section 6.6 (Establishment
of Second Source).

1.2.204. “Secondary Indication” means a use of a Collaboration Product or Option
Product for an indication that is not the first indication of such Collaboration
Product or Option Product to receive Regulatory Approval, but is intended to be
the subject of a supplemental application submitted to a Regulatory Authority
that includes clinical trial data from a Clinical Study seeking Regulatory
Approval to market the Collaboration Product or Option Product for such use.

1.2.205. “Secondary Indication Study” means a human clinical study of a
Collaboration Product or Option Product that is not necessary for receipt of the
first anticipated Regulatory Approval for such Collaboration Product or Option
Product in a country or territory but is intended to support receipt of
Regulatory Approval for a Secondary Indication.

1.2.206. “Serious Adverse Event” means an adverse drug experience or
circumstance that results in any of the following outcomes (a) death,
(b) life-threatening condition, (c) inpatient hospitalization or a significant
prolongation of existing hospitalization, (d) persistent or significant
disability or incapacity or substantial disruption of the ability to conduct
normal life functions, (e) or a congenital anomaly/birth defect or
(f) significant intervention required to prevent permanent impairment or damage.

1.2.207. “siRNA” means an oligonucleotide composition of native or chemically
modified RNA that targets a gene through activation of the RNA interference
pathway, and that is not a MicroRNA, MicroRNA antagonist or MicroRNA Mimic.

1.2.208. “Stock Purchase Agreement” means that certain Stock Purchase Agreement
between Genzyme and Alnylam, executed as of the Execution Date, as the same may
be amended from time to time.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.209. “Supply Agreements” means the Clinical Supply Agreements, the
Commercial Supply Agreements, the ALN-TTR Clinical Supply Agreement and the
ALN-TTR Commercial Supply Agreement.

1.2.210. “Supply Expert” has the meaning set forth in Section 6.3 (Disputed
Supply Agreement Terms).

1.2.211. “Supply Source Notice” has the meaning set forth in Section 6.6.2.2
(Negotiating Period).

1.2.212. “Technology Transfer” has the meaning set forth in Section 6.5
(Transfer of Manufacturing Know-How).

1.2.213. “Tentative Core Pipeline Program” has the meaning set forth in
Section 3.1.1.3(b) (Pipeline Programs Lists).

1.2.214. “Tentative Core Pipeline Program List” has the meaning set forth in
Section 3.1.1.3(b) (Pipeline Programs Lists).

1.2.215. “Term” has the meaning set forth in Section 12.1 (Term).

1.2.216. “Territory” means (i) with respect to Alnylam, the Alnylam Territory
and (ii) with respect to Genzyme, the Genzyme Territory.

1.2.217. “Third Party” means an entity other than a Party and its Affiliates.

1.2.218. “Third Party CNS Agreement” has the meaning set forth in
Section 2.1.3.2 (CNS Exclusivity).

1.2.219. “Third Party License Payment” means royalties, upfront fees, milestones
or other amounts payable under an In-License in consideration for the rights
granted under such In-License with respect to a Patent Right.

1.2.220. “Third Party Pricing Terms” means, in respect of the supply of a
Product, (i) the cost per unit of Product, (ii) minimum order quantities (per
batch and annually), (iii) firm order forecast requirements, (iv) cost, if any,
for reserving capacity including any costs required to maintain compliance, and
(v) capital costs, if any, to enable manufacturing.

1.2.221. “Third Party Supply Agreement” has the meaning set forth in Section 6.7
(Third Party Manufacturer as Second Source).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

1.2.222. “Trademark” means any trademark, trade name, service mark, service
name, brand, domain name, trade dress, logo, slogan or other indicia of origin
or ownership, including the goodwill and activities associated with each of the
foregoing.

1.2.223. “Trailing Global Option Product” means a Global Option Product (i)
[***].

1.2.224. “Trailing Global Option” has the meaning set forth in 3.2.3.3 (Trailing
Global Option Grant).

1.2.225. “Trailing Regional Option Product” means a Regional Option Product
[***].

1.2.226. “Transition Period” means the period beginning on Alnylam’s receipt of
an Option Preservation Notice with respect to an Option Product and ending on
the earlier of (x) the Option Exercise Date for such Option Product or (y) the
expiration of the Option Exercise Period for such Option Product.

1.2.227. [***].

1.2.228. “TTR” means the human TTR gene and its protein product, transthyretin.
As of the Execution Date, an example of an identifier for the human TTR gene is
the NCBI RefSeq code NM_000371.3 and an example of an identifier for the human
TTR gene protein product NCBI RefSeq code NP_000362.1.

1.2.229. “Un-Blocking Genzyme In-License” means, with respect to a Collaboration
Product, any Collaboration In-License that Genzyme enters into in accordance
with Section 11.3.3 (Collaboration In-Licenses) and pursuant to which Genzyme
has a license to any Blocking Patent Right with respect to such Collaboration
Product.

1.2.230. “United States” means the United States of America and its territories,
possessions and commonwealths.

Capitalized terms used, but not defined, herein shall have the meanings ascribed
to those terms in the License Terms.

2. EFFECTIVENESS OF AGREEMENTS AND LICENSES

2.1. Effective Date.

2.1.1. Effectiveness of Collaboration Agreement. Upon the occurrence of the
Closing Date under the Stock Purchase Agreement (the “Effective Date”), the
Collaboration Agreement, which consists of this Master Agreement and the License

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Terms listed below, shall automatically, with no further action by any Party, go
into full force and effect and all of the obligations of the applicable Party
set forth therein (including in this Master Agreement) shall become the binding
obligations of the applicable Party thereto:

 

  (a) Regional License Terms;

 

  (b) Global License Terms; and

 

  (c) Co-Co License Terms.

2.1.2. Termination of Historical TTR Agreement. Simultaneous with the
Collaboration Agreement going into full force and effect on the Effective Date,
the Historical TTR Agreement shall be terminated in its entirety and superseded
in its entirety by the Collaboration Agreement on the Effective Date, provided
that all rights and obligations accrued under the Historical TTR Agreement shall
continue for and against the Parties under the terms of the Collaboration
Agreement.

2.1.3. CNS Collaboration.

2.1.3.1. CNS Exploration Period. During the [***] year period beginning on the
Effective Date (the “CNS Exploration Period”), the Parties will use commercially
reasonable efforts to assess the state of the art in the area of delivery of
siRNAs to the central nervous system (“CNS”), including identifying Third
Parties with relevant expertise and technology and, at Genzyme’s request,
(a) develop a plan to jointly undertake research and development of siRNAs for
delivery to the CNS and (b) negotiate in good faith and enter into a mutually
agreeable collaboration and license agreement pursuant to which the Parties will
conduct the research and development activities set forth in such plan (the “CNS
Collaboration and License Agreement”), which CNS Collaboration and License
Agreement shall contain customary and reasonable provisions for agreements of
its type that may be agreed by the Parties, including provisions relating to
governance, intellectual property ownership, prosecution and enforcement,
regulatory interactions and approvals, term and termination, representations and
warranties, indemnification, and confidentiality. Each Party will dedicate
employees within its organization with appropriate expertise in CNS and/or rare
diseases to conducting the activities described in this Section 2.1.3.

2.1.3.2. CNS Exclusivity. Subject to Section 2.1.3.3 (Exceptions to CNS
Exclusivity), during the CNS Exploration Period, neither Party shall enter into
any agreement with a Third Party regarding the development or commercialization
of siRNAs delivered to the CNS (a “Third Party CNS Agreement”) without the prior
written consent of the other Party, provided that Genzyme may terminate the CNS
Exploration Period at any time upon written notice to Alnylam.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.1.3.3. Exceptions to CNS Exclusivity.

(a) Existing Third Party Agreements. None of the following agreements in
existence or being negotiated on the Execution Date shall constitute a “Third
Party CNS Agreement” for purposes of this Master Agreement: (i) the agreements
between Genzyme and a Third Party that will be identified by Genzyme by the
Effective Date and added to Schedule 2.1.3.3 and (ii) the agreements between
Alnylam and a Third Party, listed on Schedule 2.1.3.3, in each case ((i) and
(ii)) as such agreements may be amended or restated in the future so long as
such amendment or restatement does not expand the field of such agreement, and
the activities thereunder and discussions with such Third Party in relation
thereto.

(b) Future Third Party Agreements. The following shall not constitute “Third
Party CNS Agreements” for purposes of this Master Agreement: (i) any agreement
between a Party and a contractor, contract research organization, contract
manufacturer or other Third Party, under which such Third Party only performs
contract services on behalf of such Party, for the research, development or
manufacture of siRNAs delivered to the CNS and for which no product-related
commercial rights are granted or (ii) any agreement between a Party and an
academic institution or non-profit institution, under which such Party and such
institution collaborate with respect to the research, development or manufacture
of siRNAs delivered to the CNS and for which no product-related commercial
rights are granted.

(c) Internal Activities. Notwithstanding anything in this Section 2.1.3 (CNS
Collaboration), either Party may conduct internal programs and other activities
regarding the research, development, manufacture and commercialization of siRNAs
to be delivered to the CNS.

2.1.3.4. ROFN for CNS.

(a) ROFN Process. If Genzyme makes a request to negotiate under Section 2.1.3.1,
but the Parties do not enter into, a CNS Collaboration and License Agreement
during the CNS Exploration Period and Genzyme does not terminate the CNS
Exploration Period prior to its expiration, then, if at any time during the
[***] year period following the CNS Exploration Period (the “CNS ROFN

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Period”), Alnylam desires to enter into a Third Party CNS Agreement, Alnylam
shall so notify Genzyme in writing, which notice shall describe the proposed
terms of such Third Party CNS Agreement (the “Proposed CNS Terms”). Upon receipt
of such notice from Alnylam, Genzyme shall have [***] days from receipt of such
written notice to notify Alnylam in writing as to whether Genzyme desires to
negotiate an agreement with Alnylam with respect to the Proposed CNS Terms (a
“CNS ROFN Exercise Notice”). If Genzyme delivers a CNS ROFN Exercise Notice
prior to the expiration of such [***] day period, Genzyme shall have the
exclusive right [***] days following the date that Genzyme delivers a CNS ROFN
Exercise Notice (the “CNS ROFN Offer Period”) to negotiate with Alnylam and to
make one or more written non-binding offers to Alnylam concerning the terms on
which Genzyme would enter into an agreement with respect to the Proposed CNS
Terms (the “CNS ROFN Non-Binding Offer”). If Genzyme delivers a CNS ROFN
Non-Binding Offer to Alnylam prior to the expiration of the CNS ROFN Offer
Period, Genzyme shall thereafter have the exclusive right for [***] days (or
such longer period as may be mutually agreed by the Parties) (the “CNS ROFN
Negotiation Period”), to finalize and enter into a definitive agreement with
Alnylam with respect to the Proposed CNS Terms.

(b) Post-ROFN MFN. Alnylam shall not, during the CNS ROFN Offer Period or CNS
ROFN Negotiation Period, enter into discussions, exchange information, or
otherwise negotiate with any Third Party with respect to the Proposed CNS Terms.
If (i) Genzyme does not provide a CNS ROFN Exercise Notice within [***] days of
receiving notice of the Proposed CNS Terms, (ii) Genzyme does not provide a CNS
ROFN Non-Binding Offer prior to the expiration of the CNS ROFN Offer Period
prior to the expiration of the CNS ROFN Offer Period, or (iii) the Parties do
not enter into a definitive agreement with respect to the Proposed CNS Terms
prior to the expiration of the CNS ROFN Negotiation Period, then Alnylam shall
be free to enter into an agreement with any Third Party with respect to such
Proposed CNS Terms, provided that, for the remainder of the CNS ROFN Period,
Alnylam shall not enter into an agreement with respect to such Proposed CNS
Terms that are, in the aggregate, materially more favorable to such Third Party
than the last terms offered in writing by Genzyme to Alnylam during the CNS ROFN
Offer Period or CNS ROFN Negotiation Period, as applicable, unless Alnylam first
re-offers to enter into an agreement with Genzyme on such more favorable terms
and Genzyme does not accept such offer and enter into such agreement with
Alnylam within [***] days after such re-offer. For clarity, prior to the CNS
ROFN Offer Period and CNS ROFN Exercise Period, Alnylam shall be free to engage
in discussions and exchange information with Third Parties with respect to
development or commercialization of siRNAs delivered to the CNS, but shall not
enter into any binding agreement with any Third Party with respect to such
rights.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(c) Notwithstanding the foregoing, in the event that Genzyme enters into any
Third Party CNS Agreement following the Execution Date without the prior written
consent of Alnylam, Genzyme’s exclusive rights under this Section 2.1.3 shall
automatically convert to non-exclusive rights and the proviso set forth in
Section 2.1.3.4(b) (Post-ROFN MFN) shall automatically no longer apply. The
foregoing shall be Alnylam’s sole and exclusive remedy with respect to any
breach of Section 2.1.3.2 (CNS Exclusivity) by Genzyme.

2.2. Effectiveness of Licenses to Collaboration Products. As promptly as
practicable following Alnylam’s delivery of a Final Option Data Package to
Genzyme, but not later than the applicable Option Exercise Date, Genzyme shall
determine whether any filing or notification is necessary or advisable under any
applicable Antitrust Law if Genzyme were to exercise the respective Option to
take a license from Alnylam to Genzyme in respect of the corresponding Option
Product pursuant to the applicable License Terms.

2.2.1. If Genzyme determines that a filing or notification under any applicable
Antitrust Law is not necessary or advisable, then Genzyme shall indicate the
same in the respective Exercise Notice for such Option.

2.2.2. If Genzyme determines that a filing or notification under any applicable
Antitrust Law is necessary or advisable, then Genzyme shall indicate the same in
the respective Exercise Notice for such Option and each of Genzyme and Alnylam
shall make or cause to be made such notifications and filings as promptly as
practicable (but in any event within [***] business days). Each Party shall be
responsible for its own costs and expenses associated with such notifications
and filings, and Genzyme shall pay any applicable premerger filing fee under the
HSR Act. Each Party shall use its commercially reasonable efforts to obtain the
expiration or termination of the applicable waiting period under the HSR Act,
and to obtain the termination or expiration of any other applicable waiting
periods or any necessary approvals or consents under any other applicable
Antitrust Law, at the earliest possible date after the date of filing.
Immediately following the later of the expiration or termination of the last
such waiting period, or receipt of any necessary approvals or consents under any
other applicable Antitrust Law, Genzyme shall send Alnylam written notice that
all waiting periods under any applicable Antitrust Law have expired or been
terminated and any necessary approvals or consents under any applicable
Antitrust Law have been obtained. The effectiveness of the Option Exercise Date
for the corresponding Collaboration Product, which will be the Implementation
Date under the applicable License Terms, shall be deemed to be delayed until the
date on which the last waiting period under any applicable Antitrust Law has
expired or been terminated or on which the last approval or consent under such
Antitrust Law is granted.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.3. Cooperation. Each of Genzyme and Alnylam shall: (i) reasonably cooperate
with each other in connection with any investigation or other inquiry relating
to the transactions contemplated by an Exercise Notice for an Option;
(ii) reasonably keep the other Party informed of any communication received by
such Party from, or given by such Party to, the FTC, the DOJ or any other Merger
Control Authority and of any communication received or given in connection with
any proceeding by a private party, in each case regarding the transactions
contemplated by an Exercise Notice for an Option; (iii) promptly respond to and
certify substantial compliance with any inquiries or requests received from the
FTC, the DOJ or any other Merger Control Authorities for additional information
or documentation; (iv) reasonably consult with each other in advance of any
meeting or conference with the FTC, the DOJ or any other Merger Control
Authority, and to the extent permitted by the FTC, the DOJ or such other Merger
Control Authority and reasonably determined by such Party to be appropriate
under the circumstances, give the other Parties or their counsel the opportunity
to attend and participate in such meetings and conferences; and (v) permit the
other Parties or their counsel to the extent reasonably practicable to review in
advance, and in good faith consider the views of the other Parties or their
counsel concerning, any submission, filing or communication (and documents
submitted therewith) intended to be given by it to the FTC, the DOJ or any other
Merger Control Authority; provided, however, such Party shall be under no
obligation to reschedule any meetings or conferences with the FTC, the DOJ or
any other Merger Control Authority to enable the other Party to attend.

2.4. No Antitrust Undertakings. Notwithstanding anything to the contrary in this
Section 2, the term “commercially reasonable efforts” as used in this Section 2
does not require that either Party (i) offer, negotiate, commit to or effect, by
consent decree, hold separate order, trust or otherwise, the sale, divestiture,
license or other disposition of any capital stock, assets, rights, products or
businesses of Genzyme, Alnylam or their respective Affiliates, (ii) agree to any
restrictions on the activities of Genzyme, Alnylam or their respective
Affiliates, or (iii) pay any material amount or take any other action to
prevent, effect the dissolution of, vacate, or lift any decree, order, judgment,
injunction, temporary restraining order, or other order in any suit or
proceeding that would otherwise have the effect of preventing or delaying any of
the transactions contemplated by an Exercise Notice for an Option.

2.5. No Effect.

2.5.1. Transaction Agreements. The Collaboration Agreement shall (i) not take
effect until the occurrence of the Closing (as defined in the Stock Purchase
Agreement) in accordance with its terms and (ii) become null and void and have
no further force or effect in the event the Stock Purchase Agreement is
terminated prior to the Closing in accordance with its terms.

2.5.2. License to an Option Product. At the election of either Party,
immediately upon notice to the other Party, Genzyme’s exercise of an Option
shall become null and void and have no further force or effect (i) in the event
that the FTC or DOJ obtains a preliminary injunction against the Parties to
enjoin the transactions contemplated by the Exercise Notice for such Option or
(ii) in the event any applicable

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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waiting periods shall not have expired or been terminated, or any necessary
approvals or consents shall not have been obtained, under any applicable
Antitrust Law on or prior to [***] months after the effectiveness of the filings
and notifications contemplated by Section 2.2.2 (Effectiveness of Licenses to
Collaboration Products). In addition, beginning on the [***] day following
Genzyme’s delivery of an Exercise Notice with respect to an Option Product but
prior to the Option Exercise Date for the corresponding Collaboration Product,
Genzyme shall have the right to nullify its exercise of such Option by providing
written notice to Alnylam. Following the voiding or nullification of Genzyme’s
exercise of an Option for any reason under this Section 2.5, the Option Product
previously subject to such Option shall be treated for all purposes under this
Master Agreement, including Section 3.5, as an Option Product in respect of
which Genzyme did not deliver an Exercise Notice to Alnylam.

3. GRANT AND EXERCISE OF OPTIONS

3.1. Alnylam Programs.

3.1.1. Program Identification.

3.1.1.1. Alnylam Development Updates. At each regularly scheduled meeting of the
PAC during the Option Period, Alnylam shall advise the PAC of any Alnylam
Program with respect to which, since the last PAC meeting, either (i) the
existence of such Alnylam Program (and the target thereof) has been publicly
disclosed by Alnylam, including as a result of the filing of an IND for such
siRNA or (ii) [***]. In addition, Alnylam may elect to advise the PAC of any
Alnylam Program at any time. The PAC shall discuss the selection of new targets
for new Core Pipeline Programs and the research and development strategy for
Option Products. Alnylam shall consider in good faith recommended new targets
proposed by Genzyme.

3.1.1.2. PAC Categorization of Alnylam Programs. The PAC, acting reasonably,
shall seek to determine whether such Alnylam Program is a Core Pipeline Program
or a Non-Core Pipeline Program and advise the Parties of its consensus view (if
any).

3.1.1.3. Pipeline Programs Lists.

(a) If the PAC recommends to the AJSC and to the Parties that any Alnylam
Program is a Core Pipeline Program or a Non-Core Pipeline Program, then the
Parties may agree that such Alnylam Program shall be identified on the Core
Pipeline Program List or the Non-Core Program Pipeline List, respectively. Any
Alnylam Program and the corresponding human gene and siRNA, for as long as
listed on the Core Pipeline Program List or Non-Core Pipeline Program List,
shall be treated as a Core Pipeline Program or Non-Core Pipeline Program, as
applicable, for all purposes of this Master Agreement, subject to this
Section 3.1.1.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

(b) If, within [***] days of the PAC meeting referred to in Section 3.1.1.2 (PAC
Categorization of Alnylam Programs), the Parties, acting reasonably, are unable
to agree on whether any such Alnylam Program is a Core Pipeline Program or a
Non-Core Pipeline Program, then such Alnylam Program shall be deemed to be a
“Tentative Core Pipeline Program” and shall be identified on a list of such
Tentative Core Pipeline Programs (the “Tentative Core Pipeline Program List”)
and, for the sake of clarity, except as provided in Section 3.1.1.5 (Requested
Dispute Resolution), such disagreement shall not be subject to resolution
pursuant to Section 5.1.8 (Decision-Making). Any Alnylam Program and the
corresponding human gene and siRNA, for as long as listed on the Tentative Core
Pipeline Program List, shall be treated as a Core Pipeline Program for purposes
of Section 3.1.2.1 (Information Sharing for Core Pipeline Programs),
Section 3.1.2.2 (Meetings with Regulatory Authorities), Section 3.1.2.3 (Design
of Human POP Studies), Section 3.6 (Exclusivity during Option Period),
Section 5.3.3 (IP Committee Responsibilities) and Section 11 (Intellectual
Property), subject to Section 3.1.1 (Program Identification).

3.1.1.4. Locking of Alnylam Programs. Alnylam shall notify the PAC promptly
after the first IND with respect to an Alnylam Program becomes, or is deemed to
be, effective and (i) if such Alnylam Program is on the Core Pipeline Program
List or Non-Core Pipeline Program List, it will automatically be moved to the
Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List,
as applicable, upon delivery of such notice; or (ii) if such Alnylam Program is
on the Tentative Core Pipeline Program List, then the Parties will seek to reach
consensus as to whether such Alnylam Program is a Core Pipeline Program or
Non-Core Pipeline Program within [***] days after delivery of such notice. If
the Parties agree on the categorization of such Tentative Core Pipeline Program
within such [***] day period, such Alnylam Program will automatically be moved
to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program
List, as applicable. If the Parties cannot agree within such [***] day period,
either Party may submit the categorization of such Alnylam Program to the AJSC
for resolution pursuant to Section 5.1.8 (Decision-Making) and, following any
such resolution of such categorization, such Alnylam Program will automatically
be moved to the Locked Core Pipeline Program List or the Locked Non-Core
Pipeline Program List, as applicable. Once an Alnylam Program has been moved to
the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program
List, such Core Pipeline Programs shall remain Core Pipeline Programs and such
Non-Core Pipeline Programs shall remain Non-Core

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Pipeline Programs, respectively, for all purposes under the Collaboration
Agreement, except as the Parties, each acting in its sole discretion, may later
mutually agree in writing. Notwithstanding the foregoing, if Alnylam enters into
an agreement with a Third Party granting such Third Party any rights or options
to a Non-Core Pipeline Program (or any siRNA arising therefrom) prior to the
first IND with respect to such Non-Core Pipeline Program becoming effective,
Alnylam shall notify the PAC of the existence of such an agreement (but not the
counterparty thereto or any terms thereof) and the human gene(s) targeted by
such Non-Core Pipeline Program (or any siRNA arising therefrom) and such
Non-Core Pipeline Program will automatically then be moved to the “Locked
Non-Core Pipeline Program List” as of the date of such agreement, [***].

3.1.1.5. Requested Dispute Resolution. If an Alnylam Program is not listed on
the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program
List and the Parties, at any time, are unable to agree on whether any such
Alnylam Program is a Core Pipeline Program or a Non-Core Pipeline Program then,
upon the request of either Party, such categorization of such Alnylam Program
shall be submitted to the AJSC for resolution pursuant to Section 5.1.8
(Decision-Making), and, following resolution, such Alnylam Program will
automatically be moved to the Locked Core Pipeline Program List or the Locked
Non-Core Pipeline Program List, as applicable.

3.1.1.6. Updating Program Lists. Solely as an administrative manner, Alnylam
shall be responsible for updating the Core Pipeline Program List, the Locked
Core Pipeline Program List, the Non-Core Pipeline Program List, the Locked
Non-Core Pipeline Program List and the Tentative Core Pipeline Program List from
time to time, in all cases in accordance with this Section 3.1.1. Promptly
following any such update, Alnylam shall provide a copy of the applicable list
to each of the PAC representatives.

3.1.2. Core Pipeline Programs.

3.1.2.1. Information Sharing for Core Pipeline Programs.

(a) During the Option Period, Alnylam shall update the PAC, at each regularly
scheduled meeting thereof, on the status of the Core Pipeline Programs, which
update shall include a summary of the Development activities undertaken by
Alnylam with respect to such Core Pipeline Programs since the last update
provided to the PAC or planned to be undertaken by Alnylam. [***]. In addition,
in connection with each regularly scheduled meeting of the PAC during the Option
Period, Alnylam will provide to the PAC and Genzyme copies of all then-available
preclinical, clinical, regulatory and supporting reports and material
correspondence with Regulatory Authority with respect to any Core Pipeline

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

Program and, if available, a copy of any Development plan for each Core Pipeline
Program. Notwithstanding the foregoing, Alnylam shall not be obligated pursuant
to the foregoing to provide information the disclosure of which would: (a) in
the reasonable opinion of Alnylam’s counsel, adversely affect the
attorney-client privilege between Alnylam and its counsel; or (b) violate or
cause a breach by Alnylam of any confidentiality or non-disclosure agreement
with any Third Party. Once Alnylam delivers an Initial Option Data Package for
an Option Product, Alnylam will provide information related to such Option
Product solely pursuant to Section 3.3 (Option Exercise Period), including
Section 3.3.3.2 (Governance) if Genzyme delivers an Option Preservation Notice
for such Option Product to Alnylam, and Alnylam shall not have any obligations
related to such Option Product and its related Core Pipeline Program under
Sections 3.1.1 (Program Identification), 4.5 (Oversight), 5 (Collaboration
Management) or 11.2 (Patent Prosecution Information Sharing).

(b) Following the filing of an IND with respect to a Core Pipeline Program,
Alnylam shall (x) promptly provide (i) any patent, regulatory or CMC
information, (ii) any material, complete sets of preclinical or clinical data
and (iii) raw data tables, in each case ((i), (ii) and (iii)) then available to
Alnylam that Genzyme may reasonably request, to the extent that such information
was not previously provided by Alnylam to Genzyme and subject to customary and
reasonable due diligence procedures to preserve the confidential nature of any
such information, regarding such Option Product to assist Genzyme in deciding
whether to exercise an Option for such Option Product if and when any such
Option becomes exercisable; and (y) afford to Genzyme and its representatives,
reasonable access during normal business hours to Alnylam’s personnel that
Genzyme may reasonably request regarding such Option Product to assist Genzyme
in deciding whether to exercise an exercisable Option for such Option Product.

3.1.2.2. Meetings with Regulatory Authorities. Alnylam shall provide Genzyme
with reasonable advance notice of any pre-IND meetings with any Regulatory
Authority with respect to any Core Pipeline Program, or with as much advance
notice as practicable under the circumstances. [***].

3.1.2.3. Design of Human POP Studies. During the Option Period, Alnylam shall
reasonably consult with the AJSC regarding the design of each Human POP Study
proposed to be conducted for any siRNA generated by a Core Pipeline Program. In
addition, at least [***] days prior to submitting a final protocol for such
Human POP Study to a Regulatory Authority as part of an IND, Alnylam shall
submit a draft of such protocol (or, if a draft protocol is not available, a
full protocol concept sheet) to the AJSC for review and comment. If a draft
protocol was not available, Alnylam shall provide the draft protocol to the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

AJSC as soon as it becomes available. Alnylam shall reasonably consider in good
faith any comments provided by the AJSC (or its members) within [***] days of
the submission of such draft protocol or full protocol concept sheet to the
AJSC; provided, however, in any event, the AJSC shall have at least [***] days
to review and comment on the draft protocol. [***].

3.1.2.4. Improperly Designated Programs. In the event that (i) it is determined
[***] and (iii) Alnylam continues to conduct such Alnylam Program following such
[***] determination as a Non-Core Pipeline Program, but does not initiate a
Phase II Study for any siRNA generated by such Non-Core Pipeline Program in a
non-Orphan Disease or any cancer or infectious disease within [***] following
the date on which such siRNA received Regulatory Approval in respect of an
Orphan Disease, then Alnylam and Genzyme shall in good faith negotiate together
the terms under which such siRNA could be deemed a Regional Option Product (even
if such [***] year period ends after the expiration of the Regional Option
Period), including [***]. Following agreement on such terms, Alnylam shall
provide Genzyme with an Initial Option Notice with respect to the applicable
siRNAs as soon as reasonably practicable. If the Parties are unable to agree
upon the terms under which such siRNA could be deemed a Regional Option Product
during the first [***] days of such negotiation, [***].

3.2. Option Grants.

3.2.1. Regional Option Grants.

3.2.1.1. Regional Option Grants. Alnylam hereby grants Genzyme a series of
exclusive options (each, a “Regional Option”), under each of which Genzyme shall
have the right, but not the obligation, to take a license on the terms set forth
in the Regional License Terms to any Regional Option Product that achieves Human
POP Study Completion during the Regional Option Period. Each Regional Option may
be exercised by Genzyme at any time during the applicable Option Exercise Period
for a Regional Option Product that achieves Human POP Study Completion in
accordance with the terms and conditions set forth in Sections 3.3 (Option
Exercise Period) and 3.4 (Exercise of an Option).

3.2.1.2. [***].

3.2.1.3. [***].

3.2.2. Co-Co/Global Option Grant. Alnylam hereby grants Genzyme one
(1) exclusive option (the “Co-Co/Global Option”) under which Genzyme shall have
the right, but not the obligation, to either (i) take a license on the terms set
forth in the Global License Terms to ALN-AS1 or (ii) take a license on the terms
set forth in the Co-Co

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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License Terms to ALN-AT3. Genzyme may wait to exercise such Co-Co/Global Option
until both ALN-AS1 and ALN-AT3 achieve Human POP Study Completion as described
below in this Section 3.2.2, or may terminate such Co-Co/Global Option prior to
both ALN-AS1 and ALN-AT3 achieving Human POP Study Completion (in which case,
the Additional Global Option will become exercisable pursuant to Section 3.2.3.2
(Additional Global Option Grant)). The Co-Co/Global Option may be exercised by
Genzyme at any time during the applicable Option Exercise Period for a
Co-Co/Global Option Product in accordance with the terms and conditions set
forth in Sections 3.3 (Option Exercise Period) and 3.4 (Exercise of an Option),
subject to the conditions set forth in this Section 3.2.2.

3.2.2.1. First Co-Co/Global Option Product. For the first Co-Co/Global Option
Product to achieve Human POP Study Completion (the “First Co-Co/Global Option
Product”), Genzyme may do any of the following:

(a) exercise a Regional Option (or 2019 Trailing Regional Option or 2021
Trailing Regional Option, if and as applicable) for such First Co-Co/Global
Option Product, in which case the Co-Co/Global Option shall remain exercisable
with respect to the First Co-Co/Global Option Product on the terms set forth in
Sections 3.2.2.2(a) (Second Co-Co/Global Option Product) and 3.2.2.4
(Discontinuation of Second Co-Co/Global Option Product);

(b) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product,
in which case the Co-Co/Global Option shall be fully exercised; or

(c) not exercise any Option for the First Co-Co/Global Option Product, in which
case the Co-Co/Global Option shall cease to be exercisable with respect to the
First Co-Co/Global Option Product but shall remain exercisable for the Second
Co-Co/Global Option Product.

3.2.2.2. Second Co-Co/Global Option Product. For the second Co-Co/Global Option
Product (i.e., if the First Co-Co/Global Option Product is ALN-AT3, then ALN-AS1
or, if the First Co-Co/Global Option Product is ALN-AS1, then ALN-AT3) to
achieve Human POP Study Completion (the “Second Co-Co/Global Option Product”),
Genzyme may do any of the following:

(a) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product,
in which case the Co-Co/Global Option shall be fully exercised;

(b) exercise the Co-Co/Global Option for the Second Co-Co/Global Option Product,
in which case the Co-Co/Global Option shall be fully exercised;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

(c) exercise a Regional Option (or 2019 Trailing Regional Option or 2021
Trailing Regional Option, if and as applicable) for the Second Co-Co/Global
Option Product, in which case, the Co-Co/Global Option shall be terminated in
full and the Additional Global Option will become exercisable pursuant to
Section 3.2.3.2 (Additional Global Option Grant) (for clarity, Genzyme may do
both (a) and (c) of this Section 3.2.2.2); or

(d) not exercise any Option for the Second Co-Co/Global Option Product, in which
case

(i) if the Second Co-Co/Global Option Product achieved Clinical Success (and
Genzyme does not exercise the Co-Co/Global Option for the First Co-Co/Global
Option Product or the Second Co-Co/Global Option Product or Genzyme has
terminated the Co-Co/Global Option pursuant to Section 3.2.2.5 (Genzyme Elective
Termination of Co-Co/Global Option)), the Co-Co/Global Option shall terminate in
full at the end of the Option Exercise Period for the Second Co-Co/Global Option
Product and the Additional Global Option will become exercisable pursuant to
Section 3.2.3.2 (Additional Global Option Grant);

(ii) if the Second Co-Co/Global Option Product did not achieve Clinical Success,
but the First Co-Co/Global Option Product did achieve Clinical Success (and
Genzyme does not exercise the Co-Co/Global Option for the First Co-Co/Global
Option Product or the Second Co-Co/Global Option Product or Genzyme has
terminated the Co-Co/Global Option pursuant to Section 3.2.2.5 (Genzyme Elective
Termination of Co-Co/Global Option)), then the Co-Co/Global Option shall
terminate in full at the end of the Option Exercise Period for the Second
Co-Co/Global Option Product and the Additional Global Option will become
exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant);

(iii) if both the Second Co-Co/Global Option Product and the First Co-Co/Global
Option Product failed to achieve Clinical Success, then the Co-Co/Global Option
shall remain exercisable but only with respect to the next Co-Co/Global Option
Product, if any, to achieve Clinical Success (the “Back-Up Co-Co/Global Option
Product”).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

3.2.2.3. Back-Up Co-Co/Global Option Product. If the Co-Co/Global Option is
exercisable with respect to the Back-Up Co-Co/Global Option Product pursuant to
Section 3.2.2.2(d)(iii), Genzyme may do any of the following:

(a) exercise the Co-Co/Global Option for the Back-Up Co-Co/Global Option
Product, in which case the Co-Co/Global Option shall be fully exercised; or

(b) not exercise the Co-Co/Global Option for the Back-Up Co-Co/Global Option
Product, in which case the Co-Co/Global Option shall terminate in full at the
end of the Option Exercise Period for the Back-Up Co-Co/Global Option Product
and the Additional Global Option will become exercisable pursuant to
Section 3.2.3.2 (Additional Global Option Grant).

3.2.2.4. Discontinuation of Second Co-Co/Global Option Product. If Genzyme
exercises a Regional Option for the First Co-Co/Global Option Product and
Alnylam decides to abandon or terminate Development of the other Co-Co/Global
Option Product prior to achieving Human POP Study Completion, then Alnylam shall
promptly deliver written notice of such abandonment or termination to Genzyme
(any such notice, the “Co-Co/Global Option Trigger Notice”) and Genzyme may do
either of the following:

(a) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product,
in which case the Co-Co/Global Option shall be fully exercised and the First
Co-Co/Global Option Product shall cease to be a Regional Licensed Product; or

(b) not exercise the Co-Co/Global Option for the First Co-Co/Global Option
Product, in which case the Co-Co/Global Option shall terminate in full at the
end of the applicable Option Exercise Period, the First Co-Co/Global Option
Product shall continue to be a Regional Licensed Product and the Additional
Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional
Global Option Grant).

3.2.2.5. Genzyme Elective Termination of Co-Co/Global Option. At any time prior
to the exercise of the Co-Co/Global Option, Genzyme may, in its sole discretion,
terminate the Co-Co/Global Option by providing written notice of termination to
Alnylam and, upon delivery of such notice, the Co-Co/Global Option shall
irrevocably and perpetually terminate in full, the Option Exercise Period for
the Co-Co/Global Option shall expire, and the Additional Global Option will
become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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3.2.3. Global Option Grants.

3.2.3.1. Global Option Grant. Alnylam hereby grants Genzyme one (1) exclusive
option (the “Global Option”), under which Genzyme shall have the right, but not
the obligation, to take a license on the terms set forth in the Global License
Terms to any Global Option Product for which it is anticipated that Human POP
Study Completion will be achieved during the Global Option Period. The Global
Option may be exercised by Genzyme at any time during the applicable Option
Exercise Period for a Global Option Product for which a Human POP Study is
conducted during the Global Option Period in accordance with the terms and
conditions set forth in Sections 3.3 (Option Exercise Period) and 3.4 (Exercise
of an Option). The Global Option shall terminate in full upon the Option
Exercise Date for any Global Option Product with respect to which Genzyme
exercises the Global Option.

3.2.3.2. [***].

3.2.3.3. [***].

3.3. Option Exercise Period.

3.3.1. Initial Option Data Package. As soon as is reasonably practicable on or
after [***] (i) any Option Product that achieves Human POP Study Completion
during the applicable Option Period or (ii) any Trailing Regional Option Product
or Trailing Global Option Product that achieves Human POP Study Completion after
the end of the applicable Option Period; (y) Genzyme notifies Alnylam that it
desires to exercise the Co-Co/Global Option with respect to ALN-AS1 prior to the
achievement of Human POP Study Completion; or (z) Genzyme notifies Alnylam that
it desires to exercise the Global Option or the Additional Global Option with
respect to a Global Option Product prior to the achievement of Human POP Study
Completion, Alnylam shall complete all activities necessary for Alnylam to
prepare a complete Initial Option Data Package for the applicable Option Product
and provide a written notice to Genzyme (such notice, an “Initial Option
Notice”). Alnylam shall include in each such Initial Option Notice::

(a) a letter indicating which Option(s) is(are) applicable to the Option
Product;

(b) the Initial Option Data Package for the Option Product (and all such data
therein shall be made available to Genzyme through an electronic data room
promptly following the date that such Initial Option Notice is delivered); and

(c) a certification of an officer of Alnylam as to the accuracy and completeness
of the provided information.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Within [***] days after Genzyme’s receipt of an Initial Option Notice, Genzyme
shall acknowledge receipt of such Initial Option Notice in writing to Alnylam or
be deemed to have acknowledged such receipt as of such date. For clarity, if
Genzyme requests the delivery of an Initial Option Notice with respect to
ALN-AS1 or a Global Option Product prior to the time determined in accordance
with clause (x) of this Section 3.3.1, Alnylam shall only be obligated to
provide such information in the Initial Option Data Package as is available to
Alnylam as of the date of such request from Genzyme.

3.3.2. Initial Evaluation Period. If an Initial Option Notice is delivered by
Alnylam to Genzyme pursuant to clause (x) of Section 3.3.1 (Initial Option
Package) (i.e., after an Option Product achieves Human POP Completion), then, if
Genzyme desires to preserve its right to exercise an Option for such Option
Product, Genzyme shall notify Alnylam in writing of Genzyme’s desire to exercise
an Option and the type of Option that Genzyme desires to exercise (an “Option
Preservation Notice”) prior to the expiration of the Initial Evaluation Period
with respect to such Option Product. If Genzyme delivers an Option Preservation
Notice to Alnylam prior to the expiration of the Initial Evaluation Period for
an Option Product, then Section 3.3.3 (Effect of Option Preservation) shall
apply. If Genzyme does not deliver an Option Preservation Notice to Alnylam
prior to the expiration of the Initial Evaluation Period for an Option Product,
then such Option Product shall be treated for all purposes under this Master
Agreement, including Section 3.5 (Option Not Exercised), as an Option Product in
respect of which Genzyme did not deliver an Exercise Notice to Alnylam.

3.3.3. Effects of Option Preservation. If Genzyme delivers an Option
Preservation Notice prior to the expiration of the Initial Evaluation Period for
an Option Product pursuant to Section 3.3.2 (Initial Evaluation Period), then
the provisions of this Section 3.3.3 shall apply.

3.3.3.1. Final Option Data Package. Within [***] days after the earlier of
[***], Alnylam shall complete all activities necessary for Alnylam to prepare a
complete Final Option Data Package for the applicable Option Product and deliver
such Final Option Data Package to Genzyme. Within [***] days after Genzyme’s
receipt of a Final Option Data Package, Genzyme shall acknowledge receipt of
such Final Option Data Package in writing to Alnylam or be deemed to have
acknowledged such receipt as of such date. Notwithstanding the foregoing,
Alnylam shall not deliver a Final Option Data Package to Genzyme unless and
until all of the activities necessary to generate the information to be included
in such Final Option Data Package have been completed.

3.3.3.2. Governance. At Genzyme’s request following the delivery of an Option
Preservation Notice for an Option Product, the Parties shall form the committee
that would be responsible for facilitating the Collaboration with respect to
such Option Product under the applicable License Terms if Genzyme

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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exercised the Option identified in such Option Preservation Notice (i.e. if the
identified Option is the Global Option, the Parties will form the JTT described
in Section 5.1 (Joint Transition Team) of the Global License Terms; and if the
identified Option is the Co-Co/Global Option, the Regional Option, the 2019
Trailing Regional Option or the 2021 Trailing Regional Option, the Parties will
form the PJSC described in Section 5.1 (Product Joint Steering Committee) of the
Co-Co License Terms or Section 5.1 (Product Joint Steering Committee) of the
Regional License Terms, as applicable). Such committee shall have the
responsibilities allocated to such committee under the applicable License Terms,
except that such committee shall serve solely in an advisory committee and shall
not have any decision-making authority with respect to the applicable Option
Product unless and until Genzyme exercises an Option with respect to such Option
Product. Such committee shall be disbanded if Genzyme does not exercise an
Option with respect to the applicable Option Product prior to the end of the
Option Exercise Period for such Option Product.

3.3.3.3. [***]

(a) [***]

(b) [***]

(c) [***]

3.3.3.4. No Rights. Except for the right to exercise an Option in respect of an
Option Product following receipt of a Final Option Data Package in respect
thereof, Genzyme shall not obtain any ownership interest or other right to
Develop or Commercialize (or to compel Alnylam Develop or Commercialize) such
Option Product during the Transition Period, provided that the foregoing shall
not relieve Alnylam of any of its obligations under this Master Agreement in
respect of such Option Product during the Transition Period.

3.3.4. Updates to Option Data Packages.

3.3.4.1. Incomplete Option Data Package.

(a) Notice of Missing Information. Following receipt of an Option Data Package,
Genzyme shall have [***] days to notify Alnylam if such Option Data Package is
missing any information, which notice shall describe the information that is
missing. Alnylam shall provide Genzyme with such missing information identified
in such notice as soon as reasonably practicable (if and to the extent that such
information is available to Alnylam).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) Disputed Missing Information. If, notwithstanding any information
subsequently delivered by Alnylam pursuant to Section 3.3.4.1(a) (Notice of
Missing Information), Genzyme, acting in good faith, still believes that the
Option Data Package is missing material information, then Genzyme shall have the
right to request that the AJSC review the Option Data Package (including any
information subsequently delivered by Alnylam pursuant to Section 3.3.4.1(a)
(Notice of Missing Information) or Section 3.3.4.2 (Supplements to Option Data
Package)) within [***] days and determine whether material information is then
missing from such Option Data Package. The AJSC is hereby empowered to compel
Alnylam to produce any missing material information (if and to the extent that
such information is available to Alnylam) within [***] days of such order.

3.3.4.2. Supplements to Option Data Package. Following delivery of an Option
Data Package, Alnylam shall have the right to provide supplemental updates to
any of the information included in such Option Data Package. In addition,
Alnylam shall be required to promptly provide supplemental update(s) to Genzyme
if [***]. In either such case, any such supplemental information shall be deemed
to constitute a part of such Option Data Package for all purposes of this
Collaboration Agreement (and to supersede previously provided information, to
the extent such supplement information is identified, or would reasonably be
apparent to Genzyme, as superseding previously provided information [***].

3.3.4.3. Information Sharing during Initial Evaluation Period and Option
Exercise Period. During the Option Exercise Period (including, if applicable,
the Initial Evaluation Period) for an Option Product, Alnylam shall (a) promptly
provide to Genzyme (i) any patent, regulatory or CMC information, (ii) any
material, complete sets of preclinical or clinical data and (iii) raw data
tables, in each case ((i), (ii) and (iii)) then available to Alnylam that
Genzyme may reasonably request, to the extent that such information was not
previously provided by Alnylam to Genzyme and subject to customary and
reasonable due diligence procedures to preserve the confidential nature of any
such information, regarding such Option Product to assist Genzyme in deciding
whether to exercise an Option for such Option Product if and when any such
Option becomes exercisable, and (b) afford to Genzyme and its representatives
reasonable access during normal business hours to Alnylam’s personnel, in each
case ((a) and (b)) that Genzyme may reasonably request regarding such Option
Product to assist Genzyme in deciding whether to exercise the Option for such
Option Product, to the extent that such information was not previously provided
by Alnylam to Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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3.3.4.4. Extension of Initial Evaluation Period and Option Exercise Period. If
any information is provided to Genzyme following the receipt of an Option Data
Package pursuant to Section 3.3.4.1 (Incomplete Data Option Package), 3.3.4.2
(Supplements to Option Data Package) or 3.3.4.3 (Information Sharing During
Option Exercise Period) and such information is, in Genzyme’s reasonable
discretion, material information not previously provided to Genzyme relating to
the applicable Option Product, the Initial Evaluation Period or Option Exercise
Period, as applicable, shall, if necessary and upon notice from Genzyme to
Alnylam, be extended such that there is at least [***] days between Genzyme’s
receipt of such material information and the expiration of such Initial
Evaluation Period or Option Exercise Period, provided that in no event shall any
Initial Evaluation Period or Option Exercise Period be extended by more than
[***] days in the aggregate.

3.3.5. Information Excluded from Option Data Packages. Notwithstanding anything
in this Master Agreement to the contrary, Alnylam shall not be obligated to
include in any Option Data Package or to disclose pursuant to Section 3.3.4
(Updates to Option Data Packages) any information the disclosure of which would
(i) in the reasonable opinion of Alnylam’s counsel, adversely affect the
attorney-client privilege between Alnylam and its counsel or (ii) [***], and the
exclusion of such information from any Option Data Package, as applicable, shall
not constitute missing information for purposes of Section 3.3.4.1 (Incomplete
Option Data Package), render the Option Data Package deficient in any respect or
otherwise result in Genzyme having any right or claim against Alnylam. If
material information may be excluded from any Option Data Package pursuant to
clause (i) in the immediately preceding sentence, the Parties will enter into a
common interest agreement designed to preserve such privilege and, after
execution of such agreement, Alnylam will provide Genzyme with access to such
information.

3.4. Exercise of an Option. Genzyme shall exercise an Option, if at all, by
properly delivering a complete Exercise Notice in respect of such Option to
Alnylam at any time during the respective Option Exercise Period for such
Option.

3.4.1. [***].

3.4.2. Exercise of Preserved Option.

3.4.2.1. Except as provided in Section 3.4.2.3, in the event that Genzyme
exercises an Option for an Option Product for which an Option Preservation
Notice was delivered pursuant to Section 3.3.2 (Initial Evaluation Period), then
Genzyme may only exercise the Option identified in such Option Preservation
Notice for such Option Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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3.4.2.2. Except as provided in Section 3.4.2.3, if Genzyme identified the Global
Option or the Additional Global Option as the Option it was preserving in an
Option Preservation Notice and Genzyme does not deliver to Alnylam an Exercise
Notice with respect to the exercise of such Option prior to the expiration of
the applicable Option Exercise Period, then such Option shall terminate in full
at the end of the Option Exercise Period and Genzyme shall not thereafter be
permitted to exercise such unexercised Global Option or Additional Global
Option, as applicable (such failure to deliver an Exercise Notice, a
“Global/Additional Global Option Forfeiture”).

3.4.2.3. Notwithstanding the foregoing, if prior to the expiration of the Option
Exercise Period for an Option Product (i) Genzyme receives material
(a) clinical, GLP toxicology or nonclinical data or (b) regulatory guidance or a
regulatory determination involving such Option Product, including in the Final
Option Data Package, that was not included in (or, in the case of clause b,
reasonably ascertainable from) the Initial Option Data Package or information
presented to the AJSC or the PAC (and reflected in the written meeting minutes
thereof) (such new data, regulatory guidance or a regulatory determination, “New
Information”) and (ii) such New Information is adversely material to the
expected clinical or commercial success of such Option Product such that Genzyme
would not have exercised the Global Option or Additional Global Option if it
possessed such New Information at the time it delivered such Option Preservation
Notice, then Genzyme shall have the right (but not the obligation) to deliver an
Option Exercise Notice to exercise a Regional Option during the applicable
Option Exercise Period or it may elect not to exercise any Option with respect
to such Option Product and, in either such case, Genzyme’s failure to exercise
the Global Option or the Additional Global Option, as applicable, shall not
constitute a Global/Additional Global Option Forfeiture and the Global Option or
Additional Global Option, as applicable shall remain exercisable.

3.4.2.4. If development milestone(s) become payable under any License Terms,
including because an Option Product is dosed in a patient in a Phase III Study,
prior to the expiration of the Option Exercise Period for such Option Product
and Genzyme exercises an Option in respect of such Option Product and such
Option Product becomes a Collaboration Product, then Genzyme shall promptly, and
in any event within [***] days following receipt of an invoice, pay such
development milestone(s) to Alnylam as though such Option Product was a
Collaboration Product at the time such development milestone(s) became payable
Alnylam.

3.4.3. Regional Options. On the applicable Option Exercise Date for the exercise
of any Regional Option, 2019 Trailing Regional Option or 2021 Trailing Regional
Option, the applicable Regional Option Product or Trailing Regional Option

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Product shall automatically be deemed to be a Regional Licensed Product for all
purposes under the Collaboration Agreement and the license from Alnylam to
Genzyme for such Regional Licensed Product shall automatically, with no further
action by any Party, go into full force and effect and all of the obligations of
Alnylam and Genzyme set forth in the Regional License Terms, including the
payment obligations set forth therein, shall become the binding obligations of
the applicable Party in respect of such Regional Licensed Product. As part of
the effectiveness of such license, the Regional License Terms shall
automatically, with no further action by any Party, be deemed to be amended to
incorporate the human gene target for such Regional Licensed Product as a
Licensed Target under the Regional License Terms and to incorporate as part of
the Regional License Terms or this Master Agreement the schedules, appendices
and exhibits in respect of such Regional Licensed Product that were included in
the last Option Data Package delivered by Alnylam for such Regional Licensed
Product or, in the case of the Global Development Strategy for such Regional
Licensed Product, mutually agreed upon by the Parties prior to the Option
Exercise Date. The Parties may, at their option, prepare an updated version of
the Regional License Terms and this Master Agreement that includes such
schedules, appendices and exhibits.

3.4.4. Co-Co/Global Option.

3.4.4.1. ALN-AT3. If Genzyme exercises the Co-Co/Global Option for ALN-AT3, then
on the applicable Option Exercise Date, ALN-AT3 shall automatically be deemed to
be Co-Co Licensed Product for all purposes under the Collaboration Agreement and
the license from Alnylam to Genzyme to such Co-Co Licensed Product shall
automatically, with no further action by any Party, go into full force and
effect and all of the obligations of Alnylam and Genzyme set forth in the Co-Co
License Terms, including the payment obligations set forth therein, shall become
the binding obligations of the applicable Party in respect of ALN-AT3. As part
of the effectiveness of such license, the Co-Co License Terms shall
automatically, with no further action by any Party, be deemed to be amended to
incorporate AT3 as a Licensed Target under the Co-Co License Terms and to
incorporate as part of the Co-Co License Terms or this Master Agreement the
schedules, appendices and exhibits in respect of such Co-Co Licensed Product
that were included in the last Option Data Package delivered by Alnylam or, in
the case of the Global Development Strategy for such Co-Co Licensed Product,
mutually agreed upon by the Parties prior to the Option Exercise Date. The
Parties may, at their option, prepare an updated version of the Co-Co License
Terms and this Master Agreement that includes such schedules, appendices and
exhibits.

3.4.4.2. ALN-AS1. If Genzyme exercises the Co-Co/Global Option for ALN-AS1, then
on the applicable Option Exercise Date, the applicable Co-Co/Global Option
Product shall automatically be deemed to be a Global Licensed

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Product for all purposes under the Collaboration Agreement and the license from
Alnylam to Genzyme to such Global Licensed Product shall automatically, with no
further action by any Party, go into full force and effect and all of the
obligations of Alnylam and Genzyme set forth in the Global License Terms,
including the payment obligations set forth therein, shall become the binding
obligations of the applicable Party in respect of such Global Licensed Product.
As part of the effectiveness of such license, the Global License Terms shall
automatically, with no further action by any Party, be deemed to be amended to
incorporate ALN-AS1 as a Licensed Target under the Global License Terms and to
incorporate as part of the Global License Terms or this Master Agreement the
schedules, appendices and exhibits in respect of such Global Licensed Product
that were included in the last Option Data Package delivered by Alnylam for such
Global Licensed Product. The Parties may, at their option, prepare an updated
version of the Global License Terms and this Master Agreement that includes such
schedules, appendices and exhibits.

3.4.5. Global Options. On the applicable Option Exercise Date for the exercise
of a Global Option or Trailing Global Option, the applicable Global Option
Product or Trailing Global Option Product shall automatically be deemed to be a
Global Licensed Product for all purposes under the Collaboration Agreement and
the license from Alnylam to Genzyme to such Global Licensed Product shall
automatically, with no further action by any Party, go into full force and
effect and all of the obligations of Alnylam and Genzyme set forth in the Global
License Terms, including the payment obligations set forth therein, shall become
the binding obligations of the applicable Party in respect of such Global
Licensed Product. As part of the effectiveness of such license, the Global
License Terms shall automatically, with no further action by any Party, be
deemed to be amended to incorporate the human gene target for such Global
Licensed Product as a Licensed Target under the Global License Terms and to
incorporate as part of the Global License Terms or this Master Agreement the
schedules, appendices and exhibits in respect of such Global Licensed Product
that were included in the last Option Data Package delivered by Alnylam for such
Global Licensed Product. The Parties may, at their option, prepare an updated
version of the Global License Terms and this Master Agreement that includes such
schedules, appendices and exhibits.

3.4.6. Development and Commercialization Following Option Exercise. Following
the Option Exercise Date for a Collaboration Product, the Development and
Commercialization of such Collaboration Product shall thereafter be governed by
the applicable License Terms.

3.5. Option Not Exercised. If Genzyme does not deliver to Alnylam an Exercise
Notice, or if Genzyme elects and delivers written notice to Alnylam to terminate
an Option, with respect to an Option Product prior to the expiration of the
applicable Option Exercise Period, then Genzyme’s Option with respect to such
Option Product shall expire, Genzyme’s other rights

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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with respect to such Option Product (including any rights under Section 4
(Development and Pharmacovigilance) and Section 5 (Collaboration Management)),
shall lapse, and Alnylam shall thereafter be free to Develop, Manufacture or
Commercialize, alone or with one or more Third Parties, such Option Product, in
each case without any further obligation to Genzyme. In addition, so long as
Alnylam continues to actively Develop an Option Product following the expiration
of Genzyme’s Option or Alnylam grants any rights to an Option Product to a Third
Party, then other siRNAs Developed by Alnylam or any such Third Party (or its
licensees or sublicensees, through multiple tiers) that target the same human
gene as such Option Product (except for siRNAs described in clause (ii) of
Section 1.2.21 (ALN-AT3) or clause (ii) of Section 1.2.20 (ALN-AS1) if any such
siRNA is potentially subject to the Co-Co/Global Option) shall not be considered
Option Products for purposes of this Master Agreement and Genzyme shall not have
any Option hereunder with respect to such other siRNAs; provided, however, that
if Alnylam ceases active Development of such Option Product, then the other
siRNAs that target the same human gene as such Option Product shall again be
considered Option Products for the purposes of this Master Agreement. [***].

3.6. Exclusivity during Option Period.

3.6.1. Exclusivity for Core Pipeline Programs. Subject to Section 13.16.2
(Future Acquisition of a Party or its Business), during the Option Period,
Alnylam and its Affiliates shall not enter into any agreement with any Third
Party that grants such Third Party any rights with respect to any Core Pipeline
Program that would be in conflict with the Collaboration Agreement following an
siRNA becoming a Collaboration Product under the Collaboration Agreement,
provided that this restriction shall not apply to:

3.6.1.1. following the expiration of the Option Exercise Period for an Option
Product, an agreement with a Third Party that grants such Third Party rights
with respect to such Option Product and other siRNAs that target the same human
gene as such Option Product;

3.6.1.2. an agreement with a Third Party that grants such Third Party rights
with respect to any Named Pipeline Program (excluding ALN-TTR02, ALN-TTRsc,
ALN-AT3 and ALN-AS1) solely in the Alnylam Territory, provided that Alnylam
complies with the provisions of Section 3.6.3 (ROFN for Available Third Party
Rights) and 3.6.4 (Permitted Third Party Agreements);

3.6.1.3. following the exercise of the Co-Co/Global Option with respect to
either Co-Co/Global Option Product, an agreement with a Third Party that grants
such Third Party rights with respect to the other Co-Co/Global Option Product
solely in the Alnylam Territory, provided that Alnylam complies with the
provisions of Section 3.6.3 (ROFN for Available Third Party Rights) and 3.6.4
(Permitted Third Party Agreements); or

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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3.6.1.4. following the exercise of the Global Option, an agreement with a Third
Party that grants such Third Party rights with respect to any Core Pipeline
Program solely in the Alnylam Territory, provided that Alnylam complies with the
provisions of Section 3.6.3 (ROFN for Available Third Party Rights) and 3.6.4
(Permitted Third Party Agreements).

3.6.2. Other Exclusivity Requirements in License Terms. Upon the exercise of any
Option (which will cause an Option Product to become a Collaboration Product),
the exclusivity provisions set forth in the applicable License Terms will go
into effect with respect to such Collaboration Product.

3.6.3. ROFN for Available Third Party Rights. If Alnylam desires to enter into
an agreement described in Section 3.6.1.2, 3.6.1.3 or 3.6.1.4, other than in
accordance with Section 4.4 (Third Parties), then Alnylam shall so notify
Genzyme in writing, which notice shall describe the rights that Alnylam intends
to grant to a Third Party pursuant to such agreement (the “Available Third Party
Rights”). Genzyme shall have [***] days from receipt of such written notice to
notify Alnylam in writing as to whether Genzyme desires to negotiate for such
Available Third Party Rights (a “ROFN Exercise Notice”). If Genzyme delivers a
ROFN Exercise Notice prior to the expiration of such [***]-day period, Genzyme
shall have the exclusive right for [***] days following the date that Genzyme
delivers a ROFN Exercise Notice (the “ROFN Offer Period”) to negotiate with
Alnylam and to make one or more written non-binding offers to Alnylam concerning
the terms on which Genzyme would enter into an agreement to acquire the
Available Third Party Rights (a “ROFN Non-Binding Offer”). If Genzyme delivers a
ROFN Non-Binding Offer to Alnylam prior to the expiration of the ROFN Offer
Period, Genzyme shall thereafter have the exclusive right for [***] days (or
such longer period as may be mutually agreed by the Parties) (the “ROFN
Negotiation Period”), to finalize and enter into a definitive agreement with
Alnylam for the acquisition of such Available Third Party Rights. Alnylam shall
not, during the ROFN Offer Period or Negotiation Period, enter into discussions,
exchange information, or otherwise negotiate with any Third Party with respect
to any of the Available Third Party Rights. If (i) Genzyme does not provide a
ROFN Exercise Notice within [***] days of receiving notice of Available Third
Party Rights, (ii) Genzyme does not provide a ROFN Non-Binding Offer prior to
the expiration of the ROFN Offer Period, or (iii) the Parties do not execute a
definitive agreement with respect to the Available Third Party Rights prior to
the expiration of the ROFN Negotiation Period, then Alnylam shall be free to
enter into an agreement with any Third Party with respect to such Available
Third Party Rights (any such agreement, a “Permitted Third Party Agreement”),
provided that, during the period of [***] months after the later of the
expiration of the ROFN Offer Period or expiration of the ROFN Negotiation
Period, Alnylam shall not enter into a Permitted Third Party Agreement with
respect to such Available Third Party Rights on terms that are, in the
aggregate, materially more favorable to such Third Party than the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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last terms offered in writing by Genzyme to Alnylam during the ROFN Offer Period
or ROFN Negotiation Period, as applicable, unless (a) Alnylam first re-offers to
enter into an agreement with Genzyme on such more favorable terms and Genzyme
does not accept such offer and enter into such agreement with Alnylam within
[***] days after such re-offer. For clarity, prior to the ROFN Offer Period and
ROFN Exercise Period with respect to any Available Third Party Rights, Alnylam
shall be free to engage in discussions and exchange information with Third
Parties with respect to such Available Third Party Rights, but shall not enter
into any binding agreement with any Third Party with respect to such Available
Third Party Rights.

3.6.4. Permitted Third Party Agreements. If Alnylam enters into a Permitted
Third Party Agreement pursuant to Section 3.6.3 (ROFN For Available Third Party
Rights) with respect to any Regional Option Product, such Permitted Third Party
Agreement shall be compliant with Alnylam’s obligations under, and consistent
with the terms of, the Regional License Terms.

3.6.5. Gate-Keeping. Promptly following the Effective Date, Alnylam shall
establish a commercially reasonable mechanism to ensure that it does not grant
any Third Party any rights with respect to a Core Pipeline Program in violation
of Section 3.6.1 (Exclusivity for Core Pipeline Programs), whether pursuant to a
new agreement or an amendment to, or any action or inaction pursuant to, any
agreement between a Third Party and Alnylam that is in effect on the Effective
Date.

4. DEVELOPMENT AND PHARMACOVILIGANCE

4.1. Overview. Alnylam shall control and be responsible for the Development of
its Core Pipeline Programs. In connection therewith, Alnylam shall be
responsible for all communications, interactions and filings with, submissions
to, and other actions related to, each Regulatory Authority regarding the Core
Pipeline Programs.

4.2. Diligence. Subject to and without limiting any obligation set forth in any
License Terms, during the Option Period, Alnylam shall use commercially
reasonable efforts to initiate Core Pipeline Programs and undertake the
Development of Option Products from its Core Pipeline Programs through
achievement of Human POP Study Completion and thereafter through the end of the
applicable Option Exercise Period in accordance with industry standards in the
biotechnology and pharmaceutical industry. During the Transition Period, Alnylam
shall use commercially reasonable efforts to Develop the applicable Option
Product. In addition, both Parties shall use commercially reasonable efforts to
plan for the transition to Genzyme of any Global Option Product during the
applicable Transition Period upon the Implementation Date of the applicable
License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.3. Scientific Records. Alnylam shall maintain scientific records, in
sufficient detail and in sound scientific manner appropriate for patent and
regulatory purposes and in compliance with GLP with respect to activities
intended to be submitted in regulatory filings (including INDs), which shall
fully and properly reflect all work done and results achieved in the performance
of the Development activities with respect to potential Option Products by
Alnylam.

4.4. Third Parties. Alnylam shall be entitled to utilize the services of Third
Parties to perform the Development activities with respect to Option Products
under this Master Agreement, provided that (a) Alnylam shall require that such
Third Party operates in a manner consistent with the terms of the Collaboration
Agreement and (b) Alnylam shall remain at all times fully liable for its
responsibilities and (c) the Parties will make reasonable efforts to share
through the PAC information regarding any prior experience with specific CROs
that are anticipated to be engaged to perform work for any Core Pipeline
Program. Alnylam shall require, however, that any such Third Party agreement
(other than an agreement with an academic institution) include commercially
reasonable confidentiality and non-use provisions that are, in the aggregate,
not materially less stringent than those included in the Collaboration
Agreement. Lastly, Alnylam shall use commercially reasonable efforts to obtain
ownership of, and/or a fully sublicensable license under and to, any Know-How
and Patent Rights that are developed by such Third Party in the performance of
such agreement and are reasonably expected to be necessary or useful to Develop,
Manufacture and/or Commercialize Option Products.

4.5. Oversight. The Collaboration shall be conducted under the oversight of the
Alliance Joint Steering Committee which shall have the responsibilities outlined
in the Collaboration Agreement.

4.6. Pharmacovigilance. At least [***], the Parties will negotiate in good faith
and enter into a Safety Data Exchange Agreement (“SDEA”), which will define the
pharmacovigilance responsibilities of the Parties and include safety data
exchange procedures governing the coordination of collection, investigation,
reporting and exchange of information concerning any adverse experiences, and
any product quality and product complaints associated with adverse experiences,
related to such Collaboration Product sufficient to enable each Party (and their
respective Related Parties, if any) to comply with its legal and regulatory
obligations. In addition, as appropriate, such SDEAs will include the safety
data exchange procedures governing the exchange of information affecting the
class (e.g., serious adverse events, emerging safety issues).

5. COLLABORATION MANAGEMENT

5.1. Alliance Joint Steering Committee.

5.1.1. Composition. The AJSC shall be comprised of three (3) representatives who
are employees of each Party. Each Party shall appoint its respective
representatives to the AJSC as of the Effective Date and may substitute one or
more of its

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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representatives, in its sole discretion, effective upon notice to the other
Party of such change. Each Party shall have at least two (2) AJSC
representatives who are executive level employees (vice president or above), and
all AJSC representatives shall have appropriate expertise, seniority,
decision-making authority and ongoing familiarity with the Collaboration.
Additional representatives or consultants may from time to time, by mutual
consent of the Parties, be invited to attend AJSC meetings, subject to such
representatives and consultants (or the representative’s or consultant’s
employer) undertaking confidentiality obligations, whether in a written
agreement or by operation of law, no less stringent than the requirements of
Section 7.1 (Nondisclosure Obligation).

5.1.2. AJSC Chairperson. The AJSC shall be co-chaired, with one chairperson
designated by Alnylam and one chairperson designated by Genzyme, whose
responsibilities shall include conducting meetings, including, when feasible,
ensuring that objectives for each meeting are set and achieved. Responsibility
for running each meeting of the AJSC will alternate between the chairpersons
from meeting-to-meeting, with Alnylam’s chairperson running the first meeting.

5.1.3. Alliance Managers.

5.1.3.1. Each Party shall appoint an alliance manager who is an employee of such
Party (each, an “Alliance Manager”). Each Alliance Manager will be responsible
to ensure a collaborative work environment between the Parties to ensure that
the alliance is run smoothly, professionally and productively. Each Alliance
Manager shall act in his or her discretion to facilitate the execution of the
Collaboration throughout their organization and will oversee and support
implementation plans; promote effectiveness of the governance model and
implementation of contractual provisions and lead any changes to enhance the
alliance; and facilitate the AJSC (and other bodies) for effective decision
making in a timely manner. The Alliance Managers will serve as a primary point
of contact for the other Party under the Collaboration and will undertake such
other tasks as are detailed in the Collaboration Agreement or as may be assigned
by the AJSC. Each Alliance Manager shall attend each meeting of the AJSC. Each
Party may change its Alliance Manager at any time in its sole discretion with
written notice to the other Party.

5.1.3.2. The Alliance Managers shall be responsible for (i) scheduling meetings
of the AJSC, (ii) setting agendas for meetings with solicited input from other
members and (iii) for acting as secretary at each meeting and preparing the
draft minutes of such meeting, which shall provide a description in reasonable
detail of the discussions held at the meeting and a list of any actions,
decisions or determinations approved by the AJSC. [***] days after each meeting,
the drafting Alliance Manager shall provide the draft minutes to the other
Alliance Manager for review and comment. The drafting Alliance Manager

 

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“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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shall reasonably consider all comments from the other Alliance Manager that are
provided within [***] days. The drafting Alliance Manager shall prepare and
submit revised minutes for approval within [***] days after receipt of such
comments or upon the expiration of such [***] day comment period. Beginning with
Alnylam’s Alliance Manager, such responsibilities shall alternate between the
Alliance Managers on a meeting-by-meeting basis after each meeting of the
applicable committee.

5.1.4. Meetings. The AJSC shall meet in accordance with a schedule established
by mutual written agreement of the Parties, but no less frequently than once per
Calendar Quarter during the Term, provided that either Party may from time to
time reasonably request that the AJSC meet to undertake its duties under
Section 5.1.7(c), 5.1.7(d), 5.1.7(e), 5.1.7(f), 5.1.7(h) or 5.1.7(i). The
location for any such meetings shall alternate between Alnylam and Genzyme
facilities (or such other locations as are mutually agreed by the Parties).
Alternatively, the AJSC may meet by means of teleconference, videoconference or
other similar communications equipment. All meetings and proceedings for the
AJSC or its subcommittees shall take place in English. Each Party shall bear its
own expenses relating to attendance at such meetings by its representatives.

5.1.5. Subcommittee Minutes. For each subcommittee created pursuant to
Section 5.1.6 (Subcommittees), each Party shall designate a secretary, who may
be such Party’s Alliance Manager, to prepare draft minutes of each meeting,
which shall provide a description in reasonable detail of the discussions held
at the meeting and a list of any actions, decisions or determinations approved
by such committee. Beginning with the Alnylam secretary, the responsibility for
preparing the minutes shall alternate between the secretaries on a
meeting-by-meeting basis after each meeting of such subcommittee. Within [***]
days after each meeting, the drafting secretary shall provide the draft minutes
to the other secretary for review and comment. The drafting secretary shall
reasonably consider all comments from the other secretary that are provided
within [***] days. The drafting secretary shall prepare and submit revised
minutes for approval within [***] days after receipt of such comments or upon
the expiration of such [***] day comment period.

5.1.6. Subcommittees.

5.1.6.1. The Parties or the AJSC shall have the right to create such
subcommittees of the AJSC as they or it may deem appropriate or necessary (such
as a finance subcommittee, or other appropriate subcommittees). Each such
subcommittee shall report to the AJSC, which shall have authority to approve or
reject recommendations or actions proposed thereby, subject to the terms of the
Collaboration Agreement. Each Party shall bear its own expenses relating to
attendance at any meetings of such subcommittees by its representatives. Each
such subcommittee shall have a chairperson, designated by Alnylam, whose
responsibilities shall include conducting meetings, including ensuring that
objectives for each meeting are set and achieved.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.1.6.2. The Parties hereby establish a Pipeline Advisory Committee and an IP
Committee as subcommittees of the AJSC, each of which shall have the
responsibilities outlined in the Collaboration Agreement.

5.1.6.3. Each PJSC established pursuant to the License Terms will be a
subcommittee of the AJSC; provided, however, that the membership, operation and
responsibilities of each PJSC shall be governed by the applicable License Terms
and not this Section 5.1.6. As a general matter, the Parties expect that the
representatives on the AJSC will be more senior than the representatives on the
PJSC(s).

5.1.7. AJSC Responsibilities. The AJSC shall have the following responsibilities
with respect to the Development, Manufacturing and Commercialization of Option
Products from the Core Pipeline Programs and Collaboration Products pursuant to
the Collaboration:

(a) coordinating the activities of the Parties under the Collaboration,
including budget matters;

(b) overseeing the AJSC’s subcommittees and ensuring effective participation in
each such committee’s operations by any of its members;

(c) considering (but not deciding) whether any Clinical Study, or protocol
therefor, will satisfy the criteria of a Human POP Study in accordance with
Section 3.1.2.3 (Design of Human POP Studies), [***];

(d) attempting to resolve disputes as to whether an Alnylam Program should be
categorized as a Core Pipeline Program or a Non-Core Pipeline Program;

(e) resolving whether an Option Data Package is missing information pursuant to
Section 3.3.4.1(b) (Disputed Missing Information);

(f) resolving any disputed terms of any Supply Agreement under Section 6.3
(Disputed Supply Agreement Terms);

(g) reviewing the status of Collaboration Products, including material
Development and Commercialization matters;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(h) resolving disputes on behalf of each PJSC in accordance with, and subject to
the limitations set forth in, the applicable License Terms;

(i) addressing any other matters referred to the AJSC by the terms of the
Collaboration Agreement; and

(j) performing such other activities as the Parties agree in writing shall be
the responsibility of the AJSC.

5.1.8. Decision-Making.

5.1.8.1. Voting. With respect to decisions of the AJSC, the representatives of
each Party shall have collectively one vote on behalf of such Party. For each
meeting of the AJSC, at least two (2) representatives of each Party shall
constitute a quorum. Action on any matter may be taken at a meeting, by
teleconference, by videoconference or by written agreement.

5.1.8.2. Escalation. The AJSC shall attempt to resolve any and all disputes
before it for decision by consensus.

(a) If the AJSC is unable to reach consensus with respect to a dispute arising
under this Master Agreement for a period in excess of [***] days, then the
dispute shall be submitted to [***] for resolution. If such dispute cannot be
resolved for a period in excess of [***] days following escalation (or such
other period as the Parties may agree), then [***].

(b) If the AJSC is unable to reach consensus with respect to a dispute related
to any Collaboration Product or otherwise arising under any of the License
Terms, then the dispute shall be resolved as set forth in the applicable License
Terms [***].

5.1.8.3. Resolution of Core Pipeline Disputes. [***].

5.1.9. Term. Either Party shall have the right to terminate the AJSC upon the
expiration of the later to expire of (i) the Option Periods and (ii) all of the
License Terms. Notwithstanding the foregoing, on a Regional Licensed
Product-by-Regional Licensed Product basis and on a Global Licensed
Product-by-Global Licensed Product basis, Alnylam shall have the right (but not
the obligation) to continue to participate in the AJSC in relation to any such
Collaboration Product following the earlier of (i) the [***] anniversary of the
Option Exercise Date for such Collaboration Product and (ii) the termination of
the Product Joint Steering Committee (as such term is defined in the Regional
License Terms) or the Joint Transition Team (as such term is defined in the
Global License Terms), as applicable, for such Collaboration Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.2. Pipeline Advisory Committee.

5.2.1. Composition. The Pipeline Advisory Committee shall be comprised of three
(3) representatives who are employees of each Party. Each Party shall appoint
its respective representatives to the PAC within thirty (30) days of the
Effective Date, and from time to time may substitute one or more of its
representatives, in its sole discretion, effective upon notice to the other
Party of such change. Each Party shall have at least one PAC representative who
is a senior level (vice president or above) employee. All PAC representatives
shall have appropriate expertise, seniority, decision-making authority and
ongoing familiarity with the Collaboration and each Party’s representatives
collectively shall have relevant expertise in research, development and
commercial matters. Additional representatives or consultants may from time to
time, by mutual consent of the Parties, be invited to attend PAC meetings,
subject to such representatives and consultants (or the representative’s or the
consultant’s employer) undertaking confidentiality obligations, whether in a
written agreement or by operation of law, no less stringent than the
requirements of Section 7.1 (Nondisclosure Obligation).

5.2.2. Meetings. The PAC shall meet in person once per Calendar Quarter at
Alnylam, provided that either Party may from time to time reasonably request
that the PAC meet to undertake its duties under Section 3.1.1 (Program
Identification) at a location mutually agreed by the Parties.

5.2.3. PAC Development Responsibilities. The PAC shall provide input to Alnylam
and the AJSC regarding the following with respect to the Development of Option
Products from the Core Pipeline Programs prior to their achieving Human POP
Study Completion and pursuant to the Collaboration:

(a) the selection of targets for new Core Pipeline Programs;

(b) the inclusion of Alnylam Programs on the Tentative Core Pipeline Program
List, Core Pipeline Program List and the Non-Core Pipeline Program List pursuant
to Section 3.1.1 (Program Identification);

(c) reviewing and discussing periodic updates from Alnylam to the PAC regarding
the development status of potential Option Products; and

(d) such other matters as the Parties agree in writing shall be the
responsibility of the PAC.

5.2.4. Decision-Making. The PAC shall be an advisory committee for the
Collaboration and to the AJSC. The PAC shall not have any final decision making
power.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.2.5. Term. Either Party shall have the right to terminate the PAC upon the
expiration of the last to expire of the Option Periods.

5.3. IP Committee.

5.3.1. Composition. The IP Committee shall be comprised of at least one
(1) representative who is an employee of each Party. Each Party shall appoint
its respective representatives to the IP Committee within thirty (30) days of
the Effective Date, and from time to time, may substitute one or more of its
representatives, in its sole discretion, effective upon notice to the other
Party of such change. All IP Committee representatives shall have appropriate
expertise, seniority, decision-making authority and ongoing familiarity with the
Collaboration and each Party’s representatives collectively shall have relevant
expertise in intellectual property portfolio management and licensing matters.
Additional representatives or consultants may from time to time, by mutual
consent of the Parties, be invited to attend IP Committee meetings, subject to
such representatives and consultants (or the representative’s or consultant’s
employer) undertaking confidentiality obligations, whether in a written
agreement or by operation of law, no less stringent than the requirements of
Section 7.1 (Nondisclosure Obligation).

5.3.2. Meetings. The IP Committee shall meet as necessary to carry out its
duties under Section 5.3.3 (IP Committee Responsibilities), but no more often
than once per Calendar Quarter, unless otherwise agreed by its members. The IP
Committee shall meet in-person at Alnylam or Genzyme or, alternatively, by means
of teleconference, videoconference or other similar communications equipment.

5.3.3. IP Committee Responsibilities. The IP Committee shall provide input to
Alnylam regarding the following with respect to Option Products from the Core
Pipeline Programs and as indicated in the Global License Terms, the Regional
License Terms and the Co-Co License Terms:

(a) strategies for managing certain Patents Rights pursuant to Section 11.2
(Patent Prosecution Information Sharing);

(b) the necessity and terms of any Proposed In-License pursuant to
Section 11.3.3.1 (Proposed In-Licenses); and

(c) such other matters as the Parties agree in writing shall be the
responsibility of the IP Committee.

5.3.4. Decision-Making. The IP Committee shall be an advisory committee for the
Collaboration and to Alnylam and shall make recommendations by consensus. The IP
Committee shall not have any final decision making power. If there is a
disagreement between the Parties’ representatives on the IP Committee, at either
Party’s request, the General Counsel or other Senior Counsel of each Party will
attend a follow-up meeting of the IP Committee to discuss the matter further.
The IP Committee may escalate matters to the AJSC as it deems appropriate.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.3.5. Term. Either Party shall have the right to terminate the IP Committee
upon the expiration of the last to expire of the Option Periods, except that no
Party shall have the right to terminate the IP Committee in respect of the
Collaboration Product(s) prior to the termination of the License Terms, as
applicable. Notwithstanding the foregoing, on a Collaboration
Product-by-Collaboration Product basis , Alnylam shall have the right (but not
the obligation) to continue to participate in the IP Committee in relation to
any such Collaboration Product following the [***] anniversary of the Option
Exercise Date for such Collaboration Product.

5.4. Manufacturing Committee.

5.4.1. Composition. The Manufacturing Committee shall be comprised of at least
one (1) representative who is an employee of each Party. Each Party shall
appoint its respective representative to the Manufacturing Committee within
thirty (30) days of the Effective Date, and from time to time, may substitute
one or more of its representatives, in its sole discretion, effective upon
notice to the other Party of such change. All Manufacturing Committee
representatives shall have appropriate expertise, seniority, decision-making
authority and ongoing familiarity with the Collaboration and each Party’s
representatives collectively shall have relevant expertise in matters related to
the Manufacturing and supply of human therapeutic products. Additional
representatives or consultants may from time to time, by mutual consent of the
Parties, be invited to attend Manufacturing Committee meetings, subject to such
representatives and consultants (or the representative’s or consultant’s
employer) undertaking confidentiality obligations, whether in a written
agreement or by operation of law, no less stringent than the requirements of
Section 7.1 (Nondisclosure Obligation).

5.4.2. Meetings. The Manufacturing Committee shall meet as necessary to carry
out its duties under Section 5.4.3 (Manufacturing Committee Responsibilities),
but no more often than once per Calendar Quarter, unless otherwise agreed by its
members. The Manufacturing Committee shall meet in-person at Alnylam or Genzyme
or, alternatively, by means of teleconference, videoconference or other similar
communications equipment.

5.4.3. Manufacturing Committee Responsibilities. The Manufacturing Committee
shall provide a forum for the discussion and review of matters related to the
Manufacturing and supply of Collaboration Products, including the following:

(a) worldwide Manufacturing and sourcing strategies in support of the
Development and Commercialization of Collaboration Products, including the
strategic aspects of Manufacture and release of finished Collaboration Product;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) use of Third Parties to Manufacture and supply any Collaboration Product;

(c) logistical strategies, capacity planning and inventory levels for each
Collaboration Product for consistency with the then-current Development Plans
and Commercialization Plans for such Collaboration Product;

(d) results of regulatory inspections related to Collaboration Products and
reviewing steps to be taken by the Parties to address any deficiencies noted;

(e) capacity planning and supply continuity plans for each Collaboration Product
for consistency with the then-current Development Plan and Commercialization
Plan for such Collaboration Product; regulatory compliance related to the
Manufacture of Collaboration Products;

(f) material quality-related issues concerning the Collaboration Products;

(g) costs of Manufacture;

(h) providing updates to the AJSC or a PJSC, as applicable, upon request
relating to Manufacturing issues; and

(i) such other matters as the Parties agree in writing shall be the
responsibility of the Manufacturing Committee.

5.4.4. Decision-Making. The Manufacturing Committee shall be an advisory
committee for the Collaboration and shall make recommendations by consensus. The
Manufacturing Committee shall not have any final decision making power.

5.4.5. Term. Either Party shall have the right to terminate the Manufacturing
Committee upon the expiration of the last to expire of the (i) Option Periods,
and (ii) all of the License Terms. Notwithstanding the foregoing, on a Regional
Licensed Product-by-Regional Licensed Product basis and on a Global Licensed
Product-by-Global Licensed Product basis, Alnylam shall have the right (but not
the obligation) to continue to participate in the Manufacturing Committee in
relation to any such Collaboration Product following the earlier of (i) the
[***] anniversary of the Option Exercise Date for such Collaboration Product and
(ii) the termination of the Product Joint Steering Committee (as such term is
defined in the Regional License Terms) or the Joint Transition Team (as such
term is defined in the Global License Terms), as applicable, for such
Collaboration Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.5. Product Joint Steering Committees. Pursuant to the License Terms, the
Parties will form a PJSC (as defined in each of the License Terms) that has
certain responsibilities with respect to the Development and Commercialization
of each Collaboration Product as set forth in the License Terms for such
Collaboration Product. For the avoidance of doubt, the same representatives from
each Party may serve on the PJSC for more than one Collaboration Product and,
where membership of a PJSC for a Collaboration Product is the same as one or
more other PJSCs for other Collaboration Product(s), such PJSCs may have a
single meeting to discuss each Collaboration Product for which they have
responsibility.

5.6. No Power to Amend. Unless otherwise agreed to by the Parties in writing,
the AJSC, PAC, IP Committee, Manufacturing Committee and each PJSC will have
only the powers expressly assigned to it in the Collaboration Agreement. In no
event will any of them have any power to amend, modify, or waive compliance with
this Agreement.

5.7. Confidentiality. All information disclosed by either Party or its
representatives to the other Party or its representatives under this Section 5
shall be deemed to be Confidential Information of the disclosing Party and
maintained in accordance with Section 7 (Confidentiality and Publication).

5.8. Modifications. The Parties shall meet from time to time to discuss whether
any changes to the governance structure for the Collaboration are necessary or
advisable.

5.9. Other Governance Terms. Governance provisions related to each Collaboration
Product are located in the applicable License Terms.

6. MANUFACTURE AND SUPPLY OF THE COLLABORATION PRODUCTS

6.1. ALN-TTR02 Supply Agreements. Subject to the terms and conditions of this
Section 6 (Manufacture and Supply of the Collaboration Products), within [***]
days after receiving written notice from Genzyme requesting such negotiations,
the Parties will negotiate in good faith and enter into a supply agreement (and
any other necessary ancillary agreements) for clinical supply of ALN-TTR02 by
Alnylam (or for Alnylam by Alnylam’s Third Party manufacturer) (the “ALN-TTR02
Clinical Supply Agreement”), which will be consistent with the terms set forth
on Schedule 6.1. In addition, at the request of Genzyme at least [***] months in
advance of the first Regulatory Approval of ALN-TTR02 in the Genzyme Territory,
the Parties will negotiate in good faith and enter into a supply agreement (and
any other necessary ancillary agreements), before such [***]-month date, for
commercial supply of ALN-TTR02 by Alnylam (or for Alnylam, by Alnylam’s Third
Party manufacturer) (the “ALN-TTR02 Commercial Supply Agreement”), which will
also be consistent with the terms set forth on Schedule 6.1. Notwithstanding the
foregoing, the breach of any such Manufacturing terms as applied to a
Collaboration Product shall be treated as a breach under the Regional License
Terms, and not under this Master Agreement. When the Parties enter into an
ALN-TTR02 Clinical Supply Agreement or ALN-TTR02 Commercial Supply agreement,
such agreement will supersede the terms set forth in Schedule 6.1 with respect
to Manufacture and supply of ALN-TTR02.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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6.2. Collaboration Product Supply Agreements. Subject to the terms and
conditions of this Section 6 (Manufacture and Supply of the Collaboration
Products), following the Implementation Date with respect to any given
Collaboration Product other than ALN-TTR02, and within [***] days following a
written notice by Genzyme requesting such negotiation, the Parties will
negotiate in good faith and enter into a supply agreement (and any other
necessary ancillary agreements) for clinical supply of such Collaboration
Product by Alnylam (or for Alnylam by Alnylam’s Third Party manufacturer) (each,
a “Clinical Supply Agreement”), which will be consistent with the terms set
forth on Schedule 6.2. In addition, at least [***] months in advance of the
first Regulatory Approval of each Collaboration Product (other than ALN-TTR02)
the Parties will negotiate in good faith and enter into a supply agreement (and
any other necessary ancillary agreements), before such [***]-month date, for
commercial supply of such Collaboration Product by Alnylam (or for Alnylam by
Alnylam’s Third Party manufacturer) (each, a “Commercial Supply Agreement”),
which will also be consistent with the terms set forth on Schedule 6.2;
provided, however, in the case of any Global Licensed Product, the Parties shall
only negotiate and enter into a Commercial Supply Agreement at the request of
Genzyme. Notwithstanding the foregoing, the breach of any such Manufacturing
terms as applied to a Collaboration Product shall be treated as a breach under
its respective License Terms, and not under this Master Agreement. When the
Parties enter into a Clinical Supply Agreement or Commercial Supply Agreement,
such agreement will supersede the terms set forth in Schedule 6.2 with respect
to the Manufacture and supply of the applicable Collaboration Product.

6.3. General Supply Agreement Requirements. In addition to reflecting terms
consistent with those set forth on Schedule 6.1 or Schedule 6.2, as applicable,
each Alnylam Supply Agreement will include key performance indicators for
Alnylam (including criteria regarding Manufacturing capacity, quantity,
timeliness of delivery, quality and cost that are consistent with prevailing
industry standards for Third Party contract manufacturing agreements)
(collectively, the “KPIs”). Further, for each Alnylam Supply Agreement for a
given Collaboration Product, the Parties shall also enter into a quality
technical agreement, which will be designed to ensure sufficient oversight by
Genzyme of quality matters related to the Manufacture and testing of such
Collaboration Product by Alnylam and its Third Party manufacturers and will set
forth the quality responsibilities and obligations of both Genzyme and Alnylam.

6.4. Disputed Supply Agreement Terms. If the Parties are unable to reach
agreement on any terms of any of the Alnylam Supply Agreements, as required by
Sections 6.1 (ALN-TTR02 Supply Agreements), 6.2 (Collaboration Product Supply
Agreements) and 6.3 (General Supply Agreement Requirements), then any such
disputed terms shall be submitted to the AJSC for resolution pursuant to
Section 5.1.8 (Decision-Making). If the AJSC is unable to resolve any such
disputed terms, then those unresolved disputed terms shall be [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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6.5. Transfer of Manufacturing Know-How. [***].

6.6. Establishment of Second Source and Back-Up Sources.

6.6.1. [***].

6.6.2. [***].

6.6.2.1. [***].

6.6.2.2. [***].

6.6.2.3. [***].

6.6.2.4. [***].

6.6.2.5. [***].

6.7. Third Party Manufacturers and Subcontracting. If, following the Effective
Date, either Party desires to enter into an agreement with a Third Party
manufacturer for the supply of Product, then (a) the other Party shall have the
right to review and approve (such approval not unreasonably withheld,
conditioned or delayed) such Third Party manufacturer and (b) each Party shall
keep the other Party reasonably informed through the Manufacturing Committee of
the status of any proposed supply agreement to be entered into with any such
Third Party manufacturer with respect to the Manufacture and supply of such
Product (a “Third Party Supply Agreement”) and submit any such Third Party
Supply Agreement to the Manufacturing Committee for review and good faith
discussion prior to its execution. For the avoidance of doubt, if a Party is
subject to an existing binding agreement with a Third Party manufacturer for the
supply of Product as of the Effective Date (each an “Existing Third Party Supply
Agreement”), then, provided that such existing binding agreement is not
materially amended at any time following the Effective Date (i) such existing
binding agreement shall be deemed a Third Party Supply Agreement and (ii) the
provisions of clauses a and b (immediately above) shall not apply to such
existing binding agreement or the Third Party manufacturer party thereto.
Without the consent of the other Party, but subject to the terms of this
Section 6, either Party may subcontract (in whole or in part) its Manufacturing
obligations under any Alnylam Supply Agreement or Genzyme Supply Agreement, as
applicable, to a qualified Third Party manufacturer pursuant to a binding Third
Party Supply Agreement; provided, however, that (A) the subcontracting Party
shall remain solely responsible to the other Party for the performance of the
subcontracting Party’s obligations under each Alnylam Supply Agreement or
Genzyme Supply Agreement, as applicable and (B) the terms and/or conditions of
any Third Party Supply

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Agreement shall not in any way amend, modify or diminish the subcontracting
Party’s obligations to the other Party under any Alnylam Supply Agreement or
Genzyme Supply Agreement, as applicable. If the forecasting or order
timing/method provisions of a Third Party Supply Agreement do not align with the
corresponding provisions of a relevant Alnylam Supply Agreement or Genzyme
Supply Agreement, as applicable, then, at the request of the subcontracting
Party, the Parties shall discuss in good faith appropriate modifications to such
Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable, to bring
the relevant provisions into alignment with such Third Party Supply Agreement,
provided, however, that the non-subcontracting Party shall have no obligation to
agree to any amendment to such Alnylam Supply Agreement or Genzyme Supply
Agreement that can reasonably be expected to materially disadvantage the
non-subcontracting Party.

6.8. Waivers. In the event that any Collaboration Product must be substantially
Manufactured in the United States pursuant to applicable Law, then, at Genzyme’s
request, Alnylam will use commercially reasonable efforts, at Genzyme’s expense,
to secure a waiver of such requirement for such Collaboration Product under 35
U.S.C. § 204 or any analogous applicable Law outside the United States. If a
waiver of the substantially manufactured requirement is obtained, then such
Collaboration Product used or sold in the United States may be Manufactured as
such waiver permits.

7. CONFIDENTIALITY AND PUBLICATION

7.1. Nondisclosure Obligation.

7.1.1. All Confidential Information disclosed by one Party to the other Party
under the Collaboration Agreement, Stock Purchase Agreement and Investor
Agreement shall be maintained in confidence by the receiving Party and shall not
be disclosed to a Third Party or used for any purpose except as set forth herein
without the prior written consent of the disclosing Party, except to the extent
that such Confidential Information:

(a) is known by the receiving Party at the time of its receipt, and not through
a prior disclosure by the disclosing Party, as documented by the receiving
Party’s business records;

(b) is known to the public before its receipt from the disclosing Party, or
thereafter becomes generally known to the public through no breach of the
Collaboration Agreement, Stock Purchase Agreement or Investor Agreement by the
receiving Party;

(c) is subsequently disclosed to the receiving Party by a Third Party who is not
known by the receiving Party to be under an obligation of confidentiality to the
disclosing Party; or

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) is developed by the receiving Party independently of Confidential
Information received from the disclosing Party, as documented by the receiving
Party’s business records.

7.1.2. Notwithstanding the obligations of confidentiality and non-use set forth
above and in Section 7.1.3 below, a receiving Party may provide Confidential
Information disclosed to it, and disclose the existence and terms of the
Collaboration Agreement, Stock Purchase Agreement or Investor Agreement as may
be reasonably required in order to perform its obligations and to exploit its
rights under the Collaboration Agreement, Stock Purchase Agreement or Investor
Agreement, and specifically to (i) Related Parties, and their employees,
directors, agents, consultants, advisors or other Third Parties for the
performance of its obligations hereunder (or for such entities to determine
their interest in performing such activities) in accordance with the
Collaboration Agreement, Stock Purchase Agreement or Investor Agreement in each
case who are under an obligation of confidentiality with respect to such
information that is no less stringent than the terms of this Section 7.1;
(ii) governmental or other Regulatory Authorities in order to obtain patents or
perform its obligations or exploit its rights under the Collaboration Agreement,
Stock Purchase Agreement or Investor Agreement, provided that such Confidential
Information shall be disclosed only to the extent reasonably necessary to do so;
(iii) the extent required by Law, including by the rules or regulations of the
United States Securities and Exchange Commission or similar regulatory agency in
a country other than the United States or of any stock exchange or listing
entity; (iv) any bona fide actual or prospective acquirers, underwriters,
investors, lenders or other financing sources and any bona fide actual or
prospective collaborators or strategic partners and to consultants and advisors
of such Party, in each case who are under an obligation or confidentiality with
respect to such information that is no less stringent than the terms of this
Section 7.1; and (v) to Third Parties to the extent a Party is required to do so
pursuant to the terms of an In-License. If a Party is required by Law to
disclose Confidential Information that is subject to the non-disclosure
provisions of this Section 7.1, such Party shall promptly inform the other Party
of the disclosure that is being sought in order to provide the other Party an
opportunity to challenge or limit the disclosure. Notwithstanding Section 7.1.1,
Confidential Information that is required to be disclosed by Law shall remain
otherwise subject to the confidentiality and non-use provisions of this
Section 7.1. If either Party concludes that a copy of any of the Collaboration
Agreement, Stock Purchase Agreement or Investor Agreement must be filed with the
United States Securities and Exchange Commission or similar regulatory agency in
a country other than the United States, such Party shall provide the other Party
with a copy of such agreement showing any provisions hereof as to which the
Party proposes to request confidential treatment, shall provide the other Party
with an opportunity to comment on any such proposed redactions and to suggest
additional redactions, and shall take such Party’s reasonable comments into
consideration before filing such agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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7.1.3. Alnylam acknowledges that Genzyme may use Confidential Information of
Alnylam for purposes of making investment and voting decisions with respect to
the shares of Common Stock owned by Genzyme, provided that (i) Genzyme hereby
acknowledges to Alnylam that Genzyme is aware that the United States securities
laws prohibit any Person who has material, non-public information concerning a
company from purchasing or selling securities of such company or from
communicating such information to any other Person under circumstances in which
it is reasonably foreseeable that such Person is likely to purchase or sell such
securities and (ii) Genzyme hereby acknowledges that it is are aware of the
sanctions under the United States securities laws attaching to misuse or such
improper disclosure of any material, non-public information relating to Alnylam.

7.1.4. Each Party recognizes that the value to the other Party of the
transactions under the Collaboration Agreement, Stock Purchase Agreement and
Investor Agreement depend, in part, on each Party protecting the secrecy of its
Know-How. Therefore, without limiting any Party’s right’s right to license its
Know-How, subject to the terms of the Collaboration Agreement, Stock Purchase
Agreement or Investor Agreement, in any way it chooses, each Party shall use
commercially reasonable efforts to protect the confidentiality of its Know-How
as determined in such Party’s reasonable business judgment.

7.1.5. Notwithstanding any provision of the Collaboration Agreement to the
contrary but subject to the occurrence of the Effective Date, Residual Knowledge
shall not be considered Confidential Information for purposes of this Section
7.1.

7.2. Publication and Publicity.

7.2.1. Publication. Genzyme and Alnylam each acknowledge the other Party’s
interest in publishing certain key results of the Collaboration. Each Party also
recognizes the mutual interest in obtaining valid patent protection and in
protecting trade secret information. Consequently, except for disclosures
permitted pursuant to Section 7.1 (Nondisclosure Obligation) and 7.2.2
(Publicity), either Party wishing to make a publication or public presentation
that contains the Confidential Information of the other Party shall deliver to
the other Party a copy of the proposed written publication or presentation at
least [***] days prior to submission for publication or presentation. The
reviewing Party shall have the right (i) to propose modifications to the
publication or presentation for patent reasons, trade secret reasons or business
reasons, and the publishing Party shall remove all Confidential Information of
the other Party if requested by the reviewing Party, or (ii) to request a
reasonable delay in publication or presentation in order to protect patentable
information. If the reviewing Party requests a delay, the publishing Party shall
delay submission or presentation for a period of [***] days (or such shorter
period as may be mutually agreed by the Parties) to enable the non-publishing
Party to file patent applications protecting such Party’s rights in such

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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information. With respect to any proposed publications or disclosures by
investigators or academic or non-profit collaborators, such materials shall be
subject to review under this Section 7.2.1 to the extent that Genzyme or
Alnylam, as the case may be, has the right and ability (after using commercially
reasonable efforts to obtain such right and ability) to do so.

7.2.2. Publicity. Except as set forth in Section 7.1 (Nondisclosure Obligation)
and Section 7.2.1 (Publication) above and 7.3.2 (Press Release) below, the terms
of any of the Collaboration Agreement, Stock Purchase Agreement or Investor
Agreement may not be disclosed by either Party, and neither Party shall use the
name, Trademark, trade name or logo of the other Party or its employees in any
publicity, news release or disclosure relating to any of the Collaboration
Agreement, Stock Purchase Agreement or Investor Agreement, its subject matter,
or the activities of the Parties hereunder without the prior express written
permission of the other Party, except as may be required by Law, including by
the rules or regulations of the United States Securities and Exchange
Commission, the French Financial Markets Authority, the French Prudential
Supervisory Authority or similar regulatory agency in any country other than the
United States or France or of any stock exchange or listing entity, or except as
expressly permitted by the terms hereof.

7.3. Press Release.

7.3.1. Following the execution of the Collaboration Agreement, the Parties shall
issue separate press releases in the forms set forth in Schedule 7.3 or such
other forms mutually agreed by the Parties. After such initial press releases,
except as provided in Section 7.3.2, neither Party shall issue a press release
or public announcement relating to the Collaboration Agreement without the prior
written approval of the other Party, which approval shall not be unreasonably
withheld, conditioned or delayed, except that a Party may (i) once a press
release or other public statement is approved in writing by both Parties, make
subsequent public disclosure of the information contained in such press release
or other written statement without the further approval of the other Party, and
(ii) issue a press release or public announcement as required, in the reasonable
judgment of such Party, by Law, including by the rules or regulations of the
United States Securities and Exchange Commission, the French Financial Markets
Authority, the French Prudential Supervisory Authority or similar regulatory
agency in a country other than the United States or France or of any stock
exchange or listing entity.

7.3.2. Notwithstanding anything in this Section 7.3 to the contrary, either
Party may issue a press release or make a public disclosure relating to (i) the
results of any Clinical Studies with respect to an Option Product, (ii) the
exercise of an Option, (iii) the payment or receipt of a milestone payment under
any License Terms with respect to a Collaboration Product and (iv) such Party’s
Development, Manufacturing or Commercialization activities under any License
Terms with respect to Collaboration

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Products in such Party’s Territory, provided that such press release or public
disclosure does not disclose Confidential Information of the other Party.
Furthermore, either Party may issue a press release or make a public disclosure
relating to the other Party’s Development, Manufacturing or Commercialization
activities with respect to the Collaboration Products in the other Party’s
Territory, provided that (i) such press release or public disclosure does not
disclose Confidential Information of the other Party and (ii) such press release
or public disclosure merely repeats subject matter previously disclosed by the
other Party in a manner that is substantially consistent with such prior
disclosure. Prior to making any such disclosure under this Section 7.3.2,
however, the Party making the disclosure shall provide the other Party with a
draft of such proposed disclosure a reasonable time (but at least [***] business
days) prior to disclosure to allow the other Party to review and comment prior
to making any such disclosure, for the other Party’s review and comment, and the
disclosing Party shall consider in good faith any timely comments provided by
the other Party. Notwithstanding the foregoing, except as expressly permitted by
clause (i), (ii) or (iii) above and subject to clause (ii) of Section 7.3.1,
Alnylam may not issue any other press release or make a public disclosure
relating to Genzyme’s activities for any Global Licensed Product without the
prior written consent of Genzyme.

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

8.1. Mutual Representations and Warranties as of the Execution Date. Each Party
represents and warrants to the other Party that, as of the Execution Date:

8.1.1. such Party is a corporation duly organized, validly existing and in good
standing under the laws of its jurisdiction of incorporation or formation;

8.1.2. such Party has all requisite corporate power and corporate authority to
enter into the Collaboration Agreement and to carry out its obligations under
the Collaboration Agreement;

8.1.3. all requisite corporate action on the part of such Party, its directors
and stockholders required by applicable Law for the authorization, execution and
delivery by such Party of the Collaboration Agreement, and the performance of
all obligations of such Party under the Collaboration Agreement, has been taken;

8.1.4. the execution, delivery and performance of the Collaboration Agreement,
and compliance with the provisions of the Collaboration Agreement, by such Party
do not and shall not: (a) violate any provision of applicable Law or any ruling,
writ, injunction, order, permit, judgment or decree of any Governmental
Authority, (b) constitute a breach of, or default under (or an event which, with
notice or lapse of time or both, would become a default under) or conflict with,
or give rise to any right of termination, cancellation or acceleration of, any
agreement, arrangement or instrument, whether

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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written or oral, by which such Party or any of its assets are bound, or (c)
violate or conflict with any of the provisions of such Party’s organizational
documents (including any articles or memoranda of organization or association,
charter, bylaws or similar documents), except, in the case of subsections
(a) and (b), as would not have or be reasonably likely to have a Material
Adverse Effect (as defined in the Stock Purchase Agreement);

8.1.5. no consent, approval, authorization or other order of, or filing with, or
notice to, any Governmental Authority or other Third Party is required to be
obtained or made by such Party in connection with the authorization, execution
and delivery by the Company of the Collaboration Agreement, except as required
pursuant to the HSR Act; and

8.1.6. such Party has not entered into any agreement with any Third Party that
grants such Third Party any rights that would be in conflict with the
Collaboration Agreement following an siRNA becoming a Collaboration Product
under the Collaboration Agreement.

8.2. Representations and Warranties of Alnylam. Except as provided in Schedule
8.2, Alnylam represent and warrants to Genzyme that, as of the Execution Date
and, with respect to the representations in Sections 8.2.1, 8.2.2, 8.2.5, 8.2.7,
8.2.9 and 8.2.10 below, as of the Effective Date:

8.2.1. Alnylam is the sole and exclusive owner of, or otherwise Controls
pursuant to an Existing Alnylam In-License, the Option Product Technology and
the ALN-TTR Technology.

8.2.2. Alnylam has sufficient legal and/or beneficial title and ownership of, or
sufficient license rights under, the Option Product Technology and ALN-TTR
Technology to grant the licenses to such Option Product Technology and ALN-TTR
Technology to Genzyme pursuant to the Collaboration Agreement.

8.2.3. (a) Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24
(ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core
Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents)
collectively set forth a complete and accurate list of the ALN-TTR Patents and
Option Product Patents owned, either solely or jointly, by Alnylam, and to
Alnylam’s knowledge, Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule
1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core
Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents)
collectively set forth a complete and accurate list of the ALN-TTR Patents and
Option Product Patents licensed, either exclusively or nonexclusively, to
Alnylam, (b) to Alnylam’s knowledge, each issued ALN-TTR Patent and Option
Product Patent remains in full force and effect and (c)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Alnylam or its Affiliates have timely paid all filing and renewal fees payable
with respect to such ALN-TTR Patents and Option Product Patents for which
Alnylam controls prosecution and maintenance. Schedule 1.2.22 (ALN-TTR Core
Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents),
Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162
(Option Product-Specific Patents) indicate whether each ALN-TTR Patent and
Option Product Patent is owned exclusively by Alnylam, is owned jointly by
Alnylam and one or more Third Parties, or is licensed to Alnylam. For each
ALN-TTR Patent and Option Product Patent that is owned, but not owned
exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.2.22
(ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific
Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and
Schedule 1.2.162 (Option Product-Specific Patents) identify the Third Party
owner(s) and, if applicable, the Existing Alnylam In-License pursuant to which
Alnylam Controls such ALN-TTR Patent or Option Product Patent. For each Option
Product Core Technology Patent family (other than Patent Rights licensed from
Isis Pharmaceuticals, Inc.) and each ALN-TTR Core Technology Patent family that
is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.22 (ALN-TTR
Core Technology Patents) or Schedule 1.2.159 (Option Product Core Technology
Patents), as applicable indicates the non-exclusive nature of the license. For
each Option Product-Specific Patent and ALN-TTR Product-Specific Patent that is
licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.24 (ALN-TTR
Product-Specific Patents) or Schedule 1.2.162 (Option Product-Specific Patents),
as applicable, indicates the non-exclusive nature of the license. Alnylam is the
sole and exclusive owner of all Patent Rights identified in Schedule 1.2.22
(ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific
Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and
Schedule 1.2.162 (Option Product-Specific Patents) as being owned exclusively by
Alnylam and Controls all other Patent Rights identified on such schedules.

8.2.4. Schedule 1.2.82 (Existing Alnylam In-Licenses) sets forth a complete and
accurate list of all agreements between Alnylam and a Third Party entered into
prior to the Execution Date pursuant to which Alnylam Controls Know-How or
Patent Rights that are necessary or useful to Develop, Manufacture or
Commercialize ALN-TTR02, ALN-TTRsc or any Co-Co/Global Option Product in the
Field, other than Additional Alnylam In-Licenses. [***].

8.2.5. Alnylam has complied with all applicable Laws, including any duties of
candor to applicable patent offices, in connection with the filing, prosecution
and maintenance of the ALN-TTR Patents and Option Product Patents.

8.2.6. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach
or default under any Existing Alnylam In-License, and neither Alnylam nor its
Affiliates have received any written notice of breach or default with respect to
any Existing Alnylam In-License.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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8.2.7. Alnylam has obtained from all inventors of ALN-TTR Technology or Option
Product Technology owned by Alnylam valid and enforceable agreements assigning
to Alnylam each such inventor’s entire right, title and interest in and to all
such ALN-TTR Technology or Option Product Technology, as applicable.

8.2.8. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry,
investigation or other legal action of any nature, civil, criminal, regulatory
or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or
any of its Affiliates or (b) judgment or settlement against or owed by Alnylam
or any of its Affiliates, in each case in connection with the ALN-TTR Technology
or Option Product Technology.

8.2.9. Alnylam owns or Controls all Know-How that is or has been used by Alnylam
in the Development and Manufacture of ALN-TTR02, ALN-TTRsc and the Option
Products, and has sufficient legal or beneficial title and ownership of, or
sufficient license rights under such Know-How to transfer Know-How to Genzyme as
provided in Section 6.5 (Transfer of Manufacturing Know-How).

8.2.10. Alnylam has conducted all Development activities with respect to the
Core Pipeline Programs currently in existence in compliance with all applicable
Laws, including current governmental regulations concerning, GLP, good clinical
practices and cGMP.

8.2.11. True and complete copies of the agreements set forth on Schedule 1.2.82
(Existing Alnylam In-Licenses) and Schedule 1.2.7 (Additional Alnylam
In-Licenses), and all of the agreements relating to any Option Product,
ALN-TTR02 or ALN-TTRsc have been made available to Genzyme through an electronic
data room.

For purposes of this Section 8.2 and where indicated in Section 8.4 (Certain
Covenants), with respect to each instance of Option Product Technology, Option
Product Patents, Option Product Core Technology Patents and Option
Product-Specific Patents and Option Products, those definitions shall be limited
to the Existing Core Option Products.

8.3. Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THE
COLLABORATION AGREEMENT, STOCK PURCHASE AGREEMENT OR INVESTOR AGREEMENT, NEITHER
PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER
EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY,
COLLABORATION PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THE
COLLABORATION AGREEMENT AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH
RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY
REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR
COMMERCIALIZATION OF ANY COLLABORATION PRODUCT PURSUANT TO THE COLLABORATION
AGREEMENT SHALL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO
ANY COLLABORATION PRODUCT SHALL BE ACHIEVED.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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8.4. Certain Covenants.

8.4.1. Compliance. Each Party and its Related Parties shall conduct the
Collaboration and the Development, Manufacture and Commercialization of the
Collaboration Products and any Option Products from the Core Pipeline Programs
in material compliance with all applicable Laws, including current governmental
regulations concerning GLP, good clinical practices and cGMP.

8.4.2. Clarifying Amendments. [***]. For clarity, such amendment will be an
Existing Alnylam In-License for all purposes of the Collaboration Agreement.

8.4.3. Retention of Title. During the Option Period, Alnylam shall retain and
maintain sufficient legal and/or beneficial title and ownership of, or
sufficient license rights under, any Option Product Technology relating to a
Core Pipeline Program to enable Alnylam to grant the licenses and rights to such
Option Product Technology that would be granted to Genzyme under, and as
reasonably necessary to practice, such Option Product Technology under the
applicable License Terms if Genzyme exercised an Option with respect to such
Option Product. Without limiting the generality of the foregoing, during the
Option Period, Alnylam shall not sell, transfer, lease or otherwise dispose of
any Option Product Technology, except to the extent expressly permitted under
the Collaboration Agreement or to grant a security interest, lien or other
encumbrance in, on or to any Option Product Technology as part of a financing
transaction.

8.4.4. Know-How. Alnylam shall not use any Know-How that it does not Control in
the Development or Manufacture of Option Products from the Core Pipeline
Programs. Alnylam shall obtain sufficient legal or beneficial title and
ownership of, or beneficial title and ownership of, or sufficient rights under,
and as reasonably necessary to practice, any Know-How that is used by Alnylam in
the Development or Manufacture of Option Products from the Core Pipeline
Programs to grant the licenses and rights to such Know-How that would be granted
to Genzyme pursuant to the applicable License Terms if Genzyme exercised an
Option with respect to an Option Product from the Core Pipeline Programs.

8.4.5. In-Licenses. Alnylam shall use commercially reasonable efforts to
maintain Control of all Know-How and Patent Rights licensed to Alnylam under the
Existing Alnylam In-Licenses and Additional Alnylam In-Licenses that would be
necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize any
Option Product in the Field in the Genzyme Territory pursuant to the License
Terms that

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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would apply to such Option Product if Genzyme exercised an Option for such
Option Product. Alnylam shall use commercially reasonable efforts not to
materially breach or be in material default under any of its obligations under
any Alnylam In-License. Alnylam will not voluntarily amend or terminate any
Alnylam In-License in a manner that would terminate rights that would be
sublicensed to Genzyme if Genzyme exercised an Option with respect to an Option
Product, other than Additional Alnylam In-Licenses. Alnylam will update Schedule
1.2.82 (Existing Alnylam In-Licenses) if, prior to the Effective Date, Alnylam
enters into any agreement pursuant to which Alnylam Controls Patent Rights or
Know-How necessary or useful to Develop, Manufacture or Commercialize any Option
Product (where such term is limited for these purposes in accordance with the
last sentence of Section 8.2), ALN-TTR02 or ALN-TTRsc in the Field in the
Genzyme Territory.

8.4.6. No Debarment. Each Party shall commercially reasonable efforts to not
use, in any capacity in connection with the Collaboration or the performance of
its obligations under the Collaboration Agreement, any Person that has been
debarred pursuant to Section 306 of the United States Federal Food, Drug, and
Cosmetic Act, as amended, or that is the subject of a conviction described in
such section. Each Party agrees to inform the other Party in writing immediately
if it or any Person that is performing activities in the Collaboration or under
the Collaboration Agreement, is debarred or is subject to debarment or is the
subject of a conviction described in Section 306, or if any action, suit, claim,
investigation or legal or administrative proceeding is pending or, to the best
of the notifying Party’s knowledge, is threatened, relating to the debarment or
conviction of the notifying Party or any Person or entity used in any capacity
by such Party or any of its Affiliates in connection with the Collaboration or
the performance of its other obligations under the Collaboration Agreement.

8.4.7. [***].

8.4.8. Potential License Agreements. [***].

8.4.9. [***].

8.4.10. Contractual Obligations. If any ALN-TTR Technology or Option Product
Technology is subject to any funding agreement with any government or
Governmental Authority or subject to any other agreement under which
requirements and obligations will apply to Genzyme under the Collaboration
Agreement, then, at Genzyme’s request, Alnylam will use commercially reasonable
efforts, at Genzyme’s expense, to secure a waiver of any requirements or
obligations of Genzyme under such agreements.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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8.4.11. [***].

9. ROYALTY REPORTS; PAYMENTS; AUDIT

9.1. Reports; Payment of Royalty. During the Term, following the First
Commercial Sale of any Collaboration Product by or on behalf of a Party in such
Party’s Territory under the applicable License Terms, such Party shall furnish
to the other Party a written report within [***] days after the end of each
Calendar Quarter showing, on a Collaboration Product-by-Collaboration Product
and country-by-country basis [***]. Except as expressly provided in the
Collaboration Agreement, all payments by one Party to the other Party under the
Collaboration Agreement shall be non-refundable and non-creditable and not
subject to set-off. Royalties shown to have accrued by each royalty report shall
be due and payable [***] days following the date such royalty report is due. In
addition, each Party selling a Collaboration Product shall prepare and deliver
to the other Party any additional reports for sales in such selling Party’s
Territory as required under any applicable Existing Genzyme In-Licenses,
Existing Alnylam In-Licenses or Collaboration In-Licenses.

9.2. Audits.

9.2.1. On a Collaboration Product-by-Collaboration Product basis, upon the
written request of a Party and not more than once in each Calendar Year, the
other Party and its Related Parties shall permit an independent certified public
accounting firm of internationally-recognized standing selected by the
requesting Party and reasonably acceptable to the other Party, at the requesting
Party’s expense except as set forth below, to have access during normal business
hours to such of the records of the other Party as may be reasonably necessary
to verify the accuracy of the royalty and other amounts payable or reports under
the Collaboration Agreement in respect of such Collaboration Product (including
Global R&D Costs (as defined in any of the License Terms) and Cost of Goods but
excluding S&M Costs (as defined in the Co-Co License Terms)) for any year ending
not more than [***] years prior to the date of such request for the sole purpose
of verifying the basis and accuracy of payments made under the applicable
License Terms in respect of such Collaboration Product. Notwithstanding the
foregoing, a Party may not make more than [***] in a Calendar Year, [***].

9.2.2. If such accounting firm identifies a discrepancy made during such period,
the appropriate Party shall pay the other Party the amount of the discrepancy,
together with late-payment interest in accordance with Section 9.4 (Late
Payments), within [***] days after the date the requesting Party delivers to the
other Party such accounting firm’s written report so concluding, or as otherwise
agreed by the Parties in writing. The fees charged by such accounting firm shall
be paid by the requesting Party, unless such discrepancy represents an
underpayment by the other Party of at least [***], on a Collaboration
Product-by-Collaboration Product basis, of the total amounts due in respect of
such Collaboration Product in the audited period, in which case such fees shall
be paid by the other Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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9.2.3. Each Party shall comply with all applicable audit requirements in the
In-Licenses and shall include in each sublicense granted by it pursuant to the
License Terms a provision requiring any Sublicensee (as defined under the
applicable License Terms) to make reports to the Party that is party to such
In-License, to keep and maintain records of sales made pursuant to such
sublicense and to grant access to such records by the independent accountant of
the Party that is party to such In-License to the same extent required of a
Party under the Collaboration Agreement.

9.2.4. Unless an audit for such year has been commenced prior to and is ongoing
upon the [***] anniversary of the end of such year, the calculation of
royalties, expense reimbursement and other payments payable with respect to such
year shall be binding and conclusive upon both Parties, and each Party and its
Related Parties shall be released from any further liability or accountability
with respect to such royalties or expense reimbursement for such year.

9.2.5. Each Party shall treat all financial information subject to review under
this Section 9.2 or under any sublicense agreement in accordance with the
confidentiality and non-use provisions of Section 7 (Confidentiality and
Publication), and shall cause its accounting firm to enter into a
confidentiality agreement with the other Party or its Related Parties obligating
it to retain all such information in confidence pursuant to such confidentiality
agreement, which terms shall be no less stringent than the provisions of
Section 7 (Confidentiality and Publication).

9.3. Payment Exchange Rate. All payments to be made under the Collaboration
Agreement shall be made in United States dollars and shall be paid by bank wire
transfer in immediately available funds to such bank account in the United
States as may be designated in writing by the receiving Party from time to time.
In the case of Net Sales made or expenses incurred by a Party and its Related
Parties in currencies other than United States dollars during a Calendar
Quarter, the rate of exchange to be used in computing the amount of United
States dollars due shall be the rate of exchange utilized by such Party in its
worldwide accounting system and calculated in accordance with GAAP.

9.4. Late Payments. Any amount owed by a Party to the other Party under the
Collaboration Agreement that is not paid on or before the date such payment is
due shall bear interest at a rate per annum equal to the lesser of (a) [***] or
(b) the highest rate permitted by Law, calculated on the number of days such
payments are paid after such payments are due and compounded monthly.

9.5. Blocked Payments. If, by reason of Laws in any jurisdiction in a Party’s
Territory, it becomes impossible or illegal for a Party to transfer milestone
payments, royalties or other payments under the Collaboration Agreement to the
other Party, the payor shall promptly notify the payee. During any such period
described above, the payor shall deposit such payments in local currency in the
relevant jurisdiction to the credit of the payee in a recognized banking
institution designated by the payee or, if none is designated by the payee
within a period of [***] days, in a recognized banking institution selected by
the payor and identified in a written notice given to the payee.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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9.6. Taxes. If a timely and appropriately completed and executed Internal
Revenue Service Form W-9 is provided by the receiving Party to the paying Party,
the Parties acknowledge and agree that no United States tax withholding shall be
applied with respect to any milestone payments due under any License Terms. Each
Party shall use reasonable efforts to minimize tax withholding on payments made
to the other Party. Notwithstanding such efforts, if such Party concludes that
tax withholdings under the Laws of any country are required with respect to
payments to the other Party, such Party shall first notify the other Party and
provide such Party with [***] days to determine whether there are actions such
receiving Party can undertake to avoid such withholding. During this notice
period, the paying Party shall refrain from making such payment until the
receiving Party instructs the paying Party that (a) the receiving Party intends
to take actions (satisfactory to both Parties) that shall obviate the need for
such withholding, in which case the paying Party shall make such payment only
after it is instructed to do so by the receiving Party, or (b) the paying Party
should make such payment and withhold the required amount and pay it to the
appropriate Governmental Authority. In such case, the withholding Party shall
promptly provide the other Party with copies of receipts or other evidence
reasonably required and sufficient to allow the other Party to document such tax
withholdings adequately for purposes of claiming foreign tax credits and similar
benefits. The Parties shall cooperate reasonably in completing and filing
documents required under the provisions of any applicable tax laws or under any
other applicable Law, in connection with the making of any required tax payment
or withholding payment, or in connection with any claim to a refund of or credit
for any such payment. The Parties shall cooperate to minimize such taxes in
accordance with applicable Laws, including using reasonable efforts to access
the benefits of any applicable treaties. [***].

10. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE

10.1. General Indemnification by Genzyme. Genzyme shall indemnify, hold harmless
and defend Alnylam, its Related Parties, and their respective directors,
officers, employees and agents (“Alnylam Indemnitees”) from and against any and
all Third Party claims, suits, losses, liabilities, damages, costs, fees and
expenses (including reasonable attorneys’ fees and litigation expenses)
(collectively, “Losses”) arising out of or resulting from, directly or
indirectly, (a) any breach of, or inaccuracy in, any representation or warranty
made by Genzyme in the Collaboration Agreement, or any breach or violation of
any covenant or agreement of Genzyme in or in the performance of the
Collaboration Agreement, or (b) the negligence or willful misconduct by or of
Genzyme and its Related Parties, and their respective directors, officers,
employees and agents in the performance of Genzyme’s obligations under the
Collaboration Agreement. Genzyme shall have no obligation to indemnify the
Alnylam Indemnitees to the extent that the Losses arise out of or result from,
directly or indirectly, any breach of, or inaccuracy in, any representation or
warranty made by Alnylam in the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Collaboration Agreement, or any breach or violation of any covenant or agreement
of Alnylam in or in the performance of the Collaboration Agreement, or the
negligence or willful misconduct by or of any of the Alnylam Indemnitees, or
matters for which Alnylam is obligated to indemnify Genzyme under Section 10.2
(General Indemnification by Alnylam) or 10.3 (Product Liability).

10.2. General Indemnification by Alnylam. Alnylam shall indemnify, hold
harmless, and defend Genzyme, its Related Parties and their respective
directors, officers, employees and agents (“Genzyme Indemnitees”) from and
against any and all Losses arising out of or resulting from, directly or
indirectly, (a) any breach of, or inaccuracy in, any representation or warranty
made by Alnylam in the Collaboration Agreement, or any breach or violation of
any covenant or agreement of Alnylam in or in the performance of the
Collaboration Agreement, (b) the negligence or willful misconduct by or of
Alnylam and its Related Parties, and their respective directors, officers,
employees and agents in the performance of Alnylam’s obligations under the
Collaboration Agreement or (c) any infringement (including induced infringement)
of any of the Patent Rights identified on Schedule 10.2 (Identified Patent
Rights) arising from the Development, Manufacture or Commercialization of a
Collaboration Product by Genzyme or its Affiliates. Alnylam shall have no
obligation to indemnify the Genzyme Indemnitees to the extent that the Losses
arise out of or result from, directly or indirectly, any breach of, or
inaccuracy in, any representation or warranty made by Genzyme in the
Collaboration Agreement, or any breach or violation of any covenant or agreement
of Genzyme in or in the performance of the Collaboration Agreement, or the
negligence or willful misconduct by or of any of the Genzyme Indemnitees, or
matters for which Genzyme is obligated to indemnify Alnylam under Section 10.1
(General Indemnification by Genzyme) or 10.3 (Product Liability).

10.3. Product Liability. Subject to any Supply Agreements, any Losses arising
out of Third Party product liability claims arising from the Development or
Commercialization of Collaboration Products shall be (a) borne by Genzyme, to
the extent such Losses were incurred with respect to the Development or
Commercialization by or on behalf of Genzyme or its Related Parties of a
Regional Licensed Product in or for the Genzyme Territory, a Co-Co Licensed
Product in or for the Genzyme Territory, or a Global Licensed Product anywhere
in or for the world by or on behalf of Genzyme and its Related Parties, (b) be
borne by Alnylam, to the extent such Losses were incurred with respect to
Development or Commercialization of a Regional Licensed Product in or for the
Alnylam Territory by or on behalf of Alnylam and its Related Parties, and (c) be
borne fifty percent (50%) by each of Genzyme and Alnylam, to the extent such
Losses were incurred with respect to Development or Commercialization by or on
behalf of Alnylam or its Related Parties of a Co-Co Licensed Product in or for
the Alnylam Territory. The Party bearing such Losses in accordance with the
immediately preceding sentence shall indemnify, hold harmless and defend the
other Party and its Related Parties and their respective directors, officers,
employees and agents from and against such Losses.

10.4. Indemnification Procedure. In the event of any such claim against any
Genzyme Indemnitee or Alnylam Indemnitee (individually, an “Indemnitee”), the
indemnified Party shall promptly notify the other Party in writing of the claim
and the indemnifying Party

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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shall manage and control, at its sole expense, the defense of the claim and its
settlement. The Indemnitee shall cooperate with the indemnifying Party and may,
at its option and expense, be represented in any such action or proceeding. The
indemnifying Party shall not be liable for any settlements, litigation costs or
expenses incurred by any Indemnitee without the indemnifying Party’s written
authorization. Notwithstanding the foregoing, if the indemnifying Party believes
that any of the exceptions to its obligation of indemnification of the
Indemnitees set forth in Sections 10.1 (General Indemnification by Genzyme),
10.2 (General Indemnification by Alnylam) or 10.3 (Product Liability) may apply,
the indemnifying Party shall promptly notify the Indemnitees, which shall then
have the right to be represented in any such action or proceeding by separate
counsel at their expense, provided that the indemnifying Party shall be
responsible for payment of such expenses if the Indemnitees are ultimately
determined to be entitled to indemnification from the indemnifying Party for the
matters to which the indemnifying Party notified the Indemnitees that such
exception(s) may apply.

10.5. Limitation of Liability. NEITHER PARTY HERETO SHALL BE LIABLE FOR SPECIAL,
INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF THE COLLABORATION
AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS
ARISING FROM OR RELATING TO ANY BREACH OF THE COLLABORATION AGREEMENT,
REGARDLESS OF ANY NOTICE OF SUCH DAMAGES, EXCEPT AS A RESULT OF A PARTY’S
WILLFUL MISCONDUCT OR A BREACH OF SECTION 3.6 (EXCLUSIVITY DURING OPTION
PERIOD), SECTION 7 (CONFIDENTIALITY AND PUBLICATION), SECTION 10.4.1 OF THE
CO-CO LICENSE TERMS (EXCLUSIVITY), SECTION 9.4.1 OF THE GLOBAL LICENSE TERMS
(EXCLUSIVITY) OR SECTION 8.4.1 OF THE REGIONAL LICENSE TERMS (EXCLUSIVITY).
NOTHING IN THIS SECTION 10.5 IS INTENDED TO LIMIT OR RESTRICT THE
INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY. NOTWITHSTANDING THE
FOREGOING, ALNYLAM SHALL NOT BE LIABLE FOR ANY SPECIAL, INCIDENTAL,
CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF ANY BREACH OF SECTION 3.6
(EXCLUSIVITY DURING OPTION PERIOD) UNLESS GENZYME BRINGS AN ACTION SEEKING SUCH
DAMAGES WITHIN SIX (6) MONTHS AFTER THE EARLIER OF THE DATE ON WHICH THE
TRANSACTION BETWEEN ALNYLAM AND A THIRD PARTY ENTERED INTO IN BREACH OF SECTION
3.6 (EXCLUSIVITY DURING OPTION PERIOD) FIRST BECOMES PUBLICLY KNOWN OR THE DATE
ON WHICH ALNYLAM NOTIFIES GENZYME OF SUCH TRANSACTION.

10.6. Insurance. Each Party shall maintain insurance during the Term and for a
period of at least two (2) years after the last commercial sale of any
Collaboration Product generated under the Collaboration, with a reputable,
solvent insurer in an amount appropriate for its business and products of the
type that are the subject of the Collaboration Agreement, and for its
obligations under the Collaboration Agreement. Specifically, each Party shall
maintain product liability insurance and clinical trial liability insurance with
limits of at least [***] per occurrence and in annual aggregate. Upon request,
each Party shall provide the other Party with evidence of the existence and
maintenance of such insurance coverage.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11. INTELLECTUAL PROPERTY

11.1. Prosecution and Maintenance of Patent Rights. Alnylam has the sole
responsibility to, at Alnylam’s discretion and sole expense (except as provided
below), file, conduct prosecution, and maintain (including the defense of any
interference or opposition proceedings), all Patent Rights comprising Option
Product Core Technology Patents and Option Product-Specific Patents, in
Alnylam’s name. Notwithstanding the foregoing, Alnylam shall file Option
Product-Specific Patents in the Genzyme Patent Jurisdictions and shall use
commercially reasonable efforts to prosecute and maintain such Patent Rights in
the Genzyme Patent Jurisdictions and shall timely pay all filing (including
during the pendency of any Patent Right) and renewal fees payable with respect
thereto [***].

11.2. Patent Prosecution Information Sharing. Alnylam shall consult with
Genzyme, through the IP Committee, on its strategy for the preparation, filing,
prosecution, and maintenance of the Option Product Patents and shall consider in
good faith timely comments from Genzyme thereon. Alnylam shall furnish to
Genzyme, through the IP Committee or via electronic mail or such other method as
mutually agreed by the Parties, copies of documents received from outside
counsel in the course of filing, prosecution or maintenance of or filed with the
relevant national patent offices with respect to the filing, prosecution and
maintenance of all Option Product Core Technology Patents and Option
Product-Specific Patents within a reasonable time after filing of such
documents.

11.3. In-Licenses.

11.3.1. Additional Alnylam In-Licenses. In the event that a Patent Right
licensed to Alnylam under an Additional Alnylam In-License actually is or will
be infringed by Genzyme’s Commercialization of a Collaboration Product in the
Genzyme Territory or Genzyme’s Manufacture or Development of such Collaboration
Product in accordance with the applicable License Terms, then such Additional
Alnylam In-License will thereafter automatically be deemed to be an Existing
Alnylam In-License on a Collaboration Product-by-Collaboration Product basis,
and all rights granted to Alnylam thereunder will be deemed to be “Controlled”
by Alnylam and sublicensed to Genzyme under the applicable License Terms,
effective as of the later of (a) the date the applicable Patent Right issues or
(b) the date that Genzyme’s Commercialization of such Collaboration Product in
the Genzyme Territory or Genzyme’s Manufacture of Development of such
Collaboration Product in accordance with this Master Agreement and the
applicable License Terms would infringe such Patent Right in the absence of a
license thereunder from Alnylam.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.3.2. Existing Alnylam In-Licenses. In the event that Alnylam fails to
identify a Third Party agreement under which Alnylam Controls Know-How or Patent
Rights that are necessary or useful to Develop, Manufacture or Commercialize a
Collaboration Product, then the Parties will amend the Schedules to the
applicable License Terms to include such agreements within the definition of
Existing Alnylam In-License or Additional Alnylam In-License. In any event, any
Potential Alnylam In-License under which Alnylam Controls Know-How or Patent
Rights that are necessary or useful to Develop, Manufacture or Commercialize a
Collaboration Product will be deemed to be an Existing Alnylam In-License
regardless of whether it is entered into before or after the Implementation Date
for such Collaboration Product.

11.3.3. Collaboration In-Licenses.

11.3.3.1. Proposed In-Licenses. In the event that either Party desires to enter
into an agreement with a Third Party pursuant to which such Party would acquire
a license under any Patent Rights that are necessary or useful to Develop,
Manufacture or Commercialize any Collaboration Product (a “Proposed
In-License”), then such Party shall deliver a written notice to the other that
may include the identity of such Third Party, a description of such Patent
Rights and any proposed terms of such Proposed In-License (a “Proposed
In-License Notice”) [***]. Within [***] days of delivery of the Proposed
In-License Notice, the IP Committee shall meet to discuss the Proposed
In-License and the proposing Party shall consider in good faith comments from
the other Party. If the proposing Party enters into the Proposed In-License, and
the non-proposing Party wishes to obtain a sublicense under such Proposed
In-License, then the Proposed In-License shall be deemed to be a “Collaboration
In-License” for all purposes under the Collaboration Agreement. For the sake of
clarity, if the non-proposing Party does not wish to obtain a sublicense under a
Proposed In-License, then none of the rights granted to the proposing Party
thereunder will be deemed to be “Controlled” by the proposing Party and, if the
proposing Party (or any of its sublicensees thereunder) has rights to enforce
any Patent Rights licensed to the proposing Party thereunder, the proposing
Party shall have the right to enforce such Patent Rights against the
non-proposing Party.

11.3.3.2. Requirements for Collaboration In-Licenses. In entering into any
Collaboration In-License (or Potential Alnylam In-License, in the case of
Alnylam), each Party shall [***]. Any Patent Rights licensed to a Party under a
Collaboration In-License shall be deemed to be Controlled by such Party for all
purposes under the License Terms. The Party entering into a Collaboration
In-License must notify the other Party promptly and provide the other Party with
a copy of such Collaboration In-License.

11.3.3.3. [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.3.4. Payments under In-Licenses.

11.3.4.1. In-Licenses that are not Collaboration In-Licenses.

(a) Except as provided under the Co-Co License Terms, Alnylam shall bear [***]
of any Third Party License Payments that become payable during the Term under
any (i) Existing Alnylam In-License or (ii) Potential Alnylam In-License that is
entered into after the Execution Date that becomes an Existing Alnylam
In-License pursuant to Section 11.3.2 (Existing Alnylam In-Licenses).

(b) Subject to Section 11.3.5 (Royalty Stacking), Genzyme shall bear [***] of
any Third Party License Payments that become payable under any Existing Genzyme
In-License or any Un-Blocking Genzyme In-License during the Term.

11.3.4.2. Collaboration In-Licenses. Any Third Party License Payment that
becomes payable under any Collaboration In-License (other than a Potential
Alnylam In-License) shall be allocated between the Parties as follows:

(a) if such Third Party License Payment becomes payable as a result of a Party’s
activities under the License Terms with respect to a Collaboration Product and
is either (i) [***] (a “Collaboration Product-Specific Payment”); and

(b) if such Third Party License Payment is not a Collaboration Product-Specific
Payment, then [***].

(c) If the Parties cannot agree on whether a Third Party License Payment is a
Collaboration Product-Specific Payment or not, or how to allocate a Third Party
License Payment that is not a Collaboration Product-Specific Payment, the
Parties shall submit the matter to the AJSC for resolution. If the AJSC cannot
resolve the matter within [***] days of it being referred to them, the Parties
shall submit the matter [***]. If the Party that is not a party to the
Collaboration In-License disagrees with the allocation of a Third Party License
Payment pursuant to this Section 11.3.4.2(c), then such Party may elect not to
take a sublicense under such Collaboration In-License, in which case none of the
rights granted to the other Party thereunder will be deemed to be “Controlled”
by the other Party and, if the other Party has rights to enforce any Patent
Rights licensed to such other Party thereunder, such other Party (or any of its
sublicensees thereunder) shall have the right to enforce such Patent Rights
against such Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.3.4.3. [***].

11.3.4.4. To the extent not otherwise deducted from payments by one Party to the
other Party when determining Net Sales of any Collaboration Product and without
duplication of Genzyme’s rights under Section 11.3.5 (Royalty Stacking), either
Party that advances any payment for which the other Party is actually
responsible under this Section 11.3.4 shall invoice the other Party for such
advanced amount on a quarterly basis. The Party receiving such invoice shall
make payment of such amount to the invoicing Party within [***] days of the date
of such invoice and otherwise in accordance with Section 9 (Royalty Reports;
Payments; Audits) of this Master Agreement.

11.3.5. [***].

11.3.6. Amendments to In-Licenses. If a Party amends an In-License to which it
is a Party in a manner that increases the royalty payable by the other Party
under such In-License without the prior written consent of the other Party, such
Party shall be solely responsible for any such additional payments due under
such In-License.

11.3.7. Stand-by Licenses. Upon Genzyme’s reasonable request during the Term,
Alnylam shall reasonably cooperate in good faith with Genzyme’s efforts to
obtain stand-by license agreements related to any Collaboration Product with
respect to any Alnylam In-License, pursuant to which, upon termination of the
relevant In-License, Genzyme would receive a direct license from the applicable
Third Party licensor under any Patent Rights and Know-How that are sublicensed
to Genzyme pursuant to the Collaboration Agreement. Such stand-by license
agreement will be in a form approved in advance by Alnylam. Any costs incurred
by Alnylam in cooperating with Genzyme’s efforts to obtain any such stand-by
license agreement shall be reimbursed by Genzyme.

11.3.8. Breach or Termination of In-Licenses. In the event that (a) a Party
receives notice of an alleged breach by such Party under an In-License to which
it is a party, or (b) a Party intends to terminate an In-License to which it is
a party, then such Party shall promptly, but in no event less than ten (10) days
thereafter, provide written notice thereof to the other Party.

11.4. Common Interest. All information exchanged between the Parties
representatives regarding the preparation, filing, prosecution, maintenance, or
enforcement of the Patents Rights under this Section 11 will be deemed
Confidential Information. In addition, the Parties acknowledge and agree that,
with regard to such preparation, filing, prosecution, maintenance and
enforcement of the Patents Rights under this Section 11, the interests of the
Parties as collaborators and licensor and licensee are to obtain the strongest
patent protection possible, and as such, are aligned and are legal in nature.
The Parties agree and acknowledge that they have not waived, and nothing in this
Master Agreement constitutes a waiver of, any legal privilege concerning the
Patents Rights under this Section 11, including privilege under the common
interest doctrine and similar or related doctrines.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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12. TERM AND TERMINATION

12.1. Term. The Collaboration Agreement shall be effective as of the Execution
Date and, unless terminated earlier pursuant to Section 12.2 (Termination
Rights), the Collaboration Agreement shall continue in effect until the later of
(i) the expiration of the last to expire of the Option Periods and (ii) the last
to expire of the License Terms (“Term”).

12.2. Termination Rights. This Master Agreement may not be terminated by either
Party except as provided in this Section 12.2.

12.2.1. Termination for Convenience. Genzyme shall have the right to terminate
the Collaboration Agreement in its entirety at any time after the Execution Date
on six (6) months’ prior written notice to Alnylam, provided that any such
termination for convenience of the Collaboration Agreement shall automatically
be treated, without any other action or notice required of either Party, as a
termination for convenience of each License Terms under Sections 10.2.1, 12.2.1
and 11.2.1 of the Regional License Terms, the Co-Co License Terms and the Global
License Terms, respectively, and provided further that if termination under any
such License Terms is not then possible, then Genzyme shall not have any right
to terminate under this Section 12.2.1.

12.2.2. Termination of License Terms for Cause. The rights to a Collaboration
Product under the applicable License Terms may be terminated for cause during
the Term on a Collaboration Product-by-Collaboration Product basis pursuant
Sections 10.2.2, 12.2.2 and 11.2.2 of the Regional License Terms, the Co-Co
License Terms and the Global License Terms, respectively, as applicable.

12.2.3. Termination of this Master Agreement for Cause. This Master Agreement
may be terminated at any time during the Term upon written notice by either
Party if the other Party is in material breach of its obligations hereunder and
has not cured such breach within thirty (30) days in the case of a payment
breach, or within ninety (90) days in the case of all other breaches, after
notice requesting cure of the breach; provided, however, that if any breach
other than a payment breach is not reasonably curable within ninety (90) days
and if a Party is making a bona fide effort to cure such breach, such
termination shall be delayed for a time period to be agreed by both Parties, not
to exceed an additional ninety (90) days, in order to permit such Party a
reasonable period of time to cure such breach; provided, further, that in the
event that the breach relates to a dispute between the Parties regarding
Alnylam’s obligations to use commercially reasonable efforts to undertake the
Development of Option Products from its Core Pipeline Programs and Alnylam
disputes whether it has breached such obligation or whether such breach gives
Genzyme the right to terminate this Master Agreement and initiates a legal
action against Genzyme to resolve such dispute within the foregoing ninety
(90) day cure period, then this Master Agreement shall not terminate during the
pendency of such legal action; provided that if Alnylam is found in an
unappealable decision by a court of

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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competent jurisdiction or an appealable decision of a court of competent
jurisdiction that has not been appealed in the time allowed for an appeal in
such legal action to have materially breached this Master Agreement or if
Alnylam admits in such legal action or settlement thereof that it has materially
breached this Master Agreement then this Master Agreement shall terminate
immediately following the Parties’ receipt of such decision or immediately
following such admission, as applicable.

12.2.4. Challenges of Patent Rights. If, during the Term, Genzyme or any of its
Affiliates (a) commences or participates in any action or proceeding (including
any patent opposition or re-examination proceeding), or otherwise asserts any
claim, challenging or denying the validity or enforceability of any claim of the
Alnylam Core Technology Patents (as defined in any of the License Terms) that
Covers any siRNA in any Option Product or Collaboration Product or is licensed
by Genzyme under any License Terms or (b) actively assists any other Person in
bringing or prosecuting any action or proceeding (including any patent
opposition or re-examination proceeding) challenging or denying the validity or
enforceability of any claim of such Patent Rights (each of (a) and (b), a
“Patent Challenge”), then, to the extent permitted by the applicable Laws,
Alnylam shall have the right, exercisable within sixty (60) days following
receipt of notice regarding such Patent Challenge, in its sole discretion, to
give notice to Genzyme that Alnylam may terminate the Collaboration Agreement
ninety (90) days following such notice (or such longer period as Alnylam may
designate in such notice), and, unless Genzyme or such Affiliate withdraws or
causes to be withdrawn all such challenge(s) (or in the case of ex-parte
proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or
Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to
be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any
other party to such Patent Challenge and, to the extent Genzyme or a Genzyme
Affiliate is a party to such Patent Challenge, it withdraws from such Patent
Challenge) within such ninety (90)-day period, Alnylam shall have the right to
terminate the Collaboration Agreement by providing written notice thereof to
Genzyme. The foregoing sentence shall not apply (i) with respect to any claim of
an Alnylam Core Technology Patent that Covers any siRNA in any Option Product or
Collaboration Product or is licensed by Genzyme under any License Terms that
Alnylam first asserts against Genzyme or any of its Affiliates where the Patent
Challenge is made in defense of such assertion, or (ii) with respect to any
Patent Challenge commenced by a Third Party that after the Execution Date
acquires or is acquired by Genzyme or its Affiliates or its or their business or
assets, whether by stock purchase, merger, asset purchase or otherwise, but only
with respect to Patent Challenges commenced prior to the closing of such
acquisition.

12.3. Effect of Termination.

12.3.1. Termination of Collaboration Agreement for Convenience. Without limiting
any other legal or equitable remedies that either Party may have, if the
Collaboration Agreement is terminated by Genzyme pursuant to Section 12.2.1

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(Termination for Convenience) then (a) this Master Agreement and all Options
granted to Genzyme hereunder shall terminate and (b) each of the License Terms
shall terminate and the consequences of termination of the entire License Terms
for convenience set forth in each of the License Terms shall apply.

12.3.2. Termination of Master Agreement for Cause. Without limiting any other
legal or equitable remedies that either Party may have, if this Master Agreement
is terminated by either Party pursuant to Section 12.2.3 (Termination of this
Master Agreement for Cause), then (a) each of the License Terms shall survive
and (b) this Master Agreement and all Options granted to Genzyme hereunder shall
terminate, provided that any terms of this Master Agreement applicable to any
Collaboration Product that is subject to any of the License Terms on the
effective date of termination shall survive.

12.3.3. Termination of Collaboration Agreement for Patent Challenge. Without
limiting any other legal or equitable remedies that either Party may have, if
the Collaboration Agreement is terminated by Alnylam pursuant to Section 12.2.4
(Challenges of Patent Rights) then (a) this Master Agreement and all Options
granted to Genzyme hereunder shall terminate and (b) each of the License Terms
shall terminate and the consequences of termination of the entire License Terms
for cause by Alnylam set forth in each of the License Terms shall apply.

12.3.4. Effect of Expiration or Termination; Survival. Expiration or termination
of the Collaboration Agreement or this Master Agreement shall not relieve the
Parties of any obligation accruing prior to such expiration or termination. Any
expiration or termination of the Collaboration Agreement or this Master
Agreement shall be without prejudice to the rights of either Party against the
other accrued or accruing under the Collaboration Agreement or this Master
Agreement, as applicable, prior to expiration or termination, including the
obligation to pay royalties for the Collaboration Product sold prior to such
expiration or termination or other payments under the Collaboration Agreement.
The provisions of Sections 1 (Definitions), 7 (Confidentiality and Publication),
9 (Royalty Reports; Payments; Audit), 10 (Indemnification; Limitation of
Liability; Insurance), 12 (Term and Termination) and 13 (Miscellaneous) shall
survive any expiration or termination of the Collaboration Agreement and, in
addition, the provisions of 2.1.3.3 (ROFN for CNS) and 3.1.2.4 (Improperly
Designated Programs) shall survive any termination of the Collaboration
Agreement by Genzyme pursuant to Section 12.2.3 (Termination of this Master
Agreement for Cause). Except as otherwise set forth in this Section 12, upon
termination or expiration of the Collaboration Agreement or this Master
Agreement all rights and obligations of the Parties under the Collaboration
Agreement or this Master Agreement, as applicable, shall cease.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

13. MISCELLANEOUS

13.1. Assignment. Except as provided in this Section 13.1, the Collaboration
Agreement may not be assigned or otherwise transferred, nor may any right or
obligation hereunder be assigned or transferred, by either Party without the
written consent of the other Party. Notwithstanding the foregoing, either Party
may, without the other Party’s written consent, assign the Collaboration
Agreement and its rights and obligations hereunder in whole or in part to an
Affiliate or to a party that acquires, by or otherwise in connection with,
merger, sale of assets or otherwise, all or substantially all of the business of
the assigning Party to which the subject matter of the Collaboration Agreement
relates. The assigning Party shall remain responsible for the performance by its
assignee of the Collaboration Agreement or any obligations hereunder so
assigned. An assignment to an Affiliate shall terminate, and all rights so
assigned shall revert to the assigning Party, if and when such Affiliate ceases
to be an Affiliate of the assigning Party. Any purported assignment in violation
of this Section 13.1 shall be void.

13.2. Governing Law. The Collaboration Agreement shall be construed and the
respective rights of the Parties determined in accordance with the substantive
Laws of the State of New York, notwithstanding any provisions of New York Law or
any other Law governing conflicts of laws to the contrary, and the patent Laws
of the relevant jurisdiction without reference to any rules of conflict of laws.

13.3. Jurisdiction. Each Party by its execution hereof, (a) hereby irrevocably
submits to the jurisdiction of the United States District Court and state courts
located in New York, New York for the purpose of any dispute arising between the
Parties in connection with the Collaboration Agreement (each, an “Action”),
except as otherwise expressly provided in the Collaboration Agreement;
(b) hereby waives, to the extent not prohibited by applicable Law, and agrees
not to assert, by way of motion, as a defense or otherwise, in any such Action,
any claim that (i) it is not subject personally to the jurisdiction of the
above-named court, (ii) its property is exempt or immune from attachment or
execution, (iii) any such Action brought in the above-named court should be
dismissed on grounds of forum non conveniens, should be transferred or removed
to any court other than the above-named court, or should be stayed by reason of
the pendency of some other proceeding in any other court other than the
above-named court, or (iv) the Collaboration Agreement or the subject matter
hereof may not be enforced in or by such court; and (c) hereby agrees not to
commence any such Action other than before the above-named court.
Notwithstanding the previous sentence a Party may commence any Action in a court
other than the above-named court solely for the purpose of enforcing an order or
judgment issued by the above-named court.

13.4. Venue. Each Party agrees that for any Action between the Parties arising
in whole or in part under or in connection with the Collaboration Agreement,
such Party bring Actions only in the federal courts of the United States of
America located in New York, New York and any appellate court having
jurisdiction over appeals from such courts. Each Party further waives any claim
and shall not assert that venue should properly lie in any other location within
the selected jurisdiction.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

13.5. Entire Agreement; Amendments. The Collaboration Agreement contains the
entire understanding of the Parties with respect to the subject matter hereof,
and supersedes all previous arrangements with respect to the subject matter
hereof, whether written or oral, including, effective as of the Effective Date,
that Mutual Confidential Disclosure Agreement between the Parties dated as of
August 27, 2009, as amended through the Execution Date (provided that all
information disclosed or exchanged under such agreement will be treated as
Confidential Information hereunder). This Master Agreement (other than the
Appendices and Schedules attached hereto) may be amended, or any term hereof
modified, only by a written instrument duly-executed by authorized
representatives of both Parties hereto. The Appendices and Schedules attached
hereto may be amended, or any term hereof modified, only by a written instrument
duly-executed by authorized representatives of both Parties hereto, except to
the extent expressly provided in the Collaboration Agreement.

13.6. Severability. If any provision hereof should be held invalid, illegal or
unenforceable in any respect in any jurisdiction, the Parties hereto shall
substitute, by mutual consent, valid provisions for such invalid, illegal or
unenforceable provisions, which valid provisions in their economic effect are
sufficiently similar to the invalid, illegal or unenforceable provisions that it
can be reasonably assumed that the Parties would have entered into the
Collaboration Agreement with such valid provisions. In case such valid
provisions cannot be agreed upon, the invalid, illegal or unenforceable of one
or several provisions of the Collaboration Agreement shall not affect the
validity of the Collaboration Agreement as a whole, unless the invalid, illegal
or unenforceable provisions are of such essential importance to the
Collaboration Agreement that it is to be reasonably assumed that the Parties
would not have entered into the Collaboration Agreement without the invalid,
illegal or unenforceable provisions.

13.7. Headings. The captions to the Sections hereof are not a part of the
Collaboration Agreement, but are merely for convenience to assist in locating
and reading the several Sections hereof.

13.8. Waiver of Rule of Construction. Each Party has had the opportunity to
consult with counsel in connection with the review, drafting and negotiation of
the Collaboration Agreement. Accordingly, the rule of construction that any
ambiguity in the Collaboration Agreement shall be construed against the drafting
Party shall not apply.

13.9. Interpretation. Except where the context expressly requires otherwise,
(a) the use of any gender herein shall be deemed to encompass references to
either or both genders, and the use of the singular shall be deemed to include
the plural (and vice versa); (b) the words “include”, “includes” and “including”
shall be deemed to be followed by the phrase “without limitation” and shall not
be interpreted to limit the provision to which it relates; (c) the word “will”
shall be construed to have the same meaning and effect as the word “shall”;
(d) any definition of or reference to any agreement, instrument or other
document herein shall be construed as referring to such agreement, instrument or
other document as from time to time

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

amended, supplemented or otherwise modified (subject to any restrictions on such
amendments, supplements or modifications set forth herein); (e) any reference
herein to any Person shall be construed to include the Person’s successors and
assigns; (f) the words “herein”, “hereof” and “hereunder”, and words of similar
import, shall be construed to refer to this Master Agreement or any of the
License Terms in each of their entirety, as the context requires, and not to any
particular provision hereof; (g) all references herein to Sections, Appendices
or Schedules shall be construed to refer to Sections, Appendices or Schedules of
this Master Agreement, and references to this Master Agreement include all
Schedules hereto (but not Appendices); (h) the word “notice” means notice in
writing (whether or not specifically stated) and shall include notices,
consents, approvals and other written communications contemplated under the
Collaboration Agreement; (i) provisions that require that a Party, the Parties
or any committee hereunder “agree,” “consent” or “approve” or the like shall
require that such agreement, consent or approval be specific and in writing,
whether by written agreement, letter, approved minutes or otherwise (but
excluding e-mail and instant messaging); (j) references to any specific law,
rule or regulation, or article, section or other division thereof, shall be
deemed to include the then-current amendments thereto or any replacement or
successor law, rule or regulation thereof; and (k) the term “or” shall be
interpreted in the inclusive sense commonly associated with the term “and/or.”

13.10. No Implied Waivers; Rights Cumulative. No failure on the part of Alnylam
or Genzyme to exercise, and no delay in exercising, any right, power, remedy or
privilege under the Collaboration Agreement, or provided by statute or at Law or
in equity or otherwise, shall impair, prejudice or constitute a waiver of any
such right, power, remedy or privilege or be construed as a waiver of any breach
of the Collaboration Agreement or as an acquiescence therein, nor shall any
single or partial exercise of any such right, power, remedy or privilege
preclude any other or further exercise thereof or the exercise of any other
right, power, remedy or privilege.

13.11. Notices. All notices which are required or permitted hereunder shall be
in writing and sufficient if delivered personally, sent by facsimile (and
promptly confirmed by personal delivery, registered or certified mail or
overnight courier), sent by nationally-recognized overnight courier or sent by
registered or certified mail, postage prepaid, return receipt requested,
addressed as follows:

 

If to Alnylam, to:   

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, Massachusetts 02142

Attention: Vice President - Legal

Facsimile No.: (617) 551-8101

With a copy to:   

Goodwin Procter LLP

Exchange Place

53 State Street

Boston, Massachusetts 02109

Attention: Kingsley L. Taft, Esq.

Facsimile No.: (617) 523-1231

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

If to Genzyme, to:   

Genzyme Corporation

500 Kendall Street

Cambridge, Massachusetts 02142

Attention: Head of Rare Diseases Business Unit

Facsimile No.: (617) 374-2424

With a copy to:   

Genzyme Corporation

500 Kendall Street

Cambridge, Massachusetts 02142

Attention: General Counsel

Facsimile No.: (617) 252-7553

And to:   

Ropes & Gray LLP

Prudential Tower

800 Boylston Street

Boston, MA 02199-3600

Attention: David M. McIntosh, Esq.

Facsimile No.: (617) 235-0507

or to such other address as the Party to whom notice is to be given may have
furnished to the other Party in writing in accordance herewith. In addition,
each Party shall deliver a courtesy copy to the other Party’s Alliance Manager
concurrently with such notice. Any such notice shall be deemed to have been
given: (a) when delivered if personally delivered or sent by facsimile on a
business day (or if delivered or sent on a non-business day, then on the next
business day); (b) on receipt if sent by overnight courier; or (c) on receipt if
sent by mail.

13.12. Compliance with Export Regulations. Neither Party shall export any
technology licensed to it by the other Party under the Collaboration Agreement
except in compliance with U.S. export Laws and regulations.

13.13. Force Majeure. Neither Party shall be held liable to the other Party nor
be deemed to have defaulted under or breached the Collaboration Agreement for
failure or delay in performing any obligation under the Collaboration Agreement
to the extent that such failure or delay is caused by or results from causes
beyond the reasonable control of the affected Party, potentially including
embargoes, war, acts of war (whether war be declared or not), insurrections,
riots, civil commotions, strikes, lockouts or other labor disturbances, fire,
floods, or other acts of God. The affected Party shall notify the other Party of
such force majeure circumstances as soon as reasonably practical, and shall
promptly undertake all reasonable efforts necessary to cure such force majeure
circumstances.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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MASTER AGREEMENT

 

13.14. Independent Parties. It is expressly agreed that Alnylam and Genzyme
shall be independent contractors and that the relationship between Alnylam and
Genzyme shall not constitute a partnership, joint venture or agency. Alnylam
shall not have the authority to make any statements, representations or
commitments of any kind, or to take any action, which shall be binding on
Genzyme, without the prior written consent of Genzyme, and Genzyme shall not
have the authority to make any statements, representations or commitments of any
kind, or to take any action, which shall be binding on Alnylam without the prior
written consent of Alnylam.

13.15. Counterparts. The Agreement may be executed in two or more counterparts,
including by facsimile or PDF signature pages, each of which shall be deemed an
original, but all of which together shall constitute one and the same
instrument.

13.16. Performance by Affiliates.

13.16.1. Use of Affiliates. Each Party acknowledges and accepts that the other
Party may exercise its rights and perform its obligations under this Master
Agreement either directly or through one or more of its Affiliates. A Party’s
Affiliates will have the benefit of all rights (including all licenses) of such
Party under this Master Agreement. Accordingly, in this Master Agreement
“Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and
“Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where
necessary to give each Party’s Affiliates the benefit of the rights provided to
such Party in this Master Agreement; provided, however, that in any event each
Party will remain responsible for the acts and omissions, including financial
liabilities, of its Affiliates.

13.16.2. Future Acquisition of a Party or its Business. [***].

13.17. Binding Effect; No Third Party Beneficiaries. As of the Execution Date,
the Collaboration Agreement shall be binding upon and inure to the benefit of
the Parties and their respective permitted successors and permitted assigns.
Except as expressly set forth in the Collaboration Agreement, no Person other
than the Parties and their respective Affiliates and permitted assignees
hereunder shall be deemed an intended beneficiary hereunder or have any right to
enforce any obligation of the Collaboration Agreement.

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

IN WITNESS WHEREOF, the Parties have executed this Master Agreement as of the
Execution Date.

 

GENZYME CORPORATION    ALNYLAM PHARMACEUTICALS, INC. BY:  

/s/ David Meeker

   BY:   

/s/ John M. Maraganore

NAME: David Meeker, M.D.

TITLE: President and Chief Executive Officer

     

NAME: John M. Maraganore, Ph.D.

TITLE: Chief Executive Officer

Signature page to the Master Collaboration Agreement

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.7

ADDITIONAL ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.21

ALN-AT3

ALN-AT3 is an investigational ribonucleic acid interference (RNAi) therapeutic
agent that is comprised of active pharmaceutical ingredient ALN-[***] (see
sequence and diagram below), [***].

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.22

ALN-TTR CORE TECHNOLOGY PATENTS

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.24

ALN-TTR PRODUCT-SPECIFIC PATENTS

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.26

ALN-TTR02

ALN-TTR02 is an investigational ribonucleic acid interference (RNAi) therapeutic
agent that is comprised of active pharmaceutical ingredient [***].

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.29

ALN-TTRsc

ALN-TTRsc is an investigational ribonucleic acid interference (RNAi) therapeutic
agent that is comprised of active pharmaceutical ingredient [***].

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.34

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.71

CORE PIPELINE PROGRAM LIST

Section A

 

Alnylam
siRNA
identifier

(if any)

  

Gene

Target

Name

  

Gene

Target

Symbol

  

NCBI

Human
Gene

  

NCBI’s

Reference
Sequences

Transcript*

  

NCBI’s

Reference
Sequences

Protein*

  

Alias(es)

  

Description

ALN-TTR02    TTR    TTR    7276    NM_000371    NP_000362    CTS; CTS1; HsT2651;
PALB; TBPA    transthyretin ALN-TTRsc    TTR    TTR    7276    NM_000371   
NP_000362    CTS; CTS1; HsT2651; PALB; TBPA    transthyretin ALN-AT3    AT3   
SERPINC1    462    NM_000488    NP_000479    AT3; AT3D; ATIII; THPH7    serpin
peptidase inhibitor, clade C (antithrombin), member 1 ALN-CC5    CC5    C5   
727    NM_001735    NP_001726    C5a; C5b; CPAMD4    complement component 5
ALN-AS1    ALAS1    ALAS1    211    NM_000688    NP_000679    ALAS; MIG4; ALAS3;
ALASH    aminolevulinate, delta-, synthase 1 ALN-AAT    AAT    SERPINA1    5265
   NM_000295    NP_000286    PI; A1A; AAT; PI1; A1AT; PRO2275; alpha1AT   
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin),
member 1 ALN-TMP    TMPRSS6    TMPRSS6    164656    NM_153609    NP_705837   
IRIDA    transmembrane protease, serine 6 ALN-ANG    ANGPTL3    ANGPTL3    27329
   NM_014495    NP_055310    ANL3; ANG-5; FHBL2; ANGPT5    angiopoietin-like 3

Updated as of: the Execution Date

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

Updated as of: the Execution Date

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

Schedule 1.2.80

FORM OF EXERCISE NOTICE

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

[                    , 20    ]

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, MA 02142

Attn: Vice President - Legal

Dear Sir or Madam:

In accordance with Sections 2.2 and 3.4 of that certain Master Collaboration
Agreement by and between Alnylam Pharmaceuticals, Inc. (“Alnylam”) and Genzyme
Corporation (“Genzyme”) executed as of January 11, 2014 (the “Master
Agreement”), Genzyme hereby provides written notice exercising the option to
acquire the Option Product(s) set forth in Exhibit A attached hereto, pursuant
to the terms of the Master Agreement. Capitalized terms used but not defined
herein will have the meanings assigned to them in the Master Agreement.

Please acknowledge receipt of this option exercise by countersigning this letter
and returning it to me. Failure to return the letter countersigned will not
affect the effectiveness of this option exercise by Genzyme.

 

Very truly yours,

 

GENZYME CORPORATION

By:      

Name:

Title:

 

cc: Goodwin Proctor LLP

   Exchange Place

   55 State Street

   Boston, MA 02109

   Attn: Kingsley L. Taft, Esq.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

Accepted and agreed:

ALNYLAM PHARMACEUTICALS, INC.

 

By:      

Name:

Title:

Exhibit A

 

  1. Option Product:                                     .

 

  2. Genzyme is exercising its option to acquire the Option Product(s) listed
above, pursuant to:

 

  ¨ the Regional License Terms

 

  ¨ the Global License Terms (if applicable)

 

  ¨ the Co-Co License Terms (if applicable)

 

  3. Genzyme has determined that:

 

  ¨ a filing or notification under applicable Antitrust Laws is not necessary.

 

  ¨ a filing or notification must be made under applicable Antitrust Laws.

Summary of any such filing(s) or notification(s):

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

Schedule 1.2.82

EXISTING ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.88

FINAL OPTION DATA PACKAGE

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.116

HUMAN POP PROPOSED STUDIES

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.123

INITIAL OPTION DATA PACKAGE

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.134

LOCKED CORE PIPELINE PROGRAM LIST

 

Alnylam
siRNA
identifier

(if any)

  

Gene

Target

Name

  

Gene

Target

Symbol

  

NCBI

Human

Gene

  

NCBI’s

Reference

Sequences

Transcript*

  

NCBI’s

Reference

Sequences

Protein*

  

Alias(es)

  

Description

ALN-TTR02    TTR    TTR    7276    NM_000371    NP_000362    CTS; CTS1; HsT2651;
PALB; TBPA    transthyretin ALN-TTRsc    TTR    TTR    7276    NM_000371   
NP_000362    CTS; CTS1; HsT2651; PALB; TBPA    transthyretin ALN-AT3    AT3   
SERPINC1    462    NM_000488    NP_000479    AT3; AT3D; ATIII; THPH7    serpin
peptidase inhibitor, clade C (antithrombin), member 1 ALN-CC5    CC5    C5   
727    NM_001735    NP_001726    C5a; C5b; CPAMD4    complement component 5
ALN-AS1    ALAS1    ALAS1    211    NM_000688    NP_000679    ALAS; MIG4; ALAS3;
ALASH    aminolevulinate, delta-, synthase 1 ALN-AAT    AAT    SERPINA1    5265
   NM_000295    NP_000286    PI; A1A; AAT; PI1; A1AT; PRO2275; alpha1AT   
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin),
member 1 ALN-TMP    TMPRSS6    TMPRSS6    164656    NM_153609    NP_705837   
IRIDA    transmembrane protease, serine 6

Updated as of: the Execution Date

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

Schedule 1.2.135

LOCKED NON-CORE PIPELINE PROGRAM LIST

 

Alnylam

siRNA

identifier

(if any)

  

Gene

Target

Name

   Gene
Target
Symbol    NCBI
Human
Gene    NCBI’s
Reference
Sequences
Transcript*    NCBI’s
Reference
Sequences
Protein*    Alias(es)    Description ALN-VSP    VEGF    VEGFA    7422   
NM_003376    NP_003367    VPF;
VEGF;
MVCD1    Vacular
endothelial
growth
factor A ALN-VSP    KSP (kinesin spindle protein)    KIF11    3832    NM_004523
   NP_004514    EG5;
HKSP;
KNSL1;
MCLMR;
TRIP5    Kinesin
family
member 11 ALN-PCS    PCSK9    PCSK9    255738    NM_174936    NP_777596    FH3;
PC9;
NARC1;
LDLCQ1;
NARC-1;
HCHOLA3    proprotein
convertase
subtilisin/
kexin type
9 ALN-RSV01    RSV genome    RSV
genome    N/A    NC_001803    N/A       RSV
Refseq
Genome ALN-RSV02    RSV genome    RSV
genome    N/A    NC_001803    N/A       RSV
Refseq
Genome ALN-HTT    HTT    HTT    3064    NM_002111    NP_002102    HD; IT15   
huntingtin

[***]

Updated as of: the Execution Date

--------------------------------------------------------------------------------

Schedule 1.2.146

NAMED PIPELINE PROGRAMS

 

Alnylam
siRNA
identifier

(if any)

   Gene
Target
Name    Gene
Target
Symbol    NCBI
Human
Gene    NCBI’s
Reference
Sequences
Transcript*    NCBI’s
Reference
Sequences
Protein*    Alias(es)    Description ALN-TTR02    TTR    TTR    7276   
NM_000371    NP_000362    CTS; CTS1;
HsT2651;
PALB; TBPA    transthyretin ALN-TTRsc    TTR    TTR    7276    NM_000371   
NP_000362    CTS; CTS1;
HsT2651;
PALB; TBPA    transthyretin ALN-AT3    AT3    SERPINC1    462    NM_000488   
NP_000479    AT3; AT3D;
ATIII; THPH7    serpin peptidase
inhibitor, clade
C (antithrombin),
member 1 ALN-CC5    CC5    C5    727    NM_001735    NP_001726    C5a; C5b;
CPAMD4    complement
component 5 ALN-AS1    ALAS1    ALAS1    211    NM_000688    NP_000679    ALAS;
MIG4; ALAS3;
ALASH    aminolevulinate,
delta-, synthase 1 ALN-AAT    AAT    SERPINA1    5265    NM_000295    NP_000286
   PI; A1A; AAT;
PI1; A1AT;
PRO2275;
alpha1AT    serpin peptidase
inhibitor, clade
A (alpha-1
antiproteinase,
antitrypsin),
member 1

Updated as of: the Execution Date

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.149

NON-CORE PIPELINE PROGRAM LIST

 

Alnylam

siRNA

identifier

(if any)

  

Gene

Target

Name

   Gene
Target
Symbol    NCBI
Human
Gene    NCBI’s
Reference
Sequences
Transcript*    NCBI’s
Reference
Sequences
Protein*    Alias(es)    Description ALN-VSP    VEGF    VEGFA    7422   
NM_003376    NP_003367    VPF;
VEGF;
MVCD1    Vacular
endothelial
growth
factor A ALN-VSP    KSP (kinesin spindle protein)    KIF11    3832    NM_004523
   NP_004514    EG5;
HKSP;
KNSL1;
MCLMR;
TRIP5    Kinesin
family
member 11 ALN-PCS    PCSK9    PCSK9    255738    NM_174936    NP_777596    FH3;
PC9;
NARC1;
LDLCQ1;
NARC-1;
HCHOLA3    proprotein
convertase
subtilisin/
kexin type
9 ALN-RSV01    RSV genome    RSV
genome    N/A    NC_001803    N/A       RSV
Refseq
Genome ALN-RSV02    RSV genome    RSV
genome    N/A    NC_001803    N/A       RSV
Refseq
Genome ALN-HTT    HTT    HTT    3064    NM_002111    NP_002102    HD; IT15   
huntingtin

[***]

Updated as of: the Execution Date

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.159

OPTION PRODUCT CORE TECHNOLOGY PATENTS

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.162

OPTION PRODUCT-SPECIFIC PATENTS

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 1.2.178

POTENTIAL ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 2.1.3.3

Exempted Third Party CNS Agreements

Amended and Restated Collaboration Agreement dated as of July 27, 2007 by and
between Alnylam Pharmaceuticals, Inc. and Medtronic, Inc.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 6.1

ALN-TTR02 SUPPLY AGREEMENT TERMS

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 3 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 6.2

SUPPLY AGREEMENT TERMS

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 4 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 7.3

PRESS RELEASES

See attached.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 8.2

DISCLOSURE SCHEDULE

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

MASTER AGREEMENT

 

Schedule 10.2

IDENTIFIED PATENT RIGHTS

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

EXECUTION VERSION

APPENDIX A

REGIONAL PRODUCT LICENSE AND COLLABORATION

TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

TABLE OF CONTENTS

 

         PAGE  

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

     5   

1.1.

  Relationship with Master Agreement      5   

1.2.

  Definitions      6   

2. DEVELOPMENT COLLABORATION

     22   

2.1.

  Overview      22   

2.2.

  Development Plans      22   

2.3.

  Responsibilities for Development Activities and Costs      30   

2.4.

  Diligence      33   

2.5.

  Records; Reports; Information Sharing      34   

2.6.

  Third Parties      35   

3. REGULATORY MATTERS

     35   

3.1.

  Regulatory Filings and Interactions      35   

3.2.

  EMA Regulatory Strategy      38   

3.3.

  Costs of Regulatory Affairs      38   

3.4.

  Right of Reference      38   

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

     39   

4.1.

  Responsibility, Cost and Diligence      39   

4.2.

  Genzyme Territory Commercialization Plan      39   

4.3.

  Alnylam Territory Commercialization Plan      39   

4.4.

  Advertising and Promotional Materials      40   

4.5.

  Commercialization Reporting Obligations      40   

4.6.

  Recalls, Market Withdrawals or Corrective Actions      42   

4.7.

  Ex-Territory Sales; Export Monitoring      42   

5. COLLABORATION MANAGEMENT

     42   

5.1.

  Product Joint Steering Committee      42   

5.2.

  Appointment of Subcommittees, Project Teams and RLP Alliance Managers      43
  

5.3.

  PJSC Meetings      44   

5.4.

  PJSC Minutes      44   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

- i -

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

5.5.

  PJSC Responsibilities      44   

5.6.

  PJSC Decision-Making      46   

5.7.

  Term of PJSC      47   

5.8.

  Alnylam Third Party Partner      47   

6. LICENSES

     49   

6.1.

  License Grants to Genzyme      49   

6.2.

  License Grants to Alnylam      51   

6.3.

  Joint Collaboration IP      52   

6.4.

  Compliance with In-Licenses      52   

6.5.

  Alnylam Territory Right of First Negotiation      53   

6.6.

  Bankruptcy      53   

6.7.

  No Other Rights      54   

7. CERTAIN FINANCIAL TERMS

     54   

7.1.

  Milestone Fees      54   

7.2.

  Royalties      56   

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

     58   

8.1.

  Representations and Warranties of Alnylam      58   

8.2.

  Representations and Warranties of Genzyme      60   

8.3.

  Warranty Disclaimer      60   

8.4.

  Certain Covenants      60   

9. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

     62   

9.1.

  Inventorship      62   

9.2.

  Ownership      62   

9.3.

  Prosecution and Maintenance of Patent Rights      62   

9.4.

  Third Party Infringement      65   

9.5.

  Patent Term Extensions      67   

9.6.

  Common Interest      67   

9.7.

  Trademarks      67   

9.8.

  Cooperative Research and Technology (CREATE) Act Acknowledgment      68   

10. TERM AND TERMINATION

     69   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

- ii -

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

10.1.

  Term      69   

10.2.

  Termination Rights      69   

10.2.4.

  Challenges of Patent Rights      71   

10.3.

  Effect of Termination      72   

10.4.

  Fundamental Breach of Alnylam’s Development Obligations      77   

10.5.

  Effect of Expiration or Termination; Survival      78   

11. PERFORMANCE BY AFFILIATES

     79   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

- iii -

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

SCHEDULES

 

Schedule 1.2.13-1

   Alnylam Core Technology Patents for ALN-TTR02

Schedule 1.2.18-1

   Alnylam Product-Specific Patents for ALN-TTR02

Schedule 2.2.1-1

   Global Development Strategy for ALN-TTR02

Schedule 2.2.2.1-1

   Global Development Plan for ALN-TTR02

Schedule 2.2.2.6(d)-1

   Alnylam Territory Development Plan for ALN-TTR02

Schedule 2.2.4-1

   Genzyme Territory Development Plan for ALN-TTR02

Schedule 8.1

   Disclosure Schedule

Schedule 8.1.12

   Existing Alnylam In-Licenses / Additional Alnylam In-Licenses

Schedule 8.4.1.3(c)

   Exceptions to Exclusivity

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

- iv -

--------------------------------------------------------------------------------

REGIONAL PRODUCT LICENSE AND COLLABORATION TERMS

THESE REGIONAL PRODUCT LICENSE AND COLLABORATION TERMS are Appendix A to the
Master Agreement, dated as of the Execution Date, by and between Alnylam
Pharmaceuticals, Inc., a corporation organized and existing under the laws of
the State of Delaware (“Alnylam”), and Genzyme Corporation, a corporation
organized and existing under the laws of the Commonwealth of Massachusetts
(“Genzyme”).

RECITALS:

WHEREAS, Alnylam and Genzyme are parties to that certain Master Collaboration
Agreement (dated as of the Execution Date) (the “Master Agreement”) pursuant to
which Genzyme has an option to receive licenses and other rights with respect to
Regional Licensed Products from Alnylam in the Genzyme Territory;

WHEREAS, the Parties have agreed that ALN-TTR02 is a Regional Licensed Product;

WHEREAS, Genzyme may exercise a Regional Option, 2019 Trailing Regional Option
or 2021 Trailing Regional Option pursuant to the Master Agreement for any
Regional Option Product thereunder and such Regional Option Product will then be
deemed a Regional Licensed Product;

WHEREAS, the Parties desire for Alnylam to continue to develop such Regional
Licensed Products for the Alnylam Territory and the Genzyme Territory;

WHEREAS, Alnylam desires to retain the right to commercialize such Regional
Licensed Products in the Alnylam Territory; and

WHEREAS, Alnylam and Genzyme now wish to set forth the terms and conditions
under which Genzyme will have the right to Develop and Commercialize such
Regional Licensed Products in the Genzyme Territory.

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the Parties hereby agree as follows:

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1. Relationship with Master Agreement. These Regional License Terms become
effective on a Regional Licensed Product-by-Regional Licensed Product basis on
the Implementation Date in accordance with the Master Agreement. The Master
Agreement generally governs the Parties’ relationship with respect to Regional
Licensed Products during the period of time before Genzyme exercises its
Regional Option under the Master Agreement (i.e., before such product became a
Regional Licensed Product). The Master Agreement also contains terms that are
generally applicable to Regional Licensed Products, Global Licensed Products (as
defined in the Master Agreement) and Co-Co Licensed Products (as defined in the
Master

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

5

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

Agreement). Accordingly, the following Sections of the Master Agreement are
incorporated herein by reference: Section 2.2 (Effectiveness of Licenses to
Collaboration Products); Section 5 (Collaboration Management); Section 6
(Manufacture and Supply of the Collaboration Products); Section 7
(Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit);
Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4
(Challenges of Patent Rights); and Section 13 (Miscellaneous).

1.2. Definitions. Unless specifically set forth to the contrary herein, the
following terms, whether used in the singular or plural, shall have the
respective meanings set forth below:

1.2.1. “Acquired Business” has the meaning set forth in Section 11.3 (Acquired
Programs).

1.2.2. “Acquirer” has the meaning set forth in Section 11.2 (Future Acquisition
of a Party or its Business).

1.2.3. “Additional Development Activities” has the meaning set forth in
Section 2.2.2.6(a) (Additional Development Proposals).

1.2.4. “Additional Development Opt-In Date” has the meaning set forth in
Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities).

1.2.5. “Additional Development Opt-In Notice” has the meaning set forth in
Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities).

1.2.6. “Additional Development Proposal” has the meaning set forth in
Section 2.2.2.6(a) (Additional Development Proposals).

1.2.7. “AF11 Lipid Nanoparticle Formulation” has the meaning set forth in the
Master Agreement.

1.2.8. “Affiliate” means, with respect to a Person, any other Person which
controls, is controlled by, or is under common control with the applicable
Person. For purposes of this definition, “control” shall mean: (a) in the case
of corporate entities, direct or indirect ownership of at least fifty percent
(50%) of the stock or shares entitled to vote for the election of directors, or
otherwise having the power to control or direct the affairs of such Person; and
(b) in the case of non-corporate entities, direct or indirect ownership of at
least fifty percent (50%) of the equity interest or the power to direct the
management and policies of such non-corporate entities.

1.2.9. “AJSC” has the meaning set forth in the Master Agreement.

1.2.10. “ALN-TTR02” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

6

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

1.2.11. “ALN-TTR02 Clinical Supply Agreement” has the meaning set forth in the
Master Agreement.

1.2.12. “ALN-TTR02 Commercial Supply Agreement” has the meaning set forth in the
Master Agreement.

1.2.13. “Alnylam Core Technology Patents” means Patent Rights Controlled by
Alnylam during the Term that are [***]. The Alnylam Core Technology Patents
existing as of the Effective Date for ALN-TTR02 are those Patent Rights
identified on Schedule 1.2.13-1. The Alnylam Core Technology Patents existing as
of the Implementation Date for any other Regional Licensed Product will be
identified as the “Alnylam Core Technology Patents” in the Option Data Package
for such Regional Licensed Product provided by Alnylam to Genzyme under the
Master Agreement and then attached hereto as Schedules 1.2.13-2, 1.2.13-3, and
so forth.

1.2.14. “Alnylam Developed siRNA Product” means an siRNA with respect to which
(a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a
product first satisfies the criterion set forth in this clause (a) such
criterion shall be deemed satisfied at all times thereafter as to such product,
and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the
Development.

1.2.15. “Alnylam In-License” means any Existing Alnylam In-License or any
Collaboration In-License to which Alnylam is a party.

1.2.16. “Alnylam Know-How” means Know-How Controlled by Alnylam during the Term
that is reasonably necessary or useful for Genzyme to Develop, Manufacture
and/or Commercialize Regional Licensed Products in the Field in the Genzyme
Territory, other than Alnylam’s interest in Know-How included in Joint
Collaboration IP.

1.2.17. “Alnylam Patents” means Alnylam Core Technology Patents and Alnylam
Product-Specific Patents.

1.2.18. “Alnylam Product-Specific Patents” means Patent Rights Controlled by
Alnylam during the Term that claim [***]. The Alnylam Product-Specific Patents
existing as of the Effective Date for ALN-TTR02 are those Patent Rights
identified on Schedule 1.2.18-1. The Alnylam Product-Specific Patents existing
as of the Implementation Date for any other Regional Licensed Product will be
identified as the “Alnylam Product-Specific Patents” in the Option Data Package
for such Regional Licensed Product provided by Alnylam to Genzyme under the
Master Agreement and then attached hereto as Schedules 1.2.18-2, 1.2.18-3, and
so forth. [***].

1.2.19. “Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam
Patents and Alnylam’s interest in Joint Collaboration IP.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

7

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REGIONAL LICENSE TERMS

 

1.2.20. “Alnylam Territory” means the United States, Canada, Austria, Belgium,
Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the
Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway, Switzerland,
Liechtenstein, Andorra, Iceland and Greenland.

1.2.21. “Alnylam Territory Commercialization Plan” has the meaning set forth in
Section 4.4 (Alnylam Territory Commercialization Plan).

1.2.22. “Alnylam Territory Development Plan” has the meaning set forth in
Section 2.2.3 (Alnylam Territory Development Plan).

1.2.23. “Alnylam Territory MMC” [***].

1.2.24. “Alnylam Trademark” has the meaning set forth in Section 9.7(b)
(Trademarks).

1.2.25. “ANDA” means an Abbreviated New Drug Application (or any successor
application or procedure) as defined in regulations promulgated by the FDA under
the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as
applicable, any other analogous application filed with a Regulatory Authority in
any country other than the U.S. in the Genzyme Territory) for Regulatory
Approval for marketing and selling a Regional Licensed Product in the Genzyme
Territory.

1.2.26. “Appendix” means this Appendix A (Regional Product License and
Collaboration Terms).

1.2.27. “Bankrupt Party” has the meaning set forth in Section 6.6 (Bankruptcy).

1.2.28. “Budget Adjustment Triggers” has the meaning set forth in
Section 2.2.2.3 (Managing and Amending Global Development Plans and Global
Development Budgets).

1.2.29. “Calendar Quarter” means the respective periods of three (3) consecutive
calendar months ending on March 31, June 30, September 30 and December 31 of
each Calendar Year, provided that (a) the first Calendar Quarter of the Term
shall begin on the Effective Date and end on the first to occur of
March 31, June 30, September 30 or December 31 thereafter and the last Calendar
Quarter of the Term shall end on the last day of the Term and (b) the first
Calendar Quarter of a Royalty Term for a Regional Licensed Product in a country
shall begin on the First Commercial Sale of a Regional Licensed Product in such
country and end on the first to occur of March 31, June 30, September 30 or
December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end
on the last day of such Royalty Term.

1.2.30. “Calendar Year” means each successive period of twelve (12) months
commencing on January 1 and ending on December 31, provided that (a) the first
Calendar Year of the Term shall begin on the Effective Date and end on the first
December 31 thereafter and the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

8

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

last Calendar Year of the Term shall end on the last day of the Term and (b) the
first Calendar Year of a Royalty Term for a Regional Licensed Product in a
country shall begin on the First Commercial Sale of a Regional Licensed Product
in such country and end on the first December 31 thereafter and the last
Calendar Year of the Term shall end on the last day of such Royalty Term.

1.2.31. “Carbohydrate Conjugate” has the meaning set forth in the Master
Agreement.

1.2.32. “Clinical Study” has the meaning set forth in the Master Agreement.

1.2.33. “Co-Co/Global Option” has the meaning set forth in the Master Agreement.

1.2.34. “Co-Co License Terms” has the meaning set forth in the Master Agreement.

1.2.35. “Co-Co Licensed Product” has the meaning set forth in the Master
Agreement.

1.2.36. “Collaboration In-License” has the meaning set forth in the Master
Agreement.

1.2.37. “Commercialization” or “Commercialize” has the meaning set forth in the
Master Agreement.

1.2.38. “Commercially Reasonable Efforts” means [***].

1.2.39. “Competing Program” has the meaning set forth in Section 11.3 (Acquired
Programs).

1.2.40. “Competitive Infringement” has the meaning set forth in Section 9.4.1
(Notices).

1.2.41. “Confidential Information” has the meaning set forth in the Master
Agreement.

1.2.42. “Control”, “Controls” or “Controlled by” has the meaning set forth in
the Master Agreement.

1.2.43. “Cost of Goods” has the meaning set forth in the Master Agreement.

1.2.44. “Cover,” “Covering” or “Covers” has the meaning set forth in the Master
Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

9

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

1.2.45. “CPI” shall mean the Consumer Price Index – Urban Wage Earners and
Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the
United States Department of Labor, Bureau of Labor Statistics (or its successor
equivalent index) in the United States.

1.2.46. “CRO” means a contract research organization.

1.2.47. “Development,” “Developing” or “Develop” has the meaning set forth in
the Master Agreement.

1.2.48. “Development Plan” means, with respect to each Regional Licensed
Product, (a) with respect to Alnylam, the Alnylam Territory Development Plan for
such Regional Licensed Product, (b) with respect to Genzyme, the Genzyme
Territory Development Plan for such Regional Licensed Product, and (c) with
respect to both Parties, the Global Development Plan for such Regional Licensed
Product.

1.2.49. “Disputing Party” has the meaning set forth in Section 2.3.1.2 (Global
R&D Costs).

1.2.50. “Effective Date” means the date that the Master Agreement becomes
effective in accordance with its terms.

1.2.51. “EMA” means the European Medicines Agency and any successor Governmental
Authority having substantially the same function.

1.2.52. “End of Phase II Package” has the meaning set forth in
Section 2.2.2.4(c)(ii).

1.2.53. “EU” means the European Union, as its membership may be altered from
time to time, and any successor thereto.

1.2.54. “Excess Global R&D Costs” has the meaning set forth in Section 2.3.1.2
(Global R&D Costs).

1.2.55. “Exclusivity Period” means, on a Regional Licensed Product-by-Regional
Licensed Product and country-by-country basis within the Genzyme Territory,
[***].

1.2.56. “Execution Date” has the meaning set forth in the Master Agreement.

1.2.57. “Existing Alnylam In-License” has the meaning set forth in the Master
Agreement.

1.2.58. “Existing Genzyme In-License” has the meaning set forth in the Master
Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

10

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

1.2.59. “FDA” means the United States Food and Drug Administration and any
successor Governmental Authority having substantially the same function.

1.2.60. “FDCA” means the United States Federal Food, Drug, and Cosmetic Act of
1938, as amended from time to time, and the regulations and guidelines
promulgated thereunder.

1.2.61. “Field” means the treatment, diagnosis and/or prevention of all human
diseases.

1.2.62. “First Commercial Sale” means, with respect to a country, the first sale
for end use or consumption of a Regional Licensed Product in such country,
except for compassionate use or patient access programs, after all Regulatory
Approvals legally required for such sale have been granted by the Regulatory
Authority of such country.

1.2.63. “First Regulatory Approval by the EMA” means, with respect to a Regional
Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought
through the EMA centralized procedure, receipt of Regulatory Approval for such
Regional Licensed Product from the EMA or (ii) if Regulatory Approval in the EU
is sought through a national authorization procedure, receipt of Regulatory
Approval for such Regional Licensed Product in the first (1st) MMC country in
the EU.

1.2.64. “First Regulatory Approval in Japan” means, with respect to a Regional
Licensed Product, receipt of Regulatory Approval for such Regional Licensed
Product in Japan.

1.2.65. “Force Majeure” means embargoes, war, acts of war (whether war be
declared or not), terrorism, insurrections, riots, civil commotions, strikes,
lockouts or other labor disturbances, fire, floods, or other acts of God.

1.2.66. “Fundamental Breach” [***].

1.2.67. “GAAP” has the meaning set forth in the Master Agreement.

1.2.68. “GalNAc Conjugate” has the meaning set forth in the Master Agreement.

1.2.69. “Generic Competition” means, with respect to a Regional Licensed Product
in any country in the Genzyme Territory in a given Calendar Quarter, that,
during such Calendar Quarter, (a) one or more Generic Products with respect to
such Regional Licensed Product are commercially available in such country, and
(b) Net Sales of such Regional Licensed Product in such country in such Calendar
Quarter equal less than [***] of the average Net Sales of such Regional Licensed
Product over the [***] consecutive Calendar Quarters immediately prior to the
Calendar Quarter in which one or more Generic Products first became commercially
available in such country.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

11

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

1.2.70. “Generic Product” means, on a Regional Licensed Product-by-Regional
Licensed Product and country-by-country basis, a pharmaceutical product that
(a) is sold by a Person that is not a Related Party of Genzyme under a marketing
authorization granted by a Regulatory Authority in such country to a Third
Party; (b) [***]; and (c) is approved by the Regulatory Authority in such
country pursuant to an approval process that relies in part on pivotal safety
and/or efficacy data in such Regulatory Authority’s previous grant of marketing
authorization for such Regional Licensed Product.

1.2.71. “Genzyme Collaboration IP” means (a) any Know-How, first identified,
discovered or developed solely by employees of Genzyme or its Affiliates or
other persons not employed by Alnylam acting on behalf of Genzyme, in the
conduct of the Collaboration and (b) any Patent Rights that claim or Cover such
Know-How and are Controlled by Genzyme at any time during the Term. Genzyme
Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each
case (a) and (b), other than Genzyme Manufacturing IP.

1.2.72. “Genzyme Disclosed Manufacturing Know-How” means Know-How (a) Controlled
by Genzyme at any time during the Term that is useful in the Manufacture of a
Regional Licensed Product and (b) that Genzyme, in its sole discretion,
discloses in writing to Alnylam in the course of the Collaboration.

1.2.73. “Genzyme In-License” means any Existing Genzyme In-License, Un-Blocking
Genzyme In-License, or any Collaboration In-License to which Genzyme is a party.

1.2.74. “Genzyme Know-How” means Know-How Controlled by Genzyme during the Term
that is reasonably necessary or useful for Alnylam to Develop, Commercialize
and/or Manufacture Regional Licensed Products in the Field in the Alnylam
Territory (other than Genzyme’s rights in Joint Collaboration IP, Genzyme
Collaboration IP and Genzyme Manufacturing IP).

1.2.75. “Genzyme Manufacturing IP” means (a) any Know-How related to the
Manufacture of Regional Licensed Products (or oligonucleotides generally)
Controlled by Genzyme at any time during the Term, and (b) any Patent Rights
that claim or cover such Know-How and are Controlled by Genzyme at any time
during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme
Disclosed Manufacturing Know-How.

1.2.76. “Genzyme Patent Jurisdiction” has the meaning set forth in the Master
Agreement.

1.2.77. “Genzyme Patent Rights” means those Patent Rights Controlled by Genzyme
during the Term that are reasonably necessary or useful to Develop,
Commercialize and/or Manufacture Regional Licensed Products in the Field in the
Alnylam Territory; Genzyme Patent Rights excludes Patent Rights included in
Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and
Genzyme Manufacturing IP.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

12

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REGIONAL LICENSE TERMS

 

1.2.78. “Genzyme Technology” means, collectively, Genzyme Know-How, Genzyme
Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint
Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.79. “Genzyme Territory” means all countries and territories of the world
other than the Alnylam Territory.

1.2.80. “Genzyme Territory Commercialization Plan” has the meaning set forth in
Section 4.3 (Genzyme Territory Commercialization Plan).

1.2.81. “Genzyme Territory Development Plan” has the meaning set forth in
Section 2.2.4 (Genzyme Territory Development Plan).

1.2.82. “Genzyme Territory MMC” [***].

1.2.83. “Genzyme Trademark” has the meaning set forth in Section 9.7(b)
(Trademarks).

1.2.84. “Global Branding Strategy” has the meaning set forth in Section 4.5.1
(Global Branding).

1.2.85. “Global Clinical Study” has the meaning set forth in Section 2.2.2.5(b)
(Oversight of the Global Development Plans).

1.2.86. “Global Development Activity(ies)” has the meaning set forth in
Section 2.2.2.1 (Global Development Plans).

1.2.87. “Global Development Budget” has the meaning set forth in Section 2.2.2.2
(Global Development Budgets).

1.2.88. “Global Development Plan” has the meaning set forth in Section 2.2.2.1
(Global Development Plans).

1.2.89. “Global Development Strategy” has the meaning set forth in Section 2.2.1
(Global Development Strategy).

1.2.90. “Global License Terms “has the meaning set forth in the Master
Agreement.

1.2.91. “Global Licensed Product” has the meaning set forth in the Master
Agreement.

1.2.92. “Global R&D Cost Opt-In Date” has the meaning set forth in
Section 2.3.1.2 (Global R&D Costs).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

13

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REGIONAL LICENSE TERMS

 

1.2.93. “Global R&D Costs” means, with respect to a Regional Licensed Product,
R&D Costs incurred in connection with any Global Development Activity for such
Regional Licensed Product.

1.2.94. “Global R&D Costs Report” has the meaning set forth in Section 2.3.1.2
(Global R&D Costs).

1.2.95. “Governmental Authority” means any applicable government authority,
court, tribunal, arbitrator, agency, department, legislative body, commission or
other instrumentality of (a) any government of any country or territory, (b) any
nation, state, province, county, city or other political subdivision thereof or
(c) any supranational body.

1.2.96. “Human POP Study” has the meaning set forth in the Master Agreement.

1.2.97. “IFRS” has the meaning set forth in the Master Agreement.

1.2.98. “Implementation Date” means, with respect to ALN-TTR02, the Effective
Date and, with respect to each other Regional Licensed Product, the Option
Exercise Date for such Regional Licensed Product.

1.2.99. “Improvement Manufacturing Patent Right” means a Patent Right owned
exclusively by Genzyme or its Affiliates that claims an invention related to the
Manufacture of a Regional Licensed Product that was made (a) by Genzyme or its
Affiliates after the Effective Date in connection with Manufacturing Regional
Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam
Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s
Confidential Information under Section 7 of the Master Agreement
(Confidentiality and Publication).

1.2.100. “IND” has the meaning set forth in the Master Agreement.

1.2.101. “In-License” has the meaning set forth in the Master Agreement.

1.2.102. “Infringement Action” has the meaning set forth in Section 9.4.2(a)
(Rights to Enforce – Genzyme Technology).

1.2.103. “JCOT” has the meaning set forth in Section 2.2.2.5 (Oversight of the
Global Development Plans).

1.2.104. “Joint Collaboration IP” means, collectively, (a) any Know-How first
identified, discovered or developed jointly by employee(s), agent(s) or
consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand,
and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its
Affiliates, on the other hand, in the conduct of the Collaboration that is
Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such
Know-How and are Controlled by Alnylam and Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

14

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REGIONAL LICENSE TERMS

 

1.2.105. “Know-How” has the meaning set forth in the Master Agreement.

1.2.106. “Laws” has the meaning set forth in the Master Agreement.

1.2.107. “Licensed Target” means, for ALN-TTR02, TTR, and for each other
Regional Licensed Product, the human gene that is targeted by such Regional
Licensed Product, as identified in the Option Data Package for such Regional
Licensed Product and then attached hereto as Schedules 1.2.107-1, 1.2.107-2, and
so forth.

1.2.108. “Lipid Nanoparticle Formulation” has the meaning set forth in the
Master Agreement.

1.2.109. “Manufacturing” or “Manufacture” has the meaning set forth in the
Master Agreement.

1.2.110. “Manufacturing Claim” means a claim within a Patent Right directed
solely to Manufacturing a Regional Licensed Product.

1.2.111. “MMC” means any Alnylam Territory MMC or Genzyme Territory MMC.

1.2.112. “NDA” has the meaning set forth in the Master Agreement.

1.2.113. “Net Sales” means, with respect to a Regional Licensed Product, the
aggregate gross invoiced sales prices from sales of all units of such Regional
Licensed Product sold by Genzyme and its Related Parties to independent Third
Parties (other than a Sublicensee) after deducting, if not previously deducted,
from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of
useful life or otherwise);

(c) Third Party rebates, chargebacks, hospital buying group/group purchasing
organization administration fees or managed care organization rebates actually
given;

(d) rebates and similar payments made with respect to sales paid for by any
governmental or regulatory authority such as Federal or state Medicaid, Medicare
or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

15

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REGIONAL LICENSE TERMS

 

(g) value added, sales and use, excise and other similar taxes and surcharges,
customary transportation and insurance, custom duties, and other governmental
charges; and

(h) amounts previously included in Net Sales of such Regional Licensed Product
that are adjusted or written-off by Genzyme or its Related Parties as bad debt
or otherwise uncollectible in accordance with the standard practices of Genzyme
or its Related Parties for writing off uncollectible amounts consistently
applied; provided, however, if any such written-off amounts are subsequently
collected, such collected amounts shall be included in Net Sales in the period
in which they are subsequently collected.

Such amounts shall be determined from the books and records of Genzyme or its
Related Parties, maintained in accordance with IFRS.

In the case of any sale or other disposal for value, such as barter or
counter-trade, of a Regional Licensed Product, or part thereof, other than in an
arm’s length transaction exclusively for cash, Net Sales shall be calculated as
above on the value of the non-cash consideration received or the fair market
price (if higher) of such Regional Licensed Product in the country of sale or
disposal, as determined in accordance with IFRS.

Notwithstanding the foregoing, the following will not be included in Net Sales:
(1) sales between or among Genzyme and its Related Parties (but Net Sales shall
include sales to the first Third Party (other than a Sublicensee) by Genzyme or
its Related Parties); (2) samples of Regional Licensed Product used to promote
additional Net Sales, in amounts consistent with normal business practices of
Genzyme; and (3) disposal or use of Regional Licensed Products in Clinical
Studies or under compassionate use, patient assistance, named patient use, or
test marketing programs or non-registrational studies or other similar programs
or studies where the Regional Licensed Product is supplied without charge or at
the actual manufacturing cost thereof (without allocation of indirect costs or
any mark-up).

In the case where a Regional Licensed Product is sold as part of a Combination
Product in a country in the Licensed Territory, Net Sales for the Regional
Licensed Product included in such Combination Product in such country shall be
calculated as follows:

(i) if the Regional Licensed Product is sold separately in such country and the
other active ingredient or ingredients in the Combination Product are sold
separately in such country, Net Sales for the Regional Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/(A+B), where A is the invoice price of the Regional
Licensed Product when sold separately in such country and B is the total invoice
price of the other active ingredient or ingredients in the Combination Product
when sold separately in such country;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

16

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REGIONAL LICENSE TERMS

 

(ii) if the Regional Licensed Product is sold separately in such country but the
other active ingredient or ingredients in the Combination Product are not sold
separately in such country, Net Sales for the Regional Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/D, where A is the invoice price of the Regional
Licensed Product when sold separately in such country and D is the invoice price
of the Combination Product in such country;

(iii) if the Regional Licensed Product is not sold separately in such country
but the other active ingredient or ingredients in the Combinations Product are
sold separately in such country, Net Sales for the Regional Licensed Product
shall be calculated by multiplying actual Net Sales of such Combination Product
by the fraction 1 – (B/D), where B is the invoice price of the other active
ingredient or ingredients in the Combination Product when sold separately in
such country and D is the invoice price of the Combination Product in such
country; or

(iv) if neither the Regional Licensed Product nor the other active ingredient or
ingredients in the Combination Product are sold separately in such country, the
Parties shall determine Net Sales for the Regional Licensed Product in such
Combination Product by mutual agreement based on the relative contribution of
the Regional Licensed Product and each other active ingredient to the
Combination Product, and shall take into account in good faith any applicable
allocations and calculations that may have been made for the same period in
other countries.

For purposes of this Section, “Combination Product” means a product that
includes at least one active ingredient other than a Regional Licensed
Product. Drug delivery vehicles, adjuvants, and excipients shall not be deemed
to be “active ingredients”, except in the case where such delivery vehicle,
adjuvant, or excipient is recognized by the FDA as an active ingredient in
accordance with 21 C.F.R. 210.3(b)(7).

1.2.114. “Non-Bankrupt Party” has the meaning set forth in Section 6.6
(Bankruptcy).

1.2.115. “Non-Disputing Party” has the meaning set forth in Section 2.3.1.2(d)
(Global R&D Costs).

1.2.116. “Non-Proposing Party” has the meaning set forth in Section 2.2.2.6(c)
(Independent Performance of Additional Development Activities).

1.2.117. “Option Data Package” has the meaning set forth in the Master
Agreement.

1.2.118. “Option Exercise Date” has the meaning set forth in the Master
Agreement.

1.2.119. “Party” means Genzyme and/or Alnylam.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

17

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REGIONAL LICENSE TERMS

 

1.2.120. “Patent Challenge” has the meaning set forth in Section 10.2.4
(Challenges of Patents).

1.2.121. “Patent Rights” has the meaning set forth in the Master Agreement.

1.2.122. “Person” means any natural person, corporation, unincorporated
organization, partnership, association, sole proprietorship joint stock company,
joint venture, limited liability company, trust or government, or any
Governmental Authority, or any other similar entity.

1.2.123. “Phase 2 Budget” has the meaning set forth in Section 2.2.2.4 (Budget
Caps; Adjustment and Compensation).

1.2.124. [***].

1.2.125. “Phase 3 Budget” has the meaning set forth in Section 2.2.2.4 (Budget
Caps; Adjustment and Compensation).

1.2.126. [***].

1.2.127. “Phase I Study” has the meaning set forth in the Master Agreement.

1.2.128. “Phase II Study” has the meaning set forth in the Master Agreement.

1.2.129. “Phase III Study” has the meaning set forth in the Master Agreement.

1.2.130. “Post-Marketing Study” has the meaning set forth in the Master
Agreement.

1.1.2. “Post-Phase 3 Budget” has the meaning set forth in Section 2.2.2.4
(Budget Caps; Adjustment and Compensation).

1.2.131. [***].

1.2.132. “Product Joint Steering Committee” or “PJSC” means the joint steering
committee as more fully described in Section 5.1 (Product Joint Steering
Committee).

1.2.133. “Product Trademark(s)” means the Trademarks used, or intended for use,
in connection with the distribution, marketing, promotion and sale of the
Regional Licensed Products. Product Trademarks specifically exclude the
corporate names and logos of the Parties and their Affiliates. Product Trademark
includes both the Alnylam Trademarks and the Genzyme Trademarks.

1.2.134. “Promotional Materials” has the meaning set forth in Section 4.5.2
(Alnylam A&P).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

18

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REGIONAL LICENSE TERMS

 

1.2.135. “Proposing Party” has the meaning set forth in Section 2.2.2.6(a)
(Additional Development Proposals).

1.2.136. “R&D Costs” means, with respect to a Regional Licensed Product, costs
and expenses incurred in connection with the performance of any Development
activity for such Regional Licensed Product, including [***].

1.2.137. “R&D FTE” means [***] of work per annum devoted to or in support of the
Development or Manufacture of a Regional Licensed Product that is carried out by
one or more qualified scientific or technical employees (excluding Third Party
contractors) of a Party or its Affiliates.

1.2.138. “R&D FTE Cost” means, for any period, the R&D FTE Rate multiplied by
the number of R&D FTEs in such period.

1.2.139. “R&D FTE Rate” means [***] per FTE, increased annually beginning on
January 1, 2015 and thereafter on January 1 of each succeeding year by the
percentage increase in the CPI as of December 31 of the then most recently ended
Calendar Year over the level of the CPI on December 31, 2013.

1.2.140. “Regional Licensed Product” means: (i) ALN-TTR02 as of the Effective
Date and (ii) if Genzyme exercises the Regional Option pursuant to the Master
Agreement for any Regional Option Product, then such Regional Option Product as
of the applicable Option Exercise Date. For the sake of clarity (but not for
purposes of interpretation of the Collaboration Agreement), although ALN-TTRsc
is not a Regional Licensed Product, it is exclusively licensed to Genzyme in the
Genzyme Territory in much the same way that Regional Licensed Products are
licensed to Genzyme in the Genzyme Territory under these Regional License Terms.
As a Co-Co Licensed Product, however, ALN-TTRsc is licensed to Genzyme under the
Co-Co License Terms, which also grant Genzyme a license to co-Commercialize
ALN-TTRsc in the Alnylam Territory.

1.2.141. “Regional Option Period” has the meaning set forth in the Master
Agreement.

1.2.142. “Regional Option Product” has the meaning set forth in the Master
Agreement.

1.2.143. “Regional Option” has the meaning set forth in the Master Agreement.

1.2.144. “Regional Out-of-Pocket Costs” means, with respect to certain
activities hereunder, direct expenses paid or payable by either Party or its
Affiliates to Third Parties and specifically identifiable and incurred to
conduct such activities for a Regional Licensed Product, including payments to
contract personnel; provided, however, that amounts paid to contract sales and
marketing personnel will not be considered Regional Out-of-Pocket Costs.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

19

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REGIONAL LICENSE TERMS

 

1.2.145. “Regulatory Approval” has the meaning set forth in the Master
Agreement.

1.2.146. “Regulatory Authority” has the meaning set forth in the Master
Agreement.

1.2.147. “Regulatory Exclusivity” means, with respect to a Regional Licensed
Product in a country, any exclusive marketing right, data exclusivity right,
orphan drug designation or other country-wide exclusive right or status
conferred by any Governmental Authority with respect to such Regional Licensed
Product in such country, other than a Patent Right, that limits or prohibits a
Person from [***].

1.2.148. “Related Party” means a Party’s Affiliates, permitted Sublicensees and,
with respect to Alnylam, licensees in the Alnylam Territory.

1.2.149. “Reverted Regional Licensed Product” has the meaning set forth in
Section 10.3.1.3(a) (Effects of Termination of Regional License Terms in Their
Entirety by Alnylam for Cause or by Genzyme for Convenience).

1.2.150. “RLP Alliance Manager” has the meaning set forth in Section 5.2
(Appointment of Subcommittees, Project Teams and RLP Alliance Managers).

1.2.151. “RLP Collaboration” means the collaboration of the Parties in the
Development, Manufacture and Commercialization of Regional Licensed Products
under these Regional License Terms.

1.2.152. “RLP Clinical Supply Agreements” means, collectively, the ALN-TTR02
Clinical Supply Agreement and each other clinical supply agreement entered into
between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement
(Collaboration Product Supply Agreements) pursuant to which Alnylam will provide
clinical supplies of a specified Regional Licensed Product to Genzyme.

1.2.153. “RLP Commercial Supply Agreements” means, collectively, the ALN-TTR02
Commercial Supply Agreement and each other commercial supply agreement entered
into between Alnylam and Genzyme as described in Section 6.2 of the Master
Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam
will provide commercial supplies of a specified Regional Licensed Product to
Genzyme.

1.2.154. “RLP Supply Agreements” means, collectively, the RLP Clinical Supply
Agreements and the RLP Commercial Supply Agreements.

1.2.155. “Regional License Terms” means this Appendix and the terms of the
Master Agreement to the extent applicable to Regional Licensed Products.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

20

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REGIONAL LICENSE TERMS

 

1.2.156. “Royalty Term” has the meaning set forth in Section 7.2.2 (Royalty
Term).

1.2.157. “Safety Concern” has the meaning set forth in the Master Agreement.

1.2.158. “Secondary Indication” has the meaning set forth in the Master
Agreement.

1.2.159. “Secondary Indication Study” has the meaning set forth in the Master
Agreement.

1.2.160. “Serious Adverse Event” has the meaning set forth in the Master
Agreement.

1.2.161. “siRNA” has the meaning set forth in the Master Agreement.

1.2.162. “SPCs” has the meaning set forth in Section 9.5 (Patent Term
Extensions).

1.2.163. “Sublicensee” means a Third Party to whom a Party grants a sublicense
under any Alnylam Technology or Genzyme Technology, as the case may be, to
Develop, Manufacture or Commercialize a Regional Licensed Product in the Field
pursuant to Section 6.1.4 (Sublicensing Terms) or Section 6.2.4 (Sublicensing
Terms).

1.2.164. “Term” has the meaning set forth in Section 10.1 (Term).

1.2.165. “Territory” means (a) with respect to Alnylam, the Alnylam Territory
and (b) with respect to Genzyme, the Genzyme Territory.

1.2.166. “Third Party” has the meaning set forth in the Master Agreement.

1.2.167. “Third Party Collaboration Agreement” has the meaning set forth in
Section 5.8 (Alnylam Third Party Partner).

1.2.168. “Third Party License Payment” has the meaning set forth in the Master
Agreement.

1.2.169. “Third Party Partner” has the meaning set forth in Section 5.8 (Alnylam
Third Party Partner).

1.2.170. “Trademark” has the meaning set forth in the Master Agreement.

1.2.171. “TTR” has the meaning set forth in the Master Agreement.

1.2.172. “Un-Blocking Genzyme In-License” has the meaning set forth in the
Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

21

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REGIONAL LICENSE TERMS

 

1.2.173. “United States” means the United States of America and its territories,
possessions and commonwealths.

1.2.174. “Valid Claim” means a claim of: (a) an issued and unexpired patent,
which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or
held unenforceable or invalid by an unappealable decision of a court or other
governmental agency of competent jurisdiction, or has not been appealed within
the time allowed for appeal, or by an appealed decision of a court or other
governmental agency of competent jurisdiction where the appeal has been pending
for more than [***] years (unless and until such decision is subsequently
overturned on appeal) and which has not been abandoned, disclaimed, denied or
admitted to be invalid or unenforceable through reissue, re-examination or
disclaimer or otherwise; or (b) a patent application that has been pending less
than [***] years from the date of filing of the earliest patent application from
which such patent application claims priority, which claim has not been
cancelled, withdrawn or abandoned or finally rejected by an administrative
agency action from which no appeal can be taken.

1.2.175. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and
Amending Global Development Plans and Global Development Budgets).

1.2.176. “[***] Budget” has the meaning set forth in Section 2.2.2.3(a)
(Managing and Amending Global Development Plans and Global Development Budgets).

1.2.177. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and
Amending Global Development Plans and Global Development Budgets).

1.2.178. “[***] Budget” has the meaning set forth in Section 2.2.2.3(a)
(Managing and Amending Global Development Plans and Global Development Budgets).

2. DEVELOPMENT COLLABORATION

2.1. Overview. The Parties will collaborate in the Development of each Regional
Licensed Product pursuant to the applicable Global Development Plan, Alnylam
Territory Development Plan and Genzyme Territory Development Plan. The PJSC will
have primary responsibility for the oversight of the Global Development Plans.
Alnylam will have primary responsibility for execution of those Global
Development Plans, and sole responsibility for the Alnylam Territory Development
Plans, as described below. Genzyme will have sole responsibility for the Genzyme
Territory Development Plans, as described below.

2.2. Development Plans.

2.2.1. Global Development Strategy. For each Regional Licensed Product, the key
Development principles for such Regional Licensed Product will be set forth in a
written summary of the global Development strategy for such Licensed Product,
including the indication(s) (including Secondary Indications), for which
Regulatory Approval will be sought (each, a “Global Development Strategy”). The
initial Global Development Strategy for ALN-

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

22

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REGIONAL LICENSE TERMS

 

TTR02 will be provided by Alnylam to Genzyme within [***] days after the
Effective Date, agreed upon by the PJSC within [***] days after the Effective
Date, and then attached hereto as Schedule 2.2.1-1. The initial Global
Development Strategy for each subsequent Regional Licensed Product will be
included in the Option Data Package for such Regional Licensed Product, mutually
agreed upon by the Parties prior to Genzyme’s exercise of the Regional Option
with respect to such Regional Licensed Product in accordance with the Master
Agreement, and then attached hereto as Schedules 2.2.1-2, 2.2.1-3 and so forth.
Any Global Development Strategy may be amended from time to time only by the
PJSC responsible for the applicable Regional Licensed Product.

2.2.2. Global Development Plan.

2.2.2.1. Global Development Plans. For each Regional Licensed Product, the
Development activities that are necessary or useful to be undertaken for such
Regional Licensed Product to achieve initial Regulatory Approval for each of the
indications to be sought pursuant to the Global Development Strategy in at least
all of the MMCs in a proximal fashion (including the design of necessary or
useful Clinical Studies) will be set forth in reasonable detail in a written
work plan and time table (each, a “Global Development Plan”). Alnylam will
provide a draft of the initial Global Development Plan for ALN-TTR02 to Genzyme
on or before [***], and within [***] days thereafter the PJSC will review,
update and approve such Global Development Plan and it will be attached hereto
as Schedule 2.2.2.1-1. The initial Global Development Plan for each subsequent
Regional Licensed Product will be included in the Option Data Package for such
Regional Licensed Product provided by Alnylam to Genzyme under the Master
Agreement, and within [***] days of the Implementation Date for such Regional
Licensed Product the PJSC responsible for such Regional Licensed Product will
review, update and approve such Global Development Plan and it will be attached
hereto as Schedules 2.2.2.1-2, 2.2.2.1-3 and so forth. Each Global Development
Plan must, at all times, be consistent with the Global Development Strategy and
include all Development activities that (i) are reasonably necessary to obtain
initial Regulatory Approval of the applicable Regional Licensed Product in each
MMC for each of the indications, including Secondary Indications, to be sought
pursuant to the Global Development Strategy in a proximal fashion and
(ii) Secondary Indication Studies included in the initial Global Development
Plan or added pursuant to Section 2.2.2.6 (Secondary Indications) (all such
Development activities collectively, the “Global Development Activities”);
provided, however, that, unless otherwise agreed by the Parties, in no event
will any Global Development Plan include (a) any Post-Marketing Study or
Secondary Indication Study, except for Secondary Indication Studies included in
the initial Global Development Plan or added to a Global Development Plan
pursuant to Section 2.2.2.6 (Secondary Indications), (b) any Development
activity solely intended or designed to achieve initial Regulatory Approval in a
country other than an MMC or (c) after the last Regulatory

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

23

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REGIONAL LICENSE TERMS

 

Approval in all MMCs, any Development activity that is useful solely to achieve
initial Regulatory Approval in a country that is not an MMC, except for
Secondary Indication Studies included in the initial Global Development Plan or
added to a Global Development Plan pursuant to Section 2.2.2.6 (Secondary
Indications). Each Global Development Plan will allocate responsibility for the
performance of each Global Development Activity to one of the Parties. The time
table for the completion of the Global Development Activities included in each
Global Development Plan will be designed to obtain initial Regulatory Approval
of the applicable Regional Licensed Product in each MMC in a proximal fashion
and as soon as reasonably possible. The terms of, and Development activities set
forth in, each Global Development Plan will at all times be designed to be in
compliance with all applicable Laws and in accordance with professional and
ethical standards customary in the pharmaceutical industry.

2.2.2.2. Global Development Budgets. Each Global Development Plan will contain a
[***] year rolling budget for the probable Global Development Activities to be
performed during [***], and a forecast of the budgets for each subsequent
Calendar Year thereafter through completion of all Global Development Activities
set forth in any such Global Development Plan, provided that each initial Global
Development Plan will also include such a budget for the partial Calendar Year
commencing as of the date of such Global Development Plan and ending December 31
of such Calendar Year (each such [***] budget plus any such partial Calendar
Year is a “Global Development Budget”). Each Global Development Budget will be
updated annually by the PJSC responsible for the applicable Regional Licensed
Product in accordance with Section 2.2.2.3 (Managing and Amending Global
Development Plans and Global Development Budgets). The initial Global
Development Budget for a Regional Licensed Product, and each update thereto,
will be prepared by the PJSC in accordance with[***]

(a) [***];

(b) [***]

(c) [***].

Alnylam will enter such Global Development Budget in a template that the Parties
agree is efficient for both Parties to communicate such information.

2.2.2.3. Managing and Amending Global Development Plans and Global Development
Budgets. The PJSC responsible for a Regional Licensed Product will update and
amend the applicable Global Development Plan from time-to-time as it deems
necessary and, until such time as no further Global Development Activities are
occurring or expected to occur with respect to such Regional Licensed Product,
the PJSC will update such Global Development Plan annually as follows:

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

24

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REGIONAL LICENSE TERMS

 

(a) No later than [***] of each Calendar Year, the applicable PJSC will prepare
an updated draft of the Global Development Plan, which shall contain a proposed
Global Development Budget covering [***].

(b) No later than [***] of each Calendar Year, the applicable PJSC will review
and tentatively approve an updated Global Development Plan and Global
Development Budget, and such updated Global Development Plan and Global
Development Budget will become effective upon such tentative approval by the
PJSC, provided that the Parties acknowledge and agree that each Party’s internal
process for receiving final approval of such Global Development Plan and Global
Development Budget from its Board of Directors and/or senior management may
occur after [***] (but, in any event, before [***]) and such Global Development
Plan and Global Development Budget will not become final unless and until such
approvals are obtained [***].

2.2.2.4. [***] Adjustments and Compensation. In addition to the Global
Development Budget for each Regional Licensed Product, Alnylam shall prepare,
and submit to the PJSC for approval, three Development budget(s) for each
Regional Licensed Product, the first of which shall cover the period commencing
as of the Implementation Date for such Regional Licensed Product and ending on
the anticipated date of initiation of the first Phase III Study for such
Regional Licensed Product (as further described below, each a “Phase 2 Budget”),
the second of which shall cover the period commencing as of the anticipated date
of initiation of the first Phase III Study for such Regional Licensed Product
and ending on the anticipated date of filing of an application for Regulatory
Approval of such Regional Licensed Product in the first MMC (as further
described below, each a “Phase 3 Budget”), and the third of which shall cover
the period commencing as of the anticipated date of filing of an application for
Regulatory Approval for such Regional Licensed Product in the first MMC and
ending on the date that there are no further Development activities to performed
under the Global Development Plan for such Regional Licensed Product (as further
described below, each a “Post-Phase 3 Budget”), provided that if the period
covered by the Post-Phase 3 Budget is longer than three (3) years, Alnylam shall
prepare a new Post-Phase 3 Budget to cover each subsequent three (3) year
period. Each Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget shall be
[***].

(a) Preparation of Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget. Each
Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget submitted to the PJSC
will be prepared by Alnylam in accordance with [***].

(b) [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

25

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REGIONAL LICENSE TERMS

 

(c) Delivery and Effectiveness of Phase 2 Budget, Phase 3 Budget and Post-Phase
3 Budget.

(i) Alnylam shall include a Phase 2 Budget [***] with the initial Global
Development Plan for each Regional Licensed Product. Such Phase 2 Budget [***]
shall become effective, subject to adjustment in accordance with the foregoing
Section 2.2.2.4(b), upon the Implementation Date for the relevant Regional
Licensed Product.

(ii) Alnylam shall provide to the PJSC for approval a Phase 3 Budget [***] for
each Regional Licensed Product no less than [***] days prior to the anticipated
initiation of the first Phase III Study for each Regional Licensed Product,
along with top line data and data tables from any completed Phase II Studies and
other completed non-clinical studies (including all Serious Adverse Event and
Safety Concern data), as well as a draft of the end of Phase II briefing
package, in each case to the extent not previously provided or made available to
Genzyme (such budget, data and draft, collectively the “End of Phase II
Package”). Such Phase 3 Budget [***] shall become effective at the end of such
[***] day period.

(iii) Alnylam shall provide to the PJSC for approval a Post-Phase 3 Budget [***]
for each Regional Licensed Product no less than [***] days prior to the
anticipated completion of the first Phase III Study for each Regional Licensed
Product. Such Post-Phase 3 Budget [***] shall become effective upon approval by
the PJSC.

(d) [***].

2.2.2.5. Oversight of the Global Development Plans. The PJSC for ALN-TTR02 shall
create a Joint Clinical Operations Team (“JCOT”), with two (2) representatives
from each Party, to review, coordinate and provide such PJSC with feedback
regarding:

(a) the implementation of the Global Development Plan for ALN-TTR02, including
the implementation and management of the Global Development Activities set forth
in such Global Development Plan;

(b) the performance of any Clinical Study included in such Global Development
Activities (a “Global Clinical Study”) by any CRO retained by a Party to perform
such Global Clinical Study, against the criteria and timelines in such Global
Development Plan; and

(c) such other activities as the PJSC deems shall be the responsibility of the
JCOT.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

26

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REGIONAL LICENSE TERMS

 

Unless otherwise agreed by the Parties, each Party’s representatives on the JCOT
must be employees of such Party. The JCOT shall meet from time-to-time, in
person or via teleconference, as it shall reasonably determine.

2.2.2.6. Secondary Indications.

(a) Additional Development Proposals. If a Party desires to conduct a Secondary
Indication Study of a Regional Licensed Product for the purpose of seeking
Regulatory Approval to market such Regional Licensed Product for a Secondary
Indication, such Party (the “Proposing Party”) will submit to the PJSC
responsible for such Regional Licensed Product a proposal to add such Secondary
Indication Study to the applicable Global Development Plan (an “Additional
Development Proposal”). Each Additional Development Proposal will describe in
reasonable detail the Secondary Indication Study(ies) that the Proposing Party
desires to conduct, including a synopsis of the trial, the proposed enrollment
criteria, number of patients to be included, endpoints to be measured, and
statistical design and powering (the “Additional Development Activities”), as
well as a proposed timeline and budget and an analysis of the business
opportunity and revenue potential for such Additional Development Activities and
Secondary Indication.

(b) PJSC Decision Regarding Additional Development Activities. The PJSC shall
approve or reject an Additional Development Proposal within [***] days after
receipt thereof from the Proposing Party as set forth in this Section 2.2.2.6.

(i) If the PJSC approves an Additional Development Proposal, upon such an
approval, the applicable Global Development Plan will be amended to include the
Additional Development Activities, including the proposed timeline and budget
for such Additional Development Activities, set forth in such Additional
Development Proposal (as may be amended by the PJSC) upon such approval. Any
Additional Development Activities included in a Global Development Plan pursuant
to this Section 2.2.2.6(b) shall be deemed to be Global Development Activities
for all purposes under these Regional License Terms (including the definition of
Global R&D Costs).

(ii) If the PJSC fails to approve an Additional Development Proposal, upon such
a failure, the Secondary Indication Study proposed in the Additional Development
Proposal will not be deemed a Global Development Activity for any purpose under
these Regional License Terms, and Sections 2.2.2.6(c) (Independent Performance
of Additional Development Activities) and 2.2.2.6(d) (Opt-In for Additional
Development Activities) shall apply.

(c) Independent Performance of Additional Development Activities.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

27

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REGIONAL LICENSE TERMS

 

(i) If the PJSC fails to approve for inclusion in the Global Development Plan an
Additional Development Proposal proposed by Alnylam for a Secondary Indication
Study(ies) in the Alnylam Territory for a Regional Licensed Product, Alnylam
may, upon notice to Genzyme, conduct the proposed Secondary Indication
Study(ies) at its own expense; [***].

(ii) If, after receipt of Regulatory Approval for a Regional Licensed Product in
an Alnylam Territory MMC, the PJSC fails to approve for inclusion in the Global
Development Plan an Additional Development Proposal proposed by Genzyme for a
Secondary Indication Study(ies) in the Genzyme Territory for such Regional
Licensed Product, Genzyme may, upon notice to Alnylam, conduct the proposed
Secondary Indication Study(ies) at its own expense [***].

(iii) Notwithstanding anything in Section 3.4 (Right of Reference) to the
contrary, if the PJSC does not approve an Additional Development Proposal,
unless and until the Non-Proposing Party delivers an Additional Development
Opt-In Notice with respect to such Additional Development Activity, as described
in Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities), the
Non-Proposing Party will not have any rights under Section 3.4 (Right of
Reference) with respect to any information or data generated from any Secondary
Indication Study that was the subject of the unapproved Additional Development
Proposal. For avoidance of doubt, if the PJSC rejects for inclusion in all
Development Plans an Additional Development Proposal for a Secondary Indication
Study(ies) proposed by Genzyme prior to receipt of Regulatory Approval for a
Regional Licensed Product in an MMC in the Alnylam Territory, then Genzyme shall
not have any right to proceed with the Secondary Indication Study(ies) described
therein unless and until the PJSC determines that such Additional Development
Activities should be permitted or until otherwise permitted under this
Section 2.2.2.6(c)(iii).

(d) Opt-In for Additional Development Activities. In the event that the
Proposing Party conducts Secondary Indication Study(ies) pursuant to
Section 2.2.2.6(c) (Independent Performance of Additional Development
Activities), the Non-Proposing Party may elect, in its discretion and upon
written notice to the Proposing Party no later than [***] days after the date on
which the [***] (an “Additional Development Opt-In Notice”), to opt in with
respect to any Secondary Indication Study that was the subject of such
Additional Development Proposal that the Proposing Party elected to conduct in
accordance with Section 2.2.2.6(c) (Independent Performance of Additional
Development Activities), and then (i) such Secondary Indication Study shall be
deemed to be a Global Development Activity under the Global Development Plan for
the applicable Regional Licensed Product from and after the date on which such
Additional Development Opt-In Notice is received by the Proposing Party (the
“Additional Development Opt-In Date”); (ii) the then-current plan and budget of
the Proposing Party with respect to such Secondary Indication Study shall be
deemed to be included within, and part of, the Global Development Plan for such
Regional Licensed Product as of the Additional Development Opt-In Date, and
shall control with respect to such

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Secondary Indication Study unless and until an amendment to the Global
Development Plan providing for a different or modified plan and budget is
approved by the applicable PJSC; and (iii) the Non-Proposing Party will have all
rights granted to it under Section 3.4 (Right of Reference) with respect to the
information and data generated from such Secondary Indication Study as if such
Secondary Indication Study was conducted under the Global Development Plan for
such Regional Licensed Product [***].

2.2.2.7. Additional Clinical Study Sites in Genzyme Territory. With respect to
any Clinical Study in a Global Development Plan, at Genzyme’s request, Alnylam
will add a study site in a country in the Genzyme Territory, [***]. If Alnylam
adds such a study site at Genzyme’s request, Genzyme will reimburse Alnylam for
any incremental R&D FTE Costs or Regional Out-of-Pocket Costs required as a
result of adding such study site. Genzyme will pay Alnylam such reimbursement
within [***] days of receipt of an invoice from Alnylam.

2.2.3. Alnylam Territory Development Plan. The Development activities other than
Global Development Activities to be undertaken with respect to each Regional
Licensed Product by or on behalf of Alnylam with respect to the Alnylam
Territory, including Secondary Indication Studies and Post-Marketing Studies,
will be set forth in a written work plan and time table (each, an “Alnylam
Territory Development Plan”). Each Alnylam Territory Development Plan shall be
consistent with the requirements of the Global Development Strategy. Alnylam
will prepare the Alnylam Territory Development Plan for ALN-TTR02 and then
promptly thereafter will submit it to the PJSC for review and approval.
Following approval by the PJSC, it will then be attached to the PJSC meeting
minutes and deemed to be attached hereto as Schedule 2.2.2.6(d)-1. The initial
Alnylam Development Plan for each subsequent Regional Licensed Product will be
prepared by Alnylam and following review and approval by the PJSC, will then be
attached to the PJSC meeting minutes and deemed to be attached hereto as
Schedules 2.2.2.6(d)-2, 2.2.2.6(d)-3 and so forth on the Implementation Date for
such Regional Licensed Product. Each Alnylam Territory Development Plan will set
forth a rolling written work plan and time table with respect to the Development
of and Secondary Indication Studies for the applicable Regional Licensed Product
from the Implementation Date until the later of (a) two (2) years from date of
such plan, and (b) receipt of Regulatory Approval for such Regional Licensed
Product. Each Alnylam Territory Development Plan shall subsequently be updated
by Alnylam from time-to-time at least once each Calendar Year not later than
September 1 until such time as no further Development or Secondary Indication
Studies are occurring or expected to occur with respect to the applicable
Regional Licensed Product. Alnylam will present each Alnylam Territory
Development Plan and any proposed amendments thereto to the applicable PJSC at
least [***] days in advance of implementation of the Alnylam Territory
Development Plan, and following review and approval by the PJSC, will then be
attached to the PJSC meeting minutes and deemed to be attached hereto as the
applicable Schedule. In addition, notwithstanding anything to the contrary in
these Regional License Terms, Alnylam shall not conduct any Clinical Study for a
Regional Licensed Product in a country in the Genzyme Territory after receipt of
initial Regulatory Approval of such Regional Licensed Product in such country in
the Genzyme Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.2.4. Genzyme Territory Development Plan. Other than Global Development
Activities, all Development activities to be undertaken with respect to each
Regional Licensed Product by or on behalf of Genzyme with respect to the Genzyme
Territory, including Secondary Indication Studies and Post-Marketing Studies,
will be set forth in a written work plan and time table (each, a “Genzyme
Territory Development Plan”). Each Genzyme Territory Development Plan shall be
consistent with the requirements of the then-current Global Development Strategy
(provided that Alnylam did not exercise its deciding vote with respect thereto
pursuant to Section 5.6.3 ([***]). Prior to [***], Genzyme will prepare the
Genzyme Territory Development Plan for ALN-TTR02 and then promptly thereafter
will submit it to the PJSC for review and approval. Following review and
approval by the PJSC, it will then be attached to the PJSC meeting minutes and
deemed to be attached hereto as Schedule 2.2.4-1. The initial Genzyme Territory
Development Plan for each subsequent Regional Licensed Product will be prepared
by Genzyme and following review and approval by the PJSC, will then be attached
to the PJSC meeting minutes and deemed to be and attached hereto as Schedules
2.2.4-2, 2.2.4-3 and so forth. Each Genzyme Territory Development Plan will set
forth a rolling written work plan and time table with respect to the Development
of and Secondary Indication Studies for the applicable Regional Licensed Product
from the Implementation Date until the later of (a) two (2) years from date of
such plan, and (b) receipt of Regulatory Approval for such Regional Licensed
Product. Each Genzyme Territory Development Plan shall subsequently be updated
by Genzyme from time-to-time at least once each Calendar Year not later than
[***] until such time as no further Development or Secondary Indication Studies
are occurring or expected to occur with respect to the applicable Regional
Licensed Product. Genzyme will present each Genzyme Territory Development Plan
and any proposed amendments thereto to the applicable PJSC at least [***] days
in advance of implementation of the Genzyme Territory Development Plan, and
following review and approval by the PJSC, will then be attached to the PJSC
meeting minutes and deemed to be attached hereto as the applicable Schedule. In
addition, notwithstanding anything to the contrary in these Regional License
Terms, Genzyme shall not conduct any Clinical Study for a Regional Licensed
Product in a country in the Alnylam Territory after receipt of initial
Regulatory Approval of such Regional Licensed Product in such country in the
Alnylam Territory.

2.3. Responsibilities for Development Activities and Costs.

2.3.1. Global Development.

2.3.1.1. Generally. With respect to each Regional Licensed Product, except to
the extent that the Global Development Plan for such Regional Licensed Product
allocates responsibility for any Global Development Activities to Genzyme,
Alnylam shall be primarily responsible for the global Development of such
Regional Licensed Product and all Development activities under such Global
Development Plan. Each Party and its Affiliates shall conduct each

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Global Development Activity for which it is responsible in sound scientific
manner and in compliance with applicable Law. Notwithstanding anything to the
contrary in these Regional License Terms, neither Party will be obligated to
undertake or continue any Global Development Activity if (a) such Party
reasonably determines that performance of such Global Development Activity would
violate applicable Law; or (b) with respect to any Global Clinical Study, (i) a
Regulatory Authority or independent safety data review board for such Global
Clinical Study has required or recommended termination or suspension of such
Global Clinical Study or (ii) such Party believes in good faith that termination
or suspension of such Global Clinical Study is warranted because of safety or
tolerability risks or the lack of suitable risk benefit ratio to the study
subjects. In the event that a Party determines not to undertake or continue any
Global Development Activity in accordance with the immediately preceding
sentence, such Party shall promptly notify the other Party of such
determination, and shall use all reasonable efforts to notify and consult with
the other Party prior to making such determination.

2.3.1.2. Global R&D Costs.

(a) With respect to ALN-TTR02, Alnylam shall be responsible for eighty percent
(80%) of all Global R&D Costs and Genzyme shall be responsible for twenty
percent (20%) of all Global R&D Costs, in each case for Global Development
Activities that occur on or after [***], and amounts specified in clauses
(ii) and (iii) of Section 2.3.1.2(c) below, if any. Alnylam shall be responsible
for one-hundred percent (100%) of Global R&D Costs for Global Development
Activities for ALN-TTR02 that occur prior to [***], except for amounts specified
in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(b) With respect to each other Regional Licensed Product, Alnylam shall be
responsible for eighty percent (80%) of all Global R&D Costs and Genzyme shall
be responsible for twenty percent (20%) of all Global R&D Costs, in each case
for Global Development Activities that occur after the later of (i) [***] and
(ii) the earlier of (A) the Implementation Date for such Regional Licensed
Product and (B) the date of the dosing of the first patient in the first
Clinical Study initiated subsequent to the Human POP Study for such Regional
Licensed Product (such later date, the “Global R&D Cost Opt-In Date”), and
amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.
Alnylam shall be responsible for one-hundred percent (100%) of Global R&D Costs
for Global Development Activities for any such Regional Licensed Product that
occur prior to the Global R&D Cost Opt-In Date, except for amounts specified in
clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(c) The Global R&D Costs to be shared by the Parties pursuant to Sections
2.3.1.2(a) and 2.3.1.2(b) above shall only include amounts that are within one
or more of the following four (4) categories:

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(i) [***];

(ii) [***];

(iii) [***]

(iv) [***].

(d) For clarity, Global R&D Costs to be shared by the Parties pursuant to
2.3.1.2(a) and 2.3.1.2(b) shall exclude any amounts paid after the Global R&D
Cost Opt-In Date to Third Parties with respect to services rendered or materials
procured in connection with the conduct of any Clinical Study or other
Development activities, in either case, that is completed prior to the Global
R&D Cost Opt-In Date.

(e) Global R&D Costs for each Regional Licensed Product shall initially be borne
by the Party incurring the cost or expense. Each Party will calculate and
maintain records of Global R&D Costs incurred by it and its Affiliates with
respect to a Regional Licensed Product and, within [***] days following the end
of each Calendar Quarter, each Party shall submit to the other a report
detailing the Global R&D Costs incurred by it and its Affiliates during such
Calendar Quarter, and, if requested, reasonable supporting documentation will be
provided (a “Global R&D Costs Report”). In addition, each Party shall use good
faith efforts to notify the other Party of any material Global R&D Costs
incurred by such Party during such Calendar Quarter within [***] days after the
end of such Calendar Quarter. The Party that incurs more than its share of the
total actual Global R&D Costs with respect to a Regional Licensed Product during
any Calendar Quarter shall be paid by the other Party an amount of cash
sufficient to reconcile to its agreed percentage of Global R&D Costs for such
Regional Licensed Product, which payment shall be made within [***] days after
delivery of the Global R&D Cost Reports for such Calendar Quarter.
Notwithstanding the foregoing, if following receipt of a Global R&D Costs Report
a Party (the “Disputing Party”) disputes any Global R&D Costs under such Global
R&D Costs Report, it shall have [***] days to notify the other Party (the
“Non-Disputing Party”). Upon receiving such notice from the Disputing Party, the
Non-Disputing Party shall, at the reasonable request of the Disputing Party,
provide to the Disputing Party supporting documentation relating to any such
disputed Global R&D Costs. The Parties agree to use reasonable efforts to
resolve any such dispute as soon as reasonably practicable, and any undisputed
portion of Global R&D Costs in such Global R&D Costs Report shall be paid within
[***] days after delivery of such Global R&D Costs Report. Once the Parties have
resolved such dispute, any disputed amounts still owed by either Party will be
paid within [***] days of resolution of such dispute.

(f) [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(g) Notwithstanding anything to the contrary in these Regional License Terms,
the Parties shall not share Global R&D Costs incurred in a Calendar Year with
respect to Global Development Activities for a Regional Licensed Product to the
extent such Global R&D Costs exceed [***] of the amounts included in the final
[***] Budget that was applicable to such Current Calendar Year (the amount in
excess of such [***] limit is the “Excess Global R&D Costs”). One hundred
percent (100%) of any Excess Global R&D Costs for such Regional Licensed Product
will be borne by the Party that incurred such Excess Global R&D Costs.

2.3.2. Genzyme Development. Except with respect to Global R&D Costs (which shall
be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)),
Genzyme shall be responsible for one hundred percent (100%) of all costs and
expenses incurred with respect to Development activities that are conducted by
Genzyme pursuant to any Genzyme Territory Development Plan. Genzyme will conduct
all Development of each Regional Licensed Product for the Genzyme Territory
solely in accordance with the applicable Global Development Plan and Genzyme
Territory Development Plan, as such Global Development Plan and Genzyme
Territory Development Plan may be amended in accordance with these Regional
License Terms, and in sound scientific manner and in compliance with applicable
Law.

2.3.3. Alnylam Development. Except with respect to Global R&D Costs (which shall
be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)),
Alnylam shall be responsible for one hundred percent (100%) of all costs and
expenses incurred with respect to Development activities that are conducted by
Alnylam pursuant to any Alnylam Territory Development Plan. Alnylam will conduct
all Development of each Regional Licensed Product for the Alnylam Territory
solely in accordance with the applicable Global Development Plan and Alnylam
Territory Development Plan, as such Global Development Plan and Alnylam
Territory Development Plan may be amended in accordance with these Regional
License Terms, and in sound scientific manner and in compliance with applicable
Law.

2.4. Diligence.

2.4.1. Genzyme Diligence. With respect to each Regional Licensed Product,
Genzyme will use Commercially Reasonable Efforts to [***].

2.4.2. Alnylam Diligence. With respect to each Regional Licensed Product,
Alnylam will use Commercially Reasonable Efforts to (a) Develop such Regional
Licensed Product and obtain Regulatory Approval therefor by the FDA in the U.S.
or by the EMA in the European Union; (b) perform the Global Development
Activities allocated to it under the Global Development Plan for such Regional
Licensed Product; and (c) perform the Development activities set forth in the
Alnylam Territory Development Plan for such Regional Licensed Product, as such
Alnylam Territory Development Plan may be amended in accordance with these
Regional License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.5. Records; Reports; Information Sharing.

2.5.1. Development Activities Reports. Each Party will periodically provide to
the PJSC responsible for a Regional Licensed Product, but in no event less than
on a Calendar Quarter basis, or more frequently as reasonably requested by the
other Party, an update regarding Development activities conducted by or on
behalf of such Party with respect to such Regional Licensed Product, as well as
any Secondary Indication Studies and Post-Marketing Studies conducted by or on
behalf of such Party with respect to such Regional Licensed Product. The Parties
will periodically report to the PJSC responsible for a Regional Licensed
Product, but in no event less than on a Calendar Quarter basis, regarding their
respective activities conducted under the Global Development Plan for such
Regional Licensed Product. In addition, each Party will promptly share with the
other Party all material developments and information that it comes to possess
relating to the Development of any Regional Licensed Products, including Safety
Concerns and study reports and data generated from Clinical Studies of such
Regional Licensed Product.

2.5.2. Scientific Records. Each Party will maintain scientific records, in
sufficient detail and in sound scientific manner appropriate for patent and
regulatory purposes, which will fully and properly reflect all work done and
results achieved in the performance of the Development activities and Secondary
Indication Studies with respect to Regional Licensed Products by such Party.

2.5.3. Information Exchange and Development Assistance. Until the expiration or
termination of the final Global Development Plan, upon the reasonable request of
the other Party, each Party shall provide to the other Party, without additional
compensation (except as provided in Section 6.5 of the Master Agreement
(Transfer of Manufacturing Know-How)) and in a commercially reasonable format,
Know-How Controlled by such Party and/or its Related Parties that is licensed to
the other Party under these Regional License Terms (i.e. Know-How included in
Genzyme Technology for Genzyme and Know-How included in Alnylam Technology for
Alnylam) to the extent that it is reasonably necessary or useful for Developing
a Regional Licensed Product in the requesting Party’s Territory or for obtaining
or maintaining Regulatory Approval for a Regional Licensed Product in the
requesting Party’s Territory, including copies of (a) all scientific information
and data related to such Regional Licensed Product (including all data made,
collected or otherwise generated in the conduct of any pre-clinical studies,
Clinical Studies, Secondary Indication Studies or early access/named patient
programs for the Regional Licensed Products, as well as CMC information), and
(b) protocols and investigator brochures, in each case, that are reasonably
necessary for the other Party (or its Related Parties) to perform its
obligations or exploit its rights under these Regional License Terms with
respect to such Regional Licensed Product. Notwithstanding the foregoing,
Genzyme shall have no obligation to transfer or disclose to Alnylam any Know-How
included in the Genzyme Manufacturing IP; provided, however, that if Genzyme
elects, in its sole discretion, to transfer or disclose any such Know-How to
Alnylam in writing, it shall be “Genzyme Disclosed Manufacturing Know-How” under
these Regional License Terms and licensed to Alnylam in accordance with
Section 6.2.3 (License to Genzyme Disclosed Manufacturing Know-How).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.5.4. Personnel. Each Party may request, through the PJSC or the other Party’s
RLP Alliance Manager responsible for a Regional Licensed Product, that the other
Party reasonably make available for consultation regarding the Development of
such Regional Licensed Product certain of its employees engaged in Development
activities and Secondary Indication Studies with respect to such Regional
Licensed Product. The PJSC or the RLP Alliance Managers responsible for a
Regional Licensed Product will reasonably coordinate, upon reasonable notice
during normal business hours and at their respective places of employment,
consultation between the Parties on the progress of the Development and
Secondary Indication Studies for such Regional Licensed Product.

2.5.5. Confidentiality. All information exchanged by the Parties under this
Section 2.5 will be deemed to be Confidential Information of the disclosing
Party and maintained in accordance with Section 7 of the Master Agreement
(Confidentiality and Publication).

2.6. Third Parties.

2.6.1. The Parties shall be entitled to utilize the services of Third Parties to
perform their respective Development and Manufacturing activities under these
Regional License Terms, provided that (a) each Party shall require that such
Third Party operates in a manner consistent with these Regional License Terms,
(b) each Party shall remain at all times fully liable for its respective
responsibilities and (c) the Parties will make reasonable efforts to share,
through the PJSC, information regarding any prior experience with specific CROs
that are anticipated to be engaged to perform work under the Global Development
Plan. Each Party shall require that any Third Party agreement entered into
pursuant to this Section 2.6.1 include confidentiality and non-use provisions
that are no less stringent than those set forth in Section 7 of the Master
Agreement (Confidentiality and Publication) and shall obtain ownership of,
and/or a fully sublicensable license under and to, any Know-How and Patent
Rights that are developed by such Third Party in the performance of such
agreement and are reasonably necessary or useful to Develop, Manufacture and/or
Commercialize Regional Licensed Products in the Field. The Party utilizing the
services of a Third Party service provider shall be solely responsible for
direction of and communications with such Third Party, but such Party shall
provide the other Party with reasonably detailed updates regarding any such
activities from time to time.

2.6.2. [***].

3. REGULATORY MATTERS

3.1. Regulatory Filings and Interactions.

3.1.1. Responsibilities.

3.1.1.1. Pursuant to the Global Development Plan for a Regional Licensed Product
and, except as otherwise provided in such Global Development Plan, except as
otherwise set forth in Sections 3.1.1.2 and 3.2 (EMA Regulatory Strategy) below,
each Party will be solely responsible for all regulatory matters relating to
such Regional Licensed Product in its Territory and will own all INDs, NDAs and
related regulatory documents submitted to the applicable Regulatory

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Authorities in its Territory with respect to such Regional Licensed Product,
excluding any drug master files maintained by or on behalf of Alnylam, which
shall be and remain Alnylam’s sole responsibility. Notwithstanding the
foregoing, the Parties acknowledge that Alnylam shall continue to own all INDs,
NDAs and related regulatory documents for ALN-TTR02 in the Genzyme Territory and
the provisions of this Section 3.1.1 and Section 3.1.3 (Regulatory Meetings)
shall not apply. Within [***] days after the Implementation Date for ALN-TTR02,
the Parties will agree to such other arrangements as are appropriate for such
regulatory documents. At Genzyme’s request, following the Implementation Date
for a Regional License Product other than ALN-TTR02, Alnylam will promptly
assign and transfer to Genzyme all INDs, NDAs and other regulatory documentation
submitted to any Regulatory Authority in the Genzyme Territory with respect to
such Regional Licensed Product that is in the possession and control of Alnylam,
and each Party will submit to the applicable Regulatory Authority all filings,
letters and other documentation necessary to effect such assignment and transfer
no later than [***] days after such request for such Regional Licensed Product,
in each case, excluding any drug master files maintained by or on behalf of
Alnylam. Each Party will have the sole right to (i) oversee, monitor and
coordinate all regulatory actions, communications and filings with, and
submissions to, each Regulatory Authority in its Territory with respect to such
Regional Licensed Product; (ii) interface, correspond and meet with each
Regulatory Authority in its Territory with respect to such Regional Licensed
Product, and (iii) seek and maintain all regulatory filings in its Territory
with respect to such Regional Licensed Product.

3.1.1.2. Notwithstanding the foregoing, for every Clinical Study conducted under
a Global Development Plan, Alnylam will draft the protocol, develop the IND
strategy, and file INDs globally, including in the Genzyme Territory, after
input and review by Genzyme, and Alnylam will use reasonable efforts to address
any concerns raised by Genzyme in connection with such activities. Unless
otherwise agreed by the Parties, on a country-by-country basis, following the
acceptance or approval of the IND and the first dosing of the first patient in
the first Phase III Study of the relevant Regional Licensed Product in such
country, as set forth in Section 3.1.1.1 above, Alnylam will assign the IND in
such country in the Genzyme Territory to Genzyme and from that point forward,
Genzyme will be primarily responsible for the related regulatory activities with
respect thereto in its Territory. [***]

3.1.2. Communications. Each Party will notify the PJSC responsible for each
Regional Licensed Product in writing, including a brief description in English,
of the principal issues raised in each material communication with Regulatory
Authorities with respect to such Regional Licensed Product within [***] days
after receipt thereof. Upon request, each Party will provide to the other Party:
(a) at the providing Party’s expense, a summary translation of such material
communications in English, (b) at the providing Party’s expense, complete copies
of the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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original correspondence in their native language, or (c) at the requesting
Party’s expense, a full translation of such material communications in English,
in each case (a) through (c) within a reasonable period of time following such
request. For the purposes of this Section 3.1, “material communications” with
Regulatory Authorities include meetings with Regulatory Authorities and
Regulatory Authority questions or concerns with respect to significant issues,
including any of the following: key product quality attributes (e.g., purity),
safety findings affecting the platform (e.g., Serious Adverse Events, emerging
safety signals), clinical or nonclinical findings affecting patient safety, lack
of efficacy or receipt or denial of Regulatory Approval.

3.1.3. Regulatory Meetings. Each Party shall provide the other Party with
reasonable advance notice of all substantive meetings with the Government
Authorities in its Territory pertaining to each Regional Licensed Product, and
Alnylam shall provide Genzyme with reasonable advance notice of all substantive
meetings with the Governmental Authorities in the Genzyme Territory pertaining
to each Regional Licensed Product, or with as much advance notice as practicable
under the circumstances. Each Party shall use reasonable efforts, to the extent
reasonably practicable, to permit the other Party to have, at the other Party’s
expense, mutually acceptable representatives of the other Party to attend,
solely as a non-participating observer, material, substantive meetings,
including pre-IND and end of Phase II Study meetings, with the Governmental
Authorities within such Party’s Territory pertaining to such Regional Licensed
Product; provided, however, that neither Party shall be obligated to change the
schedule of such a meeting in order to accommodate the schedule of the other
Party’s representatives. Prior to the acceptance or approval of the IND and the
first dosing of the first patient in the first Phase III Study of a Regional
Licensed Product by Alnylam in a country in the Genzyme Territory, Alnylam shall
provide Genzyme with reasonable advance notice of all substantive meetings with
Regulatory Authorities in the Genzyme Territory pertaining to such Regional
Licensed Product, or with as much advance notice as practicable under the
circumstances. Alnylam shall use reasonable efforts, to the extent reasonably
practicable, to permit Genzyme to have, at Genzyme’s expense, mutually
acceptable representatives of Genzyme to attend, as full and equal participants,
material, substantive meetings, including pre-IND and end of Phase II Study
meetings, with Regulatory Authorities in the Genzyme Territory pertaining to
such Regional Licensed Product.

3.1.4. Submissions. Each Party shall provide the other Party with written notice
of each of the following events with regard to each Regional Licensed Product
within a reasonable period of time following the occurrence thereof, to the
extent notice was not provided prior to the Implementation Date for such
Regional Licensed Product: (a) the filing of any IND for such Regional Licensed
Product; (b) the submission of any filings or applications for Regulatory
Approval (including orphan drug applications and designations) of such Regional
Licensed Product in such Party’s Territory to any Regulatory Authority and
(c) receipt or denial of Regulatory Approval for such Regional Licensed Product
obtained or denied; provided, however, that in all circumstances, each Party
shall inform the other Party of such event prior to public disclosure of such
event by such Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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3.2. EMA Regulatory Strategy. Within [***] before the anticipated MAA filing for
a Regional Licensed Product, the PJSC will determine an EMA regulatory strategy
for such Regional Licensed Product pursuant to which the PJSC will determine
(a) whether Alnylam will seek Regulatory Approval for such Regional Licensed
Product in the EU using the EMA centralized or a national authorization
procedure and (b) whether Genzyme will file a duplicate license with respect to
any MAA held by Alnylam in the Alnylam Territory [***]. In determining the EMA
regulatory strategy, the Parties agree to reasonably consider in good faith each
Party’s interests. In the event that Genzyme files a duplicate license in the
Genzyme Territory, Alnylam will coordinate communications with EMA, and provide
support to enable Genzyme to efficiently obtain such duplicate license to
provide for marketing in Genzyme countries under a separate, Genzyme trade name,
to the extent not inconsistent with the Global Branding Strategy for such
Regional Licensed Product.

3.3. Costs of Regulatory Affairs. Except as provided in Section 2.3
(Responsibilities for Development Activities and Costs) and Section 3.1.1.2,
each Party shall be responsible for all costs and expenses incurred in
connection with applying for, obtaining and maintaining Regulatory Approval with
respect to Regional Licensed Products in its Territory, and related regulatory
affairs activities.

3.4. Right of Reference. Each Party hereby grants to the other Party, and at the
request of the other Party will grant to the other Party’s Related Parties, a
“Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any
successor rule or analogous Law recognized outside of the United States), to,
and a right to copy, access, and otherwise use, all information and data
(including all CMC information as well as data made, collected or otherwise
generated in the conduct of any Clinical Studies or Secondary Indication Studies
or early access/named patient programs for the Regional Licensed Products)
included in or used in support of any regulatory filing, Regulatory Approval,
drug master file or other regulatory documentation (including orphan drug
applications and designations) owned or controlled by such Party or its Related
Parties that relates to (a) any Regional Licensed Product or (b) with respect to
such information and data provided to Genzyme, the siRNA Controlled by Alnylam
and known as ALN-TTR01, to the extent necessary or useful to obtain Regulatory
Approval of a Regional Licensed Product in the Genzyme Territory, and such Party
shall provide a signed statement to this effect, if requested by the other
Party, in accordance with 21 C.F.R. § 314.50(g)(3) (or any successor or
analogous Law outside of the United States). In addition, upon request of either
Party (on behalf of itself or a Sublicensee), the other Party shall obtain and
provide to the requesting Party certificates or other formal or official
attestations concerning the regulatory status of the Regional Licensed Products
in the Genzyme Territory or the Alnylam Territory, as applicable (e.g.,
Certificates of Free Sale, Certificates for Export, Certificates to Foreign
Governments). Notwithstanding anything to the contrary in these Regional License
Terms, neither Party shall withdraw or inactivate any regulatory filing that the
other Party references or otherwise uses pursuant to this Section 3.4.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

4.1. Responsibility, Cost and Diligence.

4.1.1. Genzyme. Genzyme shall be solely responsible, at its expense, for all
Commercialization activities relating to Regional Licensed Products in the Field
in the Genzyme Territory. [***].

4.1.2. Alnylam. Alnylam shall be solely responsible, at its expense, for all
Commercialization activities relating to Regional Licensed Products in the Field
in the Alnylam Territory.

4.1.3. Joint Commercialization. In the event that the Parties mutually agree to
conduct any joint Commercialization activities regarding a Regional Licensed
Product, the Parties will (a) agree in writing to a written work plan and time
table for conducting such activities; (b) agree in writing to management and
governance mechanisms for such joint activities, including coordination of such
activities through the PJSC responsible for such Regional Licensed Product; and
(c) negotiate in good faith a budget therefor and an equitable allocation of
costs between the Parties. At either Party’s request, the Parties will start
discussion regarding beneficial joint Commercialization activities [***] years
prior to the anticipated First Commercial Sale of the Regional Licensed Product,
with any agreement to be preferably finalized not less than [***] years prior to
the anticipated First Commercial Sale of the Regional Licensed Product.

4.2. Global Commercial Strategy. Within [***] days after the Implementation Date
for a Regional Licensed Product, Alnylam shall provide and within [***] days
after provision the PJSC shall review, update and approve a written summary of
the global Commercial strategy for such Regional Licensed Product (the “Global
Commercial Strategy”).

4.3. Genzyme Territory Commercialization Plan. No less than [***] months in
advance of the reasonably expected first Regulatory Approval in the Genzyme
Territory with respect to a Regional Licensed Product, and on an annual basis
thereafter, Genzyme shall prepare and deliver to the PJSC responsible for such
Regional Licensed Product for review a reasonable written plan that summarizes
the Commercialization activities to be undertaken with respect to such Regional
Licensed Product in the Genzyme Territory in the next Calendar Year and, to the
extent commercially reasonable, Genzyme’s plans to obtain further Regulatory
Approvals and Commercialize such Regional Licensed Product in countries in the
Genzyme Territory in which Genzyme is not then Commercializing such Regional
Licensed Product, and the dates by which such activities are targeted to be
accomplished (the “Genzyme Territory Commercialization Plan”). Each Genzyme
Territory Commercialization Plan shall be consistent with the requirements of
the initial Global Commercialization Strategy or the most recently approved by
the PJSC[***]. The Genzyme Territory Commercialization Plan for a Regional
Licensed Product shall subsequently be updated and modified by Genzyme, from
time to time at its discretion and no less frequently than once per Calendar
Year, based upon, among other things, Genzyme’s Commercialization activities
with respect to such Regional Licensed Product in the Genzyme Territory, a copy
of which updated plan Genzyme will provide to the PJSC responsible for such
Regional Licensed Product. [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.4. Alnylam Territory Commercialization Plan. No less than [***] months in
advance of the reasonably expected first Regulatory Approval in the Alnylam
Territory with respect to a Regional Licensed Product, and on an annual basis
thereafter, Alnylam shall prepare and deliver to the PJSC responsible for such
Regional Licensed Product for review a reasonable written plan that summarizes
the Commercialization activities to be undertaken with respect to such Regional
Licensed Product in the Alnylam Territory in the next Calendar Year and, to the
extent commercially reasonable, Alnylam’s plans to obtain further Regulatory
Approvals and Commercialize such Regional Licensed Product in countries in the
Alnylam Territory in which Alnylam is not then Commercializing such Regional
Licensed Product, and the dates by which such activities are targeted to be
accomplished (the “Alnylam Territory Commercialization Plan”). The Alnylam
Territory Commercialization Plan shall at all times remain consistent with the
Global Commercialization Strategy. The Alnylam Territory Commercialization Plan
for a Regional Licensed Product shall subsequently be updated and modified by
Alnylam, from time to time at its discretion and no less frequently than once
per Calendar Year, based upon, among other things, Alnylam’s Commercialization
activities with respect to such Regional Licensed Product in the Alnylam
Territory, a copy of which updated plan Alnylam will provide to the PJSC
responsible for such Regional Licensed Product. [***].

4.5. Advertising and Promotional Materials.

4.5.1. Global Branding. Alnylam shall have the right, from time to time during
the Term, to develop (and thereafter modify and update) a global branding
strategy (including global positioning, colors and other visual branding
elements) for each Regional Licensed Product for use in the Field throughout the
world (the “Global Branding Strategy”), which the PJSC responsible for such
Regional Licensed Product shall, in accordance with Sections 5.5.2(b) (PJSC
Commercialization Responsibilities) and 5.6 (PJSC Decision-Making), review and
approve, and which the Parties shall, following such review and approval,
implement. Alnylam will submit the Global Branding Strategy for a Regional
Licensed Product to the PJSC responsible for such Regional Licensed Product at
least annually (or more frequently if reasonably requested by Genzyme). Alnylam
shall consider in good faith any timely comments Genzyme may have with respect
to any Global Branding Strategy, but shall have final decision-making authority
with respect to such Global Branding Strategy. Notwithstanding the foregoing,
Alnylam shall ensure that the Global Branding Strategy complies with applicable
Laws in the Genzyme Territory, and that any branding elements selected for
inclusion in the Global Branding Strategy do not infringe any Third Party
trademarks or other intellectual property rights. If any such Global Branding
Strategy infringes Third Party trademarks or other intellectual property rights
or otherwise does not comply with applicable Law in the Genzyme Territory,
Alnylam shall take action to end such infringement or other noncompliance
(including by modifying such Global Branding Strategy) and Genzyme will not be
obligated to implement such Global Branding Strategy in the Genzyme Territory
pursuant to this Section 4.5.1 unless and until such infringement or
noncompliance is ended.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.5.2. Alnylam A&P. Alnylam will be responsible for the creation, preparation,
production, reproduction and filing with the applicable Regulatory Authorities,
of relevant written sales, promotion and advertising materials relating to each
Regional Licensed Product (“Promotional Materials”) for use in the Alnylam
Territory. All such Promotional Materials will be compliant with applicable Law
and, if applicable, consistent in all material respects with the Global Branding
Strategy for such Regional Licensed Product. Alnylam will submit representative
samples of its Promotional Materials developed by it for use in the Alnylam
Territory to the PJSC, at least annually (or more frequently if reasonably
requested by Genzyme). Alnylam shall consider in good faith any timely comments
Genzyme may have with respect to any such Promotional Materials, but shall have
final decision-making authority with respect to such Promotional Materials.
Notwithstanding the foregoing, Alnylam will incorporate any changes to
Promotional Materials requested by Genzyme in a timely fashion in cases where
Genzyme indicates that believes in good faith based on the advice of counsel
that such change is necessary to enable it to comply with any applicable Law.

4.5.3. Genzyme A&P. Genzyme will be responsible for the creation, preparation,
production, reproduction and filing with the applicable Regulatory Authorities,
of relevant Promotional Materials relating to each Regional Licensed Product for
use in the Genzyme Territory. All such Promotional Materials will be compliant
with applicable Law, consistent in all material respects with the Genzyme
Territory Commercialization Plan and, if applicable, consistent in all material
respects with the Global Branding Strategy for such Regional Licensed Product in
the Genzyme Territory. Genzyme will submit representative samples of its
Promotional Materials developed by it for use in the Genzyme Territory to the
PJSC at least annually thereafter (or more frequently if reasonably requested by
Alnylam). Genzyme shall consider in good faith any timely comments Alnylam may
have with respect to any such Promotional Materials, but shall have final
decision-making authority in the Genzyme Territory with respect to such
Promotional Materials.

4.5.4. Reporting Obligations. Genzyme shall report to the PJSC responsible for a
Regional Licensed Product in writing, by no later than each [***] following the
first Regulatory Approval of such Regional Licensed Product in the Field in the
Genzyme Territory (for the period ending December 31 of the prior Calendar
Year), summarizing in reasonable detail Genzyme’s Commercialization activities
for such Regional Licensed Product performed to date (or updating such report
for activities performed since the last such report was given hereunder, as
applicable). In addition, Genzyme shall provide Alnylam with written notice of
the First Commercial Sale of each Regional Licensed Product in the Genzyme
Territory within [***] days after such event; provided, however, that in all
circumstances, Genzyme shall inform Alnylam of such event prior to public
disclosure of such event by Genzyme. Each Party shall provide such other
information to the PJSC responsible for a Regional Licensed Product as the other
Party may reasonably request with respect to Commercialization of such Regional
Licensed Product and shall keep such PJSC reasonably informed of such Party’s
Commercialization activities with respect to such Regional Licensed Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.6. Commercialization Reporting Obligations. Each Party and its Related Parties
shall be responsible for booking sales in its Territory. Each Party and its
Related Parties may warehouse Regional Licensed Products both inside and outside
of such Party’s Territory, provided that any sales with respect to such Regional
Licensed Products are booked in such Party’s Territory. If a Party receives any
orders for any Regional Licensed Product in the other Party’s Territory, it
shall refer such orders to the other Party, to the extent it is not prohibited
from doing so under applicable Law. Moreover, each Party and its Related Parties
shall be solely responsible for handling all returns of any Regional Licensed
Product sold in its Territory, as well as all aspects of Regional Licensed
Product order processing, invoicing and collection, distribution, inventory and
receivables of Regional Licensed Products sold in its Territory.

4.7. Recalls, Market Withdrawals or Corrective Actions. In the event that any
Regulatory Authority issues or requests a recall or takes a similar action in
connection with a Regional Licensed Product in a Territory, or in the event
either Party determines that an event, incident or circumstance has occurred
that may result in the need for a recall or market withdrawal of a Regional
Licensed Product in its Territory, the Party notified of such recall or similar
action, or the Party that desires such recall or similar action, shall within
[***] hours notify the other Party’s RLP Alliance Manager and PJSC
representatives thereof by telephone or e-mail. Each Party, in consultation with
the other Party, shall decide whether to conduct a recall of a Regional Licensed
Product in its own Territory and the manner in which any such recall shall be
conducted (except in the case of a government mandated recall, when such Party
may act without such advance notice but shall notify the other Party as soon as
possible). Except as may otherwise be agreed to by the Parties, each Party shall
bear the expense of any such recall in its own Territory. Each Party will make
available all of its pertinent records that may be reasonably requested by the
other Party in order to effect a recall of a Regional Licensed Product in the
other Party’s Territory. The Parties’ rights and obligations under this
Section 4.7 shall be subject to the terms of any supply agreement(s) entered
into between the Parties. In the event of a conflict between the provisions of
any such supply agreement and this Section 4.7, the provisions of such supply
agreement shall govern.

4.8. [***]

4.8.1. [***]

4.8.2. [***].

5. COLLABORATION MANAGEMENT

5.1. Product Joint Steering Committee. The Parties shall establish a product
joint steering committee (a “PJSC”) to facilitate the RLP Collaboration with
respect to each Regional Licensed Product as follows:

5.1.1. Composition of the Product Joint Steering Committee. The Development and
Commercialization of each Regional Licensed Product pursuant to the RLP
Collaboration will be conducted under the oversight of a PJSC, which shall
comprise three (3)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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representatives of each Party. The PJSC for ALN-TTR02 shall be established as of
the Effective Date. Each Party shall appoint its respective representatives to
the PJSC for each other Regional Licensed Product from time to time following
the Implementation Date for such Regional Licensed Product, and may substitute
one or more of its representatives on any PJSC, in its sole discretion,
effective upon notice to the other Party of such change. Each Party shall have
at least one representative on each PJSC who is a senior employee (vice
president level or above), and all representatives on each PJSC shall have
appropriate expertise, seniority, decision-making authority and ongoing
familiarity with the RLP Collaboration and the applicable Regional Licensed
Product. For the avoidance of doubt, the same representatives from each Party
may serve on the PJSC for more than one Regional Licensed Product. Unless
otherwise agreed by the Parties, each Party’s representatives on any PJSC must
be employees of such Party. Additional representatives or consultants may from
time to time, by mutual consent of the Parties, be invited to attend PJSC
meetings, subject to such representatives and consultants undertaking
confidentiality obligations, whether in a written agreement or by operation of
law, no less stringent than the requirements of Section 7 of the Master
Agreement (Confidentiality and Publication).

5.1.2. PJSC Chairperson. The chairperson of each PJSC shall rotate every twelve
(12) months between a PJSC representative of Alnylam and a PJSC representative
of Genzyme. The initial chairperson of each PJSC shall be a representative of
Alnylam. Each PJSC chairperson’s responsibilities shall include chairing
meetings, including ensuring that objectives for each meeting are set and
achieved.

5.2. Appointment of Subcommittees, Project Teams and RLP Alliance Managers. Each
PJSC shall be empowered to create such subcommittees and project teams as it may
deem appropriate or necessary, such as for specific oversight of Development,
Manufacturing, Commercialization or intellectual property issues relating to the
Regional Licensed Product for which such PJSC is responsible. Each such project
team created by a PJSC shall report to such PJSC, which shall have authority to
approve or reject recommendations or actions proposed by such project team,
subject to these Regional License Terms. For the avoidance of doubt, the same
representatives from each Party may serve on the project team for more than one
Regional Licensed Product. Each Party will designate an alliance manager for
each Regional Licensed Product (each, a “RLP Alliance Manager”) to serve as a
primary point of contact for the other Party with respect to all activities
under the RLP Collaboration related to such Regional Licensed Product. Each RLP
Alliance Manager’s responsibilities shall include (a) scheduling meetings of the
PJSC at least once per Calendar Quarter, but more frequently if the PJSC
determines it necessary; (b) setting agendas for PJSC meetings with solicited
input from the RLP Alliance Manager for the other Party and other members of the
PJSC; and (c) coordinating the delivery of draft minutes to the PJSC for review
and final approval. Beginning with Alnylam’s RLP Alliance Manager, such
responsibilities shall alternate between the RLP Alliance Managers from each
Party on a meeting-by-meeting basis after each meeting of the applicable
committee. Each Party may change any of its RLP Alliance Managers at any time in
its sole discretion with written notice to the other Party, provided that each
RLP Alliance Manager will be individually identified at all times and will have
such experience, authority, responsibility and accountability as is reasonably
sufficient to enable such person to fulfill his or her responsibilities as a RLP
Alliance Manager under these Regional License Terms on behalf of the applicable
Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.3. PJSC Meetings. Each PJSC shall meet in accordance with a schedule
established by mutual written agreement of the Parties, but no less frequently
than once per Calendar Quarter during the Term, with the location for such
meetings alternating between Alnylam and Genzyme facilities (or such other
locations as are mutually agreed by the Parties). Alternatively, a PJSC may meet
by means of teleconference, videoconference or other similar communications
equipment, but at least two (2) meetings of such PJSC per Calendar Year shall be
conducted in person. All proceedings for each PJSC shall take place in English.
Where the membership of a PJSC for a Regional Licensed Product is the same as
one or more other PJSCs for other Regional Licensed Product(s), such PJSCs may
have a single meeting to discuss each Regional Licensed Product for which they
have responsibility. Each Party shall bear its own expenses relating to
attendance at such meetings by its representatives.

5.4. PJSC Minutes. A RLP Alliance Manager shall be appointed secretary for each
meeting of each PJSC and shall prepare minutes of the meeting, which shall
provide a description in reasonable detail of the discussions held at the
meeting and a list of any actions, decisions or determinations approved by such
PJSC. Within [***] days after each meeting, the drafting RLP Alliance Manager
shall provide the draft minutes to the other RLP Alliance Manager for review and
comment. The drafting RLP Alliance Manager shall reasonably consider all
comments from the other RLP Alliance Manager within [***] days. The drafting RLP
Alliance Manager shall prepare and submit revised minutes within [***] days
after receipt of such comments or upon expiration of such [***] day period.

5.5. PJSC Responsibilities.

5.5.1. PJSC Development Responsibilities. Each PJSC shall have the following
responsibilities with respect to the Development of the Regional Licensed
Product for which it is responsible:

(a) developing and approving updates and amendments to the Global Development
Strategy for such Regional Licensed Product in accordance with Section 2.2.1
(Global Development Strategy);

(b) developing and approving updates and amendments to the Global Development
Plan for such Regional Licensed Product in accordance with Section 2.2.2.3
(Managing and Amending Global Development Plans and Global Development Budgets);

(c) reviewing and approving the initial Genzyme Territory Development Plan and
the initial Alnylam Territory Development Plan for such Regional Licensed
Product in accordance with Sections 2.2.3 (Alnylam Territory Development Plan)
and 2.2.4 (Genzyme Territory Development Plan);

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) reviewing and discussing updates and amendments to the Genzyme Territory
Development Plan and the Alnylam Territory Development Plan for such Regional
Licensed Product in accordance with Sections 2.2.3 (Alnylam Territory
Development Plan) and 2.2.4 (Genzyme Territory Development Plan), and providing
each Party with feedback regarding the same;

(e) reviewing and discussing updates provided by each Party regarding the
Development of such Regional Licensed Product in such Party’s Territory in
accordance with Section 2.5.1 (Development Activities Reports), and providing
each Party with feedback regarding the same;

(f) monitoring and coordinating Development activities in the Genzyme Territory
and the Alnylam Territory for such Regional Licensed Product, and regulatory and
pharmacovigilance requirements and matters;

(g) reviewing and discussing updates provided by each Party regarding any Global
Development Activities in accordance with the Global Development Plan for such
Regional Licensed Product (including the Global Development Budget);

(h) approving a global list of clinical sites for each Global Clinical Study for
such Regional Licensed Product;

(i) approving the appointment of the global CRO to manage any Phase II Study or
Phase III Study for such Regional Licensed Product;

(j) overseeing any manufacturing and supply relationship between the Parties
with respect to the Manufacture of such Regional Licensed Product for
Development activities (subject to the provisions of the RLP Clinical Supply
Agreement, if any); and

(k) performing such other activities as the Parties agree in writing shall be
the responsibility of such PJSC or that are otherwise assigned to such PJSC
under these Regional License Terms.

5.5.2. PJSC Commercialization Responsibilities. Each PJSC shall have the
following responsibilities with respect to the Commercialization of the Regional
Licensed Product for which it is responsible, to the extent permissible under
applicable Laws:

(a) reviewing and discussing reports and information provided by each Party
regarding the Commercialization of such Regional Licensed Product in such
Party’s Territory in accordance with Section 4.6 (Commercialization Reporting
Obligations);

(b) reviewing and approving, any Global Branding Strategy developed by Alnylam
for such Regional Licensed Product in accordance with Section 4.5.1 (Global
Branding);

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(c) reviewing and discussing the Genzyme Territory Commercialization Plan for
such Regional Licensed Product and updates thereto provided by Genzyme pursuant
to Section 4.3 (Genzyme Territory Commercialization Plan);

(d) reviewing and discussing Promotional Material for such Regional Licensed
Product of both Parties in accordance with Sections 4.5.2 (–Alnylam A&P) and
4.5.3 (–Genzyme A&P);

(e) providing a forum for the Parties to discuss the Commercialization of such
Regional Licensed Product in the Field worldwide, including coordination
regarding Regional Licensed Product positioning and messaging, key opinion
leader relationship management, medical affairs, and marketing and selling
materials;

(f) providing a forum for the Parties to discuss collaborating on commercial
activities with respect to such Regional Licensed Product that can be leveraged
for both Parties’ respective Territories and how the Parties would share the
costs of such mutually agreed joint Commercialization activities;

(g) overseeing any manufacturing and supply relationship between the Parties
with respect to the Manufacture of such Regional Licensed Product for
Commercialization activities (subject to the provisions of the RLP Commercial
Supply Agreement, if any); and

(h) performing such other activities as the Parties agree in writing shall be
the responsibility of such PJSC or that are otherwise assigned to such PJSC
under these Regional License Terms.

5.6. PJSC Decision-Making.

5.6.1. PJSC Decisions. With respect to decisions of each PJSC, the
representatives of each Party on such PJSC shall have collectively one vote on
behalf of such Party. For each meeting of a PJSC, at least two
(2) representatives of each Party shall constitute a quorum. Action on any
matter may be taken at a meeting, by teleconference, videoconference or by
written agreement. Each PJSC shall attempt to resolve any and all disputes
before it for decision by consensus. For the avoidance of doubt, the phrase
“approval by the PJSC” and similar phrases used in these Regional License Terms
shall mean approval in accordance with this Section 5.6 (PJSC Decision-Making),
including [***].

5.6.2. Escalation. If a PJSC is unable to reach a consensus with respect to any
dispute for a period in excess of [***] days, then the dispute shall be
submitted to the AJSC (as defined in the Master Agreement) at a meeting or
meetings (whether in-person or by teleconference or videoconference). During
such meeting(s), each Party shall provide analysis to support its position with
respect to such dispute. If the dispute is still unresolved after a further
[***] days, such dispute shall be [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.6.3. [***]. If a dispute cannot be resolved under Section 5.6.2 (Escalation),
then, subject to Sections 5.6.4 [***]

5.6.3.1. [***]

5.6.3.2. [***]

5.6.3.3. [***]

5.6.4. [***]

5.6.4.1. [***]

5.6.4.2. [***]

5.6.5. [***]

(i) [***]

(ii) [***]

(iii) [***]

(iv) [***]

(v) [***]

5.7. Term of PJSC. With respect to each Regional Licensed Product, after the
[***] anniversary of the Implementation Date for such Regional Licensed Product,
Alnylam shall have the right, but not the obligation, to continue its
participation in the PJSC responsible for such Regional Licensed Product.

5.8. Alnylam Third Party Partner. If, at any time during the Term, Alnylam
enters into an agreement (a “Third Party Collaboration Agreement”) with one or
more Third Party(ies) (each, a “Third Party Partner”) to Develop and/or
Commercialize any Regional Licensed Product in the Field in the Alnylam
Territory, Alnylam shall ensure that such agreement is consistent with these
Regional License Terms.

5.8.1. Required Terms. Without limitation, Alnylam shall negotiate terms in the
Third Party Collaboration Agreement (a) regarding intellectual property
necessary to permit Alnylam to license or sublicense to Genzyme any Patent
Rights and Know-How developed in the course of activities pursuant to the Third
Party Collaboration Agreement that are necessary for Genzyme to Develop,
Manufacture and Commercialize Regional Licensed Products in accordance with
these Regional License Terms, if any; (b) providing Genzyme with a right of
reference as set forth in Section 3.4 (Right of Reference); (c) requiring such
Third Party Partner to maintain records substantially as set forth in
Section 2.5.2 (Scientific Records); (d) enabling

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

47

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Alnylam to provide Genzyme with copies of data and reports, including Clinical
Study reports, in a commercially reasonable format, made, collected or otherwise
generated by or on behalf of the Third Party Partner in the conduct of any
pre-clinical studies, Clinical Studies or early access/named patient programs
for any Regional Licensed Products (excluding, for clarity, information
generated in Secondary Indication Studies and CMC information), and protocols
and investigator brochures related to any Regional Licensed Product, in each
case that are reasonably necessary for Genzyme (or its Related Parties) to
Develop and obtain Regulatory Approval for the Regional Licensed Products in the
Genzyme Territory; (e) enabling Alnylam to provide Genzyme with information with
respect to matters in the Third Party Partner’s territory as are required to be
provided to Genzyme under Sections 2.5.1 (Development Activities Reports), 3.1.2
(Communications) (to the extent requiring a brief description in English of
principal issues raised in material communications from Regulatory Authorities
and otherwise to the extent reasonably necessary to assist Genzyme with
obtaining Regulatory Approvals of Regional Licensed Products), and 3.1.4
(Submissions); (f) regarding pharmacovigilance that are consistent with
Section 4.6 of the Master Agreement (Pharmacovigilance) and the SDEA; and
(g) regarding recalls that are consistent with Section 4.7 (Recalls, Market
Withdrawals or Corrective Actions).

5.8.2. [***].

5.8.3. Global Coordination Committee. Alnylam shall use reasonable efforts to
include in any Third Party Collaboration Agreement relating to rights licensed
to a Third Party Partner in the United States and/or major markets in Europe,
the discretionary participation by such Third Party Partner with Genzyme and
Alnylam in a global coordination committee, which shall include representatives
of Alnylam, Genzyme and the Third Party Partner and which shall be responsible
for facilitating discussions between the parties with respect to the global
Development, Manufacture and Commercialization of Regional Licensed Products.

5.8.4. Notice. Alnylam shall promptly provide Genzyme with a copy of any fully
executed Third Party Collaboration Agreement, which may be redacted to remove
provisions which are not necessary to monitor compliance with this Section 5.8
and such Third Party Collaboration Agreement will be deemed Alnylam Confidential
Information for the purposes of Section 7 of the Master Agreement
(Confidentiality and Publication).

5.8.5. Sublicenses. If any Third Party Collaboration Agreement grants the Third
Party Partner a sublicense under the Genzyme Technology, Alnylam shall ensure
that such Third Party Collaboration agreement complies with Section 6.2.4
(Sublicensing Terms).

5.8.6. Breach; Responsibility. If Alnylam becomes aware of a material breach of
the provisions of any Third Party Collaboration Agreement by a Third Party
Partner, compliance with which is necessary for Alnylam’s compliance with these
Regional License Terms, Alnylam shall promptly notify Genzyme of the particulars
of the same and use Commercially Reasonable Efforts to cause the Third Party
Partner to comply with all the provisions of the Third Party Collaboration
Agreement necessary for Alnylam’s compliance with these Regional License Terms.
Notwithstanding any Third Party Collaboration Agreement, Alnylam shall remain
primarily liable to Genzyme for the performance of all of Alnylam’s obligations
under, and Alnylam’s compliance with all provisions of, these Regional License
Terms with respect to the entire Alnylam Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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6. LICENSES

6.1. License Grants to Genzyme.

6.1.1. Development License in the Genzyme Territory. On a Regional Licensed
Product-by-Regional Licensed Product basis, subject to these Regional License
Terms (including Section 8.4.1.3(c) (Exclusivity)) and any RLP Clinical Supply
Agreement, effective upon the Implementation Date for each Regional Licensed
Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in
Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to
Section 6.1.4 (Sublicensing Terms)) exclusive (even as to Alnylam) license under
Alnylam Technology to Develop such Regional Licensed Product in the Field in the
Genzyme Territory and the Alnylam Territory, in each case solely as and to the
extent provided in any approved Genzyme Territory Development Plan or any Global
Development Plan, and in each case, solely for Regulatory Approval and
Commercialization in the Genzyme Territory. Notwithstanding the foregoing,
Alnylam retains (a) the exclusive right under the Alnylam Technology, with the
right to grant licenses through multiple tiers without restriction, to Develop
Regional Licensed Products anywhere in the world for Regulatory Approval and
Commercialization in the Alnylam Territory, and (b) the co-exclusive right (with
Genzyme) to Develop each Regional Licensed Product anywhere in the world for
Regulatory Approval and Commercialization by Genzyme in the Genzyme Territory in
accordance with the Global Development Plan for such Regional Licensed Product.

6.1.2. Commercialization License in the Genzyme Territory. On a Regional
Licensed Product-by-Regional Licensed Product basis, subject to these Regional
License Terms (including Section 8.4.1.3(c) (Exclusivity)) and any RLP
Commercial Supply Agreement, effective upon the Implementation Date for each
Regional Licensed Product, Alnylam hereby grants Genzyme a non-transferable
(except as provided in Section 13.1 of the Master Agreement (Assignment)),
sublicensable (subject to Section 6.1.4 (Sublicensing Terms)) exclusive (even as
to Alnylam) license under Alnylam Technology to Commercialize such Regional
Licensed Product in the Field in the Genzyme Territory. Such license shall be
royalty-bearing for the Royalty Term applicable to each Regional Licensed
Product in each country in the Genzyme Territory, and, after the Royalty Term
applicable to such Regional Licensed Product in such country, shall convert to a
fully-paid perpetual exclusive license to Commercialize such Regional Licensed
Product in the Field in such country.

6.1.3. Manufacturing Licenses. On a Regional Licensed Product-by-Regional
Licensed Product basis, subject to these Regional License Terms (including
Section 8.4.1.3(c)) and any RLP Clinical Supply Agreement and RLP Commercial
Supply Agreement, effective upon the Implementation Date for each Regional
Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as
provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 6.1.4(Sublicensing Terms)), worldwide, exclusive (even as to
Alnylam) license under Alnylam Technology to Manufacture

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

49

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such Regional Licensed Product inside or outside of the Genzyme Territory solely
for Commercialization in the Genzyme Territory and, to the extent permitted
pursuant to Section 2.3.2 (Genzyme Development), for Development for the Alnylam
Territory. Notwithstanding the foregoing, Alnylam retains the exclusive right
under the Alnylam Technology, with the right to grant licenses through multiple
tiers without restriction, to Manufacture Regional Licensed Products anywhere in
the world (a) for Development and Commercialization in the Alnylam Territory
and, to the extent permitted pursuant to Section 2 (Development Collaboration)
for Development in the Genzyme Territory, and (b) to supply (or have supplied
to) Genzyme pursuant to the RLP Supply Agreements to be agreed by the Parties
pursuant to Section 6.2 of the Master Agreement (Collaboration Product Supply
Agreements).

6.1.4. Sublicensing Terms.

(a) Genzyme shall have the right to sublicense any of its rights under Sections
6.1.1 (Development License in the Genzyme Territory), 6.1.2 (Commercialization
License in the Genzyme Territory) and 6.1.3 (Manufacturing Licenses) to any of
its Affiliates or to any Third Party (which sublicensed rights may be further
sublicensable through multiple tiers) without the prior consent of Alnylam,
subject to the requirements of this Section 6.1.4. [***].

(b) Each sublicense granted by Genzyme pursuant to this Section 6.1.4 shall be
subject and subordinate to these Regional License Terms and shall contain
provisions consistent with those in these Regional License Terms. Genzyme shall
promptly provide Alnylam with a copy of the fully executed sublicense agreement
covering any sublicense granted hereunder (which copy may be redacted to remove
provisions which are not necessary to monitor compliance with this
Section 6.1.4), and each such sublicense agreement shall contain the following
provisions: (i) a requirement that the Sublicensee comply with the
confidentiality and non-use provisions of Section 7 of the Master Agreement
(Confidentiality and Publication) with respect to Alnylam’s Confidential
Information, (ii) if such sublicense agreement contains a sublicense of Regional
Licensed Product Commercialization rights, such sublicense agreement shall also
contain the following provisions: (x) a requirement that the Sublicensee submit
applicable sales or other reports to Genzyme to the extent necessary or relevant
to the reports required to be made or records required to be maintained under
these Regional License Terms; and (y) the audit requirement set forth in
Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the
Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the provisions of any
sublicense by any Genzyme Sublicensee, compliance with which is necessary for
Genzyme’s compliance with these Regional License Terms, Genzyme shall promptly
notify Alnylam of the particulars of the same and use Commercially Reasonable
Efforts to cause the Sublicensee to comply with all the provisions of the
sublicense necessary for Genzyme’s compliance with these Regional License Terms.
[***]. Notwithstanding any sublicense, Genzyme shall remain primarily liable to
Alnylam for the performance of all of Genzyme’s obligations under, and Genzyme’s
compliance with all provisions of, these Regional License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

50

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6.2. License Grants to Alnylam.

6.2.1. Commercialization License in the Alnylam Territory. Subject to these
Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except
as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 6.2.4 (Sublicensing Terms)), non-exclusive, royalty-free
license under Genzyme Collaboration IP to Develop and Commercialize Regional
Licensed Products in the Field in the Alnylam Territory.

6.2.2. License to Improvement Manufacturing Patent Rights. Subject to these
Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except
as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 6.2.4 (Sublicensing Terms)), worldwide, non-exclusive
license under the Improvement Manufacturing Patent Rights, to Manufacture
(a) Alnylam Developed siRNA Products targeting any human gene; and (b) Regional
Licensed Products for Development and Commercialization in the Alnylam Territory
and, to the extent permitted pursuant to Section 2.3.3 (Alnylam Development),
for Development in the Field in the Genzyme Territory.

6.2.3. License to Genzyme Disclosed Manufacturing Know-How. Subject to these
Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except
as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 6.2.4 (Sublicensing Terms)), worldwide, non-exclusive
license under the Genzyme Disclosed Manufacturing Know-How to Manufacture
Regional Licensed Products for Development and Commercialization in the Alnylam
Territory and, to the extent permitted pursuant to Section 2.3.3 (Alnylam
Development), for Development in the Field in the Genzyme Territory.

 

  6.2.4. Sublicensing Terms.

(a) Subject to Section 6.5 (Alnylam Territory Right of First Negotiation),
Alnylam shall have the right to sublicense any of its rights under Section 6.2.1
(Commercialization License in the Alnylam Territory), 6.2.2 (License to
Improvement Manufacturing Patent Rights) and 6.2.3 (License to Genzyme Disclosed
Manufacturing Know-How) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 6.2.4 shall be
subject and subordinate to these Regional License Terms and shall contain
provisions consistent with those in these Regional License Terms. Alnylam shall
promptly provide Genzyme with a copy of the fully executed sublicense agreement
covering any sublicense granted hereunder (which copy may be redacted to remove
provisions which are not necessary to monitor compliance with this
Section 6.2.4), and each such sublicense

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

51

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agreement shall contain the following provisions: (i) a requirement that the
Sublicensee comply with the confidentiality and non-use provisions of Section 7
of the Master Agreement (Confidentiality and Publication) with respect to
Genzyme’s Confidential Information and (ii) a requirement that the Sublicensee
comply with the applicable provisions under any Genzyme In-License.

(c) If Alnylam becomes aware of a material breach of any sublicense by any
Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance
with these Regional License Terms, Alnylam shall promptly notify Genzyme of the
particulars of the same and use Commercially Reasonable Efforts to cause the
Sublicensee to comply with all the provisions of the sublicense necessary for
Alnylam’s compliance with these Regional License Terms. [***]. Notwithstanding
any sublicense, Alnylam shall remain primarily liable to Genzyme for the
performance of all of Alnylam’s obligations under, and Alnylam’s compliance with
all provisions of, these Regional License Terms.

6.3. Joint Collaboration IP. Subject to the rights and licenses granted to, and
the obligations (including royalty obligations) of, each Party under these
Regional License Terms, either Party is entitled to practice Joint Collaboration
IP for all purposes on a worldwide basis and license Joint Collaboration IP
without consent of and without a duty of accounting to the other Party. Each
Party will grant and hereby does grant all permissions, consents and waivers
with respect to, and all licenses under, the Joint Collaboration IP, throughout
the world, necessary to provide the other Party with such rights of use and
exploitation of the Joint Collaboration IP, and will execute documents as
necessary to accomplish the foregoing.

6.4. Compliance with In-Licenses. All licenses and other rights granted to
Genzyme under this Section 6 are subject to the rights and obligations of
Alnylam under the Alnylam In-Licenses. All licenses and other rights granted to
Alnylam under this Section 6 are subject to the rights and obligations of
Genzyme under the Genzyme In-Licenses. Each Party shall comply with all
applicable provisions of the In-Licenses, and shall perform and take such
actions as may be required to allow the Party that is party to such In-License
to comply with its obligations thereunder, including obligations relating to
sublicensing, patent matters, confidentiality, reporting, audit rights,
indemnification and diligence. Without limiting the foregoing, each Party shall
prepare and deliver to the other Party any additional reports required under the
applicable In-Licenses and requested by such other Party, in each case
sufficiently in advance to enable the Party that is party to such In-License to
comply with its obligations under the applicable In-Licenses. Each Party agrees,
upon the other Party’s request, to provide the other Party with copies of any
In-Licenses to which it is a party. Confidential Information of the providing
Party or its counterparty may be redacted from such copies, except to the extent
that such information is required in order to enable the other Party to comply
with its obligations to the providing Party under these Regional License Terms
with respect to such In-License or in order to enable the providing Party to
ascertain compliance with these Regional License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

52

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6.5. Alnylam Territory Right of First Negotiation. If, at any time during the
Term, Alnylam desires to grant any Third Party rights to Develop and/or
Commercialize one or more Regional Licensed Product(s) in any portion of the
Alnylam Territory, Alnylam shall notify Genzyme in writing of its intent.
Genzyme shall have [***] days from receipt of such written notice to notify
Alnylam in writing as to whether Genzyme desires to negotiate for such rights in
such territory, and if Genzyme so notifies Alnylam that it does desire to
negotiate for such rights in such territory, Genzyme shall have the exclusive
right for [***] days from the date of such notification to Alnylam to negotiate
with Alnylam and to make one or more written non-binding offers to Alnylam
concerning the acquisition of such rights in such territory by Genzyme. Genzyme
shall have the exclusive right for [***] days (or such longer period as may be
mutually agreed by the Parties) after such [***] day period, to finalize and
enter into a definitive agreement with Alnylam for such rights in such
territory, provided that, if either Genzyme does not provide such written notice
within such [***] day period or Genzyme does provide such written non-binding
offer within such subsequent [***] day period, or Genzyme provides such notice
of interest and such written offer but for any reason Genzyme and Alnylam do not
enter into a definitive agreement within the [***] day negotiation period,
Alnylam shall be free to enter into an agreement with a Third Party(ies)
relating to such rights in such territory, without further obligation to
Genzyme. Alnylam shall not, during the exclusive [***] day negotiating periods
described above, enter into discussions, exchange information, or otherwise
negotiate with any Third Party with respect to an agreement with respect to the
Development and/or Commercialization of the applicable Regional Licensed
Product(s) in the Alnylam Territory. Notwithstanding the foregoing, during the
period of [***] months after the termination of any such negotiation that does
not result in a definitive agreement between Alnylam and Genzyme, Alnylam shall
not enter into a transaction with respect to such rights in such territory with
any Third Party on terms that are, in the aggregate, materially more favorable
to the Third Party than the last terms offered in writing by Genzyme to Alnylam
unless Alnylam first re-offers such transaction to Genzyme on such more
favorable terms and Genzyme does not accept such offer and enter into such
transaction with Alnylam within [***] days after such re-offer. For clarity,
prior to the exclusive negotiating periods described above, Alnylam shall be
free to engage in discussions and exchange information with Third Parties with
respect to the applicable Regional Licensed Product(s) rights, but shall not
enter into any binding agreement with any Third Party with respect to such
rights.

6.6. Bankruptcy. All rights and licenses granted under or pursuant to these
Regional License Terms by a Party to the other, including those set forth in
Sections 6.1 (License Grants to Genzyme), 6.2 (License Grants to Alnylam), and
3.4 (Right of Reference), are and shall otherwise be deemed to be, for purposes
of Section 365(n) of the U.S. Bankruptcy Code, licenses of right to
“intellectual property” as defined under Section 101 of the U.S. Bankruptcy
Code. The Parties agree that the Parties and their respective Sublicensees, as
sublicensees of such rights under these Regional License Terms, shall retain and
may fully exercise all of their rights and elections under the U.S. Bankruptcy
Code and any foreign counterpart thereto. The Parties further agree that upon
commencement of a bankruptcy proceeding by or against a Party (the “Bankrupt
Party”) under the Bankruptcy Code, the other Party (the “Non-Bankrupt Party”)
will be entitled to a complete duplicate of, or complete access to (as the
Non-Bankrupt Party

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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deems appropriate), all such intellectual property and all embodiments of such
intellectual property. Such intellectual property and all embodiments of such
intellectual property will be promptly delivered to the Non-Bankrupt Party
(a) upon any such commencement of a bankruptcy proceeding and upon written
request by the Non-Bankrupt Party, unless the Bankrupt Party elects to continue
to perform all of its obligations under these Regional License Terms, or (b) if
not delivered under (a) above, upon the rejection of these Regional License
Terms by or on behalf of the Bankrupt Party and upon written request by the
Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to
Genzyme a right of access to and to obtain possession of (i) copies of research
data, (ii) laboratory samples, (iii) samples of Regional Licensed Product,
(iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related
to clinical trials, (vii) regulatory filings and approvals, (viii) rights of
reference in respect of regulatory filings and approvals, (ix) pre-clinical
research data and results, and (x) marketing, advertising and promotional
materials, all of which (in clauses (i) through (x)) constitute “embodiments” of
intellectual property pursuant to Section 365(n) of the Bankruptcy Code and
(xi) all other embodiments of such intellectual property, and in respect of each
of the foregoing clauses (i) through (xi), solely for the purpose of the
exercise of Genzyme’s rights and licenses under these Regional License Terms,
whether any of the foregoing are in Alnylam’s possession or control or in the
possession and control of Third Parties. The Bankrupt Party (in any capacity,
including debtor-in-possession) and its successors and assigns (including any
trustee) agree not to interfere with the exercise by the Non-Bankrupt Party or
its Related Parties of its rights and licenses to such intellectual property and
such embodiments of intellectual property in accordance with these Regional
License Terms, and agrees to assist the Non-Bankrupt Party and its Related
Parties in obtaining such intellectual property and such embodiments of
intellectual property in the possession or control of Third Parties as are
reasonably necessary or desirable for the Non-Bankrupt Party to exercise such
rights and licenses in accordance with these Regional License Terms. The
foregoing provisions are without prejudice to any rights the Non-Bankrupt Party
may have arising under the Bankruptcy Code or other Laws.

6.7. No Other Rights. Except as otherwise expressly provided in these Regional
License Terms, under no circumstances shall a Party, as a result of these
Regional License Terms, obtain any ownership interest or other right in any
Know-How, Patent Rights or other intellectual property rights of the other
Party, including items owned, controlled or developed by the other Party, or
provided by the other Party to the receiving Party at any time pursuant to these
Regional License Terms.

7. CERTAIN FINANCIAL TERMS

7.1. Milestone Fees.

7.1.1. Development Milestones for Regional Licensed Products. Genzyme shall
provide Alnylam with written notice of the achievement by Genzyme or any of its
Related Parties of any development milestone event set forth below in this
Section 7.1.1 and Alnylam shall provide Genzyme with written notice of the
achievement by Alnylam or any of its Related Parties of any development
milestone event set forth below in this Section 7.1.1, in each case

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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within [***] days after such event has occurred; provided, however, that the
notifying Party shall inform the other Party of such event prior to any public
disclosure of such event by the notifying Party. Alnylam shall invoice Genzyme
within [***] days of receipt of such written notice by either Party, and Genzyme
shall remit the associated development milestone payment within [***] days of
the receipt of such invoice. Each development milestone payment by Genzyme to
Alnylam hereunder shall be payable only once with respect to each Regional
Licensed Product, regardless of the number of times a development milestone
event is achieved with respect to any Regional Licensed Product.

7.1.1.1. Development Milestones for ALN-TTR02. Genzyme shall pay Alnylam the
following amounts upon achievement of the following development milestone events
with respect to ALN-TTR02:

 

Development Milestone Event

   Development Milestone
Payment  

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

7.1.1.2. Development Milestones for Regional Licensed Products other than
ALN-TTR02. Genzyme shall pay Alnylam the following amounts upon achievement of
the following development milestone events with respect to any Regional Licensed
Product other than ALN-TTR02:

 

Development Milestone Event

   Development Milestone
Payment  

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

7.1.2. Sales Milestones for Regional Licensed Products other than ALN-TTR02.
Genzyme shall provide Alnylam with written notice of the achievement by Genzyme
or any of its Related Parties of any of the sales milestone events set forth
below in this Section 7.1.2 within [***] days after such event has occurred.
Alnylam shall invoice Genzyme within [***]days of receipt of such written
notice, and Genzyme shall remit the associated sales milestone payment within
[***] days of the receipt of such invoice.

 

Sales Milestone Event

   Sales Milestone Payment  

[***]

     [***]   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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[***].

7.2. Royalties.

7.2.1. Royalties Payable on Regional Licensed Products.

7.2.1.1. Royalties Payable on ALN-TTR02. Subject to these Regional License
Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales by Genzyme and
its Related Parties of ALN-TTR02 in the Genzyme Territory, as follows:

 

Calendar Year

Net Sales of ALN-TTR02 in the Genzyme Territory

   Royalty
(as a percentage of Net Sales)

[***]

   [***]

[***]

   [***]

[***]

   [***]

Royalties on annual Net Sales of ALN-TTR02 shall be paid at the rate applicable
to the portion of Net Sales within each of the Net Sales levels above during
such Calendar Year. By way of example only, if Genzyme receives [***]

[***]

7.2.1.2. Royalties Payable on Other Regional Licensed Products. Subject to these
Regional License Terms, Genzyme shall pay to Alnylam royalties on annual Net
Sales by Genzyme and its Related Parties of each Regional Licensed Product other
than ALN-TTR02 in the Genzyme Territory, as follows:

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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REGIONAL LICENSE TERMS

 

Calendar Year

Net Sales of a Regional Licensed Product

other than ALN-TTR02 in the Genzyme

Territory

  Royalty
(as a percentage of Net Sales of a Regional Licensed
Product)

[***]

  [***]

[***]

  [***]

[***]

  [***]

[***]

  [***]

[***]

  [***]

By way of example only, if Genzyme receives [***]

[***]

[***]

7.2.2. Royalty Term. Subject to Section 7.2.6 (Royalty Floor), the period during
which the royalties set forth in Section 7.2.1(Royalties Payable on Regional
Licensed Products) shall be payable, on a Regional Licensed Product-by-Regional
Licensed Product and country-by-country basis, shall commence with the First
Commercial Sale of a Regional Licensed Product in a country and continue until
the latest of (a) the expiration of the last Valid Claim of [***] in the country
of sale; (b) the expiration of Regulatory Exclusivity for such Regional Licensed
Product in such country; or (c) subject to the last sentence of this
Section 7.2.2, the [***] anniversary of the First Commercial Sale of such
Regional Licensed Product in such country (each such period, a “Royalty Term”).
[***]

7.2.3. Third Party Royalty Offsets. Genzyme shall be permitted to reduce any
royalties payable under Section 7.2.1 (Royalties Payable on Regional Licensed
Products) for a Regional Licensed Product [***].

7.2.4. [***].

7.2.5. [***].

7.2.6. Royalty Floor. Anything in these Regional License Terms to the contrary
notwithstanding, in no event during the applicable Royalty Term for a Regional
Licensed Product in a country of the Genzyme Territory shall the royalties
payable to Alnylam hereunder for such Regional Licensed Product in such country
for any Calendar Quarter be reduced [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

57

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7.2.7. Validation Information. At Genzyme’s request, Alnylam will provide
Genzyme with such information as Genzyme may reasonably request to validate the
amount of the royalty floor described in Section 7.2.6 (Royalty Floor).

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

8.1. Representations and Warranties of Alnylam. Except as provided in the
Disclosure Schedule to this Section 8.1 (which Disclosure Schedule with respect
to ALN-TTR02 is attached hereto and with respect to any other Regional Licensed
Product will be provided by Alnylam to Genzyme as part of the Option Data
Package for such Regional Licensed Product), Alnylam represents and warrants to
Genzyme that, with respect to each Regional Licensed Product other than
ALN-TTR02, as of the Implementation Date, and, with respect to ALN-TTR02, as of
the Execution Date:

8.1.1. Alnylam is the sole and exclusive owner of, or otherwise Controls
pursuant to an Alnylam In-License, the Alnylam Technology, and all of the
Alnylam Technology licensed to Genzyme hereunder in the Genzyme Territory that
is solely and exclusively owned by Alnylam is free and clear of liens, charges
or encumbrances other than licenses granted to Third Parties that are not
inconsistent with the rights and licenses granted to Genzyme under these
Regional License Terms.

8.1.2. Alnylam has sufficient legal and/or beneficial title and ownership of, or
sufficient license rights under, the Alnylam Technology to grant the licenses to
such Alnylam Technology granted to Genzyme pursuant to these Regional License
Terms.

8.1.3. (a) Schedule 1.2.13 and Schedule 1.2.18 collectively set forth a complete
and accurate list of the Alnylam Patents owned, either solely or jointly, by
Alnylam, and to Alnylam’s knowledge, Schedule 1.2.13 and Schedule 1.2.18
collectively set forth a complete and accurate list of the Alnylam Patents
licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s
knowledge, each issued Alnylam Patent remains in full force and effect and
(c) Alnylam or its Affiliates have timely paid all filing and renewal fees
payable with respect to such Alnylam Patents for which Alnylam controls
prosecution and maintenance. Schedule 1.2.13 and Schedule 1.2.18 indicate
whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by
Alnylam and one or more Third Parties, or is licensed to Alnylam. For each
Alnylam Patent that is owned, but not owned exclusively, by Alnylam, or that is
licensed to Alnylam, Schedule 1.2.13 and Schedule 1.2.18 identify the Third
Party owner(s) and, if applicable, the Alnylam In-License pursuant to which
Alnylam Controls such Alnylam Patent. For each Alnylam Product-Specific Patent
that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.18
indicates the non-exclusive nature of the license. For each Alnylam Core
Technology Patent family (other than Patent Rights licensed from Isis
Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to
Alnylam, Schedule 1.2.13 indicates the non-exclusive nature of the license.
Alnylam is the sole and exclusive owner of all Patent Rights identified in
Schedule 1.2.13 and Schedule 1.2.18 as being owned exclusively by Alnylam and
Controls all other Patent Rights identified on such schedules.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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8.1.4. To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or,
upon issuance, will be, valid and enforceable patents and no Third Party has
challenged or threatened to challenge the scope, validity or enforceability of
any Alnylam Product-Specific Patent (including, by way of example, through
opposition or the institution or written threat of institution of interference,
nullity or similar invalidity proceedings before the United States Patent and
Trademark Office or any analogous foreign Governmental Authority).

8.1.5. Alnylam has complied with all applicable Laws, including any duties of
candor to applicable patent offices, in connection with the filing, prosecution
and maintenance of the Alnylam Patent Rights.

8.1.6. Alnylam owns or Controls all Know-How that is or has been used by Alnylam
in the Development and Manufacture of such Regional Licensed Product, and has
sufficient legal or beneficial title and ownership of, or sufficient license
rights under such Know-How to transfer Know-How to Genzyme as provided in
Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

8.1.7. Alnylam Controls all Know-How and Patent Rights licensed to Alnylam under
the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to
Develop, Manufacture and/or Commercialize such Regional Licensed Product in the
Field in the Genzyme Territory. Without limiting the generality of the
foregoing, Alnylam has obtained all necessary consents and fulfilled all
necessary conditions, if any, to sublicense to Genzyme under these Regional
License Terms such Know-How and Patent Rights licensed to Alnylam under Existing
Alnylam In-Licenses.

8.1.8. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach
or default under any existing Alnylam In-License, and neither Alnylam nor its
Affiliates have received any written notice of breach or default with respect to
any existing Alnylam In-License.

8.1.9. Alnylam has obtained from all inventors of Alnylam Technology owned by
Alnylam valid and enforceable agreements assigning to Alnylam each such
inventor’s entire right, title and interest in and to all such Alnylam
Technology.

8.1.10. To Alnylam’s knowledge, the use, Development, Manufacture or
Commercialization by Alnylam or Genzyme (or their respective Related Parties) of
such Regional Licensed Product as formulated and manufactured as of the
Effective Date, or as intended to be formulated and manufactured as of the
Effective Date (a) does not and will not infringe any issued patent of any Third
Party and (b) will not infringe the claims of any published Third Party patent
application when and if such claims were to issue in their current form.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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8.1.11. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry,
investigation or other legal action of any nature, civil, criminal, regulatory
or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or
any of its Affiliates or (b) judgment or settlement against or owed by Alnylam
or any of its Affiliates, in each case in connection with the Alnylam Technology
or such Regional Licensed Product.

8.1.12. For each Regional Licensed Product, other than ALN-TTR02, Schedule
8.1.12(a) (Existing Alnylam In-Licenses) sets forth a complete and accurate list
of all agreements between Alnylam and a Third Party entered into prior to the
Implementation Date for a Regional Licensed Product pursuant to which Alnylam
Controls Know-How or Patent Rights that are necessary or useful to Develop,
Manufacture or Commercialize such Regional Licensed Product in the Field other
than Additional Alnylam In-Licenses. [***]. For the sake of clarity,
representations and warranties similar to those made pursuant to this
Section 8.1.12 with respect to Regional Licensed Products other than ALN-TTR02
are made with respect to ALN-TTR02 in the Master Agreement.

8.2. Representations and Warranties of Genzyme. Except as disclosed in Genzyme’s
Exercise Notice for a Regional Licensed Product, Genzyme represents and warrants
to Alnylam as of the Implementation Date for such Regional Licensed Product that
is not a party to any agreement with a Third Party under which it Controls
Know-How or Patent Rights that are sublicensed to Alnylam under these Regional
License Terms with respect to such Regional Licensed Product.

8.3. Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE
REGIONAL LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY
WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT
TO ANY TECHNOLOGY, REGIONAL LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER
SUBJECT MATTER OF THESE REGIONAL LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED
WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY
DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR
COMMERCIALIZATION OF ANY REGIONAL LICENSED PRODUCT PURSUANT TO THESE REGIONAL
LICENSE TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT
TO ANY REGIONAL LICENSED PRODUCT WILL BE ACHIEVED.

8.4. Certain Covenants.

8.4.1. [***]

8.4.1.1. [***]

(a) [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) [***]

(c) [***]

8.4.1.2. [***]

(a) [***]

(b) [***]

(c) [***]

8.4.1.3. [***]

(a) [***]

(b) [***]

(c) [***]

8.4.2. Compliance. Each Party and its Related Parties shall conduct the RLP
Collaboration and the Development, Manufacture and Commercialization of the
Regional Licensed Products in accordance with all Laws, including current
governmental regulations concerning Good Laboratory Practices (as defined in the
Master Agreement), good clinical practices and good manufacturing practices. In
addition, if either Party is or becomes subject to a legal obligation to a
Regulatory Authority or other Governmental Authority (such as a corporate
integrity agreement or settlement agreement with a Governmental Authority), then
the other Party shall perform such activities as may be reasonably requested by
the obligated Party to enable the obligated Party to comply with its legal
obligation to such Regulatory Authority with respect to the Regional Licensed
Products.

8.4.3. Conflicting Transactions. During the Term, Alnylam shall not (a) transfer
or assign any of its rights, title or interests in the Alnylam Technology other
than as part of a transaction pursuant to which these Regional License Terms are
also assigned and assumed in accordance with Section 13.1 of the Master
Agreement (Assignment), or (b) enter into any agreement granting a license or
other right under the Alnylam Technology that is inconsistent with these
Regional License Terms.

8.4.4. Governmental Authority. If any of the Alnylam Technology is subject to
any funding arrangement with any Governmental Authority, at Genzyme’s reasonable
request, Alnylam will reasonably cooperate in seeking a waiver or other
modification to such funding arrangement with respect to such Alnylam
Technology.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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9. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

9.1. Inventorship. Inventorship for inventions and discoveries first made during
the course of the performance of activities pursuant to these Regional License
Terms shall be determined in accordance with United States patent Laws for
determining inventorship.

9.2. Ownership. Alnylam shall own the entire right, title and interest in and to
all inventions and discoveries (and Patent Rights claiming patentable inventions
therein) first made or discovered solely by employees or consultants of Alnylam
or acquired solely by Alnylam in the course of conducting the Collaboration.
Genzyme shall own the entire right, title and interest in and to all inventions
and discoveries (and Patent Rights claiming patentable inventions therein) first
made or discovered solely by employees or consultants of Genzyme or acquired
solely by Genzyme in the course of conducting the Collaboration. The Parties
shall jointly own any inventions and discoveries (and Patent Rights claiming
patentable inventions therein) first made or discovered jointly in the course of
conducting the Collaboration.

9.3. Prosecution and Maintenance of Patent Rights.

9.3.1. IP Committee. The Parties agree that the IP Committee created pursuant to
Section 5.3 of the Master Agreement (IP Committee) shall be responsible for
overseeing and effecting the information sharing and consulting provisions under
this Section 9.3.1.

9.3.2. Genzyme Technology.

(a) Subject to Section 9.3.2(b) below, Genzyme has the sole responsibility to,
at Genzyme’s discretion and at Genzyme’s sole cost and expense, file, prosecute,
and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Genzyme Technology (other than Joint
Collaboration IP), in Genzyme’s name.

(b) In the event that Genzyme elects not to seek or continue to seek or maintain
patent protection on any Genzyme Collaboration IP in the Alnylam Territory,
Genzyme shall notify Alnylam at least [***] days before any such Patent Rights
would become abandoned, no longer available or otherwise forfeited, and subject
to the provisions of any applicable Genzyme In-License, Alnylam shall have the
right (but not the obligation), at its sole cost and expense, to seek, prosecute
and maintain in any country patent protection on such Genzyme Collaboration IP
in the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to
make available to Alnylam its authorized attorneys, agents or representatives,
and/or such of its employees as are reasonably necessary to assist Alnylam in
obtaining and maintaining the patent protection described under this
Section 9.3.2(b). Genzyme shall sign or use Commercially Reasonable Efforts to
have signed all legal documents as are reasonably necessary to file and
prosecute such patent applications or to obtain or maintain such patents.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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9.3.3. Alnylam Technology. The following will apply with respect to Alnylam
Patent Rights during the Term [***].

(a) Subject to Section 9.3.3(c) below, Alnylam has the sole responsibility to,
at Alnylam’s discretion and at Alnylam’s sole cost and expense, file, conduct
prosecution, and maintain (including the defense of any interference or
opposition proceedings), all Patent Rights comprising Alnylam Technology (other
than Joint Collaboration IP), in Alnylam’s name. Notwithstanding the foregoing,
Alnylam shall file Alnylam Product-Specific Rights in the Genzyme Patent
Jurisdictions (as defined in the Master Agreement) and shall use commercially
reasonable efforts to prosecute and maintain such Patent Rights in the Genzyme
Patent Jurisdictions and shall timely pay all filing and renewal fees payable
with respect thereto.

(b) Notwithstanding the foregoing Section 9.3.3(a), Alnylam shall consult with
Genzyme, including through the IP Committee, on its strategy for the
preparation, filing, prosecution, and maintenance of all Alnylam
Product-Specific Patents in the Genzyme Territory and the Alnylam Territory.
Alnylam shall furnish Genzyme, via electronic mail or such other method as
mutually agreed by the Parties, copies of proposed filings and documents
received from outside counsel in the course of filing, prosecution or
maintenance of and/or copies of documents filed with the relevant patent offices
with respect to Alnylam Product-Specific Patents and such other documents
directly related to the prosecution and maintenance of Alnylam Product-Specific
Patents reasonably necessary for Genzyme to exercise its rights under this
Section 9.3.3(b), and as applicable in sufficient time prior to filing such
document or making any payment due thereunder to allow for review and comment by
Genzyme and shall consider in good faith timely comments from Genzyme thereon.
Alnylam shall furnish to Genzyme, via electronic mail or such other method as
mutually agreed by the Parties, copies of documents received from outside
counsel in the course of filing, prosecution or maintenance of and/or copies of
documents filed with the relevant national patent offices with respect to the
filing, prosecution, and maintenance of Alnylam Core Technology Patents within a
reasonable time after the receipt and/or filing of such documents.

(c) In the event that Alnylam elects not to seek or continue to seek or maintain
patent protection on any Alnylam Product-Specific Patent in the Genzyme
Territory, Alnylam shall notify Genzyme at least [***] days before any such
Patent Rights would become abandoned, no longer available or otherwise
forfeited, and subject to the provisions of any applicable Alnylam In-License,
Genzyme shall have the right (but not the obligation), at its sole cost and
expense, to seek, prosecute and maintain in any country patent protection on any
such Alnylam Product-Specific Patent in the Genzyme Territory. If Genzyme
exercises such right, Alnylam shall thereafter and hereby does assign all right,
title and interest in and to such Alnylam Product-Specific Patents to Genzyme.
Alnylam shall use Commercially Reasonable Efforts to make available to Genzyme
its authorized attorneys, agents or representatives, such of its employees as
are reasonably necessary to assist Genzyme in obtaining and maintaining the
patent protection described under this Section 9.3.3(b). Alnylam shall sign or
use Commercially Reasonable Efforts to have signed all legal documents as are
reasonably necessary to file and prosecute such patent applications or to obtain
or maintain such patents.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) [***]

9.3.4. Joint Collaboration IP.

(a) [***] shall have the first right to, at [***] discretion, file, prosecute
and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Joint Collaboration IP, in the names
of both Alnylam and Genzyme. [***] shall consult with [***] on the filing,
prosecution and maintenance of all such Patent Rights. Each Party shall sign, or
use Commercially Reasonable Efforts to have signed, all legal documents as are
reasonably necessary to file and prosecute patent applications or to obtain or
maintain patents in respect of such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish [***], via electronic mail or such other method as
mutually agreed by the Parties, copies of documents received from outside
counsel in the course of such filing, prosecution or maintenance of Joint
Collaboration IP and/or copies of documents relevant to such preparation,
filing, prosecution, and maintenance in sufficient time prior to filing such
document or making any payment due thereunder to allow for review and comment by
[***] and shall consider in good faith timely comments from [***] thereon. [***]
shall furnish to Genzyme, via electronic mail or such other method as mutually
agreed by the Parties, copies of such documents as filed in the relevant patent
offices.

(c) In the event [***] elects not to file or continue to prosecute or maintain
patent protection on any Joint Collaboration IP, [***]shall have the right (but
not the obligation) to file, prosecute and maintain Patent Rights comprising
Joint Collaboration IP in the names of both Alnylam and Genzyme. [***] exercises
such right, [***] shall use Commercially Reasonable Efforts to make available to
[***] its authorized attorneys, agents or representatives, and/or such of its
employees as are reasonably necessary to assist [***] in obtaining and
maintaining the patent protection described under this Section 9.3.4(c). [***]
shall sign or use Commercially Reasonable Efforts to have signed all legal
documents as are reasonably necessary to file and prosecute such patent
applications or to obtain or maintain such patents.

(d) The Parties shall share equally the out-of-pocket patent filing, prosecution
and maintenance expenses incurred with respect to Patent Rights comprising Joint
Collaboration IP.

9.3.5. Patent Miscellaneous. Each Party hereby agrees: (a) to make its
employees, agents and consultants reasonably available to the other Party (or to
the other Party’s authorized attorneys, agents or representatives), to the
extent reasonably necessary to enable such

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Party to undertake patent prosecution; (b) to provide the other Party with
copies of all material correspondence pertaining to prosecution with the patent
offices; (c) to cooperate, if necessary and appropriate, with the other Party in
gaining patent term extensions wherever applicable to Patent Rights licensed
under these Regional License Terms; and (d) to endeavor in good faith to
coordinate its efforts with the other Party to minimize or avoid interference
with the prosecution and maintenance of the other Party’s patent applications.

9.3.6. [***]

9.3.6.1. [***]

9.3.6.2. [***]

9.3.6.3. [***]

9.4. Third Party Infringement.

9.4.1. Notices. Each Party shall promptly report in writing to the other Party
any (a) known or suspected infringement of any Alnylam Technology, Genzyme
Technology or Joint Collaboration IP or (b) unauthorized use or misappropriation
of any Confidential Information or Know-How of a Party by a Third Party of which
it becomes aware, in each case to the extent such infringing, unauthorized or
misappropriating activities involve, as to a Regional Licensed Product, a
competing product in the Field (a “Competitive Infringement”), and shall provide
the other Party with all available evidence of such infringement, unauthorized
use or misappropriation.

9.4.2. Rights to Enforce.

(a) Genzyme Technology. Subject to the provisions of any In-License, Genzyme
shall have the sole and exclusive right to initiate an infringement or other
appropriate suit (an “Infringement Action”) anywhere in the world against any
Third Party as to any infringement, or suspected infringement, of any Patent
Rights, or as to any use or suspected use without proper authorization of any
Know-How comprising Genzyme Patent Rights, Genzyme Know-How or Genzyme
Collaboration IP. Genzyme will consider in good faith any request from Alnylam
to initiate an Infringement Action against any Third Party with respect to
Competitive Infringement in the Alnylam Territory of Genzyme Patent Rights,
Genzyme Know-How or Genzyme Collaboration IP licensed to Alnylam under Section 6
(Licenses); provided, however, that Genzyme shall not be required to initiate
any such Infringement Action or permit Alnylam to initiate any such Infringement
Action.

(b) Alnylam Technology. Subject to the provisions of any In-License, Genzyme
shall have the first right to initiate an Infringement Action against any Third
Party with respect to any Competitive Infringement in the Genzyme Territory of
any Alnylam Product-Specific Patent or Joint Collaboration IP, or, with
Alnylam’s prior

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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written consent, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam
will consider in good faith any request from Genzyme to initiate an Infringement
Action against any Third Party with respect to a Competitive Infringement in the
Genzyme Territory of any Alnylam Core Technology Patent; provided, however, that
Alnylam shall not be required to initiate any such Infringement Action or permit
Genzyme to initiate any such Infringement Action.

(c) Step-In Rights.

(i) If within [***] days (or such shorter period of time as required by
applicable Law to avoid loss of material enforcement rights) after Genzyme’s
receipt of a notice of a Competitive Infringement with respect to any Alnylam
Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any
Infringement Action against such Competitive Infringement in the Genzyme
Territory, Alnylam may in its sole discretion, bring and control any
Infringement Action in connection therewith at its sole cost and expense.

(ii) [***]

9.4.3. Procedures; Expenses and Recoveries. The Party having the right to
initiate any Infringement Action under Section 9.4.2 (Rights to Enforce) above
shall have the sole and exclusive right to select counsel for any such
Infringement Action and shall pay all expenses of the suit, including attorneys’
fees and court costs and reimbursement of the other Party’s reasonable Regional
Out-of-Pocket Costs in rendering assistance requested by the initiating Party.
If required under applicable Law in order for the initiating Party to initiate
and/or maintain the Infringement Action, or if either Party is unable to
initiate or prosecute such Infringement Action solely in its own name or it is
otherwise advisable to obtain an effective legal remedy, in each case, the other
Party shall join as a party to such Infringement Action and will execute and
cause its Affiliates to execute all documents necessary for the initiating Party
to initiate litigation to prosecute and maintain such action. In addition, at
the initiating Party’s request, the other Party shall provide reasonable
assistance to the initiating Party in connection with an Infringement Action at
no charge to the initiating Party except for reimbursement by the initiating
Party of reasonable Regional Out-of-Pocket Costs incurred in rendering such
assistance. The non-initiating Party shall have the right to participate and be
represented in any such Infringement Action by its own counsel at its own
expense. If the Parties obtain from a Third Party, in connection with such
Infringement Action, any damages, license fees, royalties or other compensation
(including any amount received in settlement of such litigation), after payment
of any amounts required under any In-Licenses, the remaining amounts shall be
allocated in all cases as follows:

(a) first, to reimburse each Party for all expenses of the Infringement Action
incurred by the Parties, including attorneys’ fees and disbursements, court
costs and other litigation expenses;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) second, [***] of the balance to be paid to the Party initiating the
Infringement Action; and

(c) third, the remainder to the other Party.

Notwithstanding the foregoing, in the event that Alnylam elects to itself assert
an Alnylam Core Technology Patent against a Competitive Infringement in the
Genzyme Territory, the Parties shall each be entitled to [***] of the balance of
any recovery therefrom after reimbursement of expenses as described in clause
(i) above.

9.5. Patent Term Extensions.

9.5.1. Retained Alnylam Product-Specific Patents. Subject to the provisions of
any Alnylam In-License, Alnylam shall use Commercially Reasonable Efforts to
obtain all available supplementary protection certificates (“SPCs”) and other
extensions of Alnylam Product-Specific Patents in the Genzyme Territory[***]. If
more than one such Alnylam Product-Specific Patent is eligible for extension or
patent term restoration in the Genzyme Territory, Genzyme will determine, in its
sole discretion, a strategy that will be designed to maximize patent protection
and commercial value for the Regional Licensed Product, and the Parties, subject
to the provisions of any In-License, will seek patent term extensions,
restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme
Territory in accordance with that strategy. Where required under national law,
and subject to the other requirements of this Section 9.5, Alnylam will make the
filings for such extensions, restorations and SPCs for Alnylam Product-Specific
Patents in the Genzyme Territory as directed by Genzyme.

9.5.2. Further Assurances for SPCs. Each Party will execute such authorizations
and other documents and take such other actions as may be reasonably requested
by the other Party to obtain any such extensions, restorations and SPCs for
Alnylam Product-Specific Patents in the Genzyme Territory, in accordance with
this Section 9.5.

9.6. Common Interest. All information exchanged between the Parties
representatives regarding the preparation, filing, prosecution, maintenance, or
enforcement of the Patent Rights under this Section 9 will be deemed
Confidential Information. In addition, the Parties acknowledge and agree that,
with regard to such preparation, filing, prosecution, maintenance, and
enforcement of the Patents Rights under this Section 9, the interests of the
Parties as collaborators and licensor and licensee are to obtain the strongest
patent protection possible, and as such, are aligned and are legal in nature.
The Parties agree and acknowledge that they have not waived, and nothing in
these Regional License Terms constitutes a waiver of, any legal privilege
concerning the Patents Rights under this Section 9, including privilege under
the common interest doctrine and similar or related doctrines.

9.7. Trademarks.

(a) Each Party has the right to use any trademark it owns or controls for
Regional Licensed Products in its Territory at its sole discretion, and each
Party and its Affiliates shall retain all right, title and interest in and to
its and their respective corporate names and logos.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) Genzyme will develop and propose, and the PJSC shall review and comment on,
one or more Product Trademark(s) for use by Genzyme and its Related Parties
throughout the Genzyme Territory. Such Product Trademark(s) considered by the
PJSC may include, in Genzyme’s sole discretion, the Product Trademark(s)
developed and/or used by Alnylam with respect to the Commercialization of
Regional Licensed Products in the Alnylam Territory (the “Alnylam Trademarks”),
but may not include other trademarks owned or controlled by Alnylam. Any Product
Trademark(s) (other than the Alnylam Trademarks) that are used by Genzyme to
promote and sell Regional Licensed Products in the Genzyme Territory are
hereinafter referred to as the “Genzyme Trademarks.” Alnylam (or its Related
Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all
goodwill associated therewith, throughout the Alnylam Territory and the Genzyme
Territory. Genzyme (or its Related Parties, as appropriate) shall own all rights
to Genzyme Trademarks and all goodwill associated therewith, throughout the
Genzyme Territory. Alnylam shall also own rights to any Internet domain names
incorporating the applicable Alnylam Trademarks or any variation or part of such
Alnylam Trademarks used as its URL address or any part of such address; and
Genzyme shall also own rights to any Internet domain names incorporating the
applicable Genzyme Trademarks or any variation or part of such Genzyme
Trademarks used as its URL address or any part of such address.

(c) If Genzyme determines to use Alnylam Trademarks to promote and sell any
Regional Licensed Product in the Genzyme Territory, then Alnylam and Genzyme
shall enter into a separate trademark license agreement containing commercially
reasonable and customary terms pursuant to which Alnylam will grant Genzyme an
exclusive, royalty-free license to use the applicable Alnylam Trademark(s) to
Commercialize Regional Licensed Products in the Genzyme Territory.

(d) In the event either Party becomes aware of any infringement of any Product
Trademark by a Third Party, such Party shall promptly notify the other Party and
the Parties shall consult with each other and jointly determine the best way to
prevent such infringement, including by the institution of legal proceedings
against such Third Party.

(e) For the avoidance of doubt, neither Party shall have any right to use the
other Party’s or the other Party’s Affiliates’ corporate names or logos in
connection with Commercialization of Regional Licensed Products.

9.8. Cooperative Research and Technology (CREATE) Act Acknowledgment. It is the
intention of the Parties that these Regional License Terms are a “joint research
agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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10. TERM AND TERMINATION

10.1. Term. These Regional License Terms shall be effective as of the Effective
Date and, unless terminated earlier pursuant to Section 10.2 (Termination
Rights), these Regional License Terms shall continue in effect on a Regional
Licensed Product-by-Regional Licensed Product and country-by-country basis until
expiration of the last Royalty Term to expire under these Regional License Terms
(“Term”). Upon expiration of the Royalty Term for any particular Regional
Licensed Product, all licenses of the Parties under Section 6 (Licenses) with
respect to such Regional Licensed Product then in effect shall become fully
paid-up, perpetual licenses.

10.2. Termination Rights. These Regional License Terms may be terminated by the
Parties only as set forth in this Section 10.2.

10.2.1. Termination of a Regional Licensed Product for Convenience. Subject to
the remainder of this Article 10, Genzyme shall have the right to terminate
these Regional License Terms with respect to any particular Regional Licensed
Product as follows:

(a) After initiation of the first Phase II Study for such Regional Licensed
Product and prior to completion of such Phase II Study for such Regional
Licensed Product, Genzyme shall have the right to terminate these Regional
License Terms with respect to such Regional Licensed Product upon sixty
(60) days prior written notice in the event that a Safety Concern occurs,
provided that in the event of such termination Genzyme shall pay to Alnylam
[***] of the Global R&D Costs incurred through the effective date of termination
(not to exceed [***] wind down any ongoing Phase II Studies with respect to such
Regional Licensed Product in an efficient manner consistent with patient safety,
applicable Law and ethical standards.

(b) After initiation of the first Phase II Study for such Regional Licensed
Product and prior to completion of such Phase II Study for such Regional
Licensed Product, Genzyme shall have the right to terminate these Regional
License Terms with respect to such Regional Licensed Product for any reason upon
written notice (in which case, such termination shall become effective
immediately upon Alnylam’s receipt of notice of such termination), provided that
in the event of such termination Genzyme shall pay to Alnylam [***] of the
Global R&D Costs incurred in any ongoing Phase II Studies for such Regional
Licensed Product (not to exceed [***].

(c) Within sixty (60) days of Genzyme’s receipt of the Phase 3 Budget and End of
Phase II Package, Genzyme shall have the right to terminate these Regional
License Terms with respect to such Regional Licensed Product upon written notice
to Alnylam (in which case, such termination shall become effective immediately
upon Alnylam’s receipt of notice of such termination), provided that in the
event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D
Costs incurred through the effective date of termination (not to exceed [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) After initiation of the first Phase III Study for such Regional Licensed
Product and prior to completion of such Phase III Study for such Regional
Licensed Product, Genzyme shall have the right to terminate these Regional
License Terms with respect to such Regional Licensed Product upon sixty
(60) days prior written notice in the event that a Safety Concern occurs,
provided that in the event of such termination Genzyme shall pay to Alnylam
[***] of the Global R&D Costs incurred through the effective date of termination
(not to exceed [***]) to wind down any ongoing Clinical Studies with respect to
such Regional Licensed Product in an efficient manner consistent with patient
safety, applicable Law and ethical standards.

(e) After initiation of the first Phase III Study for such Regional Licensed
Product and Genzyme’s payment of the Phase III Study initiation milestone
payment described in Section 7.1.1.2(i) (Development Milestones for Regional
Licensed Products other than ALN-TTR02) (if applicable), Genzyme shall have the
right to terminate these Regional License Terms with respect to such Regional
Licensed Product at any time upon sixty (60) days prior written notice to
Alnylam, provided that in the event of such termination Genzyme shall pay to
Alnylam [***] of the Global R&D Costs incurred in conducting any ongoing Phase
III Study with respect to such Regional Licensed Product through filing of the
first NDA with respect to such Regional Licensed Product (not to exceed[***]).

(f) After completion of the first Phase III Study for such Regional Licensed
Product, Genzyme shall have the right to terminate these Regional License Terms
with respect to such Regional Licensed Product at any time upon sixty (60) days
prior written notice to Alnylam.

10.2.2. Termination of a Regional Licensed Product for Cause. These Regional
License Terms may be terminated with respect to any particular Regional Licensed
Product at any time during the Term upon written notice by either Party if
(a) the other Party is in material breach of its obligations hereunder with
respect to such Regional Licensed Product and (b) the other Party has not cured
such breach within thirty (30) days in the case of a payment breach, or within
ninety (90) days in the case of all other breaches, after notice requesting cure
of the breach; provided, however, that if any breach other than a payment breach
is not reasonably curable within ninety (90) days and if a Party is making a
bona fide effort to cure such breach, such termination shall be delayed for a
time period to be agreed by both Parties, not to exceed an additional ninety
(90) days, in order to permit such Party a reasonable period of time to cure
such breach; and provided, further, that in the event that the breach relates to
a dispute between the Parties regarding Genzyme’s obligations to use
Commercially Reasonable Efforts in Developing or Commercializing such Regional
Licensed Product and Genzyme disputes whether it has breached such obligation or
whether such breach gives Alnylam the right to terminate these Regional License
Terms with respect to such Regional Licensed Product and initiates a legal
action against Alnylam to resolve such dispute within the foregoing sixty
(60) day cure period, then these Regional License Terms shall not terminate
during the pendency of such legal action, provided that if (i) Genzyme is found,
in an unappealable decision by a court of competent

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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jurisdiction or an appealable decision of a court of competent jurisdiction that
has not been appealed in the time allowed for an appeal in such legal action, to
have materially breached these Regional License Terms with respect to such
Regional Licensed Product, or (ii) Genzyme admits in such legal action or
settlement thereof that it has materially breached these Regional License Terms
with respect to such Regional Licensed Product, then these Regional License
Terms shall terminate immediately with respect to such Regional Licensed Product
following the Parties’ receipt of such decision or immediately following such
admission, as applicable.

10.2.3. Termination of Regional Licensed Product upon Exercise of the
Co-Co/Global Option in respect of a Regional Licensed Product. These Regional
License Terms shall automatically be terminated with respect to a Regional
Licensed Product if Genzyme exercises the Co-Co/Global Option in respect of such
Regional Licensed Product under Section 3.2.2 of the Master Agreement
(Co-Co/Global Option Grant), which termination shall be effective as of the
Option Exercise Date for the Co-Co/Global Option. In such event such former
Regional Licensed Product shall be a Co-Co Licensed Product or a Global Licensed
Product, as applicable, and shall be governed by either the Co-Co License Terms
or the Global License Terms.

10.2.4. Challenges of Patent Rights. If, during the Term, Genzyme or any of its
Affiliates (a) commences or participates in any action or proceeding (including
any patent opposition or re-examination proceeding), or otherwise asserts any
claim, challenging or denying the validity or enforceability of any Alnylam
Product-Specific Patent or any claim thereof or (b) actively assists any other
Person or entity in bringing or prosecuting any action or proceeding (including
any patent opposition or re-examination proceeding) challenging or denying the
validity or enforceability of any Alnylam Product-Specific Patent for a Regional
Licensed Product or any claim thereof (each of (a) and (b), a “Patent
Challenge”), then, to the extent permitted by the applicable Laws, Alnylam shall
have the right, exercisable within sixty (60) days following receipt of notice
regarding such Patent Challenge, in its sole discretion, to give notice to
Genzyme that Alnylam may terminate these Regional Licensed Terms with respect to
the Regional Licensed Product Covered by the Alnylam Product-Specific Patent
that is the subject of the Patent Challenge (which termination will be effective
ninety (90) days following such notice (or such longer period as Alnylam may
designate in such notice)), and, unless Genzyme or such Affiliate withdraws or
causes to be withdrawn all such challenge(s) (or in the case of ex-parte
proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or
Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to
be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any
other party to such Patent Challenge and, to the extent Genzyme or a Genzyme
Affiliate is a party to such Patent Challenge, it withdraws from such Patent
Challenge) within such ninety (90)-day period, Alnylam will have the right to
terminate these Regional License Terms with respect to such Regional Licensed
Product by providing written notice thereof to Genzyme. The foregoing sentence
shall not apply with respect to (i) any Alnylam Product-Specific Patent that
Alnylam first asserts against Genzyme or any of its Affiliates where the Patent
Challenge is made in defense of such assertion or (ii) any Patent Challenge
commenced by a Third Party that, after the Effective Date, acquires or is
acquired by Genzyme or its Affiliates or its or their business or assets,
whether by stock purchase, merger, asset purchase or otherwise, but only with
respect to Patent Challenges commenced prior to the closing of such acquisition.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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10.2.5. Abandonment of Development. At any time on or after [***], either Party
may terminate these Regional License Terms in their entirety (i.e., with respect
to all Regional Licensed Products) if (a) no Regional Licensed Product has
received Regulatory Approval anywhere in the Genzyme Territory, (b) no Regional
Licensed Product is being Developed for the Genzyme Territory, (c) no Global
Development Plan or Genzyme Territory Development Plan is in effect for any
Regional Licensed Product, provided that, if Genzyme provides Alnylam with a
good faith Genzyme Territory Development Plan pursuant to Section 2.2.4 (Genzyme
Territory Development Plan) during the termination notice period set forth below
in this Section 10.2.5, then the condition set forth in this clause (c) shall be
deemed not satisfied at such time and the applicable termination notice shall be
deemed not to have effect, and (d) the absence of Development in the Genzyme
Territory or a good faith Genzyme Territory Development Plan is not the result
of a breach by the Party seeking to terminate these Regional License Terms of
its obligations under Section 2.4 (Diligence). In order to terminate these
Regional License Terms pursuant to this Section 10.2.5, the terminating Party
must provide at least six (6) months’ prior written notice to the other Party
referencing this Section 10.2.5 and specifying a termination date [***],
provided that, with respect to any such termination by Alnylam, such notice must
also include an update regarding the current status of Alnylam’s Development
activities with respect to Regional Licensed Products.

10.3. Effect of Termination.

10.3.1. Effects of Termination by Genzyme for Cause.

10.3.1.1. Effects of Termination of Regional Licensed Product by Genzyme for
Cause. Without limiting any other legal or equitable remedies that either Party
may have, if these Regional License Terms are terminated by Genzyme with respect
to any particular Regional Licensed Product pursuant to Section 10.2.2
(Termination of a Regional Licensed Product for Cause), then:

(a) these Regional License Terms shall continue to survive in all respects with
respect to all Regional Licensed Products other than the terminated Regional
Licensed Product;

(b) all license grants in these Regional License Terms with respect to the
terminated Regional Licensed Product from either Party to the other shall
immediately terminate;

(c) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all Regulatory Approvals and pricing
and reimbursement approvals relating to the Development, Manufacture or
Commercialization of the terminated Regional Licensed Product, and (ii) copies
of all non-clinical and clinical data and material regulatory correspondence
relating to the terminated Regional Licensed Product, provided that Alnylam
shall reimburse Genzyme for reasonable out-of-pocket expenses incurred by
Genzyme in connection with such transfer;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product-Specific Patents that relate solely to the
terminated Regional Licensed Product that were assigned to Genzyme pursuant to
Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme),
provided that Alnylam shall reimburse Genzyme for reasonable out-of-pocket
expenses incurred by Genzyme in connection with such assignment and transfer. In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme; and

(e) each Party shall promptly pay any amounts owed to the other Party as of the
effective date of such termination.

10.3.1.2. Effects of Termination of Regional Licensed Product upon Exercise of
the Co-Co/Global Option in respect of a Regional Licensed Product. Simultaneous
with the Option Exercise Date for the Co-Co/Global Option in respect of a
Regional Licensed Product that is ALN-AT3 or ALN-AS1, these Regional License
Terms shall automatically be terminated with respect to such Regional Licensed
Product pursuant to Section 10.2.2.3 (Termination of Regional Licensed Product
upon Exercise of the Co-Co/Global Option in respect of a Regional Licensed
Product), and all license grants in these Regional License Terms from either
Party to the other shall immediately terminate with respect to the terminated
Regional Licensed Product. In such event such former Regional Licensed Product
shall be a Co-Co Licensed Product or a Global Licensed Product, as applicable,
and shall be governed by either the Co-Co License Terms or the Global License
Terms. For clarity, notwithstanding any such termination, these Regional License
Terms shall continue to survive in all respects with respect to all Regional
Licensed Products other than such terminated Regional Licensed Product.

10.3.1.3. Effects of Termination of Regional Licensed Product by Alnylam for
Cause or by Genzyme for Convenience. Without limiting any other legal or
equitable remedies that either Party may have, if these Regional License Terms
are terminated with respect to any particular Regional Licensed Product by
Genzyme pursuant to Section 10.2.1 (Termination of Regional Licensed Product for
Convenience), by Alnylam under Section 10.2.2 (Termination of Regional Licensed
Product for Cause) or by Alnylam under Section 10.2.4 (Challenges of Patent
Rights), then the provisions of this Section 10.3.1.3 shall apply.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(a) These Regional License Terms shall continue to survive in all respects with
respect to all Regional Licensed Products other than the terminated Regional
Licensed Product.

(b) All license grants in these Regional License Terms with respect to the
terminated Regional Licensed Product from either Party to the other shall
immediately terminate.

(c) Any other siRNAs Developed by Alnylam that target the same human gene as the
terminated Regional Licensed Product shall not be considered Option Products for
purposes of the Master Agreement; provided, however, that if Alnylam ceases
active Development of such terminated Regional Licensed Product upon such
termination, then the other siRNAs that target the same human gene as such
Regional Licensed Product shall again be considered Option Products for the
purposes of the Master Agreement. [***]

(d) Genzyme will grant to Alnylam, effective upon the effective date of
termination and subject to the provisions of any applicable Genzyme In-License,
a non-transferable, sublicensable (on terms consistent with Section 6.2.4
(Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any
Collaboration IP and Genzyme Patent Rights that Cover the terminated Regional
Licensed Product, in the form that such terminated Regional Licensed Product
exists on the effective date of termination (a “Reverted Regional Licensed
Product”), solely to the extent necessary to Develop and Commercialize the
Reverted Regional Licensed Product in the Field in the Genzyme Territory.
Notwithstanding the foregoing, if (i) any Patent Rights that Cover the Reverted
Regional Licensed Product are Controlled by Genzyme pursuant to a Genzyme
In-License and (ii) such Genzyme In-License cannot be assigned to Alnylam or
does not relate exclusively to the Reverted Regional Licensed Product, Genzyme
shall promptly disclose any payment obligations under such Genzyme In-License to
Alnylam and such Genzyme Patent Rights shall be subject to the license granted
in this Section 10.3.1.3(d) only if Alnylam agrees in writing to (A) reimburse
Genzyme for one hundred percent (100%) of any amounts that become payable under
such Genzyme In-License as a result of Alnylam’s exercise of the license granted
in this Section 10.3.1.3(b), (B) comply with all applicable terms and conditions
of such Genzyme In-License and (C) perform and take such actions as may be
required to allow Genzyme to comply with its obligations under such Genzyme
In-License.

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product-Specific Patents that relate solely to the
Reverted Regional Licensed Product that were assigned to Genzyme pursuant to
Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(f) The license grants to Alnylam in Section 6.2 (License Grants to Alnylam)
shall survive and shall be expanded to include the Genzyme Territory with
respect to the Reverted Regional Licensed Product.

(g) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all governmental or regulatory
correspondence, conversation logs, filings and approvals (including all
Regulatory Approvals and pricing and reimbursement approvals) solely relating to
the Development, Manufacture or Commercialization of the Reverted Regional
Licensed Product, (ii) copies of all data, reports, records and materials, and
other sales and marketing related information in Genzyme’s possession or Control
to the extent that such data, reports, records, materials or other information
relate to the Development, Manufacture or Commercialization of the Reverted
Regional Licensed Product, including all non-clinical and clinical data relating
to the Reverted Regional Licensed Product, and customer lists and customer
contact information and all adverse event data related to the Reverted Regional
Licensed Product in Genzyme’s possession or Control, provided that, for a period
of [***] months after the effective date of termination with respect to such
Reverted Regional Licensed Product, Genzyme shall use Commercially Reasonable
Efforts to obtain for Alnylam the right to access all such data, reports,
records, materials, and other sales and marketing related information related to
the Reverted Regional Licensed Product, and (iii) all records and materials in
Genzyme’s possession or Control containing Confidential Information of Alnylam
solely relating to the Reverted Regional Licensed Product. In addition, Genzyme
shall appoint Alnylam as Genzyme’s and/or Genzyme’s Related Parties’ agent for
all matters related to the Reverted Regional Licensed Product involving
Regulatory Authorities in the Genzyme Territory until all Regulatory Approvals
and other regulatory filings have been transferred to Alnylam or its designee.

(h) If the effective date of termination is after First Commercial Sale of the
Reverted Regional Licensed Product, then Genzyme shall appoint Alnylam as its
exclusive distributor of such Reverted Regional Licensed Product in the Genzyme
Territory and grant Alnylam the right to appoint sub-distributors, until such
time as all Regulatory Approvals in the Genzyme Territory have been transferred
to Alnylam or its designee.

(i) If Genzyme or its Related Parties are Manufacturing finished product with
respect to the Reverted Regional Licensed Product on the effective date of
termination, at Alnylam’s option, Genzyme or its Related Parties shall supply
such finished product to Alnylam in the Genzyme Territory on terms no less
favorable than those on which Genzyme supplied such finished product prior to
such termination to its most favored distributor in the Genzyme Territory, until
the earlier of (i) such time as all Regulatory Approvals in the Genzyme
Territory solely related to the Reverted Regional Licensed Product have been
transferred to Alnylam or its designee, Alnylam has obtained all necessary
manufacturing approvals and Alnylam has procured or developed its own source of
such finished product supply or (ii) [***] months following the effective date
of such termination.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(j) If Alnylam so requests, and to the extent permitted under Genzyme’s
obligations to Third Parties on the effective date of termination, Genzyme shall
transfer to Alnylam any Third Party agreements relating solely and exclusively
to the Development, Manufacture or Commercialization of the Reverted Regional
Licensed Product to which Genzyme is a party (including any Genzyme In-License),
subject to any required consents of such Third Party, which Genzyme shall use
Commercially Reasonable Efforts to obtain promptly;

(k) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and
its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s)
(but not any Genzyme house marks or any trademark containing the word “Genzyme”
owned by Genzyme and used for the Reverted Regional Licensed Product in the
Field in the Genzyme Territory) owned by Genzyme and used solely and exclusively
for the Reverted Regional Licensed Products in the Field in the Genzyme
Territory.

(l) Genzyme shall transfer to Alnylam any inventory of the Reverted Regional
Licensed Products Controlled by Genzyme or its Affiliates as of the termination
date at the actual price paid by Genzyme for such supply.

(m) Genzyme shall provide any other assistance reasonably requested by Alnylam
for the purpose of allowing Alnylam or its designee to proceed expeditiously
with the Development, Manufacture and Commercialization of the Reverted Regional
Licensed Product in the Genzyme Territory, provided that Genzyme’s obligations
under this clause (m) of Section 10.3.1.3 shall expire [***] months after the
effective date of termination of such Reverted Regional Licensed Product.

(n) Genzyme shall execute all documents and take all such further actions as may
be reasonably requested by Alnylam in order to give effect to the foregoing
clauses.

10.3.2. Effects of Termination for Abandonment of Development. If these Regional
License Terms are terminated in their entirety (i.e., with respect to all
Regional Licensed Products) by either Party pursuant to Section 10.2.5
(Abandonment of Development), then the license granted to Alnylam under
Section 6.2.2 (License to Improvement Manufacturing Patent Rights) shall survive
and all other licenses granted in these Regional License Terms from either Party
to the other shall immediately terminate and:

(a) Any other siRNAs Developed by Alnylam that target the same human gene as the
terminated Regional Licensed Product shall not be considered Option Products for
purposes of the Master Agreement; provided, however, that if Alnylam ceases
active Development of such terminated Regional Licensed Product upon such
termination, then the other siRNAs that target the same human gene as such
Regional Licensed Product shall again be considered Option Products for the
purposes of the Master Agreement. [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all Regulatory Approvals and pricing
and reimbursement approvals relating to the Development, Manufacture or
Commercialization of the terminated Regional Licensed Product, and (ii) copies
of all non-clinical and clinical data and material regulatory correspondence
relating to the terminated Regional Licensed Product.

(c) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product-Specific Patents that relate solely to the
terminated Regional Licensed Product that were assigned to Genzyme pursuant to
Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme.

(d) each Party shall promptly pay any amounts owed to the other Party as of the
effective date of such termination.

10.4. Fundamental Breach of Alnylam’s Development Obligations. Without limiting
Genzyme’s rights under Section 10.2.2 (Termination of a Regional Licensed
Product for Cause) with respect to other material breaches, in the event that
Alnylam commits a Fundamental Breach of its Development obligations under
Section 2.4.2 (Alnylam Diligence) with respect to any particular Regional
Licensed Product, and Genzyme does not terminate these Regional License Terms in
their entirety (i.e., with respect to all Regional Licensed Products) or with
respect to such Regional Licensed Product for cause pursuant to Section 10.2.2
(Termination of a Regional Licensed Product for Cause), then Genzyme may elect
to receive the following remedies for such Fundamental Breach:

10.4.1.1. Genzyme’s obligation to pay development milestone fees under
Section 7.1 (Milestone Fees) with respect to such Regional Licensed Product
shall automatically terminate;

10.4.1.2. Genzyme will receive a credit, which Genzyme may offset against
royalties and sales milestones due to Alnylam with respect to such Regional
Licensed Product pursuant to Section 7 (Certain Financial Terms), in an amount
equal to one hundred fifty percent (150%) of all costs and expenses (i) incurred
by Genzyme to Develop such Regional Licensed Product for the Genzyme Territory
that are in excess of the costs budgeted by Genzyme in connection with the
Genzyme Territory Development Plan for such Regional Licensed Product in effect
at the time of Alnylam’s Fundamental Breach of Section 2.4.2 (Alnylam Diligence)
with respect to such Regional Licensed Product and (ii) are incurred by Genzyme
as a direct consequence of Alnylam’s Fundamental Breach of Section 2.4.2
(Alnylam Diligence) with respect to such Regional Licensed Product;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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10.4.1.3. Genzyme may, in its discretion, terminate any or all of the following
provisions of these Regional License Terms (or any subsection thereof) with
respect to such Regional Licensed Product: Section 3.1.3 (Regulatory Meetings),
Section 4.1.3 (Joint Commercialization), Section 4.3 (Genzyme Territory
Commercialization Plan), Section 4.4 (Alnylam Territory Commercialization Plan),
Section 4.5 (Advertising and Promotional Materials), Section 4.6
(Commercialization Reporting Obligations), and Section 5 (Collaboration
Management); and

10.4.1.4. Without limiting Genzyme’s remedies under these Regional License Terms
or otherwise with respect to breaches of Alnylam’s Development obligations under
clause (a) of Section 2.4.2 (Alnylam Diligence) other than Fundamental Breaches,
if Genzyme elects to receive the remedies set forth in this Section 10.4 with
respect to a Fundamental Breach of its Development obligations under clause
(a) of Section 2.4.2 (Alnylam Diligence) with respect to such Regional Licensed
Product, such remedies shall be Genzyme’s sole and exclusive remedies with
respect to such Fundamental Breach and Genzyme shall have no right to seek any
further remedies or damages against Alnylam and its Affiliates with respect to
such Fundamental Breach by Alnylam of clause (a) of Section 2.4.2 (Alnylam
Diligence).

10.5. Effect of Expiration or Termination; Survival. Any expiration or
termination of these Regional License Terms (a) shall not relieve the Parties of
any obligation accruing prior to such expiration or termination and (b) shall be
without prejudice to the rights of either Party against the other Party accrued
or accruing under these Regional License Terms prior to such expiration or
termination, including the obligation to pay royalties for any Regional Licensed
Product sold prior to such expiration or termination. The following provisions
shall survive any expiration or termination of these Regional License Terms in
their entirety (i.e., with respect to all Regional Licensed Products) and, if
these Regional License Terms expire or are terminated with respect to any
particular Regional Licensed Product, shall survive with respect to such
Regional Licensed Product: (a) Sections 1 (Definitions), 8.3 (Warranty
Disclaimer), 9.1 (Inventorship), 9.2 (Ownership), 10.3 (Effect of Termination),
10.5 (Effect of Termination or Expiration; Survival) and Section 11 (Performance
by Affiliates) of these Regional License Terms and (b) Sections 1 (Definitions),
7 (Confidentiality and Publication), 9 (Royalty Reports; Payments; Audit), 10
(Indemnification; Limitation of Liability; Insurance), 12 (Term and Termination)
and 13 (Miscellaneous) of the Master Agreement. Section 7.2.6 (Royalty Floor)
shall survive any termination or expiration of these Regional License Terms with
respect to any Regional Licensed Product for royalties accruing prior to such
termination or expiration. Section 9 of the Master Agreement (Royalty Reports;
Payments; Audit) will survive for so long as any royalties are due under these
Regional License Terms plus three (3) years. Except as otherwise set forth in
this Section 10 or elsewhere in these Regional License Terms, upon termination
or

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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expiration of these Regional License Terms in their entirety, all rights and
obligations of the Parties under these Regional License Terms shall cease, but,
for clarity, expiration or termination of these Regional License Terms in their
entirety (i.e., with respect to all Regional Licensed Products) shall not result
in the termination or expiration of the Master Agreement or any License Terms.
Upon termination or expiration of these Regional License Terms with respect to
any particular Regional Licensed Product, all rights and obligations of the
Parties under these Regional License Terms with respect to such Regional
Licensed Product shall cease except as otherwise set forth in this Section 10 or
elsewhere in these Regional License Terms, but, for clarity, such termination or
expiration shall not affect the Parties’ rights and obligations under these
Regional License Terms with respect to any other Regional Licensed Product.

11. PERFORMANCE BY AFFILIATES

11.1. Use of Affiliates. Each Party acknowledges and accepts that the other
Party may exercise its rights and perform its obligations under these Regional
License Terms either directly or through one or more of its Affiliates. A
Party’s Affiliates will have the benefit of all rights (including all licenses)
of such Party under these Regional License Terms. Accordingly, in these Regional
License Terms “Genzyme” will be interpreted to mean “Genzyme and/or its
Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its
Affiliates” where necessary to give each Party’s Affiliates the benefit of the
rights provided to such Party in these Regional License Terms; provided,
however, that in any event each Party will remain responsible for the acts and
omissions, including financial liabilities, of its Affiliates.

11.2. Future Acquisition of a Party or its Business. [***]

11.3. Acquired Programs.

11.3.1. [***]

11.3.2. [***]

11.4. For clarity, upon the closing of the acquisition of the stock and/or
assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp.,
all relevant acquired intellectual property rights acquired in such transaction
that may be Controlled by Alnylam (without any further action by Alnylam or
Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of
these Regional License Terms.

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 1.2.13-1

ALNYLAM CORE TECHNOLOGY PATENTS FOR ALN-TTR02

See attached.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 1.2.18-1

ALNYLAM PRODUCT-SPECIFIC PATENTS FOR ALN-TTR02

See attached.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 2.2.1-1

GLOBAL DEVELOPMENT STRATEGY FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.1)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 2.2.2.1-1

GLOBAL DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.2.1)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 2.2.2.6(d)-1

ALNYLAM TERRITORY DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.2.6(d).)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 2.2.4-1

GENZYME TERRITORY DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.4.)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 8.1

DISCLOSURE SCHEDULE

See attached.

Confidential

 

--------------------------------------------------------------------------------

REGIONAL LICENSE TERMS

 

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 8.1.12

(A) EXISTING ALNYLAM IN-LICENSES

(To be attached)

(B) ADDITIONAL ALNYLAM INLICENSES

(To be attached)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 8.4.1.3(c)

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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APPENDIX B

GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

TABLE OF CONTENTS

 

     Page  

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

     1   

1.1 Relationship with Master Agreement

     1   

1.2 Definitions

     2   

2. DEVELOPMENT

     16   

2.1 Overview

     16   

2.2 Transition

     16   

2.3 Global Development Plan

     17   

2.4 Development Costs

     17   

2.5 Diligence

     18   

2.6 Records; Reports; Information Sharing

     18   

2.7 Third Parties

     19   

3. REGULATORY MATTERS

     20   

3.1 Regulatory Filings and Interactions

     20   

3.2 Costs of Regulatory Affairs

     21   

3.3 Right of Reference

     21   

4. COMMERCIALIZATION OF THE GLOBAL LICENSED PRODUCTS

     21   

4.1 Responsibility, Cost and Diligence

     21   

4.2 Commercialization Summary

     21   

4.3 First Commercial Sale Reporting Obligations

     21   

4.4 Advertising and Promotional Materials

     21   

4.5 Sales and Distribution

     22   

4.6 Recalls, Market Withdrawals or Corrective Actions

     22   

5. TRANSITION MANAGEMENT

     22   

5.1 Joint Transition Team

     22   

5.2 Meetings

     23   

5.3 Minutes

     23   

5.4 JTT Responsibilities

     23   

5.5 Decision-Making

     23   

5.6 Term of JTT

     24   

6. MANUFACTURE AND SUPPLY OF THE GLOBAL LICENSED PRODUCTS

     24   

6.1 Manufacturing and Supply

     24   

7. LICENSES

     24   

7.1 License Grants to Genzyme

     24   

 

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“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-i-

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7.2 License Grants to Alnylam

     27   

7.3 Joint Collaboration IP

     28   

7.4 In-Licenses

     28   

7.5 Right of First Negotiation

     28   

7.6 Bankruptcy

     29   

7.7 No Other Rights

     30   

8. CERTAIN FINANCIAL TERMS

     30   

8.1 Milestone Fees

     30   

8.2 Royalties

     32   

9. REPRESENTATIONS, WARRANTIES AND COVENANTS

     35   

9.1 Representations and Warranties of Alnylam

     35   

9.2 Representations and Warranties of Genzyme

     37   

9.3 Warranty Disclaimer

     37   

9.4 Certain Covenants

     37   

10. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

     38   

10.1 Inventorship

     38   

10.2 Ownership

     38   

10.3 Prosecution and Maintenance of Patent Rights

     39   

10.4 Third Party Infringement

     43   

10.5 Patent Term Extensions

     45   

10.6 Common Interest

     46   

10.7 Trademarks

     46   

10.8 Cooperative Research and Technology (CREATE) Act Acknowledgment

     46   

11. TERM AND TERMINATION

     47   

11.1 Term

     47   

11.2 Termination Rights

     47   

11.3 Effect of Termination

     48   

11.4 Effect of Expiration or Termination; Survival

     51   

12. PERFORMANCE BY AFFILIATES

     52   

12.1 Use of Affiliates

     52   

12.2 Future Acquisition of a Party or its Business

     52   

12.3 Acquired Programs

     52   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULES

 

Schedule 1.2.8    Alnylam Core Technology Patents Schedule 1.2.15    Alnylam
Product-Specific Patents Schedule 1.2.96    Licensed Target Schedule 9.1   
Disclosure Schedule Schedule 9.1.12    Existing Alnylam In-Licenses / Additional
Alnylam In-Licenses Schedule 9.4.1(e)    Exceptions to Exclusivity

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS

THESE GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS are Appendix B to the
Master Collaboration Agreement, dated as of the Execution Date, by and between
Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the
laws of the State of Delaware (“Alnylam”), and Genzyme Corporation, a
corporation organized and existing under the laws of the Commonwealth of
Massachusetts (“Genzyme”).

RECITALS:

WHEREAS, Alnylam and Genzyme are parties to that certain Master Collaboration
Agreement (dated as of the Execution Date) (the “Master Agreement”) pursuant to
which Genzyme has options to receive licenses and other rights with respect to
up to two Global Licensed Products from Alnylam in the Licensed Territory;

WHEREAS, Genzyme may exercise its Co-Co/Global Option pursuant to the Master
Agreement for ALN-AS1 and such siRNA will then become a Global Licensed Product;

WHEREAS, Genzyme may exercise its Global Option or Trailing Global Option
pursuant to the Master Agreement for any Global Option Product thereunder and
such Global Option Product will then be deemed a Global Licensed Product;

WHEREAS, if Genzyme does not exercise the Co-Co/Global Option pursuant to the
Master Agreement for ALN-AS1 or ALN-AT3, Genzyme may exercise its Additional
Global Option pursuant to the Master Agreement for any Global Option Product
thereunder and such Global Option Product will then be deemed a Global Licensed
Product; and

WHEREAS, Alnylam and Genzyme now wish to set forth the terms and conditions
under which Genzyme will have the right to Commercialize such Global Licensed
Products in the Licensed Territory.

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the Parties hereby agree as follows:

 

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1 Relationship with Master Agreement. These Global License Terms become
effective on a Global Licensed Product-by-Global Licensed Product basis on the
Implementation Date in accordance with the Master Agreement. The Master
Agreement generally governs the Parties’ relationship with respect to Global
Licensed Products during the period of time before Genzyme exercises its
Co-Co/Global Option, Global Option or Additional Global Option under the Master
Agreement (i.e., before such product became a Global Licensed Product). The
Master Agreement also contains terms that are generally applicable to Global
Licensed Products, Regional Licensed Products (as defined in the Master
Agreement) and Co-Co Licensed Products (as defined in the Master Agreement).
Accordingly, the following Sections of the Master Agreement are

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

 

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GLOBAL LICENSE TERMS

 

incorporated herein by reference: Section 2.2 (Effectiveness of Licenses to
Collaboration Products); Section 5 (Collaboration Management); Section 6
(Manufacture and Supply of the Collaboration Products); Section 7
(Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit);
Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4
(Challenges of Patent Rights); and Section 13 (Miscellaneous).

1.2 Definitions. Unless specifically set forth to the contrary herein, the
following terms, whether used in the singular or plural, shall have the
respective meanings set forth below:

1.2.1 “Acquired Business” has the meaning set forth in Section 12.3 (Acquired
Programs).

1.2.2 “Acquirer” has the meaning set forth in Section 12.2 (Future Acquisition
of a Party or its Business).

1.2.3 “Additional Alnylam In-Licenses” has the meaning set forth in the Master
Agreement.

1.2.4 “Additional Global Option” has the meaning set forth in the Master
Agreement.

1.2.5 “AF11 Lipid Nanoparticle Formulation” has the meaning set forth in the
Master Agreement.

1.2.6 “Affiliate” means, with respect to a Person, any other Person which
controls, is controlled by, or is under common control with the applicable
Person. For purposes of this definition, “control” means: (a) in the case of
corporate entities, direct or indirect ownership of at least fifty percent
(50%) of the stock or shares entitled to vote for the election of directors, or
otherwise having the power to control or direct the affairs of such Person; and
(b) in the case of non-corporate entities, direct or indirect ownership of at
least fifty percent (50%) of the equity interest or the power to direct the
management and policies of such non-corporate entities.

1.2.7 “AJSC” has the meaning set forth in the Master Agreement.

1.2.8 “ALN-AS1” has the meaning set forth in the Master Agreement.

1.2.9 “ALN-AT3” has the meaning set forth in the Master Agreement.

1.2.10 “Alnylam Core Technology Patents” means Patent Rights Controlled by
Alnylam during the Term that are [***]. The Alnylam Core Technology Patents
existing as of the Implementation Date for any Global Licensed Product will be
identified as the “Alnylam Core Technology Patents” in the Option Data Package
for such Global Licensed Product provided by Alnylam to Genzyme under the Master
Agreement and then attached hereto as Schedules 1.2.8-1 and 1.2.8-2, if
applicable.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.11 “Alnylam Developed siRNA Product” means an siRNA with respect to which
(a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a
product first satisfies the criterion set forth in this clause (a) such
criterion shall be deemed satisfied at all times thereafter as to such product;
and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the
Development.

1.2.12 “Alnylam In-License” means any Existing Alnylam In-License or any
Collaboration In-License to which Alnylam is a party. 

1.2.13 “Alnylam Know-How” means Know-How Controlled by Alnylam during the Term
that is reasonably necessary or useful for Genzyme to Develop, Manufacture
and/or Commercialize Global Licensed Products in the Field in the Licensed
Territory, other than Alnylam’s interest in Know-How included in Joint
Collaboration IP.

1.2.14 “Alnylam Patents” means Alnylam Core Technology Patents and Alnylam
Product-Specific Patents.

1.2.15 “Alnylam Product-Specific Patents” means Patent Rights Controlled by
Alnylam during the Term that claim [***]. The Alnylam Product-Specific Patents
existing as of the Implementation Date for any Global Licensed Product will be
identified as the “Alnylam Product-Specific Patents” in the Option Data Package
for such Global Licensed Product provided by Alnylam to Genzyme under the Master
Agreement and then attached hereto as Schedules 1.2.15-2 and 1.2.15-3, if
applicable. [***]

1.2.16 “Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam
Patents and Alnylam’s interest in Joint Collaboration IP.

1.2.17 “Alnylam Trademark” has the meaning set forth in Section 10.7(a)
(Trademarks).

1.2.18 “ANDA” means an Abbreviated New Drug Application (or any successor
application or procedure) as defined in regulations promulgated by the FDA under
the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as
applicable, any other analogous application filed with a Regulatory Authority in
any country other than the U.S. in the Licensed Territory) for Regulatory
Approval for marketing and selling a Global Licensed Product in the Licensed
Territory.

1.2.19 “Back-Up Option” has the meaning set forth in Section 7.1.5 (Back-Up
Products).

1.2.20 “Back-Up Option Exercise Notice” has the meaning set forth in
Section 7.1.5 (Back-Up Products).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-3-

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GLOBAL LICENSE TERMS

 

1.2.21 “Back-Up Option Period” means [***].

1.2.22 “Back-Up Product” has the meaning set forth in Section 7.1.5 (Back-Up
Products).

1.2.23 “Bankrupt Party” has the meaning set forth in Section 7.6 (Bankruptcy).

1.2.24 “Calendar Quarter” means the respective periods of three (3) consecutive
calendar months ending on March 31, June 30, September 30 and December 31 of
each Calendar Year, provided that (a) the first Calendar Quarter of the Term
shall begin on the Effective Date and end on the first to occur of
March 31, June 30, September 30 or December 31 thereafter and the last Calendar
Quarter of the Term shall end on the last day of the Term and (b) the first
Calendar Quarter of a Royalty Term for a Global Licensed Product in a country
shall begin on the First Commercial Sale of a Global Licensed Product in such
country and end on the first to occur of March 31, June 30, September 30 or
December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end
on the last day of such Royalty Term.

1.2.25 “Calendar Year” means each successive period of twelve (12) months
commencing on January 1 and ending on December 31, provided that (a) the first
Calendar Year of the Term shall begin on the Effective Date and end on the first
December 31 thereafter and the last Calendar Year of the Term shall end on the
last day of the Term and (b) the first Calendar Year of a Royalty Term for a
Global Licensed Product in a country shall begin on the First Commercial Sale of
a Global Licensed Product in such country and end on the first December 31
thereafter and the last Calendar Year of the Term shall end on the last day of
such Royalty Term.

1.2.26 “Carbohydrate Conjugate” has the meaning set forth in the Master
Agreement.

1.2.27 “Clinical Study” has the meaning set forth in the Master Agreement.

1.2.28 “Co-Co/Global Option” has the meaning set forth in the Master Agreement.

1.2.29 “Co-Co/Global Option Product” has the meaning set forth in the Master
Agreement.

1.2.30 “Collaboration” has the meaning set forth in the Master Agreement.

1.2.31 “Collaboration In-License” has the meaning set forth in the Master
Agreement.

1.2.32 “Collaboration Product” has the meaning set forth in the Master
Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-4-

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GLOBAL LICENSE TERMS

 

1.2.33 “Commercialization” or “Commercialize” has the meaning set forth in the
Master Agreement.

1.2.34 “Commercialization Summary” has the meaning set forth in Section 4.2
(Commercialization Summary).

1.2.35 “Commercially Reasonable Efforts” means [***].

1.2.36 “Competing Program” has the meaning set forth in Section 12.3.1 (Acquired
Programs).

1.2.37 “Competitive Infringement” has the meaning set forth in Section 10.4.1
(Notices).

1.2.38 “Confidential Information” has the meaning set forth in the Master
Agreement.

1.2.39 “Control”, “Controls” or “Controlled by” has the meaning set forth in the
Master Agreement.

1.2.40 “Cost of Goods” has the meaning set forth in the Master Agreement.

1.2.41 “Cover,” “Covering” or “Covers” has the meaning set forth in the Master
Agreement.

1.2.42 “CPI” means the Consumer Price Index – Urban Wage Earners and Clerical
Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United
States Department of Labor, Bureau of Labor Statistics (or its successor
equivalent index) in the United States.

1.2.43 “Development,” “Developing” or “Develop” has the meaning set forth in the
Master Agreement.

1.2.44 “Development Information” has the meaning set forth in Section 2.2
(Transition).

1.2.45 “Effective Date” means the date that the Master Agreement becomes
effective in accordance with its terms.

1.2.46 “EMA” means the European Medicines Agency and any successor Governmental
Authority having substantially the same function.

1.2.47 “EU” means the European Union, as its membership may be altered from time
to time, and any successor thereto.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.48 “Exclusivity Period” means, on a Global Licensed Product-by-Global
Licensed Product and country-by-country basis within the Licensed Territory, the
period of time commencing on the Implementation Date for such Global Licensed
Product and continuing until the first to occur of (a) [***].

1.2.49 “Existing Alnylam In-License” has the meaning set forth in the Master
Agreement.

1.2.50 “Execution Date” has the meaning set forth in the Master Agreement.

1.2.51 “Exercise Notice” has the meaning set forth in the Master Agreement.

1.2.52 “Existing Genzyme In-License” has the meaning set forth in the Master
Agreement.

1.2.53 “FDA” means the United States Food and Drug Administration and any
successor Governmental Authority having substantially the same function.

1.2.54 “FDCA” means the United States Federal Food, Drug, and Cosmetic Act of
1938, as amended from time to time, and the regulations and guidelines
promulgated thereunder.

1.2.55 “Field” means the treatment, diagnosis and/or prevention of all human
diseases.

1.2.56 “First Commercial Sale” means, with respect to a country, the first sale
for end use or consumption of a Global Licensed Product in such country, except
for compassionate use or patient access programs, after all Regulatory Approvals
legally required for such sale have been granted by the Regulatory Authority of
such country.

1.2.57 “First Regulatory Approval by the EMA” means, with respect to a Global
Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought
through the EMA centralized procedure, receipt of Regulatory Approval for such
Global Licensed Product from the EMA or (ii) if Regulatory Approval in the EU is
sought through a national authorization procedure, receipt of Regulatory
Approval for such Global Licensed Product in the first (1st) MMC in the EU.

1.2.58 “First Regulatory Approval in Japan” means, with respect to a Global
Licensed Product, receipt of Regulatory Approval for such Global Licensed
Product in Japan.

1.2.59 “GalNAc Conjugate” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-6-

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GLOBAL LICENSE TERMS

 

1.2.60 “Generic Competition” means, with respect to a Global Licensed Product in
any country in the Licensed Territory in a given Calendar Quarter, that, during
such Calendar Quarter, (a) one or more Generic Products with respect to such
Global Licensed Product are commercially available in such country, and (b) Net
Sales of such Global Licensed Product in such country in such Calendar Quarter
equal less than [***] of the average Net Sales of such Global Licensed Product
over the [***] consecutive Calendar Quarters immediately prior to the Calendar
Quarter in which one or more Generic Products first became commercially
available in such country.

1.2.61 “Generic Product” means, on a Global Licensed Product-by-Global Licensed
Product and country-by-country basis, a pharmaceutical product that (a) is sold
by a Person that is not a Related Party of Genzyme under a marketing
authorization granted by a Regulatory Authority in such country to a Third
Party; (b) [***] and (c) is approved by the Regulatory Authority in such country
pursuant to an approval process that relies in part on pivotal safety and/or
efficacy data in such Regulatory Authority’s previous grant of marketing
authorization for such Global Licensed Product.

1.2.62 “Genzyme Collaboration IP” means (a) any Know-How, first identified,
discovered or developed solely by employees of Genzyme or its Affiliates or
other persons not employed by Alnylam acting on behalf of Genzyme, in the
conduct of the Collaboration and (b) any Patent Rights that claim or cover such
Know-How and are Controlled by Genzyme at any time during the Term. Genzyme
Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each
case (a) and (b), other than Genzyme Manufacturing IP.

1.2.63 “Genzyme Disclosed Manufacturing Know-How” means Know-How (a) Controlled
by Genzyme at any time during the Term that is useful in the Manufacture of a
Global Licensed Product and (b) that Genzyme, in its sole discretion, discloses
in writing to Alnylam in the course of the Collaboration.

1.2.64 “Genzyme In-License” means any Existing Genzyme In-License, Un-Blocking
Genzyme In-License or any Collaboration In-License to which Genzyme is a party.

1.2.65 “Genzyme Know-How” means Know-How Controlled by Genzyme during the Term
that is reasonably necessary or useful for Alnylam to Develop, Commercialize
and/or Manufacture Global Licensed Products in the Field in the Licensed
Territory (other than Genzyme’s rights in Joint Collaboration IP, Genzyme
Collaboration IP and Genzyme Manufacturing IP).

1.2.66 “Genzyme Manufacturing IP” means (a) any Know-How related to the
Manufacture of Global Licensed Products (or oligonucleotides generally)
Controlled by Genzyme at any time during the Term, and (b) any Patent Rights
that claim or cover such Know-How and are Controlled by Genzyme at any time
during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme
Disclosed Manufacturing Know-How.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-7-

--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

1.2.67 “Genzyme Patent Jurisdictions” has the meaning set forth in the Master
Agreement.

1.2.68 “Genzyme Patent Rights” means those Patent Rights Controlled by Genzyme
during the Term that are reasonably necessary or useful to Develop,
Commercialize and/or Manufacture Global Licensed Products in the Field in the
Licensed Territory. Genzyme Patent Rights excludes Patent Rights included in
Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and
Genzyme Manufacturing IP.

1.2.69 “Genzyme Technology” means, collectively, Genzyme Know-How, Genzyme
Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint
Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.70 “Genzyme Trademarks” has the meaning set forth in Section 10.7(a)
(Trademarks).

1.2.71 “Global Branding Strategy” has the meaning set forth in Section 4.4.1
(Global Branding).

1.2.72 “Global Development Plan” has the meaning set forth in Section 2.3
(Global Development Plan).

1.2.73 “Global License Terms” means this Appendix B to the Master Agreement
(Global Product License and Collaboration Terms) and the provisions of the
Master Agreement to the extent applicable to Global Licensed Products.

1.2.74 “Global Licensed Product” means (i) if Genzyme exercises the Co-Co/Global
Options for ALN-AS1 pursuant to the Master Agreement, then ALN-AS1 as of the
applicable Option Exercise Date, (ii) if Genzyme exercises the Global Option or
the Trailing Global Option for any Global Option Product pursuant to the Master
Agreement, then such Global Option Product as of the applicable Option Exercise
Date, (iii) if Genzyme exercises the Additional Global Option for any Global
Option Product pursuant to the Master Agreement, then such Global Option Product
as of the applicable Option Exercise Date, and (iv) if Genzyme exercises a
Back-Up Option for any Back-Up Product pursuant to Section 7.1.5 (Back-Up
Products), then such Back-Up Product as of the date of delivery of the Back-Up
Option Exercise Notice, in each case (i) through (iv) above, for as long as the
Global License Terms apply to ALN-AS1, such Global Option Product or such
Back-Up Product.

1.2.75 “Global Option” has the meaning set forth in the Master Agreement.

1.2.76 “Global Option Period” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-8-

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GLOBAL LICENSE TERMS

 

1.2.77 “Global Option Product” has the meaning set forth in the Master
Agreement.

1.2.78 “Global Out-of-Pocket Costs” means, with respect to certain activities
hereunder, direct expenses paid or payable by either Party or its Affiliates to
Third Parties and specifically identifiable and incurred to conduct such
activities for a Global Licensed Product, including payments to contract
personnel; provided, however, that amounts paid to contract sales and marketing
personnel will not be considered Global Out-of-Pocket Costs.

1.2.79 “GLP Clinical Supply Agreements” means each clinical supply agreement
entered into between Alnylam and Genzyme as described in Section 6.2 of the
Master Agreement (Collaboration Product Supply Agreements) pursuant to which
Alnylam will provide clinical supplies of a specified Global Licensed Product to
Genzyme.

1.2.80 “GLP Collaboration” means the collaboration of the Parties in the
Development, Manufacture and Commercialization of Global Licensed Products under
these Global License Terms.

1.2.81 “GLP Commercial Supply Agreements” means each commercial supply agreement
entered into between Alnylam and Genzyme as described in Section 6.2 of the
Master Agreement (Collaboration Product Supply Agreements) pursuant to which
Alnylam will provide commercial supplies of a specified Global Licensed Product
to Genzyme.

1.2.82 “GLP Supply Agreements” means, collectively, the GLP Clinical Supply
Agreements and the GLP Commercial Supply Agreements.

1.2.83 “Good Laboratory Practices” has the meaning set forth in the Master
Agreement.

1.2.84 “Governmental Authority” means any applicable government authority,
court, tribunal, arbitrator, agency, department, legislative body, commission or
other instrumentality of (a) any government of any country or territory, (b) any
nation, state, province, county, city or other political subdivision thereof or
(c) any supranational body.

1.2.85 “Human POP Study” has the meaning set forth in the Master Agreement.

1.2.86 “IFRS” has the meaning set forth in the Master Agreement.

1.2.87 “Implementation Date” means (i) with respect to ALN-AS1 or each Global
Licensed Product with respect to which Genzyme exercised the Global Option or
Additional Global Option, the Option Exercise Date for ALN-AS1 or such Global
Licensed Product, as applicable, and (ii) with respect to each Back-Up Product
with respect to which Genzyme exercised the Back-Up Option, the date on which
Genzyme sent to Alnylam the Back-Up Option Exercise Notice for such Back-Up
Product under Section 7.1.5 (Back-Up Products).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-9-

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GLOBAL LICENSE TERMS

 

1.2.88 “Improvement Manufacturing Patent Right” means a Patent Right owned
exclusively by Genzyme or its Affiliates that claims an invention related to the
Manufacture of a Global Licensed Product that was made (a) by Genzyme or its
Affiliates after the Effective Date in connection with Manufacturing Global
Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam
Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s
Confidential Information under Section 7 of the Master Agreement
(Confidentiality and Publication).

1.2.89 “IND” has the meaning set forth in the Master Agreement.

1.2.90 “In-License” has the meaning set forth in the Master Agreement.

1.2.91 “Infringement Action” has the meaning set forth in Section 10.4.2(a)
(Rights to Enforce – Genzyme Technology).

1.2.92 “Joint Collaboration IP” means, collectively, (a) any Know-How first
identified, discovered or developed jointly by employee(s), agent(s) or
consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand,
and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its
Affiliates, on the other hand, in the conduct of the Collaboration that is
Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such
Know-How and are Controlled by Alnylam and Genzyme.

1.2.93 “Joint Transition Team” or “JTT” means the transition team as more fully
described in Section 5.1 (Joint Transition Team).

1.2.94 “Know-How” has the meaning set forth in the Master Agreement.

1.2.95 “Laws” has the meaning set forth in the Master Agreement.

1.2.96 “Licensed Target” means, for each Global Licensed Product, the human gene
that is targeted by such Global Licensed Product, as identified in the Option
Data Package for such Global Licensed Product and then attached hereto
as Schedules 1.2.96-1 and 1.2.96-2, if applicable.

1.2.97 “Licensed Territory” means worldwide.

1.2.98 “Lipid Nanoparticle Formulation” has the meaning set forth in the Master
Agreement.

1.2.99 “Manufacturing” or “Manufacture” has the meaning set forth in the Master
Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.100 “Manufacturing Claim” means a claim within a Patent Right directed
solely to Manufacturing a Global Licensed Product.

1.2.101 “MMC” means [***].

1.2.102 “NDA” has the meaning set forth in the Master Agreement.

1.2.103 “Net Sales” means, with respect to a Global Licensed Product, the
aggregate gross invoiced sales prices from sales of all units of such Global
Licensed Product sold by Genzyme and its Related Parties to independent Third
Parties (other than a Sublicensee) after deducting, if not previously deducted,
from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of
useful life or otherwise);

(c) Third Party rebates, chargebacks, hospital buying group/group purchasing
organization administration fees or managed care organization rebates actually
given;

(d) rebates and similar payments made with respect to sales paid for by any
governmental or regulatory authority such as Federal or state Medicaid, Medicare
or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

(g) value added, sales and use, excise and other similar taxes and surcharges,
customary transportation and insurance, custom duties, and other governmental
charges; and

(h) amounts previously included in Net Sales of such Global Licensed Product
that are adjusted or written-off by Genzyme or its Related Parties as bad debt
or otherwise uncollectible in accordance with the standard practices of Genzyme
or its Related Parties for writing off uncollectible amounts consistently
applied; provided, however, if any such written-off amounts are subsequently
collected, such collected amounts shall be included in Net Sales in the period
in which they are subsequently collected.

Such amounts shall be determined from the books and records of Genzyme or its
Related Parties, maintained in accordance with IFRS.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-11-

--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

In the case of any sale or other disposal for value, such as barter or
counter-trade, of a Global Licensed Product, or part thereof, other than in an
arm’s length transaction exclusively for cash, Net Sales shall be calculated as
above on the value of the non-cash consideration received or the fair market
price (if higher) of such Global Licensed Product in the country of sale or
disposal, as determined in accordance with IFRS.

Notwithstanding the foregoing, the following will not be included in Net Sales:
(1) sales between or among Genzyme and its Related Parties (but Net Sales shall
include sales to the first Third Party (other than a Sublicensee) by Genzyme or
its Related Parties); (2) samples of Global Licensed Product used to promote
additional Net Sales, in amounts consistent with normal business practices of
Genzyme; and (3) disposal or use of Global Licensed Products in Clinical Studies
or under compassionate use, patient assistance, named patient use, or test
marketing programs or non-registrational studies or other similar programs or
studies where the Global Licensed Product is supplied without charge or at the
actual manufacturing cost thereof (without allocation of indirect costs or any
mark-up).

In the case where a Global Licensed Product is sold as part of a Combination
Product in a country in the Licensed Territory, Net Sales for the Global
Licensed Product included in such Combination Product in such country shall be
calculated as follows:

 

  (i) if the Global Licensed Product is sold separately in such country and the
other active ingredient or ingredients in the Combination Product are sold
separately in such country, Net Sales for the Global Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/(A+B), where A is the invoice price of the Global
Licensed Product when sold separately in such country and B is the total invoice
price of the other active ingredient or ingredients in the Combination Product
when sold separately in such country;

 

  (ii) if the Global Licensed Product is sold separately in such country but the
other active ingredient or ingredients in the Combination Product are not sold
separately in such country, Net Sales for the Global Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/D, where A is the invoice price of the Global Licensed
Product when sold separately in such country and D is the invoice price of the
Combination Product in such country;

 

  (iii) if the Global Licensed Product is not sold separately in such country
but the other active ingredient or ingredients in the Combinations Product are
sold separately in such country, Net Sales for the Global Licensed Product shall
be calculated by multiplying actual Net Sales of such Combination Product by the
fraction 1 – (B/D), where B is the invoice price of the other active ingredient
or ingredients in the Combination Product when sold separately in such country
and D is the invoice price of the Combination Product; or

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

  (iv) if neither the Global Licensed Product nor the other active ingredient or
ingredients in the Combination Product are sold separately in such country, the
Parties shall determine Net Sales for the Global Licensed Product in such
Combination Product by mutual agreement based on the relative contribution of
the Global Licensed Product and each other active ingredient to the Combination
Product, and shall take into account in good faith any applicable allocations
and calculations that may have been made for the same period in other countries.

For purposes of this Section, “Combination Product” means a product that
includes at least one active ingredient other than a Global Licensed Product.
Drug delivery vehicles, adjuvants, and excipients shall not be deemed to be
“active ingredients”, except in the case where such delivery vehicle, adjuvant,
or excipient is recognized by the FDA as an active ingredient in accordance with
21 C.F.R. 210.3(b)(7).

1.2.104 “Non-Bankrupt Party” has the meaning set forth in Section 7.6
(Bankruptcy).

1.2.105 “Option Data Package” has the meaning set forth in the Master Agreement.

1.2.106 “Option Exercise Date” has the meaning set forth in the Master
Agreement.

1.2.107 “Party” means Genzyme and/or Alnylam.

1.2.108 “Patent Rights” has the meaning set forth in the Master Agreement.

1.2.109 “Person” means any natural person, corporation, unincorporated
organization, partnership, association, sole proprietorship joint stock company,
joint venture, limited liability company, trust or government, or any
Governmental Authority, or any other similar entity.

1.2.110 “Phase III Study” has the meaning set forth in the Master Agreement.

1.2.111 “PJSC” has the meaning set forth in the Regional License Terms (as
defined in the Master Agreement) and the meaning set forth in the Co-Co License
Terms (as defined in the Master Agreement).

1.2.112 “Product Trademark(s)” means the Trademarks used, or intended for use,
in connection with the distribution, marketing, promotion and sale of the Global
Licensed Products. Product Trademarks specifically exclude the corporate names
and logos of the Parties and their Affiliates. Product Trademark includes both
the Alnylam Trademarks and the Genzyme Trademarks.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.113 “Promotional Materials” has the meaning set forth in Section 4.4.2
(Promotional Materials).

1.2.114 “R&D Cost Opt-In Date” has the meaning set forth in Section 2.4(a)
(Development Costs).

1.2.115 “R&D Costs” means, with respect to a Global Licensed Product, costs and
expenses incurred in connection with the performance of any Development activity
for such Global Licensed Product, including [***].

1.2.116 “R&D FTE” means [***] hours of work per annum devoted to or in support
of the Development or Manufacture of a Global Licensed Product that is carried
out by one or more qualified scientific or technical employees (excluding Third
Party contractors) of a Party or its Affiliates.

1.2.117 “R&D FTE Cost” means, for any period, the R&D FTE Rate multiplied by the
number of R&D FTEs in such period.

1.2.118 “R&D FTE Rate” means [***] per FTE, increased annually beginning on
January 1, 2015 and thereafter on January 1 of each succeeding year by the
percentage increase in the CPI as of December 31 of the then most recently ended
calendar year over the level of the CPI on December 31, 2013.

1.2.119 “Regulatory Approval” has the meaning set forth in the Master Agreement.

1.2.120 “Regulatory Authority” has the meaning set forth in the Master
Agreement.

1.2.121 “Regulatory Exclusivity” means, with respect to a Global Licensed
Product in a country, any exclusive marketing right, data exclusivity right,
orphan drug designation or other country-wide exclusive right or status
conferred by any Governmental Authority with respect to such Global Licensed
Product in such country, other than a Patent Right, that limits or prohibits a
Person [***].

1.2.122 “Related Party” means a Party’s Affiliates and permitted Sublicensees.

1.2.123 “Reverted Global Licensed Product” has the meaning set forth in
Section 11.3.2(b) (Effects of Termination of Global Licensed Product by Alnylam
for Cause or by Genzyme for Convenience).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.124 “Royalty Term” has the meaning set forth in Section 8.2.2 (Royalty
Term).

1.2.125 “Serious Adverse Event” has the meaning set forth in the Master
Agreement.

1.2.126 “siRNA” has the meaning set forth in the Master Agreement.

1.2.127 “SPCs” has the meaning set forth in Section 10.5 (Patent Term
Extensions).

1.2.128 “Sublicensee” means a Third Party to whom a Party grants a sublicense
under any Alnylam Technology or Genzyme Technology, as the case may be, pursuant
to Section 7.1.4 (Sublicensing Terms) or Section 7.2.3 (Sublicensing Terms).

1.2.129 “Term” has the meaning set forth in Section 11.1 (Term).

1.2.130 “Third Party” has the meaning set forth in the Master Agreement.

1.2.131 “Third Party License Payment” has the meaning set forth in the Master
Agreement.

1.2.132 “Trademark” has the meaning set forth in the Master Agreement.

1.2.133 “Trailing Global Option” has the meaning set forth in the Master
Agreement.

1.2.134 “Transition Activities” has the meaning set forth in Section 2.2
(Transition).

1.2.135 “Transition Period” means with respect to a Global Licensed Product, the
period beginning on the Implementation Date for such Global Licensed Product and
ending on the date that such period is terminated by Genzyme pursuant to
Section 5.6 (Term of JTT).

1.2.136 “Transition Plan” has the meaning set forth in Section 2.2 (Transition).

1.2.137 “Un-Blocking Genzyme In-License” has the meaning set forth in the Master
Agreement.

1.2.138 “United States” means the United States of America and its territories,
possessions and commonwealths.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

1.2.139 “Valid Claim” means a claim of: (a) an issued and unexpired patent,
which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or
held unenforceable or invalid by an unappealable decision of a court or other
governmental agency of competent jurisdiction, or has not been appealed within
the time allowed for appeal, or by an appealed decision of a court or other
governmental agency of competent jurisdiction where the appeal has been pending
for more than [***] years (unless and until such decision is subsequently
overturned on appeal) and which has not been abandoned, disclaimed, denied or
admitted to be invalid or unenforceable through reissue, re-examination or
disclaimer or otherwise; or (b) a patent application that has been pending less
than [***] years from the date of filing of the earliest patent application from
which such patent application claims priority, which claim has not been
cancelled, withdrawn or abandoned or finally rejected by an administrative
agency action from which no appeal can be taken.

2. DEVELOPMENT

2.1 Overview. Genzyme will have the sole right to Develop Global Licensed
Products in the Licensed Territory.

2.2 Transition. Within [***] days after the Implementation Date for a Global
Licensed Product, Alnylam shall prepare and provide to Genzyme a draft plan for
the transition of the Development of such Global Licensed Product from Alnylam
to Genzyme (a “Transition Plan”). Promptly following the delivery of such draft
Transition Plan to Genzyme (and in any event no later than [***] days following
such delivery), the JTT responsible for such Global Licensed Product shall
finalize the Transition Plan for such Global Licensed Product. The Transition
Plan for each Global Licensed Product will require Alnylam to, as soon as
reasonably practicable following the Implementation Date with respect to such
Global Licensed Product: (a) assign the Alnylam Product-Specific Patents to
Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific
Patents); (b) transfer to Genzyme all Know-How Controlled by Alnylam that is
reasonably necessary or useful for Developing such Global Licensed Product, or
obtaining or maintaining Regulatory Approval for such Global Licensed Product in
the Licensed Territory, including information and materials reasonably requested
by Genzyme, in a format reasonably acceptable to Genzyme (which shall be
specified in such Transition Plan, along with the process of transferring such
Know-How); (c) assign to Genzyme all INDs and other regulatory filings submitted
to, or filed with, any Regulatory Authority with respect to such Global Licensed
Product, as well as any related regulatory documents submitted to any Regulatory
Authority with respect to such Global Licensed Product, excluding any drug
master files maintained by or on behalf of Alnylam; (d) transfer to Genzyme all
written correspondence with any Regulatory Authority with respect to such Global
Licensed Product and all written minutes of meetings and memoranda of oral
communications with any Regulatory Authority with respect to such Global
Licensed Product; (e) assign to Genzyme any Third Party agreements relating
solely and exclusively to the Development of such Global Licensed Product to
which Alnylam is a party (including any Alnylam In-License), subject to any
required consents of such Third Party, which Alnylam shall use reasonable

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

efforts to obtain; and (f) transfer to Genzyme any other information or
materials reasonably requested by Genzyme that are reasonably necessary or
useful for Development of such Global Licensed Product in the Licensed Territory
(the items described in clauses (a) through (f) collectively, “Development
Information”). The Transition Plan for each Global Licensed Product will also
describe any Development activities with respect to such Global Licensed Product
that Alnylam is required to perform as requested by Genzyme and mutually agreed
upon by the Parties (“Transition Activities”). [***]. With respect to each of
Alnylam’s employees who were engaged in the Development of a Global Licensed
Product prior to the Implementation Date for such Global Licensed Product,
Alnylam shall (i) commit a sufficient portion of such employee’s working hours
to enable the completion of the activities set forth in the Transition Plan for
such Global Licensed Product in accordance with the timeline set forth in such
Transition Plan and (ii) make such employee available to Genzyme at Genzyme’s
reasonable request until the obligations in such Transition Plan with respect to
which such employee has or had relevant experience or knowledge are completed.

2.3 Global Development Plan. Within [***] days following the Implementation Date
with respect to a Global Licensed Product, Genzyme shall provide the JTT
responsible for such Global Licensed Product with a work plan and time table for
the Development activities and Clinical Studies to be undertaken with respect to
such Global Licensed Product in the Licensed Territory (a “Global Development
Plan”). During the Transition Period with respect to a Global Licensed Product,
Genzyme shall update the Global Development Plan for such Global Licensed
Product annually and shall provide such updated Global Development Plan to the
JTT responsible for such Global Licensed Product. Each JTT shall review and
comment on each Global Development Plan submitted to it by Genzyme and Genzyme
shall consider such JTT’s comments; provided, however, that Genzyme will have
sole discretion and control over the contents of such Global Development Plan.

2.4 Development Costs.

                (a) With respect to any Global Licensed Product, if Genzyme
exercised the Co-Co/Global Option, Global Option or Additional Global Option
with respect to such Global Licensed Product, Genzyme shall be responsible for
one-hundred percent (100%) of all R&D Costs that occur after the later of
(i) [***] (such later date, the “R&D Cost Opt-In Date”) and amounts specified in
clauses (ii) and (iii) in Section 2.4(b) below, if any. Alnylam shall be
responsible for one-hundred percent (100%) of R&D Costs for such Global Licensed
Product that occur prior to the R&D Cost Opt-In Date, except for amounts
specified in clauses (ii) and (iii) of Section 2.4(b) below, if any.

                (b) The Global R&D Costs to be shared by the Parties pursuant to
Section 2.4(a) above shall only include amounts that are within one or more of
the following four (4) categories:

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

  (i) [***]

 

  (ii) [***]

 

  (iii) [***]

 

  (iv) [***]

(c) For clarity, R&D Costs to be paid by Genzyme pursuant to Section 2.4(a)
shall exclude any amounts paid after the R&D Cost Opt-In Date to Third Parties
with respect to services rendered or services procured in connection with the
conduct of any Clinical Study or Development activity that, in either case, is
completed prior to the R&D Cost Opt-In Date.

(d) The amount of all R&D Costs to be paid by Genzyme pursuant to Section 2.4(a)
and incurred by Alnylam prior to the delivery of the Option Data Package for a
Global Licensed Product will be set forth therein.

(e) Alnylam will invoice Genzyme for the R&D Costs to be paid by Genzyme
pursuant to Section 2.4(a) and incurred by Alnylam. Alnylam will provide copies
of invoices from vendors and other supporting documentation as reasonably
requested by Genzyme. Genzyme shall reimburse Alnylam within [***] days after
receipt by Genzyme of such invoice. Genzyme shall reimburse Alnylam on a
quarterly basis for R&D FTE Costs, Global Out-of-Pocket Costs and Cost of Goods
incurred by Alnylam in the performance of Transition Activities, within [***]
days after receipt by Genzyme of an invoice for such amounts from Alnylam.

2.5 Diligence. Genzyme will use Commercially Reasonable Efforts to [***].

2.6 Records; Reports; Information Sharing.

2.6.1 Development Activities. Following the Transition Period with respect to a
Global Licensed Product, [***] Genzyme will provide to Alnylam, through the
AJSC, an update regarding Development activities conducted by or on behalf of
Genzyme with respect to such Global Licensed Product, as well as any Clinical
Studies with respect to such Global Licensed Product conducted by Genzyme.

2.6.2 Scientific Records. Genzyme will maintain scientific records, in
sufficient detail and in sound scientific manner appropriate for patent and
regulatory purposes and in compliance with Good Laboratory Practices with
respect to activities intended to be submitted in regulatory filings (including
INDs and NDAs), which will fully and properly reflect all work done and results
achieved in the performance of the Development activities and Clinical Studies
with respect to Global Licensed Products.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

2.6.3 Information Exchange and Development Assistance. Following the completion
of the Transition Plan with respect to a Global Licensed Product, Alnylam shall
deliver to Genzyme, [***] and in a commercially reasonable format, any
Development Information with respect to such Global Licensed Product that comes
into Alnylam’s Control or possession. If, following the completion of the
Transition Plan with respect to a Global Licensed Product, Alnylam discovers
that it Controls or possesses any Development Information with respect to such
Global Licensed Product that should have been transferred by Alnylam to Genzyme
under the Transition Plan but that was not so transferred, Alnylam will promptly
provide such Development Information to Genzyme.

2.6.4 Personnel. Genzyme may request that Alnylam reasonably make available for
consultation regarding the Development of a Global Licensed Product certain of
its employees engaged in Development activities with respect to such Global
Licensed Product.

2.6.5 Confidentiality. All information exchanged by the Parties under this
Section 2 will be deemed to be Confidential Information of the disclosing Party
and maintained in accordance with Section 7 of the Master Agreement
(Confidentiality and Publication); provided, however, that all Development
Information with respect to a Global Licensed Product delivered by Alnylam to
Genzyme pursuant to Section 2.2 (Transition) or 2.6.3 (Information Exchange and
Development Assistance) shall be deemed to be Confidential Information of
Genzyme.

2.7 Third Parties. The Parties shall be entitled to utilize the services of
Third Parties to perform their respective Development and Manufacturing
activities under these Global License Terms, provided that (a) each Party shall
require that such Third Party operates in a manner consistent with the terms of
these Global License Terms and (b) each Party shall remain at all times fully
liable for its respective responsibilities. Each Party shall require that any
such Third Party agreement include confidentiality and non-use provisions that
are no less stringent than those set forth in Section 7 of the Master Agreement
(Confidentiality and Publication) and shall obtain ownership of, and/or a fully
sublicensable license under and to, any Know-How and Patent Rights that are
developed by such Third Party in the performance of such agreement and are
reasonably necessary or useful to Develop, Manufacture and/or Commercialize
Global Licensed Products in the Field. The Party utilizing the services of a
Third Party service provider shall be solely responsible for direction of and
communications with such Third Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

3. REGULATORY MATTERS

3.1 Regulatory Filings and Interactions.

3.1.1 Ownership of Regulatory Filings. Genzyme will own all INDs, NDAs and
related regulatory documentation submitted to any Regulatory Authority in the
Licensed Territory with respect to any Global Licensed Product, excluding any
drug master files maintained by or on behalf of Alnylam. At Genzyme’s request
following the Implementation Date for a Global Licensed Product, Alnylam will
promptly assign and transfer to Genzyme all INDs, NDAs and other regulatory
documentation submitted to any Regulatory Authority in the Licensed Territory
with respect to such Global Licensed Product that is in the possession or
control of Alnylam, excluding any drug master files maintained by or on behalf
of Alnylam, and each Party will submit all filings, letters and other
documentation necessary to effect such assignment and transfer to the applicable
Regulatory Authority no later than [***] days after such request for such Global
Licensed Product. Alnylam hereby appoints Genzyme as Alnylam’s agent for all
matters related to each Global Licensed Product involving Regulatory Authorities
in the Licensed Territory during the period beginning on the Implementation Date
for such Global Licensed Product and ending on the date that the transfer of all
INDs, NDAs and related regulatory documents filed with or submitted to any
Regulatory Authority in the Licensed Territory that relate to such Global
Licensed Product, excluding any drug master files maintained by or on behalf of
Alnylam, becomes effective, and Genzyme hereby accepts such appointment.

3.1.2 Responsibilities for Regulatory Matters. Genzyme will be solely
responsible for all regulatory matters relating to Global Licensed Products in
the Licensed Territory, including (i) overseeing, monitoring and coordinating
all regulatory actions, communications and filings with, and submissions to,
each Regulatory Authority in the Licensed Territory with respect to Global
Licensed Products; (ii) interfacing, corresponding and meeting with each
Regulatory Authority in the Licensed Territory with respect to Global Licensed
Products; and (iii) seeking and maintaining all regulatory filings in the
Licensed Territory with respect to Global Licensed Products.

3.1.3 Communications with Regulatory Authorities. Genzyme will provide Alnylam,
through the AJSC, as part of the quarterly updates regarding Development
activities described in Section 2.6.1 (Development Activities), with a brief
description in English, of the principal issues raised in any material
communication with any Regulatory Authority in the Licensed Territory with
respect to any Global Licensed Product during the preceding Calendar Quarter.
For purposes of this Section 3.1.3, “material communication” with Regulatory
Authorities include meetings with Regulatory Authorities and Regulatory
Authority questions or concerns regarding significant issues, including any of
the following: key product quality attributes (e.g., purity), safety findings
affecting the platform (e.g., Serious Adverse Events, emerging safety signals),
clinical or nonclinical findings affecting patient safety, or lack of efficacy.

3.1.4 Submissions. With respect to each Global Licensed Product, Genzyme shall
provide Alnylam with prompt written notice of each of the following events (but
in any event within [***] days) after the occurrence of such event in the
Licensed Territory: (i) the filing of any IND for such Global Licensed Product;
(ii) the submission of any filings or applications for Regulatory Approval
(including orphan drug applications and designations) of such Global Licensed
Product to any Regulatory Authority; and (iii) receipt or denial of Regulatory
Approval for such Global Licensed Product; provided, however, that in all
circumstances, Genzyme shall inform Alnylam of such event prior to public
disclosure of such event by Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

3.2 Costs of Regulatory Affairs. Genzyme shall be responsible for all costs and
expenses incurred in connection with applying for Regulatory Approval with
respect to Global Licensed Products in the Licensed Territory, and related
regulatory affairs activities.

3.3 Right of Reference. Alnylam hereby grants to Genzyme, and at the request of
Genzyme will grant to Genzyme’s Related Parties, a “Right of Reference,” as that
term is defined in 21 C.F.R. § 314.3(b) (or any successor rule or analogous Law
recognized outside of the United States), to, and a right to copy, access, and
otherwise use, all information and data (including all CMC information as well
as data made, collected or otherwise generated in the conduct of any Clinical
Studies or early access/named patient programs for the Global Licensed Products)
included in or used in support of any drug master file maintained by or on
behalf of Alnylam or its Related Parties that relates to any Global Licensed
Product to the extent necessary or useful to Develop, Manufacture or
Commercialize Global Licensed Products in the Licensed Territory.
Notwithstanding anything to the contrary in these Global License Terms, Alnylam
shall not withdraw or inactivate any regulatory filing that the other Party
references or otherwise uses pursuant to this Section 3.3.

 

4. COMMERCIALIZATION OF THE GLOBAL LICENSED PRODUCTS

4.1 Responsibility, Cost and Diligence. Genzyme shall be solely responsible, at
its expense, for all Commercialization activities relating to Global Licensed
Products in the Field in the Licensed Territory. Genzyme shall use Commercially
Reasonable Efforts to [***].

4.2 Commercialization Summary. No less [***] months in advance of the reasonably
expected first Regulatory Approval in the Licensed Territory with respect to a
Global Licensed Product, and annually thereafter, Genzyme shall prepare and
deliver to Alnylam, through the AJSC, [***] (the “Commercialization Summary”).

4.3 First Commercial Sale Reporting Obligations. Genzyme shall provide Alnylam
with written notice of the First Commercial Sale of each Global Licensed
Product.

4.4 Advertising and Promotional Materials.

4.4.1 Global Branding. Genzyme shall have the sole right, from time to time
during the Term, to develop (and thereafter modify and update) a global branding
strategy (including global positioning, messages, logo, colors and other visual
branding elements) for each Global Licensed Product for use in the Field
throughout the Licensed

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Territory (the “Global Branding Strategy”) for review by the AJSC. Except as
prohibited by applicable Law, the labeling for each Global Licensed Product
shall include a reasonably prominent reference to such Global Licensed Product
as being sold under license from Alnylam and, if applicable, a reasonably
prominent reference to Alnylam as the manufacturer of such Global Licensed
Product.

4.4.2 Promotional Materials. Genzyme will be responsible for the creation,
preparation, production, reproduction and filing with the applicable Regulatory
Authorities, of relevant written sales, promotion and advertising materials
relating to each Global Licensed Product (“Promotional Materials”) for use in
the Licensed Territory. All such Promotional Materials will be compliant with
applicable Law.

4.5 Sales and Distribution. Genzyme and its Related Parties shall be solely
responsible for booking sales and shall warehouse and distribute Global Licensed
Products in the Licensed Territory.

4.6 Recalls, Market Withdrawals or Corrective Actions. In the event that any
Regulatory Authority issues or requests a recall or takes a similar action in
connection with a Global Licensed Product, Genzyme shall have the sole right to
decide whether to conduct a recall and the manner in which any such recall shall
be conducted. Genzyme shall bear the expense of any such recall.

 

5. TRANSITION MANAGEMENT

5.1 Joint Transition Team. The Parties shall establish a joint transition team
(a “JTT”) to facilitate the transition of each Global Licensed Product from
Alnylam to Genzyme as follows:

5.1.1 Composition of the Joint Transition Team. The transition of each Global
Licensed Product from Alnylam to Genzyme shall be conducted under the oversight
of a JTT, which shall comprise three (3) representatives of each Party. Each
Party shall appoint its respective representatives to the JTT for a Global
Licensed Product within [***] days following the Implementation Date for such
Global Licensed Product, and may substitute one or more of its representatives,
in its sole discretion, effective upon notice to the other Party of such change.
Each representative on a JTT shall have appropriate expertise and ongoing
familiarity with the applicable Global Licensed Product and the GLP
Collaboration generally. Additional representatives or consultants may from time
to time, by mutual consent of the Parties, be invited to attend JTT meetings,
subject to such representatives and consultants undertaking confidentiality
obligations, whether in a written agreement or by operation of law, no less
stringent than the requirements of Section 7 of the Master Agreement
(Confidentiality and Publication).

5.1.2 JTT Chairperson. The JTT chairperson shall be a JTT representative of
Genzyme. The JTT chairperson’s responsibilities shall include (a) scheduling
meetings; (b) setting agendas for meetings with solicited input from other
members; (c) coordinating the delivery of draft minutes to the JTT for review
and final approval; and (d) conducting meetings, including ensuring that
objectives for each meeting are set and achieved.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

5.2 Meetings. Each JTT shall meet in accordance with a schedule established by
mutual written agreement of the Parties, but no less frequently than once per
Calendar Quarter, with the location for such meetings alternating between
Alnylam and Genzyme facilities (or such other locations as are mutually agreed
by the Parties). Alternatively, a JTT may meet by means of teleconference,
videoconference or other similar communications equipment. All proceedings for
each JTT shall take place in English. Where the membership of a JTT for a Global
Licensed Product is the same as one or more other JTTs for other Global Licensed
Products or PJSCs for other Collaboration Products, such JTTs and PJSCs may have
a single meeting to discuss each Global Licensed Product and other Collaboration
Product for which they have responsibility. Each Party shall bear its own
expenses relating to attendance at such meetings by its representatives.

5.3 Minutes. A secretary shall be appointed for each meeting of each JTT and
shall prepare minutes of the meeting, which shall provide a description in
reasonable detail of the discussions held at the meeting and a list of any
actions, decisions or determinations approved by such JTT.

5.4 JTT Responsibilities. The JTT with respect to a Global Licensed Product
shall have the following responsibilities with respect to such Global Licensed
Product:

(a) finalizing and approving a Transition Plan for such Global Licensed Product
that meets the requirements set forth in Section 2.2 (Transition), including any
Transition Activities that Alnylam will be obligated to perform under such
Transition Plan;

(b) reviewing and commenting on the initial Global Development Plan for such
Global Licensed Product, and reviewing and commenting on updates to the Global
Development Plan provided by Genzyme;

(c) overseeing any manufacturing and supply relationship between the Parties
with respect to the Manufacture of such Global Licensed Product for Development
activities (subject to the terms of the GLP Clinical Supply Agreement, if any);
and

(d) performing such other activities as the Parties agree in writing shall be
the responsibility of such JTT.

5.5 Decision-Making. Each JTT shall not have any decision-making authority with
respect to any matters under these Global License Terms; provided, however, that
each JTT shall have the authority to approve the Transition Plan for the Global
Licensed Product for which such JTT is responsible. With respect to approving a

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Transition Plan, the representatives of each Party on a JTT shall have
collectively one vote on behalf of such Party and such JTT shall attempt to
approve such Transition Plan by consensus. If the applicable JTT fails to
approve a Transition Plan for a Global Licensed Product within [***] days
following the Implementation Date with respect to such Global Licensed Product,
then the matter shall be submitted to the AJSC. If the matter is still
unresolved after a further [***] days, then such matter shall be submitted to
[***].

5.5.1 [***]

(a) [***]

(b) [***]

(c) [***]

(d) [***]

(e) [***]

5.6 Term of JTT. After the commencement of a Phase III Study for a Global
Licensed Product, either Party shall have the right to terminate the Transition
Period with respect to such Global Licensed Product which will relieve the
Parties’ obligations to participate in the JTT for such Global Licensed Product.

 

6. MANUFACTURE AND SUPPLY OF THE GLOBAL LICENSED PRODUCTS

6.1 Manufacturing and Supply. The Manufacturing of each Global Licensed Product
will be addressed in the Master Agreement and breach of such Manufacturing terms
as applied to a Global Licensed Product shall be treated as a breach under these
Global License Terms, and not under the Master Agreement.

 

7. LICENSES

7.1 License Grants to Genzyme.

7.1.1 Development License. On a Global Licensed Product-by-Global Licensed
Product basis, subject to the provisions of these Global License Terms
(including Section 9.4.1(e) (Exclusivity)) and any GLP Clinical Supply
Agreement, effective upon the Implementation Date for such Global Licensed
Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in
Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to
Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license
under Alnylam Technology other than Patent Rights assigned to Genzyme pursuant
to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents) to Develop
such Global Licensed Product in the Field in the Licensed Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

7.1.2 Commercialization License. On a Global Licensed Product-by-Global Licensed
Product basis, subject to the provisions of these Global License Terms
(including Section 9.4.1(e) (Exclusivity)) and any GLP Commercial Supply
Agreement, effective upon the Implementation Date for such Global Licensed
Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in
Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to
Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license
under Alnylam Technology other than Patent Rights assigned to Genzyme pursuant
to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents) to
Commercialize such Global Licensed Product in the Field in the Licensed
Territory. Such license shall be royalty-bearing for the Royalty Term applicable
to each Global Licensed Product in each country in the Licensed Territory, and,
after the Royalty Term applicable to such Global Licensed Product in such
country, shall convert to a fully-paid, perpetual license to Commercialize such
Global Licensed Product in the Field in such country.

7.1.3 Manufacturing License. On a Global Licensed Product-by-Global Licensed
Product basis, subject to the provisions of these Global License Terms
(including Section 9.4.1(e) (Exclusivity)), any GLP Supply Agreement and any
Third Party Supply Agreement, effective upon the Implementation Date for such
Global Licensed Product, Alnylam hereby grants Genzyme a non-transferable
(except as provided in Section 13.1 of the Master Agreement (Assignment)),
sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), worldwide,
exclusive (even as to Alnylam) license under Alnylam Technology other than
Patent Rights assigned to Genzyme pursuant to Section 10.3.6.1 (Assignment of
Alnylam Product-Specific Patents) to Manufacture such Global Licensed Product.
Notwithstanding the foregoing, Alnylam retains the right under the Alnylam
Technology, with the right to grant licenses through multiple tiers without
restriction, to Manufacture Global Licensed Products anywhere in the world to
supply (or have supplied) Genzyme pursuant to any GLP Supply Agreement.

7.1.4 Sublicensing Terms.

(a) Subject to Section 7.5 (Right of First Negotiation), Genzyme shall have the
right to sublicense any of its rights under Sections 7.1.1 (Development
License), 7.1.2 (Commercialization License) and 7.1.3 (Manufacturing License) to
any of its Affiliates or to any Third Party (which sublicensed rights may be
further sublicensable through multiple tiers) without the prior consent of
Alnylam, subject to the requirements of this Section 7.1.4. [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

(b) Each sublicense granted by Genzyme pursuant to this Section 7.1.4 shall be
subject and subordinate to the provisions of these Global License Terms and
shall contain provisions consistent with those in these Global License Terms.
Genzyme shall promptly provide Alnylam with a copy of the fully executed
sublicense agreement covering any sublicense granted hereunder (which copy may
be redacted to remove provisions which are not necessary to monitor compliance
with this Section 7.1.4), and each such sublicense agreement shall contain the
following provisions: (i) a requirement that the Sublicensee comply with the
confidentiality and non-use provisions of Section 7 of the Master Agreement
(Confidentiality and Publication) with respect to Alnylam’s Confidential
Information, (ii) if such sublicense agreement contains a sublicense of Global
Licensed Product Commercialization rights, such sublicense agreement shall also
contain the following provisions: (x) a requirement that the Sublicensee submit
applicable sales or other reports to Genzyme to the extent necessary or relevant
to the reports required to be made or records required to be maintained under
these Global License Terms; and (y) the audit requirement set forth in
Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the
Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the terms of any sublicense
by any Genzyme Sublicensee, compliance with which is necessary for Genzyme’s
compliance with the terms of these Global License Terms, Genzyme shall promptly
notify Alnylam of the particulars of the same and use Commercially Reasonable
Efforts to cause the Sublicensee to comply with all the terms of the sublicense
necessary for Genzyme’s compliance with the terms of these Global License Terms.
[***] Notwithstanding any sublicense, Genzyme shall remain primarily liable to
Alnylam for the performance of all of Genzyme’s obligations under, and Genzyme’s
compliance with all provisions of, these Global License Terms.

7.1.5 Back-Up Products. Subject to Sections 12.2 (Future Acquisition of a Party
or its Business), 12.3.1 (Acquired Programs), and 12.3.2 (Acquired Programs),
Alnylam hereby grants to Genzyme a series of exclusive options (each, a “Back-Up
Option”), under each of which Genzyme shall have the right, but not the
obligation, to take a license on the terms set forth in the these Global License
Terms to any siRNA that targets the same Licensed Target as a Global Licensed
Product (a “Back-Up Product”) and for which Alnylam has determined the siRNA
composition for which GLP toxicology studies will be conducted during the
Back-Up Option Period. Genzyme may exercise the Back-Up Option with respect to
such Back-Up Product by delivering written notice to Alnylam at any time during
the Back-Up Option Period (the “Back-Up Option Exercise Notice”). Upon delivery
of the Back-Up Option Exercise Notice to Alnylam, the applicable Back-Up Product
shall automatically be deemed to be a Global Licensed Product for all purposes
under the Collaboration Agreement and the license from Alnylam to Genzyme for
such Global Licensed Product shall automatically, with no further action by any
Party, go into full force and effect and all obligations of Alnylam and Genzyme
set forth in these Global License Terms, including the payment obligations set
forth herein, shall become the binding obligations of the applicable Party in
respect of such Global Licensed Product. Upon the expiration of the Back-Up
Option Period, all Back-Up Options not previously exercised shall automatically
terminate.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

7.2 License Grants to Alnylam.

7.2.1 License to Improvement Manufacturing Patent Rights. Subject to the
provisions of these Global License Terms, Genzyme hereby grants Alnylam a
non-transferable (except as provided in Section 13.1 of the Master Agreement
(Assignment)), sublicensable (subject to Section 7.2.3 (Sublicensing Terms)),
worldwide, non-exclusive license under the Improvement Manufacturing Patent
Rights, to Manufacture (a) Alnylam Developed siRNA Products targeting any human
gene; and (b) Global Licensed Products for Development and Commercialization in
the Licensed Territory by Genzyme.

7.2.2 License to Genzyme Disclosed Manufacturing Know-How. Subject to the
provisions of these Global License Terms, Genzyme hereby grants Alnylam a
non-transferable (except as provided in Section 13.1 of the Master Agreement
(Assignment)), sublicensable (subject to Section 7.2.3 (Sublicensing Terms)),
worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing
Know-How to Manufacture Global Licensed Products for Development and
Commercialization in the Licensed Territory by Genzyme.

7.2.3 Sublicensing Terms.

(a) Subject to Section 7.5 (Right of First Negotiation), Alnylam shall have the
right to sublicense any of its rights under Sections 7.2.1 (License to
Improvement Manufacturing Patent Rights) and 7.2.2 (License to Genzyme Disclosed
Manufacturing Know-How) (which sublicensed rights may be further sublicensable
through multiple tiers) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 7.2.3 shall be
subject and subordinate to the provisions of these Global License Terms and
shall contain provisions consistent with those in these Global License Terms.
Alnylam shall promptly provide Genzyme with a copy of the fully executed
sublicense agreement covering any sublicense granted hereunder (which copy may
be redacted to remove provisions which are not necessary to monitor compliance
with this Section 7.2.3), and each such sublicense agreement shall contain the
following provisions: (i) a requirement that the Sublicensee comply with the
confidentiality and non-use provisions of Section 7 of the Master Agreement
(Confidentiality and Publication) with respect to Genzyme’s Confidential
Information and (ii) a requirement that the Sublicensee comply with the
applicable provisions under any Genzyme In-License.

(c) If Alnylam becomes aware of a material breach of any sublicense by any
Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance
with the provisions of these Global License Terms, Alnylam shall promptly notify
Genzyme of the particulars of the same and use Commercially Reasonable Efforts
to cause the Sublicensee to comply with all the terms of the sublicense
necessary for Alnylam’s compliance with the provisions of these Global License
Terms. [***]. Notwithstanding any sublicense, Alnylam shall remain primarily
liable to Genzyme for the performance of all of Alnylam’s obligations under, and
Alnylam’s compliance with all provisions of, these Global License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

7.3 Joint Collaboration IP. Subject to the rights and licenses granted to, and
the obligations (including royalty obligations) of, each Party under these
Global License Terms, either Party is entitled to practice Joint Collaboration
IP for all purposes on a worldwide basis and license Joint Collaboration IP
without consent of and without a duty of accounting to the other Party. Each
Party will grant and hereby does grant all permissions, consents and waivers
with respect to, and all licenses under, the Joint Collaboration IP, throughout
the world, necessary to provide the other Party with such rights of use and
exploitation of the Joint Collaboration IP, and will execute documents as
necessary to accomplish the foregoing.

7.4 In-Licenses.

7.4.1 Compliance with In-Licenses. All licenses and other rights granted to
Genzyme under this Section 7 are subject to the rights and obligations of
Alnylam under the Alnylam In-Licenses. All licenses and other rights granted to
Alnylam under this Section 7 are subject to the rights and obligations of
Genzyme under the Genzyme In-Licenses. Each Party shall comply with all
applicable terms and conditions of the In-Licenses, and shall perform and take
such actions as may be required to allow the Party that is party to such
In-License to comply with its obligations thereunder, including obligations
relating to sublicensing, patent matters, confidentiality, reporting, audit
rights, indemnification and diligence. Without limiting the foregoing, each
Party shall prepare and deliver to the other Party any additional reports
required under the applicable In-Licenses and requested by such other Party, in
each case sufficiently in advance to enable the Party that is party to such
In-License to comply with its obligations under the applicable In-Licenses. Each
Party agrees, upon the other Party’s request, to provide the other Party with
copies of any In-Licenses to which it is a party. Confidential Information of
the providing Party or its counterparty may be redacted from such copies, except
to the extent that such information is required in order to enable the other
Party to comply with its obligations to the providing Party under these Global
License Terms with respect to such In-License or in order to enable the
providing Party to ascertain compliance with the provisions of these Global
License Terms.

7.5 Right of First Negotiation. If, at any time during the Term, Genzyme desires
to grant any Third Party rights to Develop and/or Commercialize one or more
Global Licensed Product(s) in the Field in any portion of the Licensed Territory
(excluding customary distribution arrangements entered into in the ordinary
course of business by Genzyme), Genzyme shall notify Alnylam in writing of its
intent. Alnylam shall have [***] days from receipt of such written notice to
notify Genzyme in writing as to whether Alnylam desires to negotiate for such
rights in such territory, and if Alnylam so notifies Genzyme that it does desire
to negotiate for such rights in such territory, Alnylam shall have the exclusive
right for [***] days from the date of such notification to

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Genzyme to negotiate with Genzyme and to make one or more written non-binding
offers to Genzyme concerning the acquisition of such rights in such territory by
Alnylam. Alnylam shall have the exclusive right for [***] days (or such longer
period as may be mutually agreed by the Parties) after such [***] day period, to
finalize and enter into a definitive agreement with Genzyme for such rights in
such territory, provided that if either Alnylam does not provide such written
notice within such [***] day period or Alnylam does provide such written
non-binding offer within such subsequent [***] day period, or Alnylam provides
such notice of interest and such written offer but for any reason Genzyme and
Alnylam do not enter into a definitive agreement within the [***] day
negotiation period, Genzyme shall be free to enter into an agreement with a
Third Party(ies) relating to such rights in such territory, without further
obligation to Alnylam. Genzyme shall not, during the exclusive [***] and [***]
day negotiating periods described above, enter into discussions, exchange
information, or otherwise negotiate with any Third Party with respect to an
agreement with respect to the Development and/or Commercialization of the
applicable Global Licensed Product(s) in the Field in the Licensed Territory.
Notwithstanding the foregoing, during the period of [***] months after the
termination of any such negotiation that does not result in a definitive
agreement between Alnylam and Genzyme, Genzyme shall not enter into a
transaction with respect to such rights in such territory with any Third Party
on terms that are, in the aggregate, materially more favorable to the Third
Party than the last terms offered in writing by Alnylam to Genzyme unless
Genzyme first re-offers such transaction to Alnylam on such more favorable terms
and Alnylam does not accept such offer and enter into such transaction with
Genzyme within [***] days after such re-offer. For clarity, prior to the
exclusive negotiating periods described above, Genzyme shall be free to engage
in discussions and exchange information with Third Parties with respect to the
applicable Global Licensed Product(s) rights, but shall not enter into any
binding agreement with any Third Party with respect to such rights.

7.6 Bankruptcy. All rights and licenses granted under or pursuant to these
Global License Terms by a Party to the other, including those set forth in
Sections 3.3 (Right of Reference), 7.1 (License Grants to Genzyme), 7.2 (License
Grants to Alnylam), and 11.3.2(b) (Effects of Termination of Global Licensed
Product by Alnylam for Cause or by Genzyme for Convenience), are and shall
otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy
Code, licenses of right to “intellectual property” as defined under Section 101
of the U.S. Bankruptcy Code. The Parties agree that the Parties and their
respective Sublicensees, as sublicensees of such rights under these Global
License Terms, shall retain and may fully exercise all of their rights and
elections under the U.S. Bankruptcy Code and any foreign counterpart thereto.
The Parties further agree that upon commencement of a bankruptcy proceeding by
or against a Party (the “Bankrupt Party”) under the Bankruptcy Code, the other
Party (the “Non-Bankrupt Party”) will be entitled to a complete duplicate of, or
complete access to (as the Non-Bankrupt Party deems appropriate), all such
intellectual property and all embodiments of such intellectual property. Such
intellectual property and all embodiments of such intellectual property will be
promptly delivered to the Non-Bankrupt Party (a) upon any

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

such commencement of a bankruptcy proceeding and upon written request by the
Non-Bankrupt Party, unless the Bankrupt Party elects to continue to perform all
of its obligations under these Global License Terms, or (b) if not delivered
under (a) above, upon the rejection of these Global License Terms by or on
behalf of the Bankrupt Party and upon written request by the Non-Bankrupt Party.
Without limiting the foregoing, Alnylam hereby grants to Genzyme a right of
access to and to obtain possession of (i) copies of research data,
(ii) laboratory samples, (iii) samples of Global Licensed Product,
(iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related
to clinical trials, (vii) regulatory filings and approvals, (viii) rights of
reference in respect of regulatory filings and approvals, (ix) pre-clinical
research data and results, (x) marketing, advertising and promotional materials,
all of which (in clauses (i) through (x)) constitute “embodiments” of
intellectual property pursuant to Section 365(n) of the Bankruptcy Code and
(xi) all other embodiments of such intellectual property, and in respect of each
of the foregoing clauses (i) through (xi), solely for the purpose of the
exercise of Genzyme’s rights and licenses under these Global License Terms,
whether any of the foregoing are in Alnylam’s possession or control or in the
possession and control of Third Parties. The Bankrupt Party (in any capacity,
including debtor-in-possession) and its successors and assigns (including any
trustee) agrees not to interfere with the exercise by Non-Bankrupt Party or its
Related Parties of its rights and licenses to such intellectual property and
such embodiments of intellectual property in accordance with these Global
License Terms, and agrees to assist the Non-Bankrupt Party and its Related
Parties in obtaining such intellectual property and such embodiments of
intellectual property in the possession or control of Third Parties as
reasonably necessary or desirable for the Non-Bankrupt Party to exercise such
rights and licenses in accordance with these Global License Terms. The foregoing
provisions are without prejudice to any rights the Non-Bankrupt Party may have
arising under the Bankruptcy Code or other Laws.

7.7 No Other Rights. Except as otherwise expressly provided in these Global
License Terms, under no circumstances shall a Party, as a result of these Global
License Terms, obtain any ownership interest or other right in any Know-How,
Patent Rights or other intellectual property rights of the other Party,
including items owned, controlled or developed by the other Party, or provided
by the other Party to the receiving Party at any time pursuant to these Global
License Terms.

 

8. CERTAIN FINANCIAL TERMS

8.1 Milestone Fees.

8.1.1 Development Milestones for Global Licensed Products. Genzyme shall provide
Alnylam with written notice of the achievement by Genzyme or any of its Related
Parties of any development milestone event set forth below in this Section 8.1.1
within [***] days after such event has occurred; provided, however, that Genzyme
shall inform Alnylam of such event prior to any public disclosure of such event
by Genzyme. Alnylam shall invoice Genzyme within [***] days of receipt of such
written notice by

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Alnylam, and Genzyme shall remit the associated development milestone payment
within [***] days of the receipt of such invoice. Each development milestone
payment by Genzyme to Alnylam hereunder shall be payable only once with respect
to each Global Licensed Product, regardless of the number of times a development
milestone event is achieved with respect to such Global Licensed Product.

8.1.1.1 Development Milestones for ALN-AS1. Genzyme shall pay Alnylam the
following amounts upon achievement of the following development milestone events
with respect to ALN-AS1:

 

Development Milestone Event

   Development Milestone
Payment

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

8.1.1.2 Development Milestones for Global Licensed Products other than ALN-AS1.
Genzyme shall pay Alnylam the following amounts upon the first achievement of
the following development milestone events with respect to each Global Licensed
Product other than ALN-AS1:

 

Development Milestone Event

   Development Milestone
Payment

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

8.1.2 Sales Milestones for Global Licensed Products. Genzyme shall provide
Alnylam with written notice of the achievement by Genzyme or any of its Related
Parties of any sales milestone event set forth below in this Section 8.1.2
within [***] days after such event has occurred. Alnylam shall invoice Genzyme
within [***] days of receipt of such written notice by Alnylam, and Genzyme
shall remit the associated milestone payment within [***] days of the receipt of
such invoice. Notwithstanding the foregoing, in the event that more than one of
the sales milestone events is achieved simultaneously by a Global Licensed
Product, Genzyme will make only one sales milestone payment at such time, which
will be for the sales milestone event requiring the highest sales milestone
payment; and further, payment for achievement of the lower sales milestone shall
be due in the next Calendar Year. Each sales milestone payment by Genzyme to
Alnylam hereunder shall be payable only once with respect to each Global
Licensed Product, regardless of the number of times a sales milestone event is
achieved with respect to such Global Licensed Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

8.1.2.1 Sales Milestones for ALN-AS1. Genzyme shall pay Alnylam the following
amounts upon achievement of the following sales milestone events with respect to
ALN-AS1:

 

Sales Milestone Event

   Sales Milestone Payment  

(i) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]

     [ ***] 

(ii) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]

     [ ***] 

(i) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]

     [ ***] 

(ii) First Calendar Year in which Net Sales for ALN-AS1 exceeds[***]

     [ ***] 

8.1.2.2 Sales Milestones for Global Licensed Products other than ALN-AS1.
Genzyme shall pay Alnylam the following amounts upon achievement of the
following sales milestone events with respect to each Global Licensed Product
other than ALN-AS1:

 

Sales Milestone Event

   Sales Milestone Payment  

(i) First Calendar Year in which Net Sales for a Global Licensed Product (other
than ALN-AS1) exceeds [***]

     [ ***] 

(ii) First Calendar Year in which Net Sales for a Global Licensed Product (other
than ALN-AS1) exceeds [***]

     [ ***] 

(iii) First Calendar Year in which Net Sales for a Global Licensed Product
(other than ALN-AS1) exceeds [***]

     [ ***] 

8.2 Royalties.

8.2.1 Royalties Payable on Licensed Products. Subject to the provisions of these
Global License Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales
of each Global Licensed Product by Genzyme and its Related Parties, as
calculated on a Global Licensed Product-by-Global Licensed Product basis, in the
Licensed Territory, as follows:

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Calendar Year

Net Sales of a Global Licensed Product

in the Licensed Territory

   Royalty
(as a percentage of Net Sales of
such Global Licensed Product)

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

[***]

   [***]

Royalties on annual Net Sales of each Global Licensed Product shall be paid at
the rate applicable to [***]:

[***]

Royalties on annual Net Sales shall be paid at the rate applicable to the
portion of such Net Sales within each of the Net Sales levels above during such
Calendar Year.

8.2.2 Royalty Term. Subject to Section 8.2.6 (Royalty Floor), the period during
which the royalties set forth in Section 8.2.1 (Royalties Payable on Licensed
Products) shall be payable, on a Global Licensed Product-by-Global Licensed
Product and country-by-country basis, shall commence with the First Commercial
Sale of a Global Licensed Product in a country and continue until the latest of
(a) the expiration of the last Valid Claim of [***] in the country of sale;
(b) the expiration of Regulatory Exclusivity for such Global Licensed Product in
such country; or (c) subject to the last sentence of this Section 8.2.2, the
[***] anniversary of the First Commercial Sale of such Global Licensed Product
in such country (each such period, a “Royalty Term”). [***].

8.2.3 Third Party Royalty Offsets. Genzyme shall be permitted to reduce any
royalties payable under Section 8.2.1 (Royalties Payable on Licensed Products)
for a Global Licensed Product by [***] percent ([***]) of any amounts for which
Genzyme is responsible under Collaboration In-Licenses for such Global Licensed
Product pursuant to Section 11.3 of the Master Agreement (In-Licenses) or under
an Un-Blocking Genzyme In-License, but only to the extent that the relevant
Third Party License Payment under such Collaboration In-License or Un-Blocking
Genzyme In-License constitutes either royalties or a milestone payment based on
sales of such Global Licensed Product; provided, however, that the royalties
payable under Section 8.2.1 (Royalties Payable on Licensed Products) with
respect to such Global Licensed Product shall not be reduced in any such event
below [***]percent ([***]) of the amounts set forth in Section 8.2.1 (Royalties
Payable on Licensed Products) and; provided, further, that if any of such

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

amounts cannot be offset against royalties due with respect to such Global
Licensed Product for any given royalty period due to the preceding proviso, such
unused amount may be carried forward and offset against royalties due with
respect to such Global Licensed Product in future royalty periods.

8.2.4 No Alnylam Patents or Regulatory Exclusivity. The royalties to be paid by
Genzyme to Alnylam pursuant to Section 8.2.1 (Royalties Payable on Licensed
Products) with respect to any Global Licensed Product shall be reduced to
[***]percent ([***]) of the amounts otherwise payable pursuant to Section 8.2.1
(Royalties Payable on Licensed Products) with respect to Net Sales of such
Global Licensed Product in a country of the Licensed Territory as to which both
(a) the Manufacture, use, offer for sale, sale or importation of which is not
Covered by any Valid Claim in any Alnylam Patent or in any Patent Right included
in the Joint Collaboration IP in such country and (b) there is no applicable
Regulatory Exclusivity in such country.

8.2.5 Royalty Adjustments for Generic Products. If, during a given Calendar
Quarter when a Global Licensed Product is being Commercialized by or on behalf
of Genzyme in a particular country in the Licensed Territory, there is Generic
Competition in such country with respect to such Global Licensed Product, then,
subject to Section 8.2.6 (Royalty Floor), the royalties payable pursuant to
Section 8.2.1 (Royalties Payable on Licensed Products) on the Net Sales of such
Global Licensed Product in such country shall thereafter be reduced to [***]
percent ([***]) of the amounts otherwise payable pursuant to Section 8.2.1
(Royalties Payable on Licensed Products) with respect to such Global Licensed
Product in such country for such Calendar Quarter for so long as such Generic
Competition remains.

8.2.6 Royalty Floor. Anything in these Global License Terms to the contrary
notwithstanding, in no event during the applicable Royalty Term for a Global
Licensed Product in a country of the Licensed Territory shall the royalties
payable to Alnylam hereunder for such Global Licensed Product in such country
for any Calendar Quarter be reduced (a) by the application of the reductions or
credits described in Sections 8.2.3 (Third Party Royalty Offsets) or 8.2.4 (No
Alnylam Patents or Regulatory Exclusivity), whether taken together or
separately, to less than [***]percent ([***]) of the royalties payable pursuant
to Section 8.2.1 (Royalties Payable on Licensed Products) as to such Global
Licensed Product in such country for such Calendar Quarter, or (b) by the
application of the reductions or credits described in Sections 8.2.3 (Third
Party Royalty Offset), 8.2.4 (No Alnylam Patents or Regulatory Exclusivity),
8.2.5 (Royalty Adjustments for Generic Products) and/or 10.4.2 (Rights to
Enforce), whether taken together or separately, to less than the greater of
(1) [***] percent ([***]) of the royalties payable pursuant to Section 8.2.1
(Royalties Payable on Licensed Products) as to such Global Licensed Product in
such country for such Calendar Quarter, and (2) [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

8.2.7 Validation Information. At Genzyme’s request, Alnylam will provide Genzyme
with such information as Genzyme may reasonably request to validate the amount
of the royalty floor described in Section 8.2.6 (Royalty Floor).

 

9. REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1 Representations and Warranties of Alnylam. Except as provided in the
Disclosure Schedule to this Section 9.1 (which Disclosure Schedule with respect
to any Global Licensed Product will be provided by Alnylam to Genzyme as part of
the Option Data Package for such Global Licensed Product), with respect to each
Global Licensed Product, Alnylam represents and warrants to Genzyme that as of
the Implementation Date for such Global Licensed Product:

9.1.1 Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant
to an Alnylam In-License, the Alnylam Technology, and all of the Alnylam
Technology licensed to Genzyme hereunder in the Licensed Territory that is
solely and exclusively owned by Alnylam is free and clear of liens, charges or
encumbrances other than licenses granted to Third Parties that are not
inconsistent with the rights and licenses granted to Genzyme under these Global
License Terms.

9.1.2 Alnylam has sufficient legal and/or beneficial title and ownership of, or
sufficient license rights under, the Alnylam Technology to grant the licenses to
such Alnylam Technology granted to Genzyme pursuant to these Global License
Terms.

9.1.3(a) Schedule 1.2.8 and Schedule 1.2.15 collectively set forth a complete
and accurate list of the Alnylam Patents owned, either solely or jointly, by
Alnylam, and to Alnylam’s knowledge, Schedule 1.2.8 and Schedule 1.2.15
collectively set forth a complete and accurate list of the Alnylam Patents
licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s
knowledge, each issued Alnylam Patent remains in full force and effect and
(c) Alnylam or its Affiliates have timely paid all filing and renewal fees
payable with respect to such Alnylam Patents for which Alnylam controls
prosecution and maintenance. Schedule 1.2.8 and Schedule 1.2.15 indicate whether
each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by Alnylam
and one or more Third Parties, or is licensed to Alnylam. For each Alnylam
Patent that is owned, but not owned exclusively, by Alnylam, or that is licensed
to Alnylam, Schedule 1.2.8 and Schedule 1.2.15 identify the Third Party owner(s)
and, if applicable, the Alnylam In-License pursuant to which Alnylam Controls
such Alnylam Patent. For each Alnylam Product-Specific Patent that is licensed,
but not exclusively licensed, to Alnylam, Schedule 1.2.15 indicates the
non-exclusive nature of the license. For each Alnylam Core Technology Patent
family (other than Patent Rights licensed from Isis Pharmaceuticals, Inc.) that
is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.8 indicates
the non-exclusive nature of the license. Alnylam is the sole and exclusive owner
of all Patent Rights identified in Schedule 1.2.8 and Schedule 1.2.15 as being
owned exclusively by Alnylam and Controls all other Patent Rights identified on
such schedules.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

9.1.4 To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or,
upon issuance, will be, valid and enforceable patents and no Third Party has
challenged or threatened to challenge the scope, validity or enforceability of
any Alnylam Product-Specific Patent (including, by way of example, through
opposition or the institution or written threat of institution of interference,
nullity or similar invalidity proceedings before the United States Patent and
Trademark Office or any analogous foreign Governmental Authority).

9.1.5 Alnylam has complied with all applicable Laws, including any duties of
candor to applicable patent offices, in connection with the filing, prosecution
and maintenance of the Alnylam Patent Rights.

9.1.6 Alnylam owns or Controls all Know-How that is or has been used by Alnylam
in the Development and Manufacture of such Global Licensed Products, and has
sufficient legal or beneficial title and ownership of, or sufficient license
rights under such Know-How to transfer Know-How to Genzyme as provided in
Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

9.1.7 Alnylam Controls all Know-How and Patent Rights licensed to Alnylam under
the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to
Develop, Manufacture and/or Commercialize such Global Licensed Product in the
Field in the Licensed Territory. Without limiting the generality of the
foregoing, Alnylam has obtained all necessary consents and fulfilled all
necessary conditions, if any, to sublicense to Genzyme under these Global
License Terms such Know-How and Patent Rights licensed to Alnylam under Existing
Alnylam In-Licenses.

9.1.8 To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach
or default under any existing Alnylam In-License, and neither Alnylam nor its
Affiliates have received any written notice of breach or default with respect to
any existing Alnylam In-License.

9.1.9 Alnylam has obtained from all inventors of Alnylam Technology owned by
Alnylam valid and enforceable agreements assigning to Alnylam each such
inventor’s entire right, title and interest in and to all such Alnylam
Technology.

9.1.10 To Alnylam’s knowledge, the use, Development, Manufacture or
Commercialization by Alnylam or Genzyme (or their respective Related Parties) of
such Global Licensed Product as formulated and manufactured as of the Effective
Date, or as intended to be formulated and manufactured as of the Effective Date
(a) does not and will not infringe any issued patent of any Third Party and
(b) will not infringe the claims of any published Third Party patent application
when and if such claims were to issue in their current form.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

9.1.11 There is no (a) claim, demand, suit, proceeding, arbitration, inquiry,
investigation or other legal action of any nature, civil, criminal, regulatory
or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or
any of its Affiliates or (b) judgment or settlement against or owed by Alnylam
or any of its Affiliates, in each case in connection with the Alnylam Technology
or such Global Licensed Product.

9.1.12 For each Global Licensed Product, Schedule 9.1.12(a) sets forth a
complete and accurate list of all agreements between Alnylam and a Third Party
entered into prior to the Implementation Date for a Global Licensed Product
pursuant to which Alnylam Controls Know-How or Patent Rights that are necessary
or useful to Develop, Manufacture or Commercialize such Global Licensed Product
in the Field other than Additional In-Licenses. [***].

9.2 Representations and Warranties of Genzyme. Except as disclosed in Genzyme’s
Exercise Notice, Genzyme represents and warrants to Alnylam as of the
Implementation Date for such Global Licensed Product that it is not a party to
any agreement with a Third Party under which it Controls Know-How or Patent
Rights that are sublicensed to Alnylam under these Global License Terms with
respect to such Global Licensed Products.

9.3 Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE GLOBAL
LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF
ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY
TECHNOLOGY, GLOBAL LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT
MATTER OF THESE GLOBAL LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES
OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH
RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY
REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR
COMMERCIALIZATION OF ANY GLOBAL LICENSED PRODUCT PURSUANT TO THESE GLOBAL
LICENSE TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT
TO ANY GLOBAL LICENSED PRODUCT WILL BE ACHIEVED.

9.4 Certain Covenants.

9.4.1 [***].

(a) [***]

(b) [***]

(c) [***]

(d) [***]

(e) [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

9.4.2 Compliance. Each Party and its Related Parties shall conduct the GLP
Collaboration and the Development, Manufacture and Commercialization of the
Global Licensed Products in accordance with all Laws, including current
governmental regulations concerning Good Laboratory Practices (as defined in the
Master Agreement), good clinical practices and good manufacturing practices. In
addition, if either Party is or becomes subject to a legal obligation to a
Regulatory Authority or other Governmental Authority (such as a corporate
integrity agreement or settlement agreement with a Governmental Authority), then
the other Party shall perform such activities as may be reasonably requested by
the obligated Party to enable the obligated Party to comply with its legal
obligation to such Regulatory Authority with respect to the Global Licensed
Products.

9.4.3 Conflicting Transactions. During the Term, Alnylam shall not (a) transfer
or assign any of its rights, title or interests in the Alnylam Technology other
than as part of a transaction pursuant to which these Global License Terms is
also assigned and assumed in accordance with Section 13.1 of the Master
Agreement (Assignment), or (b) enter into any agreement granting a license or
other right under the Alnylam Technology that is inconsistent with the terms of
these Global License Terms.

9.4.4 Governmental Authority. If any of the Alnylam Technology is subject to any
funding arrangement with any Governmental Authority, at Genzyme’s reasonable
request, Alnylam will reasonably cooperate in seeking a waiver or other
modification to such funding arrangement with respect to such Alnylam
Technology.

 

10. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

10.1 Inventorship. Inventorship for inventions and discoveries first made during
the course of the performance of activities pursuant to these Global License
Terms shall be determined in accordance with United States patent Laws for
determining inventorship.

10.2 Ownership. Alnylam shall own the entire right, title and interest in and to
all inventions and discoveries (and Patent Rights claiming patentable inventions
therein) first made or discovered solely by employees or consultants of Alnylam
or acquired solely by Alnylam in the course of conducting the Collaboration.
Genzyme shall own the entire right, title and interest in and to all inventions
and discoveries (and Patent Rights claiming patentable inventions therein) first
made or discovered solely by employees or consultants of Genzyme or acquired
solely by Genzyme in the course of conducting the Collaboration. The Parties
shall jointly own any inventions and discoveries (and Patent Rights claiming
patentable inventions therein) first made or discovered jointly in the course of
conducting the Collaboration.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

10.3 Prosecution and Maintenance of Patent Rights.

10.3.1 IP Committee. The Parties agree that the IP Committee created pursuant to
Section 5.3 of the Master Agreement (IP Committee) shall be responsible for
overseeing and effecting the information sharing and consulting provisions under
this Section 10.3.

10.3.2 Genzyme Technology.

(a) Subject to Section 10.3.1(b) below, Genzyme has the sole responsibility, at
Genzyme’s discretion and at Genzyme’s sole cost and expense, to file, prosecute
and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Genzyme Technology (other than Joint
Collaboration IP and Alnylam Product-Specific Patents assigned by Alnylam to
Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific
Patents)), in Genzyme’s name.

(b) In the event that Genzyme elects not to seek or continue to seek or maintain
patent protection on any Genzyme Collaboration IP in the Licensed Territory,
Genzyme shall notify Alnylam at least [***] days before any such Patent Rights
would become abandoned, no longer available or otherwise forfeited, and subject
to the terms and conditions of any applicable Genzyme In-License, Alnylam shall
have the right (but not the obligation), at its expense, to seek, prosecute and
maintain in any country patent protection on such Genzyme Collaboration IP in
the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to make
available to Alnylam its authorized attorneys, agents or representatives, and
such of its employees as are reasonably necessary to assist Alnylam in obtaining
and maintaining the patent protection described under this Section 10.3.1(b).
Genzyme shall sign or use Commercially Reasonable Efforts to have signed, all
legal documents necessary to file and prosecute such patent applications or to
obtain or maintain such patents.

10.3.3 Alnylam Technology and Alnylam Product-Specific Patents.

(a) Subject to Sections 10.3.3(b) and 10.3.3(c), Alnylam has the sole
responsibility, at Alnylam’s discretion and at Alnylam’s sole cost and expense,
to file, conduct prosecution and maintain (including the defense of any
interference or opposition proceedings), all Patent Rights comprising Alnylam
Technology (other than Alnylam Product-Specific Patents assigned to Genzyme and
Joint Collaboration IP), in Alnylam’s name.

(b) Notwithstanding the foregoing Section 10.3.3(a), subject to the terms and
conditions of any applicable Alnylam In-License, as between the Parties Genzyme
shall have the first right, at its expense, to file, conduct prosecution and
maintain (including the defense of any interference or opposition proceedings)
all Alnylam Product-Specific Patents (regardless of whether such Alnylam
Product-Specific Patents are Controlled by Alnylam or Genzyme). Genzyme shall
consult with Alnylam, including through the IP

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

Committee, on the preparation, filing, prosecution and maintenance of all
Alnylam Product-Specific Patents but shall retain final decision making
authority on such preparation, filing, prosecution and maintenance. Genzyme
shall furnish Alnylam via electronic mail or other such method as mutually
agreed by the Parties with copies of proposed filings and documents received
from outside counsel in the course of such filing, prosecution or maintenance of
and/or copies of documents filed with the relevant patent offices with respect
to Alnylam Product-Specific Patents and such other documents directly related to
the prosecution and maintenance of Alnylam Product-Specific Patents reasonably
necessary for Alnylam to exercise its rights under this Section 10.3.3(b), and
as applicable in sufficient time prior to filing such document or making any
payment due thereunder to allow for review and comment by Alnylam. Genzyme shall
consider in good faith timely input from Alnylam thereon, but Genzyme will make
all decisions relating to the prosecution and maintenance of Alnylam
Product-Specific Patents. Alnylam shall make available to Genzyme its authorized
attorneys, agents or representatives, and such of its employees as are
reasonably necessary to assist Genzyme in obtaining and maintaining the patent
protection described under this Section 10.3.3(b). Alnylam shall sign, or have
signed, all legal documents necessary to file and prosecute such patent
applications or to obtain or maintain such patents.

(c) In the event that Genzyme elects not to seek or continue to seek or maintain
patent protection on any Alnylam Product-Specific Patent in any country in the
Licensed Territory, Genzyme shall notify Alnylam at least [***] days before such
Alnylam Product-Specific Patent would become abandoned, no longer available or
otherwise forfeit (including any decision by Genzyme not to continue to file and
prosecute at least one patent application claiming priority to an Alnylam
Product-Specific Patent issuing in any particular country). Alnylam shall have
the right (but not the obligation), at its expense, to seek, prosecute and
maintain in any country patent protection on any such Alnylam Product-Specific
Patent (including the defense of any interference or opposition proceedings). If
Alnylam exercises such right, the applicable Alnylam Product-Specific Patent
(and all Patent Rights thereafter filed by or on behalf of Alnylam claiming
priority thereto) shall no longer be treated as a “Alnylam Product-Specific
Patent” hereunder, and if Controlled by Genzyme, Genzyme shall assign and
transfer such Alnylam Product-Specific Patent to Alnylam. Genzyme shall make
available to Alnylam its authorized attorneys, agents or representatives, such
of its employees as are reasonably necessary to assist Alnylam in obtaining and
maintaining the patent protection described under this Section 10.3.3(c).
Genzyme shall sign, or have signed, all legal documents as are reasonably
necessary to assist Alnylam in obtaining and maintaining the patent protection
described under this Section 10.3.3(c).

10.3.4 Joint Collaboration IP.

(a) [***] shall have the first right to, at [***] discretion, file, prosecute
and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Joint Collaboration IP, in the names
of both Alnylam and Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

GLOBAL LICENSE TERMS

 

[***] shall consult with [***] on the filing, prosecution and maintenance of all
such Patent Rights. Each Party shall sign, or use Commercially Reasonable
Efforts to have signed, all legal documents as are reasonably necessary to file
and prosecute patent applications or to obtain or maintain patents in respect of
such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish to [***] via electronic mail or other such method as
mutually agreed by the Parties copies of documents received from outside counsel
in the course of such filing, prosecution or maintenance of Joint Collaboration
IP and/or copies of documents relevant to such preparation, filing, prosecution,
and maintenance in sufficient time prior to filing such document or making any
payment due thereunder to allow for review and comment [***] and shall consider
in good faith timely comments from [***] thereon. [***] shall furnish to [***]
via electronic mail or other such method as mutually agreed by the Parties
copies of such documents as filed in the relevant patent offices.

(c) In the event that [***] elects not to file or continue to prosecute or
maintain patent protection on any Joint Collaboration IP, Alnylam shall have the
right (but not the obligation) to file, prosecute and maintain Patent Rights
comprising Joint Collaboration IP in the names of both Alnylam and Genzyme at
[***] sole cost and expense. If [***] exercises such right, [***] shall make
available to [***] its authorized attorneys, agents or representatives, and such
of its employees as are reasonably necessary to assist [***] in obtaining and
maintaining the patent protection described under this Section 10.3.4(c). [***]
shall sign, or use Commercially Reasonable Efforts to have signed, all legal
documents as are reasonably necessary to file and prosecute such patent
applications or to obtain or maintain such patents.

(d) [***] shall bear all out-of-pocket patent filing, prosecution and
maintenance expenses incurred with respect to Patent Rights comprising Joint
Collaboration IP.

10.3.5 Patent Miscellaneous. Each Party hereby agrees: (a) to make its
employees, agents and consultants reasonably available to the other Party (or to
the other Party’s authorized attorneys, agents or representatives), to the
extent reasonably necessary to enable such Party to undertake patent
prosecution; (b) to provide the other Party with copies of all material
correspondence pertaining to prosecution with the patent offices; (c) to
cooperate, if necessary and appropriate, with the other Party in gaining patent
term extensions wherever applicable to Patent Rights licensed under these Global
License Terms; and (d) to endeavor in good faith to coordinate its efforts with
the other Party to minimize or avoid interference with the prosecution and
maintenance of the other Party’s patent applications.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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10.3.6 Alnylam Product-Specific Patents.

10.3.6.1 Assignment of Alnylam Product-Specific Patents. On the Implementation
Date with respect to a Global Licensed Product, Alnylam will assign and transfer
to Genzyme, all rights, title, and interests in and to the Alnylam
Product-Specific Patents with respect to such Global Licensed Product that are
owned by Alnylam on the Implementation Date, and all claims and causes of action
arising from or relating to such Alnylam Product-Specific Patents, including all
rights to recovery for damages from infringement arising prior to, on or after
the Implementation Date. On the Implementation Date for a Global Licensed
Product, Alnylam will execute and deliver a confirmatory assignment relating to
all Alnylam Product-Specific Patents with respect to such Global Licensed
Product assigned to Genzyme under this Section 10.3.6.1 in a mutually agreed
form.

10.3.6.2 Disclosure of Future Alnylam Product-Specific Patents. Upon becoming
aware of any potentially patentable invention Controlled by Alnylam that would,
if patented, be included within the definition of Alnylam Product-Specific
Patents with respect to any Global Licensed Product, Alnylam will promptly
disclose such invention to Genzyme in writing in reasonable detail via the IP
Committee.

10.3.6.3 Covenants in Support of Assignment. Alnylam will provide all further
cooperation which Genzyme reasonably determines is necessary to accomplish the
complete transfer of the Alnylam Product-Specific Patents with respect to a
Global Licensed Product, and all associated rights, to Genzyme on or after the
Implementation Date for such Global Licensed Product, including executing and
delivering further assignments, consents, releases and other commercially
reasonable documentation, and providing good faith testimony by affidavit,
declaration, deposition, in-person or other proper means and otherwise assisting
Genzyme in support of any effort by Genzyme to establish, perfect, defend or
enforce its rights in such Alnylam Product-Specific Patents through filing and
prosecution of such Alnylam Product-Specific Patents, interferences,
oppositions, other regulatory proceedings, litigation or other means. Alnylam
will obtain the cooperation of the individual inventors of any inventions
disclosed in such Alnylam Product-Specific Patents assigned to Genzyme pursuant
to this Section 10.3.6, including (a) obtaining signatures of such inventors on
any patent applications or other documentation reasonably necessary to obtain
patent protection for such inventions and (b) procuring (at Genzyme’s expense)
such inventors’ good faith testimony by affidavit, declaration, deposition
in-person or other proper means in support of Genzyme’s efforts in establishing,
perfecting, defending or enforcing patent rights to such inventions. To the
extent Alnylam cannot transfer and assign the Alnylam Product-Specific Patents
with respect to a Global Licensed Product, or any portion thereof, on the
Implementation Date for such Global Licensed Product, then Alnylam will transfer
and assign such Alnylam Product-Specific Patents to Genzyme at its first
opportunity to do so

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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and, pending such transfer and assignment, such Alnylam Product-Specific Patents
will be deemed to be Alnylam Patents for all purposes under these Global License
Terms. To the extent further transfer or assignment of such Alnylam
Product-Specific Patents is required or permitted, and Alnylam has not executed
and returned to Genzyme the form of assignment reasonably requested by Genzyme
within [***] business days of the delivery of such assignment to Alnylam at the
address for notices set forth in Section 13.11 of the Master Agreement
(Notices), then Alnylam hereby irrevocably appoints Genzyme as its
attorney-in-fact with the right, authority and ability to execute and enter into
such assignment on behalf of Alnylam. Alnylam stipulates and agrees that such
appointment is a right coupled with an interest and will survive the
unavailability of Alnylam at any future time.

10.3.6.4 Grant-Back License. Subject to the provisions of these Global License
Terms, Genzyme hereby grants Alnylam a non-exclusive, non-transferable license
(with no right to sublicense) under the Alnylam Product-Specific Patents to the
extent necessary to perform Alnylam’s obligations under these Global License
Terms and any GLP Supply Agreement.

10.4 Third Party Infringement.

10.4.1 Notices. Each Party shall promptly report in writing to the other Party
any (a) known or suspected infringement of any Alnylam Technology, Genzyme
Technology, Genzyme Manufacturing IP or Joint Collaboration IP or
(b) unauthorized use or misappropriation of any Confidential Information or
Know-How of a Party by a Third Party of which it becomes aware, in each case to
the extent such infringing, unauthorized or misappropriating activities involve,
as to a Global Licensed Product, a competing product in the Field (a
“Competitive Infringement”), and shall provide the other Party with all
available evidence of such infringement, unauthorized use or misappropriation.

10.4.2 Rights to Enforce.

(a) Genzyme Technology. Subject to the provisions of any In-License, Genzyme
shall have the sole and exclusive right to initiate an infringement or other
appropriate suit (an “Infringement Action”) anywhere in the world against any
Third Party as to any infringement, or suspected infringement of, any Patent
Rights, or as to any use or suspected use without proper authorization of any
Know-How, comprising Genzyme Patent Rights, Genzyme Know-How, Genzyme
Collaboration IP or Genzyme Manufacturing IP.

(b) Alnylam Technology. Subject to the provisions of any In-License, Genzyme
shall have the first right to initiate an Infringement Action anywhere in the
world against any Third Party with respect to any Competitive Infringement in
the Licensed Territory of any Alnylam Product-Specific Patent or Joint
Collaboration IP, or, with Alnylam’s prior written consent, Alnylam Core
Technology Patent or Alnylam

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Know-How. Alnylam will consider in good faith any request from Genzyme to
initiate an Infringement Action against any Third Party with respect to a
Competitive Infringement in the Licensed Territory of any Alnylam Core
Technology Patent; provided, however, that Alnylam shall not be required to
initiate any such Infringement Action or permit Genzyme to initiate any such
Infringement Action.

 

  (c) Step-In Right.

 

  (i) If, within [***] days (or such shorter period of time as required by
applicable Law to avoid loss of material enforcement rights) after Genzyme’s
receipt of a notice of a Competitive Infringement with respect to any Alnylam
Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any
Infringement Action permitted hereunder against such Competitive Infringement in
the Licensed Territory, Alnylam may elect, in its sole discretion, to bring and
control an Infringement Action in connection therewith at its sole cost and
expense by providing written notice of such election to Genzyme.

 

  (ii) If (A) there are no Alnylam Product-Specific Patents or Patent Rights
included in Joint Collaboration IP that can be asserted against a Competitive
Infringement in the Licensed Territory, for any reason other than the
unwillingness of Genzyme to consent to such assertion of any Patent Rights
included in the Joint Collaboration IP; (B) there are Alnylam Core Technology
Patent(s) that can reasonably be asserted, but Alnylam refuses to either permit
Genzyme to assert or itself assert at least one of such Alnylam Core Technology
Patent(s) that can reasonably be asserted against a Competitive Infringement in
the Licensed Territory; and (C) Genzyme and Alnylam are unable to stop the
Competitive Infringement through enforcement of any other Patent Rights or
Know-How Controlled by either Party, then the royalties to be paid by Genzyme to
Alnylam pursuant to Section 8.2 (Royalties), with respect to the applicable
Global Licensed Product in the countries in the Licensed Territory where such
Competitive Infringement exists, shall be reduced by [***] during the period
when the conditions in the foregoing clauses (A), (B) and (C) exist and such
Competitive Infringement continues, subject to the limitations set forth in
Section 8.2 (Royalties).

10.4.3 Procedures; Expenses and Recoveries. The Party having the right to
initiate any Infringement Action under Section 10.4.2 (Rights to Enforce) above
shall have the sole and exclusive right to select counsel for any such
Infringement Action and shall pay all expenses of such Infringement Action,
including attorneys’ fees and court costs and reimbursement of the other Party’s
reasonable Global Out-of-Pocket Costs in rendering assistance requested by the
initiating Party. If required under applicable Law in order for the initiating
Party to initiate and/or maintain such Infringement Action, or if

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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either Party is unable to initiate or prosecute such Infringement Action solely
in its own name or it is otherwise advisable to obtain an effective legal
remedy, in each case, the other Party shall join as a party to such Infringement
Action and will execute, and cause its Affiliates to execute, all documents
necessary for the initiating Party to initiate litigation to prosecute and
maintain such Infringement Action. In addition, at the initiating Party’s
request, the other Party shall provide reasonable assistance to the initiating
Party in connection with an Infringement Action at no charge to the initiating
Party except for reimbursement by the initiating Party of reasonable Global
Out-of-Pocket Costs incurred in rendering such assistance. The non-initiating
Party shall have the right to participate and be represented in any such
Infringement Action by its own counsel at its own expense. If the Parties obtain
from a Third Party, in connection with such Infringement Action, any damages,
license fees, royalties or other compensation (including any amount received in
settlement of such litigation), after payment of any amounts required under any
In-Licenses, the remaining amounts shall be allocated in all cases as follows:

 

  (i) first, to reimburse each Party for all expenses of such Infringement
Action incurred by the Parties, including attorneys’ fees and disbursements,
court costs and other litigation expenses;

 

  (ii) second [***] of the balance to be paid to the Party initiating such
Infringement Action; and

 

  (iii) third, the remainder to the other Party.

Notwithstanding the foregoing, in the event that Alnylam elects to itself assert
an Alnylam Core Technology Patent against a Competitive Infringement in the
Licensed Territory, the Parties shall each be entitled to [***] of the balance
of any recovery therefrom after reimbursement of expenses as described in clause
(i) above.

10.5 Patent Term Extensions.

10.5.1 Retained Alnylam Product-Specific Patent Rights. Subject to the
provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable
Efforts to obtain all available supplementary protection certificates (“SPCs”)
and other extensions of Alnylam Product-Specific Patents in the Licensed
Territory that are not assigned to Genzyme pursuant to Section 10.3.5. If more
than one Alnylam Product-Specific Patent is eligible for extension or patent
term restoration in the Licensed Territory, Genzyme will determine, in its sole
discretion, a strategy that will be designed to maximize patent protection and
commercial value for the Global Licensed Product, and the Parties, subject to
the provisions of any In-License, will seek patent term extensions, restorations
and SPCs for Alnylam Product-Specific Patents in the Licensed Territory in
accordance with that strategy. Where required under national law, and subject to
the other requirements of this Section 10.5, Alnylam will make the filings for
such extensions, restorations and SPCs for Alnylam Product-Specific Patents in
the Licensed Territory as directed by Genzyme.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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10.5.2 Further Assurances for SPCs. Each Party will execute such authorizations
and other documents and take such other actions as may be reasonably requested
by the other Party to obtain any such extensions, restorations and SPCs for
Alnylam Product-Specific Patents in the Licensed Territory, in accordance with
this Section 10.5.

10.6 Common Interest. All information exchanged between the Parties’
representatives regarding the preparation, filing, prosecution, maintenance, or
enforcement of the Patent Rights under this Section 10 will be deemed
Confidential Information. In addition, the Parties acknowledge and agree that,
with regard to such preparation, filing, prosecution, maintenance and
enforcement of the Patent Rights under this Section 10, the interests of the
Parties as collaborators and licensor and licensee are to obtain the strongest
patent protection possible, and as such, are aligned and are legal in nature.
The Parties agree and acknowledge that they have not waived, and nothing in
these Global License Terms constitutes a waiver of, any legal privilege
concerning the Patent Rights under this Section 10, including privilege under
the common interest doctrine and similar or related doctrines.

10.7 Trademarks.

(a) Genzyme has the sole and exclusive right to select and develop one or more
Product Trademark(s) for use by Genzyme and its Related Parties throughout the
Licensed Territory. Such Product Trademark(s) may not include trademarks owned
or Controlled by Alnylam (“Alnylam Trademarks”) and no right or license to any
Alnylam Trademarks are conveyed hereunder to Genzyme. Any Product Trademark(s)
that are used by Genzyme to promote and sell Licensed Products in the Licensed
Territory are hereinafter referred to as the “Genzyme Trademarks.” Genzyme (or
its Related Parties, as appropriate) shall own all rights to Genzyme Trademarks
and all goodwill associated therewith, throughout the Licensed Territory.
Genzyme shall also own rights to any Internet domain names incorporating the
applicable Genzyme Trademarks or any variation or part of such Genzyme
Trademarks used as its URL address or any part of such address.

(b) In the event that Alnylam becomes aware of any infringement of any Product
Trademark by a Third Party, Alnylam shall promptly notify Genzyme and the
Parties shall consult with each other and jointly determine the best way to
prevent such infringement, including by the institution of legal proceedings
against such Third Party.

10.8 Cooperative Research and Technology (CREATE) Act Acknowledgment. It is the
intention of the Parties that these Global License Terms are a “joint research
agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11. TERM AND TERMINATION

11.1 Term. These Global License Terms shall be effective as of the
Implementation Date and, unless terminated earlier pursuant to Section 11.2
(Termination Rights), these Global License Terms shall continue in effect on a
Global Licensed Product-by-Global Licensed Product and country-by-country basis
until expiration of the last Royalty Term to expire under these Global License
Terms (“Term”). Upon expiration of the Royalty Term for a Global Licensed
Product, all licenses of the Parties under Section 7 (Licenses) with respect to
such Global Licensed Product then in effect shall become fully paid-up,
perpetual, exclusive licenses.

11.2 Termination Rights. These Global License Terms may be terminated by the
Parties only as set forth in this Section 11.2.

11.2.1 Termination of Global Licensed Product for Convenience. Subject to the
remainder of this Article 11, Genzyme shall have the right to terminate these
Global License Terms with respect to any particular Global Licensed Product at
any time after the Implementation Date on six (6) months prior written notice to
Alnylam.

11.2.2 Termination of Global Licensed Product for Cause. These Global License
Terms may be terminated with respect to any Global Licensed Product at any time
during the Term upon written notice by either Party if (a) the other Party is in
material breach of its obligations hereunder with respect to such Global
Licensed Product, (b) such material breach relates to such Global Licensed
Product and (c) the other Party has not cured such breach within thirty
(30) days in the case of a payment breach, or within ninety (90) days in the
case of all other breaches, after notice requesting cure of the breach;
provided, however, that if any breach other than a payment breach is not
reasonably curable within ninety (90) days and if a Party is making a bona fide
effort to cure such breach, such termination shall be delayed for a time period
to be agreed by both Parties, not to exceed an additional ninety (90) days, in
order to permit such Party a reasonable period of time to cure such breach;
provided, further, that in the event that the breach relates to a dispute
between the Parties regarding Genzyme’s obligations to use Commercially
Reasonable Efforts in Developing or Commercializing such Global Licensed Product
and Genzyme disputes whether it has breached such obligation or whether such
breach gives Alnylam the right to terminate these Global License Terms with
respect to such Global Licensed Product and initiates a legal action against
Alnylam to resolve such dispute within the foregoing sixty (60) day cure period,
then these Global License Terms shall not terminate during the pendency of such
legal action, provided that if (i) Genzyme is found, in an unappealable decision
by a court of competent jurisdiction or an appealable decision of a court of
competent jurisdiction that has not been appealed in the time allowed for an
appeal in such legal action, to have materially breached these Global License
Terms with respect to such Global Licensed Product, or (ii) Genzyme admits in
such legal action or settlement thereof that it has materially breached these
Global License Terms with respect to such Global Licensed Product, then these
Global License Terms shall terminate immediately with respect to such Global
Licensed Product following the Parties’ receipt of such decision or immediately
following such admission, as applicable.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.3 Effect of Termination.

11.3.1 Effects of Termination of Global Licensed Product by Genzyme for Cause.
Without limiting any other legal or equitable remedies that either Party may
have, if these Global License Terms are terminated by Genzyme with respect to
any Global Licensed Product pursuant to Section 11.2.2 (Termination of Global
Licensed Product for Cause), then the provisions of this Section 11.3.1 shall
apply:

(a) These Global License Terms shall terminate with respect to the rights and
licenses granted to Genzyme for such terminated Global Licensed Product but
shall continue to survive in all respects with respect to all Global Licensed
Products other than the terminated Global Licensed Product.

(b) All License grants in these Global License Terms from either Party to the
other with respect to the terminated Global Licensed Product shall immediately
terminate.

(c) The Back-Up Option shall terminate with respect to all Back-Up Products for
the terminated Global Licensed Product; provided, however, that such Back-Up
Products shall, as of such date, be considered Option Products for the purposes
of the Master Agreement, and the Options granted under the Master Agreement to
siRNA that targets the same gene as the terminated Global Licensed Product shall
again apply in accordance with the terms and conditions set forth in the Master
Agreement;

(d) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all Regulatory Approvals and pricing
and reimbursement approvals relating to the Development, Manufacture or
Commercialization of the terminated Global Licensed Product, and (ii) copies of
all non-clinical and clinical data and material regulatory correspondence
relating to the terminated Global Licensed Product, provided that Alnylam shall
reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme
in connection with such transfer;

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product Specific Patents that relate solely to the
terminated Global Licensed Product that were assigned to Genzyme pursuant to
Section 10.3.5 (Alnylam Product-Specific Patents), provided that Alnylam shall
reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme
in connection with such assignment and transfer. In such event, Genzyme will
execute and deliver a patent assignment relating to such Alnylam
Product-Specific Patents in the form reasonably requested by Alnylam; and

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(f) each Party shall promptly pay any amounts owed to the other Party as of the
effective date of such termination.

11.3.2 Effects of Termination of Global Licensed Product by Alnylam for Cause or
by Genzyme for Convenience. Without limiting any other legal or equitable
remedies that either Party may have, if these Global License Terms are
terminated with respect to any Global Licensed Product by Genzyme pursuant to
Section 11.2.1 (Termination of Global Licensed Product for Convenience) or by
Alnylam pursuant to Section 11.2.2 (Termination of Global Licensed Product for
Cause), then the provisions of this Section 11.3.2 shall apply:

(a) These Global License Terms shall terminate with respect to the rights and
licenses granted to Genzyme for such terminated Global Licensed Product but
shall continue to survive in all respects with respect to all Global Licensed
Products other than the terminated Global Licensed Product.

(b) The license grants to Alnylam in Section 7.2 (License Grants to Alnylam)
shall survive such termination with respect to the Reverted Global Licensed
Product.

(c) Genzyme will grant to Alnylam, effective upon the effective date of
termination and subject to the terms of any applicable Genzyme In-License, a
non-transferable, sublicensable (on terms consistent with Section 7.1.4
(Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any
Genzyme Collaboration IP and Genzyme Patent Rights that Cover any Global
Licensed Product that is being Developed or Commercialized by Genzyme pursuant
to these Global License Terms on the effective date of termination, in the form
that such Global Licensed Product exists on the effective date of termination (a
“Reverted Global Licensed Product”), solely to the extent necessary to Develop
and Commercialize the Reverted Global Licensed Product in the Field in the
Licensed Territory. Notwithstanding the foregoing, if (i) any Patent Rights that
Cover any Reverted Global Licensed Product are Controlled by Genzyme pursuant to
a Genzyme In-License and (ii) such Genzyme In-License cannot be assigned to
Alnylam or does not relate exclusively to the Reverted Global Licensed Product,
Genzyme shall promptly disclose any payment obligations under such Genzyme
In-License to Alnylam and such Genzyme Patent Rights shall be subject to the
license granted in this Section 11.3.2(b) only if Alnylam agrees in writing to
(A) reimburse Genzyme for one hundred percent (100%) of any amounts that become
payable under such Genzyme In-License as a result of Alnylam’s exercise of the
license granted in this Section 11.3.2(b), (B) comply with all applicable terms
and conditions of such Genzyme In-License and (C) perform and take such actions
as may be required to allow Genzyme to comply with its obligations under such
Genzyme In-License.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) The Back-Up Option shall terminate with respect to all Back-Up Products for
the terminated Global Licensed Product and such Back-Up Product shall be treated
as an Option Product for which Genzyme has not exercised an Option for purposes
of Section 3.5 of the Master Agreement;

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product Specific Patents that relate solely to the
terminated Global Licensed Product that were assigned to Genzyme pursuant to
Section 10.3.5 (Alnylam Product-Specific Patents). In such event, Genzyme will
execute and deliver a patent assignment relating to such Alnylam
Product-Specific Patents in the form reasonably requested by Alnylam;

(f) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all governmental or regulatory filings
and approvals (including all Regulatory Approvals and pricing and reimbursement
approvals) and material correspondence and conversation logs relating to the
Development, Manufacture or Commercialization of the Reverted Global Licensed
Product and all Genzyme Trademarks, (ii) copies of all data, reports, records
and materials, and other sales and marketing related information in Genzyme’s
possession or Control to the extent that such data, reports, records, materials
or other information relate to the Development, Manufacture or Commercialization
of the Reverted Global Licensed Product, including all non-clinical and clinical
data relating to the Reverted Global Licensed Product, and customer lists and
customer contact information and all adverse event data related to the Reverted
Global Licensed Product in Genzyme’s possession or Control, provided that for a
period of [***] months after the effective date of termination with respect to
such Reverted Global Licensed Product, Genzyme shall use Commercially Reasonable
Efforts to obtain for Alnylam the right to access all such data, reports,
records, materials, and other sales and marketing related information), and
(iii) all records and materials in Genzyme’s possession or Control containing
Confidential Information of Alnylam exclusively related to the Reverted Global
Licensed Product. In addition, Genzyme shall appoint Alnylam as Genzyme’s and/or
Genzyme’s Related Parties’ agent for all Reverted Global Licensed
Product-related matters involving Regulatory Authorities in the Licensed
Territory until all Regulatory Approvals and other regulatory filings have been
transferred to Alnylam or its designee.

(g) If the effective date of termination is after First Commercial Sale of the
Reverted Global Licensed Product, then Genzyme shall appoint Alnylam as its
exclusive distributor of the Reverted Global Licensed Product in the Licensed
Territory and grant Alnylam the right to appoint sub-distributors, until such
time as all Regulatory Approvals in the Licensed Territory have been transferred
to Alnylam or its designee.

(h) If Genzyme or its Related Parties are Manufacturing finished product with
respect to the Reverted Global Licensed Product on the effective date of
termination, at Alnylam’s option, Genzyme or its Related Parties shall supply
such finished product to

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Alnylam in the Licensed Territory on terms no less favorable than those on which
Genzyme supplied such finished product prior to such termination to its most
favored distributor in the Licensed Territory, until the earlier of (i) such
time as all Regulatory Approvals in the Licensed Territory related to the
Reverted Global Licensed Product have been transferred to Alnylam or its
designee, Alnylam has obtained all necessary manufacturing approvals and Alnylam
has procured or developed its own source of such finished product supply or
(ii) [***] months following the effective date of termination.

(i) If Alnylam so requests, and to the extent permitted under Genzyme’s
obligations to Third Parties on the effective date of termination, Genzyme shall
transfer to Alnylam any Third Party agreements relating solely and exclusively
to the Development, Manufacture or Commercialization of the Reverted Global
Licensed Product to which Genzyme is a party (including any Genzyme In-License),
subject to any required consents of such Third Party, which Genzyme shall use
Commercially Reasonable Efforts to obtain promptly.

(j) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and
its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s)
exclusively used in connection with the Reverted Global Licensed Product (but
not any Genzyme house marks or any trademark containing the word “Genzyme”)
owned by Genzyme and used for the Reverted Global Licensed Product in the Field
in the Licensed Territory.

(k) Genzyme shall transfer to Alnylam any inventory of the Reverted Global
Licensed Product Controlled by Genzyme or its Affiliates as of the termination
date at the actual price paid by Genzyme for such supply.

(l) Genzyme shall provide any other assistance reasonably requested by Alnylam
for the purpose of allowing Alnylam or its designee to proceed expeditiously
with the Development, Manufacture and Commercialization of the Reverted Global
Licensed Product in the Licensed Territory; provided that Genzyme’s obligations
under this clause shall expire [***] months after the effective date of
termination of such Reverted Global Licensed Product.

(m) Genzyme shall execute all documents and take all such further actions as may
be reasonably requested by Alnylam in order to give effect to the foregoing
clauses.

11.4 Effect of Expiration or Termination; Survival. Any expiration or
termination of these Global License Terms (a) shall not relieve the Parties of
any obligation accruing prior to such expiration or termination and (b) shall be
without prejudice to the rights of either Party against the other Party accrued
or accruing under these Global License Terms prior to such expiration or
termination, including the obligation to pay royalties for any Global Licensed
Product sold prior to such expiration or termination. If these Global License
Terms expire or are terminated with respect to any Global Licensed Product, the
following provisions shall survive with respect to such

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

Global Licensed Product: (a) Sections 1 (Definitions), 9.3 (Warranty
Disclaimer), 10.1 (Inventorship), 10.2 (Ownership), 11.3 (Effect of
Termination), and 11.4 (Effect of Expiration or Termination; Survival), 12
(Performance of Affiliates) of these Global License Terms, and (b) Sections 1
(Definitions), 7 (Confidentiality and Publication), 9 (Royalty Reports;
Payments; Audits), 10 (Indemnification; Limitation of Liability; Insurance), 12
(Term and Termination) and 13 (Miscellaneous) of the Master Agreement.
Section 8.2.6 (Royalty Floor) shall survive any termination or expiration of
these Global License Terms with respect to royalties accruing prior to such
termination or expiration. Section 9 of the Master Agreement (Royalty Reports;
Payments; Audit) shall survive for so long as any royalties are due under these
Global License Terms plus three (3) years. Except as otherwise set forth in this
Section 11, upon termination or expiration of these Global License Terms in
their entirety (i.e., with respect to all Global Licensed Products), all rights
and obligations of the Parties under these Global License Terms shall cease,
but, for clarity, such expiration or termination of these Global License Terms
shall not result in the termination or expiration of the Master Agreement or any
License Terms. Upon termination or expiration of these Global License Terms with
respect to any particular Global Licensed Product, all rights and obligations of
the Parties under these Global License Terms with respect to such Global
Licensed Product shall cease, but such termination or expiration shall not
affect the Parties’ rights and obligations under these Global License Terms with
respect to any other Global Licensed Product.

 

12. PERFORMANCE BY AFFILIATES

12.1 Use of Affiliates. Each Party acknowledges and accepts that the other Party
may exercise its rights and perform its obligations under these Global License
Terms either directly or through one or more of its Affiliates. A Party’s
Affiliates will have the benefit of all rights (including all licenses) of such
Party under these Global License Terms. Accordingly, in these Global License
Terms “Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and
“Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where
necessary to give each Party’s Affiliates the benefit of the rights provided to
such Party in these Global License Terms; provided, however, that in any event
each Party will remain responsible for the acts and omissions, including
financial liabilities, of its Affiliates.

12.2 Future Acquisition of a Party or its Business. [***]

12.3 Acquired Programs.

12.3.1 [***]

12.3.2 [***].

12.3.3 For clarity, upon the closing of the acquisition of the stock and/or
assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp.,
all relevant acquired intellectual property rights acquired in such transaction
that may be Controlled by Alnylam (without any further action by Alnylam or
Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of
these Global License Terms.

[Remainder of page intentionally left blank]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 1.2.8

ALNYLAM CORE TECHNOLOGY PATENTS

SCHEDULE 1.2.8-1:

[To be added from the applicable Option Data Package]

SCHEDULE 1.2.8-2:

[To be added from the applicable Option Data Package]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 1.2.15

ALNYLAM PRODUCT-SPECIFIC PATENTS

SCHEDULE 1.2.15-1:

[To be added from the applicable Option Data Package]

SCHEDULE 1.2.15-2:

[To be added from the applicable Option Data Package]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 1.2.96

LICENSED TARGET

SCHEDULE 1.2.96-1:

[To be added from the applicable Option Data Package]

SCHEDULE 1.2.96-2:

[To be added from the applicable Option Data Package]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 9.1

DISCLOSURE SCHEDULE

SCHEDULE 9.1-1:

[To be added from the applicable Option Data Package]

SCHEDULE 9.1-2:

[To be added from the applicable Option Data Package]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 9.1.12

(A) EXISTING ALNYLAM IN-LICENSES

[To be added from the applicable Option Data Package]

(B) ADDITIONAL ALNYLAM IN-LICENSES

[To be added from the applicable Option Data Package]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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GLOBAL LICENSE TERMS

 

SCHEDULE 9.4.1(e)

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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EXECUTION VERSION

 

APPENDIX C

CO-CO PRODUCT LICENSE AND COLLABORATION TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

TABLE OF CONTENTS

 

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

     1   

2. DEVELOPMENT COLLABORATION

     20   

2.1. Overview

     20   

2.2. Development Plans

     20   

2.3. Joint Responsibilities for Development Activities and Costs

     26   

2.4. Diligence

     29   

2.5. Records; Reports; Information Sharing

     29   

2.6. Third Parties

     31   

3. REGULATORY MATTERS

     31   

3.1. Regulatory Filings and Interactions in the Genzyme Territory

     31   

3.2. Regulatory Filings and Interactions in the Co-Co Territory

     33   

3.3. EMA Regulatory Strategy

     35   

3.4. Costs of Regulatory Affairs

     35   

3.5. Right of Reference

     35   

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

     36   

4.1. Responsibility, Cost and Diligence

     36   

4.2. Co-Co Territory Commercialization

     36   

4.3. Genzyme Territory Commercialization Plan

     39   

4.4. Advertising and Promotional Materials

     39   

4.5. Commercialization Reporting Obligations

     41   

4.6. Recalls, Market Withdrawals or Corrective Actions

     42   

4.7. Export Monitoring

     42   

5. COLLABORATION MANAGEMENT

     42   

5.1. Product Joint Steering Committee

     42   

5.2. Appointment of Subcommittees, Project Teams and CLP Alliance Managers

     43   

5.3. PJSC Meetings

     44   

5.4. PJSC Minutes

     44   

5.5. PJSC Development Responsibilities

     44   

5.6. PJSC Commercialization Responsibilities

     45   

5.7. PJSC Decision-Making

     46   

5.8. Term of PJSC

     47   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

6. MANUFACTURE AND SUPPLY OF CO-CO LICENSED PRODUCTS

     48   

6.1. Supply Agreements

     48   

7. LICENSES

     48   

7.1. License Grants to Genzyme

     48   

7.2. License Grants to Alnylam

     51   

7.3. Joint Collaboration IP

     52   

7.4. In-Licenses

     52   

7.5. Bankruptcy

     53   

7.6. No Other Rights

     53   

8. FINANCIAL TERMS FOR GENZYME TERRITORY

     54   

8.1. Milestone Fees

     54   

8.2. Royalties

     55   

9. FINANCIAL TERMS FOR CO-CO TERRITORY

     56   

10. REPRESENTATIONS, WARRANTIES AND COVENANTS

     56   

10.1. Representations and Warranties of Alnylam

     56   

10.2. Representations and Warranties of Genzyme

     58   

10.3. Warranty Disclaimer

     58   

10.4. Certain Covenants

     59   

11. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

     60   

11.1. Inventorship

     60   

11.2. Ownership

     60   

11.3. Prosecution and Maintenance of Patent Rights

     60   

11.4. Third Party Infringement

     63   

11.5. Patent Term Extensions

     66   

11.6. Common Interest

     67   

11.7. Trademarks

     67   

11.8. Cooperative Research and Technology (CREATE) Act Acknowledgment

     68   

12. TERM AND TERMINATION

     68   

12.1. Term

     68   

12.2. Termination Rights

     68   

12.3. Effect of Termination

     71   

12.4. Fundamental Breach of Alnylam’s Development Obligations

     76   

12.5. Effect of Expiration or Termination; Survival

     76   

13. PERFORMANCE BY AFFILIATES

     77   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

SCHEDULES

 

Schedule 1.2.14-1    Alnylam Core Technology Patents for ALN-TTRsc Schedule
1.2.19-1    Alnylam Product-Specific Patents for ALN-TTRsc Schedule 2.2.1-1   
Global Development Strategy for ALN-TTRsc Schedule 2.2.2-1    Global Development
Plan for ALN-TTRsc Schedule 2.2.3-1    Genzyme Territory Development Plan for
ALN-TTRsc Schedule 2.7    TTRsc/02 Arbitration Criteria Schedule 4.2-1    Co-Co
Territory Commercialization Plan for ALN-TTRsc Schedule 10.1-1    Disclosure
Schedule Schedule 10.1.12    Existing Alnylam In-Licenses / Additional Alnylam
In-Licenses Schedule 10.4.1.4    Exceptions to Exclusivity

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

CO-CO PRODUCT LICENSE AND COLLABORATION TERMS

THESE CO-CO PRODUCT LICENSE AND COLLABORATION TERMS are Appendix C to the Master
Agreement, dated as of the Execution Date, by and between Alnylam
Pharmaceuticals, Inc., a corporation organized and existing under the laws of
the State of Delaware (“Alnylam”) and, Genzyme Corporation, a corporation
organized and existing under the laws of the Commonwealth of Massachusetts
(“Genzyme”).

RECITALS:

WHEREAS, Alnylam and Genzyme are parties to that certain Master Collaboration
Agreement (dated as of the Execution Date) (the “Master Agreement”) pursuant to
which Genzyme has an option to receive licenses and other rights with respect to
Co-Co Licensed Products from Alnylam in the Genzyme Territory;

WHEREAS, the Parties have agreed that ALN-TTRsc is a Co-Co Licensed Product;

WHEREAS, Genzyme may exercise its Co-Co/Global Option pursuant to the Master
Agreement for the siRNA known as ALN-AT3 (or a successor siRNA Controlled by
Alnylam that targets Antithrombin) and such siRNA will then become a Co-Co
Licensed Product;

WHEREAS, the Parties desire for Alnylam to continue to develop such Co-Co
Licensed Products for the Co-Co Territory and the Genzyme Territory; and

WHEREAS, Alnylam and Genzyme now wish to set forth the terms and conditions
under which Genzyme will have the right to Develop and Commercialize such Co-Co
Licensed Products in the Genzyme Territory and co-Commercialize with Alnylam
such Co-Co Licensed Products in the Co-Co Territory.

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the Parties hereby agree as follows:

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1. Relationship with Master Agreement. These Co-Co License Terms become
effective on a Co-Co Licensed Product-by-Co-Co Licensed Product basis on the
Implementation Date in accordance with the Master Agreement. The Master
Agreement generally governs the Parties’ relationship with respect to Co-Co
Licensed Products during the period of time before Genzyme exercises its
Co-Co/Global Option under the Master Agreement (i.e., before such product became
a Co-Co Licensed Product). The Master Agreement also contains terms that are
generally applicable to Co-Co Licensed Products, Global Licensed Products (as
defined in the Master Agreement) and Regional Licensed Products (as defined in
the Master Agreement). Accordingly, the following Sections of the Master
Agreement are incorporated herein by reference: Section 2.2 (Effectiveness of
Licenses to Collaboration Products); Section 5 (Collaboration Management);
Section 6 (Manufacture and Supply of the Collaboration Products); Section 7
(Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit);
Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4
(Challenges of Patent Rights); and Section 13 (Miscellaneous).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2. Definitions. Unless specifically set forth to the contrary herein, the
following terms, whether used in the singular or plural, shall have the
respective meanings set forth below:

1.2.1. “Acquired Business” has the meaning set forth in Section 13.3 (Acquired
Programs).

1.2.2. “Acquirer” has the meaning set forth in Section 13.2 (Future Acquisition
of a Party or its Business).

1.2.3. “Additional Development Activities” has the meaning set forth in
Section 2.2.2.5(a) (Additional Development Proposals).

1.2.4. “Additional Development Opt-In Date” has the meaning set forth in
Section 2.2.2.5(d)(i) (Opt-In for Additional Development Activities).

1.2.5. “Additional Development Opt-In Notice” has the meaning set forth in
Section 2.2.2.5(d)(i) (Opt-In for Additional Development Activities).

1.2.6. “Additional Development Proposal” has the meaning set forth in
Section 2.2.2.5(a) (Additional Development Proposals).

1.2.7. “AF11 Lipid Nanoparticle Formulation” has the meaning set forth in the
Master Agreement.

1.2.8. “Affiliate” means, with respect to a Person, any other Person which
controls, is controlled by, or is under common control with the applicable
Person. For purposes of this definition, “control” shall mean: (a) in the case
of corporate entities, direct or indirect ownership of at least fifty percent
(50%) of the stock or shares entitled to vote for the election of directors, or
otherwise having the power to control or direct the affairs of such Person; and
(b) in the case of non-corporate entities, direct or indirect ownership of at
least fifty percent (50%) of the equity interest or the power to direct the
management and policies of such non-corporate entities.

1.2.9. “AJSC” has the meaning set forth in the Master Agreement.

1.2.10. “ALN-AT3” has the meaning set forth in the Master Agreement.

1.2.11. “ALN-TTR02” has the meaning set forth in the Master Agreement.

1.2.12. “ALN-TTRsc” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2.13. “ALN-TTRsc Global R&D Cost Opt-In Date” has the meaning set forth in
Section 2.3.1.2(a) (Global R&D Costs).

1.2.14. “Alnylam Core Technology Patents” means Patent Rights Controlled by
Alnylam during the Term that are [***]. The Alnylam Core Technology Patents
existing as of the Effective Date for ALN-TTRsc are those Patent Rights
identified on Schedule 1.2.14-1. The Alnylam Core Technology Patents existing as
of the Implementation Date for ALN-AT3 will be identified as the “Alnylam Core
Technology Patents” in the Option Data Package for ALN-AT3 provided by Alnylam
to Genzyme under the Master Agreement and then attached hereto as Schedule
1.2.14-2.

1.2.15. “Alnylam Developed siRNA Product” means an siRNA with respect to which
(a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a
product first satisfies the criterion set forth in this clause (a) such
criterion shall be deemed satisfied at all times thereafter as to such product,
and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the
Development.

1.2.16. “Alnylam In-License” means any Existing Alnylam In-License or any
Collaboration In-License to which Alnylam is a party.

1.2.17. “Alnylam Know-How” means Know-How Controlled by Alnylam during the Term
that is reasonably necessary or useful for Genzyme to Develop, Manufacture
and/or Commercialize Co-Co Licensed Products in the Field in the Genzyme
Territory, other than Alnylam’s interest in Know-How included in Joint
Collaboration IP.

1.2.18. “Alnylam Patents” means Alnylam Core Technology Patents and Alnylam
Product-Specific Patents.

1.2.19. “Alnylam Product-Specific Patents” means Patent Rights Controlled by
Alnylam during the Term [***]. The Alnylam Product-Specific Patents existing as
of the Effective Date for ALN-TTRsc are those Patent Rights identified on
Schedule 1.2.19-1. The Alnylam Product-Specific Patents existing as of the
Implementation Date for ALN-AT3 will be identified as the “Alnylam
Product-Specific Patents” in the Option Data Package for ALN-AT3 provided by
Alnylam to Genzyme under the Master Agreement and then attached hereto as
Schedule 1.2.19-2. [***]

1.2.20. “Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam
Patents and Alnylam’s interest in Joint Collaboration IP.

1.2.21. “Alnylam Trademark” has the meaning set forth in Section 11.7(b)
(Trademarks).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2.22. “ANDA” means an Abbreviated New Drug Application (or any successor
application or procedure) as defined in regulations promulgated by the FDA under
the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as
applicable, any other analogous application filed with a Regulatory Authority in
any country other than the U.S. in the Genzyme Territory) for Regulatory
Approval for marketing and selling a Co-Co Licensed Product in the Genzyme
Territory.

1.2.23. “Antithrombin” has the meaning set forth in the Master Agreement.

1.2.24. “Appendix” means this Appendix B (Co-Co License and Collaboration
Terms).

1.2.25. “ATTR” means the human disease TTR-mediated amyloidosis.

1.2.26. “Back-Up Option” has the meaning set forth in Section 7.1.5 (Back-Up
Products).

1.2.27. “Back-Up Option Exercise Notice” has the meaning set forth in
Section 7.1.5 (Back-Up Products).

1.2.28. “Back-Up Option Period” means (i) with respect to a Back-Up Product for
ALN-TTRsc, the period beginning with the Implementation Date for ALN-TTRsc and
ending on [***] and (ii) with respect to a Back-Up Product for ALN-AT3, the
period beginning with the Implementation Date for ALN-AT3 and ending on [***].

1.2.29.

1.2.30. “Back-Up Product” has the meaning set forth for in Section 7.1.5
(Back-Up Products).

1.2.31. “Bankrupt Party” has the meaning set forth in Section 7.5 (Bankruptcy).

1.2.32. “Budget Adjustment Triggers” has the meaning set forth in
Section 2.2.2.3 (Managing and Amending Global Development Plans and Global
Development Budgets).

1.2.33. “Calendar Quarter” means the respective periods of three (3) consecutive
calendar months ending on March 31, June 30, September 30 and December 31 of
each Calendar Year, provided that (a) the first Calendar Quarter of the Term
shall begin on the Effective Date and end on the first to occur of
March 31, June 30, September 30 or December 31 thereafter and the last Calendar
Quarter of the Term shall end on the last day of the Term and (b) the first
Calendar Quarter of a Royalty Term for a Co-Co Licensed Product in a country
shall begin on the First Commercial Sale of a Co-Co Licensed Product in such
country and end on the first to occur of March 31, June 30, September 30 or
December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end
on the last day of such Royalty Term.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-4-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.34. “Calendar Year” means each successive period of twelve (12) months
commencing on January 1 and ending on December 31, provided that (a) the first
Calendar Year of the Term shall begin on the Effective Date and end on the first
December 31 thereafter and the last Calendar Year of the Term shall end on the
last day of the Term and (b) the first Calendar Year of a Royalty Term for a
Co-Co Licensed Product in a country shall begin on the First Commercial Sale of
a Co-Co Licensed Product in such country and end on the first December 31
thereafter and the last Calendar Year of the Term shall end on the last day of
such Royalty Term.

1.2.35. “Carbohydrate Conjugate” has the meaning set forth in the Master
Agreement.

1.2.36. “Clinical Study” has the meaning set forth in the Master Agreement.

1.2.37. “CLP Alliance Manager” has the meaning set forth in Section 5.2
(Appointment of Subcommittees, Project Teams and CLP Alliance Managers).

1.2.38. “Co-Co Clinical Supply Agreements” means, collectively, the ALN-TTRsc
Clinical Supply Agreement and the ALN-AT3 Clinical Supply Agreement entered into
between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement
(Collaboration Product Supply Agreements) pursuant to which Alnylam will provide
clinical supplies of the specified Co-Co Licensed Product to Genzyme.

1.2.39. “Co-Co Collaboration” means the collaboration of the Parties in the
Development, Manufacture and Commercialization of a Co-Co Licensed Product under
these Co-Co License Terms.

1.2.40. “Co-Co Commercial Supply Agreements” means, collectively, the ALN-TTRsc
Commercial Supply Agreement and the ALN-AT3 Commercial Supply Agreement entered
into between Alnylam and Genzyme as described in Section 6.2 of the Master
Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam
will provide commercial supplies of the specified Co-Co Licensed Product to
Genzyme.

1.2.41. “Co-Co/Global Option” has the meaning set forth in the Master Agreement.

1.2.42. “Co-Co License Terms” means this Appendix and the terms of the Master
Agreement to the extent applicable to Co-Co Licensed Products.

1.2.43. “Co-Co Licensed Product” means (i) ALN-TTRsc as of the Effective Date,
(ii) if Genzyme exercises the Co-Co/Global Options for ALN-AT3 pursuant to the
Master Agreement, then ALN-AT3 as of the applicable Option Exercise Date, and
(iii) if Genzyme exercises a Back-Up Option for any Back-Up Product pursuant to
Section 7.1.5 (Back-Up Products), then such Back-Up Product as of the date of
delivery of the Back-Up Option Exercise Notice, in each case (i) through
(iii) above, for as long as the Co-Co License Terms apply to ALN-TTRsc, ALN-AT3,
or such Back-Up Product. For the sake of clarity (but not for purposes of
interpretation of the Collaboration Agreement), each Co-Co Licensed Product that
becomes subject to the Co-Co License Terms will be exclusively licensed to
Genzyme in the Genzyme Territory in much the same way that each Regional
Licensed Product will be exclusively

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-5-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

licensed to Genzyme in the Genzyme Territory under the Regional License Terms,
but also will be licensed to Genzyme in the Alnylam Territory to the extent
necessary to enable Genzyme to co-Commercialize such Co-Co Licensed Product in
the Alnylam Territory as contemplated by these Co-Co License Terms.

1.2.44. “Co-Co Out-of-Pocket Costs” means, with respect to certain activities
hereunder, direct expenses paid or payable by either Party or its Affiliates to
Third Parties and specifically identifiable and incurred to conduct such
activities for a Co-Co Licensed Product, including payments to contract
personnel; provided, however, that amounts paid to contract sales and marketing
personnel will not be considered Co-Co Out-of-Pocket Costs.

1.2.45. “Co-Co Supply Agreements” means, collectively, the Co-Co Clinical Supply
Agreements and the Co-Co Commercial Supply Agreements.

1.2.46. “Co-Co Territory” means the United States, Canada, Austria, Belgium,
Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the
Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway, Switzerland,
Liechtenstein, Andorra, Iceland and Greenland.

1.2.47. “Co-Co Territory Commercialization Budget” has the meaning set forth in
Section 4.2.3 (Co-Co Territory Commercialization Budget).

1.2.48. “Co-Co Territory Commercialization Plan” has the meaning set forth in
Section 4.2.1 (Co-Co Territory Commercialization Plan).

1.2.49. “Co-Co Territory Development Milestone Payments” means any Third Party
License Payment that is payable as a result of the achievement of a Development
milestone in the Co-Co Territory.

1.2.50. “Co-Co Territory MMC” means [***].

1.2.51. “Collaboration In-License” has the meaning set forth in the Master
Agreement.

1.2.52. “Commercialization” or “Commercialize” has the meaning set forth in the
Master Agreement.

1.2.53. “Commercially Reasonable Efforts” means [***].

1.2.54. “Competing Program” has the meaning set forth in Section 13.3 (Acquired
Programs).

1.2.55. “Competitive Infringement” has the meaning set forth in Section 11.4.1
(Notices).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-6-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.56. “Confidential Information” has the meaning set forth in the Master
Agreement.

1.2.57. “Control,” “Controls” or “Controlled by” has the meaning set forth in
the Master Agreement.

1.2.58. “Cost of Goods” has the meaning set forth in the Master Agreement.

1.2.59. “Cover,” “Covering” or “Covers” has the meaning set forth in the Master
Agreement.

1.2.60. “CPI” shall mean the Consumer Price Index – Urban Wage Earners and
Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the
United States Department of Labor, Bureau of Labor Statistics (or its successor
equivalent index) in the United States.

1.2.61. “CRO” means a contract research organization.

1.2.62. “Development,” “Developing” or “Develop” has the meaning set forth in
the Master Agreement.

1.2.63. “Development Plan” means, with respect to each Co-Co Licensed Product,
(a) with respect to Genzyme, the Genzyme Territory Development Plan for such
Co-Co Licensed Product and (b) with respect to both Parties, the Global
Development Plan for such Co-Co Licensed Product.

1.2.64. “Disputing Party” has the meaning set forth in Section 2.3.1.2 (Global
R&D Costs).

1.2.65. “Effective Date” means the date that the Master Agreement becomes
effective in accordance with its terms.

1.2.66. “EMA” means the European Medicines Agency and any successor Governmental
Authority having substantially the same function.

1.2.67. “End of Phase II Package” has the meaning set forth in Section
2.2.2.4(c)(ii).

1.2.68. “EU” means the European Union, as its membership may be altered from
time to time, and any successor thereto.

1.2.69. “Excess Global R&D Costs” has the meaning set forth in Section 2.3.1.2
(Global R&D Costs).

1.2.70. “Exclusivity Period” means, on a Co-Co Licensed Product-by-Co-Co
Licensed Product and country-by-country basis within the Genzyme Territory
[***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-7-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.71. “Execution Date” has the meaning set forth in the Master Agreement.

1.2.72. “Existing Alnylam In-License” has the meaning set forth in the Master
Agreement.

1.2.73. “Existing Genzyme In-License” has the meaning set forth in the Master
Agreement.

1.2.74. “FAP” has the meaning set forth in Section 2.7 (ALN-TTRsc/ALN-TTR02).

1.2.75. “FDA” means the United States Food and Drug Administration and any
successor Governmental Authority having substantially the same function.

1.2.76. “FDCA” means the United States Federal Food, Drug, and Cosmetic Act of
1938, as amended from time to time, and the regulations and guidelines
promulgated thereunder.

1.2.77. “Field” means the treatment, diagnosis and/or prevention of all human
diseases.

1.2.78. “First Commercial Sale” means, with respect to a country, the first sale
for end use or consumption of a Co-Co Licensed Product in such country, except
for compassionate use or patient access programs, after all Regulatory Approvals
legally required for such sale have been granted by the Regulatory Authority of
such country.

1.2.79. “First Regulatory Approval by the EMA” means, with respect to a Co-Co
Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought
through the EMA centralized procedure, receipt of Regulatory Approval for such
Co-Co Licensed Product from the EMA or (ii) if Regulatory Approval in the EU is
sought through a national authorization procedure, receipt of Regulatory
Approval for such Co-Co Licensed Product in the first (1st) MMC in the EU.

1.2.80. “First Regulatory Approval in Japan” means, with respect to a Co-Co
Licensed Product, receipt of Regulatory Approval for such Co-Co Licensed Product
in Japan.

1.2.81. “Force Majeure” means embargoes, war, acts of war (whether war be
declared or not), terrorism, insurrections, riots, civil commotions, strikes,
lockouts or other labor disturbances, fire, floods or other acts of God.

1.2.82. “Fundamental Breach” [***].

1.2.83. “GAAP” has the meaning set forth in the Master Agreement.

1.2.84. “GalNAc Conjugate” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-8-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.85. “Generic Competition” means, with respect to a Co-Co Licensed Product in
any country in the Genzyme Territory in a given Calendar Quarter, that, during
such Calendar Quarter, (a) one or more Generic Products with respect to such
Co-Co Licensed Product are commercially available in such country, and (b) Net
Sales of such Co-Co Licensed Product in such country in such Calendar Quarter
equal less than [***] of the average Net Sales of such Co-Co Licensed Product
over the [***] consecutive Calendar Quarters immediately prior to the Calendar
Quarter in which one or more Generic Products first became commercially
available in such country.

1.2.86. “Generic Product” means, on a Co-Co Licensed Product-by-Co-Co Licensed
Product and country-by-country basis, a pharmaceutical product that (a) is sold
by a Person that is not a Related Party of Genzyme under a marketing
authorization granted by a Regulatory Authority in such country to a Third
Party; (b) [***]; and (c) is approved by the Regulatory Authority in such
country pursuant to an approval process that relies in part on pivotal safety
and/or efficacy data in such Regulatory Authority’s previous grant of marketing
authorization for such Co-Co Licensed Product.

1.2.87. “Genzyme Collaboration IP” means (a) any Know-How, first identified,
discovered or developed solely by employees of Genzyme or its Affiliates or
other persons not employed by Alnylam acting on behalf of Genzyme, in the
conduct of the Collaboration and (b) any Patent Rights that claim or Cover such
Know-How and are Controlled by Genzyme at any time during the Term. Genzyme
Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each
case (a) and (b), other than Genzyme Manufacturing IP.

1.2.88. “Genzyme Disclosed Manufacturing Know-How” means Know-How (a) Controlled
by Genzyme at any time during the Term that is useful in the Manufacture of a
Co-Co Licensed Product and (b) that Genzyme, in its sole discretion, discloses
in writing to Alnylam in the course of the Collaboration.

1.2.89. “Genzyme In-License” means any Existing Genzyme In-License, Un-Blocking
Genzyme In-License, or any Collaboration In-License to which Genzyme is a party.

1.2.90. “Genzyme Know-How” means Know-How Controlled by Genzyme during the Term
that is reasonably necessary or useful for Alnylam to Develop, Commercialize
and/or Manufacture Co-Co Licensed Products in the Field in the Co-Co Territory
(other than Genzyme’s rights in Joint Collaboration IP, Genzyme Collaboration IP
and Genzyme Manufacturing IP).

1.2.91. “Genzyme Manufacturing IP” means (a) any Know-How related to the
Manufacture of Co-Co Licensed Products (or oligonucleotides generally)
Controlled by Genzyme at any time during the Term, and (b) any Patent Rights
that claim or cover such Know-How and are Controlled by Genzyme at any time
during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme
Disclosed Manufacturing Know-How.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-9-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.92. “Genzyme Patent Jurisdictions” has the meaning set forth in the Master
Agreement.

1.2.93. “Genzyme Patent Rights” means those Patent Rights Controlled by Genzyme
during the Term that are reasonably necessary or useful to Develop,
Commercialize and/or Manufacture Co-Co Licensed Products in the Field in the
Co-Co Territory. Genzyme Patent Rights excludes Patent Rights included in
Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and
Genzyme Manufacturing IP.

1.2.94. “Genzyme Technology” means, collectively, Genzyme Know-How, Genzyme
Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint
Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.95. “Genzyme Territory” means all countries and territories of the world
other than the Co-Co Territory.

1.2.96. “Genzyme Territory Commercialization Plan” has the meaning set forth in
Section 4.3 (Genzyme Territory Commercialization Plan).

1.2.97. “Genzyme Territory Development Plan” has the meaning set forth in
Section 2.2.3 (Genzyme Territory Development Plan).

1.2.98. “Genzyme Territory MMC” [***].

1.2.99. “Genzyme Trademark” has the meaning set forth in Section 11.7(b)
(Trademarks).

1.2.100. “Global Branding Strategy” has the meaning set forth in Section 4.4.1
(Global Branding).

1.2.101. “Global Clinical Study” has the meaning set forth in Section 5.5.5
(PJSC Development Responsibilities).

1.2.102. “Global Development Activity(ies)” has the meaning set forth in
Section 2.2.2.1 (Global Development Plans).

1.2.103. “Global Development Budget” has the meaning set forth in
Section 2.2.2.2 (Global Development Budgets).

1.2.104. “Global Development Plan” has the meaning set forth in Section 2.2.2.1
(Global Development Plans).

1.2.105. “Global Development Strategy” has the meaning set forth in
Section 2.2.1 (Global Development Strategy).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-10-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.106. “Global Option Period” has the meaning set forth in the Master
Agreement.

1.2.107. “Global R&D Cost Opt-In Date” has the meaning set forth in
Section 2.3.1.2 (Global R&D Costs).

1.2.108. “Global R&D Costs” means, with respect to a Co-Co Licensed Product, R&D
Costs incurred in connection with any Global Development Activity for such Co-Co
Licensed Product.

1.2.109. “Global R&D Costs Report” has the meaning set forth in Section 2.3.1.2
(Global R&D Costs).

1.2.110. “Global Regulatory Costs” has the meaning set forth in Section 2.2.2.2
(Global Development Budgets).

1.2.111. “Governmental Authority” means any applicable government authority,
court, tribunal, arbitrator, agency, department, legislative body, commission or
other instrumentality of (a) any government of any country or territory, (b) any
nation, state, province, county, city or other political subdivision thereof or
(c) any supranational body.

1.2.112. “Gross Margin” means, with respect to a Co-Co Licensed Product in the
Co-Co Territory, [***].

1.2.113. “Human POP Study” has the meaning set forth in the Master Agreement.

1.2.114. “IFRS” has the meaning set forth in the Master Agreement.

1.2.115. “Implementation Date” means (i) with respect to ALN-TTRsc, the
Effective Date, (ii) with respect to ALN-AT3, the Option Exercise Date for
ALN-AT3, and (iii) with respect to each Back-Up Product with respect to which
Genzyme exercised the Back-Up Option, the date on which Genzyme sent to Alnylam
the Back-Up Option Exercise Notice for such Back-Up Product under Section 7.1.5
(Back-Up Products).

1.2.116. “Improvement Manufacturing Patent Right” means a Patent Right owned
exclusively by Genzyme or its Affiliates that claims an invention related to the
Manufacture of a Co-Co Licensed Product that was made (a) by Genzyme or its
Affiliates after the Effective Date in connection with Manufacturing Co-Co
Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam
Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s
Confidential Information under Section 7 of the Master Agreement
(Confidentiality and Publication).

1.2.117. “IND” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-11-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

1.2.118. “In-License” has the meaning set forth in the Master Agreement.

1.2.119. “Infringement Action” has the meaning set forth in Section 11.4.2(a)
(Genzyme Technology).

1.2.120. “Joint Collaboration IP” means, collectively, (a) any Know-How first
identified, discovered or developed jointly by employee(s), agent(s) or
consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand,
and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its
Affiliates, on the other hand, in the conduct of the Collaboration that is
Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such
Know-How and are Controlled by Alnylam and Genzyme.

1.2.121. “Know-How” has the meaning set forth in the Master Agreement.

1.2.122. “Laws” has the meaning set forth in the Master Agreement.

1.2.123. “Licensed Target” means, for ALN-TTRsc, TTR, and, if the Co-Co/Global
Option is exercised for ALN-AT3, then Antithrombin.

1.2.124. “Lipid Nanoparticle Formulation” has the meaning set forth in the
Master Agreement.

1.2.125. “Litigation Expenses” has the meaning set forth in Section 11.4.3
(Procedures; Expenses and Recoveries).

1.2.126. “Manufacturing” or “Manufacture” has the meaning set forth in the
Master Agreement.

1.2.127. “Manufacturing Claim” means a claim within a Patent Right directed
solely to Manufacturing a Co-Co Licensed Product.

1.2.128. “MMC” means any Co-Co Territory MMC or Genzyme Territory MMC.

1.2.129. “NDA” has the meaning set forth in the Master Agreement.

1.2.130. “Net Sales” means, with respect to a Co-Co Licensed Product, the
aggregate gross invoiced sales prices from sales of all units of such Co-Co
Licensed Product sold by a Party and its Related Parties to independent Third
Parties (other than a Sublicensee) after deducting, if not previously deducted,
from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of
useful life or otherwise);

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-12-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

(c) Third Party rebates, chargebacks, hospital buying group/group purchasing
organization administration fees or managed care organization rebates actually
given;

(d) rebates and similar payments made with respect to sales paid for by any
governmental or regulatory authority such as Federal or state Medicaid, Medicare
or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

(g) value added, sales and use, excise and other similar taxes and surcharges,
customary transportation and insurance, custom duties, and other governmental
charges; and

(h) amounts previously included in Net Sales of such Co-Co Licensed Product that
are adjusted or written-off by such Party or its Related Parties as bad debt or
otherwise uncollectible in accordance with the standard practices of such Party
or its Related Parties for writing off uncollectible amounts consistently
applied; provided, however, if any such written-off amounts are subsequently
collected, such collected amounts shall be included in Net Sales in the period
in which they are subsequently collected.

For Genzyme, such amounts shall be determined from the books and records of
Genzyme or its Related Parties, maintained in accordance with IFRS. For Alnylam,
such amounts shall be determined from the books and records of Alnylam or its
Related Parties, maintained in accordance with GAAP.

In the case of any sale or other disposal for value, such as barter or
counter-trade, of a Co-Co Licensed Product, or part thereof, other than in an
arm’s length transaction exclusively for cash, Net Sales shall be calculated as
above on the value of the non-cash consideration received or the fair market
price (if higher) of such Co-Co Licensed Product in the country of sale or
disposal, as determined in accordance with IFRS or GAAP, as applicable.

Notwithstanding the foregoing, the following will not be included in Net Sales
for a Party: (1) sales between or among such Party and its Related Parties (but
Net Sales shall include sales to the first Third Party (other than a
Sublicensee) by such Party or its Related Parties); (2) samples of Co-Co
Licensed Product used to promote additional Net Sales, in amounts consistent
with normal business practices of such Party; and (3) disposal or use of Co-Co
Licensed Products in Clinical Studies or under compassionate use, patient
assistance, named patient use, or test marketing programs or non-registrational
studies or other similar programs or studies where the Co-Co Licensed Product is
supplied without charge or at the actual manufacturing cost thereof (without
allocation of indirect costs or any mark-up).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-13-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

In the case where a Co-Co Licensed Product is sold as part of a Combination
Product in a country in the Licensed Territory, Net Sales for the Co-Co Licensed
Product included in such Combination Product in such country shall be calculated
as follows:

 

  (i) if the Co-Co Licensed Product is sold separately in such country and the
other active ingredient or ingredients in the Combination Product are sold
separately in such country, Net Sales for the Co-Co Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/(A+B), where A is the invoice price of the Co-Co
Licensed Product when sold separately in such country and B is the total invoice
price of the other active ingredient or ingredients in the Combination Product
when sold separately in such country;

 

  (ii) if the Co-Co Licensed Product is sold separately in such country but the
other active ingredient or ingredients in the Combination Product are not sold
separately in such country, Net Sales for the Co-Co Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product in such
country by the fraction A/D, where A is the invoice price of the Co-Co Licensed
Product when sold separately in such country and D is the invoice price of the
Combination Product in such country;

 

  (iii) if the Co-Co Licensed Product is not sold separately in such country but
the other active ingredient or ingredients in the Combinations Product are sold
separately in such country, Net Sales for the Co-Co Licensed Product shall be
calculated by multiplying actual Net Sales of such Combination Product by the
fraction 1 – (B/D), where B is the invoice price of the other active ingredient
or ingredients in the Combination Product when sold separately in such country
and D is the invoice price of the Combination Product in such country; or

 

  (iv) if neither the Co-Co Licensed Product nor the other active ingredient or
ingredients in the Combination Product are sold separately in such country, the
Parties shall determine Net Sales for the Co-Co Licensed Product in such
Combination Product by mutual agreement based on the relative contribution of
the Co-Co Licensed Product and each other active ingredient to the Combination
Product, and shall take into account in good faith any applicable allocations
and calculations that may have been made for the same period in other countries.

For purposes of this Section, “Combination Product” means a product that
includes at least one active ingredient other than a Co-Co Licensed Product.
Drug delivery vehicles, adjuvants, and excipients shall not be deemed to be
“active ingredients”, except in the case where such delivery vehicle, adjuvant,
or excipient is recognized by the FDA as an active ingredient in accordance with
21 C.F.R. § 210.3(b)(7).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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1.2.131. “Non-Bankrupt Party” has the meaning set forth in Section 7.5
(Bankruptcy).

1.2.132. “Non-Disputing Party” has the meaning set forth in Section 2.3.1.2
(Global R&D Costs).

1.2.133. “Option Data Package” has the meaning set forth in the Master
Agreement.

1.2.134. “Option Exercise Date” has the meaning set forth in the Master
Agreement.

1.2.135. “Option Exercise Notice” has the meaning set forth in the Master
Agreement.

1.2.136. “Party” means Genzyme and/or Alnylam.

1.2.137. “Patent Challenge” has the meaning set forth in Section 12.2.3
(Challenges of Patent Rights).

1.2.138. “Patent Rights” has the meaning set forth in the Master Agreement.

1.2.139. “Person” means any natural person, corporation, unincorporated
organization, partnership, association, sole proprietorship joint stock company,
joint venture, limited liability company, trust or government, or any
Governmental Authority, or any other similar entity.

1.2.140. “Phase 2 Budget” has the meaning set forth in Section 2.2.2.4 (Budget
Caps; Adjustment and Compensation).

1.2.141. [***].

1.2.142. “Phase 3 Budget” has the meaning set forth in Section 2.2.2.4 (Budget
Caps; Adjustment and Compensation).

1.2.143. [***].

1.2.144. “Phase I Study” has the meaning set forth in the Master Agreement.

1.2.145. “Phase II Study” has the meaning set forth in the Master Agreement.

1.2.146. “Phase III Study” has the meaning set forth in the Master Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2.147. “Post-Marketing Study” has the meaning set forth in the Master
Agreement.

1.2.148. “Post-Phase 3 Budget” has the meaning set forth in Section 2.2.2.4
(Budget Caps; Adjustment and Compensation).

1.2.149. [***].

1.2.150. “Product Joint Steering Committee” or “PJSC” means the joint steering
committee as more fully described in Section 5.1 (Product Joint Steering
Committee).

1.2.151. “Product Trademark(s)” means the Trademarks used, or intended for use,
in connection with the distribution, marketing, promotion and sale of the Co-Co
Licensed Products. Product Trademarks specifically exclude the corporate names
and logos of the Parties and their Affiliates. Product Trademark includes both
the Alnylam Trademarks and the Genzyme Trademarks.

1.2.152. “Promotional Materials” has the meaning set forth in Section 4.4.2
(Alnylam A&P).

1.2.153. “Proposing Party” has the meaning set forth in Section 2.2.2.5(a)
(Additional Development Proposals).

1.2.154. “R&D Costs” means, with respect to a Co-Co Licensed Product, costs and
expenses incurred in connection with the performance of any Development activity
for such Co-Co Licensed Product, including [***].

1.2.155. “R&D FTE” means [***] of work per annum devoted to or in support of the
Development or Manufacture of a Co-Co Licensed Product that is carried out by
one or more qualified scientific or technical employees (excluding Third Party
contractors) of a Party or its Affiliates.

1.2.156. “R&D FTE Cost” means, for any period, the R&D FTE Rate multiplied by
the number of R&D FTEs in such period.

1.2.157. “R&D FTE Rate” means [***] per FTE, increased annually beginning on
January 1, 2015 and thereafter on January 1 of each succeeding year by the
percentage increase in the CPI as of December 31 of the then most recently ended
Calendar Year over the level of the CPI on December 31, 2013.

1.2.158. “Regulatory Approval” has the meaning set forth in the Master
Agreement.

1.2.159. “Regulatory Authority” has the meaning set forth in the Master
Agreement.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2.160. “Regulatory Exclusivity” means, with respect to a Co-Co Licensed
Product in a country, any exclusive marketing right, data exclusivity right,
orphan drug designation or other country-wide exclusive right or status
conferred by any Governmental Authority with respect to such Co-Co Licensed
Product in such country, other than a Patent Right, that limits or prohibits a
Person [***].

1.2.161. “Related Party” means a Party’s Affiliates, permitted Sublicensees and,
with respect to Alnylam, licensees in the Co-Co Territory.

1.2.162. “Reverted Co-Co Licensed Product” has the meaning set forth in
Section 12.3.2(b) (Effects of Termination by Alnylam for Cause or by Genzyme for
Convenience).

1.2.163. “Royalty Term” has the meaning set forth in Section 8.2.2 (Royalty
Term).

1.2.164. “S&M Activities” means, with respect to a Co-Co Licensed Product in the
Co-Co Territory, all sales and marketing activities in the Co-Co Territory
Commercialization Budget for such Co-Co Licensed Product.

1.2.165. “S&M Costs” means, with respect to a Co-Co Licensed Product, costs and
expenses incurred in connection with the performance of any S&M Activities for
such Co-Co Licensed Product in the Co-Co Territory, including S&M FTE Costs and
fees charged by Third Party service providers and other Co-Co Out-of-Pocket
Costs. 

1.2.166. “S&M FTE” means [***] of work per annum devoted to or in support of S&M
Activities for a Co-Co Licensed Product that is carried out by one or more
qualified employees of, or contract sales and marketing personnel engaged by, a
Party or its Affiliates. For purposes of calculating S&M FTEs with respect to
S&M Activities for a Co-Co Licensed Product:

(a) [***]

(b) [***]

1.2.167. “S&M FTE Costs” means, on a Co-Co Licensed Product-by-Co-Co Licensed
Product and country-by-country basis, the S&M FTE Rate for such country
multiplied by the total number of S&M FTEs allocated to a Party in such country
pursuant to the Co-Co Territory Commercialization Budget for such Co-Co Licensed
Product in such Calendar Year. 

1.2.168. “S&M FTE Rate” means, on a country-by-country basis, the then-current
FTE rate for a Genzyme S&M FTE in such country.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

1.2.169. “Safety Concern” has the meaning set forth in the Master Agreement.

1.2.170. “Secondary Indication” has the meaning set forth in the Master
Agreement.

1.2.171. “Secondary Indication Study” has the meaning set forth in the Master
Agreement.

1.2.172. “Serious Adverse Event” has the meaning set forth in the Master
Agreement.

1.2.173. “siRNA” has the meaning set forth in the Master Agreement.

1.2.174. “SPCs” has the meaning set forth in Section 11.5 (Patent Term
Extensions).

1.2.175. “Sublicensee” means a Third Party to whom a Party grants a sublicense
under any Alnylam Technology or Genzyme Technology, as the case may be, to
Develop, Manufacture or Commercialize a Co-Co Licensed Product in the Field
pursuant to Section 7.1.4 (Sublicensing Terms) or Section 7.2.4 (Sublicensing
Terms).

1.2.176. “Term” has the meaning set forth in Section 12.1 (Term).

1.2.177. “Territory” means (a) with respect to Alnylam, the Co-Co Territory and
(b) with respect to Genzyme, the Genzyme Territory.

1.2.178. “Third Party” has the meaning set forth in the Master Agreement.

1.2.179. “Third Party License Payment” has the meaning set forth in the Master
Agreement.

1.2.180. “Trademark” has the meaning set forth in the Master Agreement.

1.2.181. “TTR” has the meaning set forth in the Master Agreement.

1.2.182. “Un-Blocking Genzyme In-License” has the meaning set forth in the
Master Agreement.

1.2.183. “United States” means the United States of America and its territories,
possessions and commonwealths.

1.2.184. “Valid Claim” means a claim of: (a) an issued and unexpired patent,
which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or
held unenforceable or invalid by an unappealable decision of a court or other
governmental agency of competent jurisdiction, or has not been appealed within
the time allowed for appeal, or by an

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

appealed decision of a court or other governmental agency of competent
jurisdiction where the appeal has been pending for more than [***] years (unless
and until such decision is subsequently overturned on appeal) and which has not
been abandoned, disclaimed, denied or admitted to be invalid or unenforceable
through reissue, re-examination or disclaimer or otherwise; or (b) a patent
application that has been pending less than [***] years from the date of filing
of the earliest patent application from which such patent application claims
priority, which claim has not been cancelled, withdrawn or abandoned or finally
rejected by an administrative agency action from which no appeal can be taken.

1.2.185. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and
Amending Global Development Plans and Global Development Budgets).

1.2.186. “[***] Budget” has the meaning set forth in Section 2.2.2.3(a)
(Managing and Amending Global Development Plans and Global Development Budgets).

1.2.187. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and
Amending Global Development Plans and Global Development Budgets).

1.2.188. “[***] Budget” has the meaning set forth in Section 2.2.2.3(a)
(Managing and Amending Global Development Plans and Global Development Budgets).

2. DEVELOPMENT COLLABORATION

2.1. Overview. The Parties will collaborate in the Development of each Co-Co
Licensed Product pursuant to the applicable Global Development Plan and Genzyme
Territory Development Plan. The PJSC will have primary responsibility for the
oversight of the Global Development Plans, with Alnylam having primary
responsibility for execution of those Global Development Plans, and Genzyme will
have sole responsibility for the Genzyme Territory Development Plans, as
described below.

2.2. Development Plans.

2.2.1. Global Development Strategy. For each Co-Co Licensed Product, the key
Development principles for such Co-Co Licensed Product will be set forth in a
written summary of the global Development strategy for such Co-Co Licensed
Product, including the indication(s) (including Secondary Indications), for
which Regulatory Approval will be sought (each, a “Global Development
Strategy”). The initial Global Development Strategy for ALN-TTRsc will be
provided by Alnylam to Genzyme within [***] days after the Effective Date,
agreed upon by the PJSC within [***] days after the Effective Date, and then
attached hereto as Schedule 2.2.1-1. The initial Global Development Strategy for
ALN-AT3 will be included in the Option Data Package, mutually agreed upon by the
Parties prior to Genzyme’s exercise of the Co-Co/Global Option with respect to
ALN-AT3 in accordance with the Master Agreement, and then attached hereto as
Schedule 2.2.1-2. Any Global Development Strategy may be amended from time to
time only by the PJSC responsible for the applicable Co-Co Licensed Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

2.2.2. Global Development Plan.

2.2.2.1. Global Development Plans. For each Co-Co Licensed Product, the
Development activities that are necessary or useful to be undertaken for such
Co-Co Licensed Product to achieve initial Regulatory Approval for each of the
indications to be sought pursuant to the Global Development Strategy in at least
all of the MMCs in a proximal fashion (including the design of necessary or
useful Clinical Studies) will be set forth in reasonable detail in a written
work plan and time table (each, a “Global Development Plan”). Alnylam will
provide a draft of the initial Global Development Plan for ALN-TTRsc to Genzyme
on or before March 31, 2014, and within [***] days thereafter the PJSC will
review, update and approve such Global Development Plan and it will be attached
hereto as Schedule 2.2.2-1. The initial Global Development Plan for ALN-AT3 will
be prepared by Alnylam and included in the Option Data Package for ALN-AT3
provided by Alnylam to Genzyme under the Master Agreement, and if Genzyme
exercises the Co-Co/Global Option for ALN-AT3, within [***] days of the
Implementation Date for ALN-AT3 the PJSC responsible for ALN-AT3 will review,
update and approve such Global Development Plan and it will be attached hereto
as Schedule 2.2.2-2. Each Global Development Plan must, at all times, be
consistent with the Global Development Strategy and include all Development
activities that (i) are reasonably necessary to obtain initial Regulatory
Approval of the applicable Co-Co Licensed Product in at least each MMC for each
of the indications, including Secondary Indications, to be sought pursuant to
the Global Development Strategy in a proximal fashion, (ii) Post-Marketing
Studies for the Co-Co Territory and (iii) Secondary Indication Studies included
in the initial Global Development Plan or added pursuant to Section 2.2.2.5
(Secondary Indications) (all such Development activities, collectively, the
“Global Development Activities”); provided, however, that, unless otherwise
agreed by the Parties, in no event will any Global Development Plan include (a)
any Post-Marketing Study in the Genzyme Territory, (b) any Secondary Indication
Study, except for Secondary Indication Studies included in the initial Global
Development Plan or added to a Global Development Plan pursuant to Section
2.2.2.4 (Secondary Indications) or (c) after the last Regulatory Approval in all
MMCs, any Development activity that is useful solely to achieve initial
Regulatory Approval in a country in the Genzyme Territory that is not a Genzyme
Territory MMC, except for Secondary Indication Studies included in the initial
Global Development Plan or added to a Global Development Plan pursuant to
Section 2.2.2.5 (Secondary Indications). In addition, for the period following
the first Regulatory Approval in an MMC of a Co-Co Licensed Product, the Global
Development Plan (and the Global Development Activities thereunder) must be
established by the PJSC in a manner that reconciles the Parties’ preferences
regarding short- and long-term profitability of such Co-Co Licensed Product.
Each Global Development Plan will allocate responsibility for the performance of
each Global Development Activity to one of the Parties. The time table for the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

completion of the Global Development Activities included in each Global
Development Plan will be designed to obtain initial Regulatory Approval of the
applicable Co-Co Licensed Product in each MMC in a proximal fashion and as soon
as reasonably possible. The terms of, and Development activities set forth in,
each Global Development Plan will at all times be designed to be in compliance
with all applicable Laws and in accordance with professional and ethical
standards customary in the pharmaceutical industry.

2.2.2.2. Global Development Budgets. Each Global Development Plan will contain a
[***] year rolling budget for the probable Global Regulatory Costs and probable
Global Development Activities to be performed during the [***], and a forecast
of the budgets for each subsequent Calendar Year thereafter through completion
of all Global Development Activities set forth in any such Global Development
Plan, provided that each initial Global Development Plan will also include such
a budget for the partial Calendar Year commencing as of the date of such Global
Development Plan and ending December 31 of such Calendar Year (each such [***]
budget plus any such partial Calendar Year is a “Global Development Budget”).
Each Global Development Budget will be updated annually by the PJSC responsible
for the applicable Co-Co Licensed Product in accordance with Section 2.2.2.3
(Managing and Amending Global Development Plans and Global Development Budgets).
The initial Global Development Budget for a Co-Co Licensed Product, and each
update thereto, will be prepared by the PJSC in accordance with [***]:

(a) [***]

(b) [***]

(c) [***]

(d) [***]

Alnylam will enter such Global Development Budget in a template that the Parties
agree is efficient for both Parties to communicate such information.

2.2.2.3. Managing and Amending Global Development Plans and Global Development
Budgets. The PJSC responsible for a Co-Co Licensed Product will update and amend
the applicable Global Development Plan from time-to-time as it deems necessary
and, until such time as no further Global Development Activities are occurring
or expected to occur with respect to such Co-Co Licensed Product, the PJSC will
update such Global Development Plan annually as follows:

(a) No later than [***] of each Calendar Year, the applicable PJSC will prepare
an updated draft of the Global Development Plan, which shall contain a proposed
Global Development Budget[***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

(b) No later than [***] of each Calendar Year, the applicable PJSC will review
and tentatively approve an updated Global Development Plan and Global
Development Budget, and such updated Global Development Plan and Global
Development Budget will become effective upon such tentative approval by the
PJSC, provided that the Parties acknowledge and agree that each Party’s internal
process for receiving final approval of such Global Development Plan and Global
Development Budget from its Board of Directors and/or senior management may
occur after [***] (but, in any event, before [***]) and such Global Development
Plan and Global Development Budget will not become final unless and until such
approvals are obtained [***].

2.2.2.4. [***]; Adjustments and Compensation. In addition to the Global
Development Budget for each Co-Co Licensed Product, Alnylam shall prepare, and
submit to the PJSC for approval, three (3) Development budget(s) for each Co-Co
Licensed Product, the first of which shall cover the period commencing as of the
Implementation Date for such Co-Co Licensed Product and ending on the
anticipated date of initiation of the first Phase III Study for such Co-Co
Licensed Product (as further described below, each a “Phase 2 Budget”), the
second of which shall cover the period commencing as of the anticipated date of
initiation of the first Phase III Study for such Co-Co Licensed Product and
ending on the anticipated date of filing of an application for Regulatory
Approval of such Co-Co Licensed Product in the first MMC (as further described
below, each a “Phase 3 Budget”) and the third of which shall cover the period
commencing as of the anticipated date of filing of an application for Regulatory
Approval for such Co-Co Licensed Product in the first MMC and ending on the date
that there are no further Development activities to be performed under the
Global Development Plan for such Co-Co Licensed Product (as further described
below, each a “Post-Phase 3 Budget”), provided that if the period covered by the
Post-Phase 3 Budget is longer than three (3) years, Alnylam shall prepare a new
Post-Phase 3 Budget to cover each subsequent three (3) year period. Each Phase 2
Budget, Phase 3 Budget and Post-Phase 3 Budget [***].

(a) Preparation of Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget. Each
Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget submitted to the PJSC
will be prepared by Alnylam in accordance with [***].

(b) [***]

(c) Delivery and Effectiveness of Phase 2 Budget, Phase 3 Budget and Post-Phase
3 Budget.

 

  (i) Alnylam shall include a Phase 2 Budget [***] with the initial Global
Development Plan for each Co-Co Licensed Product. Such Phase 2 Budget [***]
shall become effective, subject to adjustment in accordance with the foregoing
Section 2.2.2.4(b), upon the Implementation Date for the relevant Co-Co Licensed
Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

  (ii) Alnylam shall provide to the PJSC for approval a Phase 3 Budget [***] for
each Co-Co Licensed Product no less than [***] days prior to the anticipated
initiation of the first Phase III Study for each Co-Co Licensed Product, along
with the top line data and data tables from any completed Phase II Studies and
other completed non-clinical studies (including all Serious Adverse Event and
Safety Concern data), as well as a draft of the end of Phase II briefing
package, in each case to the extent not previously provided or made available to
Genzyme (such budget, data and draft, collectively the “End of Phase II
Package”). Such Phase 3 Budget [***] shall become effective at the end of such
[***] day period.

 

  (iii) Alnylam shall provide to the PJSC for approval a Post-Phase 3 Budget
[***] for each Co-Co Licensed Product no less than [***] days prior to the
anticipated completion of the first Phase III Study for each Co-Co Licensed
Product. Such Post-Phase 3 Budget [***] shall become effective upon approval by
the PJSC.

 

  (d) [***]

2.2.2.5. Secondary Indications.

(a) Additional Development Proposals. If a Party desires to conduct a Secondary
Indication Study of a Co-Co Licensed Product for the purpose of seeking
Regulatory Approval to market such Co-Co Licensed Product for a Secondary
Indication, such Party (the “Proposing Party”) will submit to the PJSC
responsible for such Co-Co Licensed Product a proposal to add such Secondary
Indication Study to the applicable Global Development Plan (an “Additional
Development Proposal”). Each Additional Development Proposal will describe in
reasonable detail the Secondary Indication Study(ies) that the Proposing Party
desires to conduct, including a synopsis of the trial, the proposed enrollment
criteria, number of patients to be included, endpoints to be measured, and
statistical design and powering (the “Additional Development Activities”), as
well as a proposed timeline and budget and an analysis of the business
opportunity and revenue potential for such Additional Development Activities and
Secondary Indication.

(b) PJSC Decision Regarding Additional Development Activities. The PJSC shall
approve or reject an Additional Development Proposal within [***] days after
receipt thereof from the Proposing Party as set forth in this Section 2.2.2.5.

 

  (i)

If the PJSC approves an Additional Development Proposal, upon such an approval,
the applicable Global Development Plan will be amended to include the Additional
Development Activities, including the proposed

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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  timeline and budget for such Additional Development Activities, set forth in
such Additional Development Proposal (as may be amended by the PJSC) upon such
approval. Any Additional Development Activities included in a Global Development
Plan pursuant to this Section 2.2.2.5(b) shall be deemed to be Global
Development Activities for all purposes under these Co-Co License Terms
(including the definition of Global R&D Costs).

 

  (ii) If the PJSC fails to approve an Additional Development Proposal, upon
such a failure, the Secondary Indication Study proposed in the Additional
Development Proposal will not be deemed a Global Development Activity for any
purpose under these Co-Co License Terms, and Sections 2.2.2.5(c) (Independent
Performance of Additional Development Activities) and Section 2.2.2.5(d) (Opt-In
for Additional Development Activities) shall apply.

 

  (c) Independent Performance of Additional Development Activities.

 

  (i) If the PJSC fails to approve for inclusion in the Global Development Plan
an Additional Development Proposal proposed by Alnylam for a Secondary
Indication Study(ies) for a Co-Co Licensed Product, Alnylam may, upon notice to
Genzyme, conduct the proposed Secondary Indication Study(ies) at its own expense
[***].

 

  (ii) If the PJSC fails to approve for inclusion in the Global Development Plan
an Additional Development Proposal proposed by Genzyme for a Secondary
Indication Study(ies) for such Co-Co Licensed Product, Genzyme may, upon notice
to Alnylam, conduct the proposed Secondary Indication Study(ies) at its own
expense [***].

 

  (iii) Notwithstanding anything in Section 3.5 (Right of Reference) to the
contrary, the Non-Proposing Party with respect to an Additional Development
Activity that is permitted to be conducted in accordance with this
Section 2.2.2.5 will not have any rights under Section 3.5 (Right of Reference)
with respect to any information or data generated from such Additional
Development Activity, except as described in Section 2.2.2.5(d) (Opt-In for
Additional Development Activities).

 

  (d) Opt-In for Additional Development Activities.

 

  (i)

In the event that the Proposing Party conducts Secondary Indication Study(ies)
pursuant to Section 2.2.2.5(c) (Independent Performance of Additional
Development Activities), the Non-Proposing Party may elect, in its discretion
and upon written notice to the Proposing Party prior to the date on which [***]
(an “Additional Development Opt-In Notice”), to

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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  opt in with respect to any Secondary Indication Study that was the subject of
such Additional Development Proposal that the Proposing Party elected to conduct
in accordance with Section 2.2.2.5(c) (Independent Performance of Additional
Development Activities), and then (i) such Secondary Indication Study shall be
deemed to be a Global Development Activity under the Global Development Plan for
the applicable Co-Co Licensed Product from and after the date on which such
Additional Development Opt-In Notice is received by the Proposing Party (the
“Additional Development Opt-In Date”); (ii) the then-current plan and budget of
the Proposing Party with respect to such Secondary Indication Study shall be
deemed to be included within, and part of, the Global Development Plan for such
Co-Co Licensed Product as of the Additional Development Opt-In Date, and shall
control with respect to such Secondary Indication Study unless and until an
amendment to the Global Development Plan providing for a different or modified
plan and budget is approved by the applicable PJSC; and (iii) the Non-Proposing
Party will have all rights granted to it under Section 3.5 (Right of Reference)
with respect to the information and data generated from such Secondary
Indication Study as if such Secondary Indication Study was conducted under the
Global Development Plan for such Co-Co Licensed Product, [***].

 

  (ii) If the Non-Proposing Party does not provide an Additional Development
Opt-In Notice to the Proposing Party prior to the date on which Regulatory
Approval for the applicable Co-Co Licensed Product is granted by a Regulatory
Authority in an MMC for the Secondary Indication proposed by such Proposing
Party, then, as of the date of such Regulatory Approval, the Non-Proposing Party
shall be deemed to have opted in and the Non-Proposing Party will have all
rights granted to it under Section 3.5 (Right of Reference) with respect to the
information and data generated from such Secondary Indication Study as if such
Secondary Indication Study was conducted under the Global Development Plan for
such Co-Co Licensed Product, [***].

2.2.2.6. Additional Clinical Study Sites in Genzyme Territory. With respect to
any Clinical Study in a Global Development Plan, at Genzyme’s request, Alnylam
will add a study site in a country in the Genzyme Territory [***]. If Alnylam
adds such a study site at Genzyme’s request, Genzyme will reimburse Alnylam for
any incremental R&D FTE Costs or Co-Co Out-of-Pocket Costs required as a result
of adding such study site. Genzyme will pay Alnylam such reimbursement within
[***] days of receipt of an invoice from Alnylam.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.2.3. Genzyme Territory Development Plan. Other than Global Development
Activities, all Development activities to be undertaken with respect to each
Co-Co Licensed Product by or on behalf of Genzyme with respect to the Genzyme
Territory, including Secondary Indication Studies and Post-Marketing Studies,
will be set forth in a written work plan and time table (each, a “Genzyme
Territory Development Plan”). Each Genzyme Territory Development Plan shall be
consistent with the requirements of the then-current Global Development
Strategy. The Genzyme Territory Development Plan for ALN-TTRsc will be prepared
by Genzyme and delivered to the applicable PJSC by [***] and, following review
and approval by the PJSC, will then be attached to the PJSC meeting minutes and
deemed to be attached hereto as Schedule 2.2.3-1. If Genzyme exercises the
Co-Co/Global Option with respect to ALN-AT3, the initial Genzyme Territory
Development Plan for ALN-AT3 (if any) will be prepared by Genzyme and following
review and approval by the PJSC, will then be attached to the PJSC meeting
minutes and deemed to be attached hereto as Schedule 2.2.3-2. Each Genzyme
Territory Development Plan will set forth a rolling written work plan and time
table with respect to the Development of and Secondary Indication Studies for
the applicable Co-Co Licensed Product from the Implementation Date until such
time as no further Development or Secondary Indication Studies are occurring or
expected to occur with respect to the applicable Co-Co Licensed Product. Genzyme
will update each such Genzyme Territory Development Plan from time-to-time but
at least annually on or before [***]. Genzyme will present each Genzyme
Territory Development Plan and any proposed amendments thereto to the applicable
PJSC at least [***] days in advance of implementation of the Genzyme Territory
Development Plan, and following review and approval by the PJSC, will then be
attached to the PJSC meeting minutes and deemed to be attached hereto as the
applicable Schedule.

2.3. Joint Responsibilities for Development Activities and Costs.

2.3.1. Global Development.

2.3.1.1. Generally. With respect to each Co-Co Licensed Product, the PJSC will
have overall responsibility for oversight of the global Development of each
Co-Co Licensed Product and all Development activities under such Global
Development Plan. Alnylam shall have overall responsibility for execution under
the Global Development Plan and each Party, in turn, shall be responsible for
execution of the activities allocated to it under the Global Development Plan.
Each Party and its Affiliates shall conduct each Global Development Activity for
which it is responsible solely in accordance with the Global Development Plan
(as such Global Development Plan may be amended from time to time in accordance
with these Co-Co License Terms) in sound scientific manner and in compliance
with applicable Law. Notwithstanding anything to the contrary in these Co-Co
License Terms, neither Party will be obligated to undertake or continue any
Global Development Activity if (a) such Party reasonably determines that
performance of such Global Development Activity would violate applicable Law; or
(b) with respect to any Global Clinical Study, (i) a Regulatory Authority or
independent safety data review board for such Global Clinical Study has required
or recommended termination or suspension of such Global Clinical Study or
(ii) such Party believes in good faith that termination or suspension of such
Global

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Clinical Study is warranted because of safety or tolerability risks or the lack
of suitable risk benefit ratio to the study subjects. In the event that a Party
determines not to undertake or continue any Global Development Activity in
accordance with the immediately preceding sentence, such Party shall promptly
notify the other Party of such determination, and shall use all reasonable
efforts to notify and consult with the other Party prior to making such
determination.

2.3.1.2. Global R&D Costs.

(a) With respect to ALN-TTRsc, each Party shall be responsible for fifty percent
(50%) of all Global Regulatory Costs and Global R&D Costs for Global Development
Activities that occur after the later of (i) [***] and (ii) [***] (such later
date, the “ALN-TTRsc Global R&D Cost Opt-In Date”), and amounts specified in
clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any. Alnylam shall be
responsible for one-hundred percent (100%) of Global Regulatory Costs and Global
R&D Costs for Global Development Activities for ALN-TTRsc that occur prior to
the ALN-TTRsc Global R&D Cost Opt-In Date, except for amounts specified in
clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(b) With respect to ALN-AT3, if Genzyme exercises the Co-Co/Global Option, each
Party shall be responsible for fifty percent (50%) of all Global Regulatory
Costs and Global R&D Costs for Global Development Activities that occur after
the later of (i) [***] and (ii) [***] (such later date, the “ALN-AT3 Global R&D
Cost Opt-In Date,” and together with the ALN-TTRsc Global R&D Cost Opt-In Date,
the “Global R&D Cost Opt-In Date”), and amounts specified in clauses (ii) and
(iii) in Section 2.3.1.2(c) below, if any. Alnylam shall be responsible for
one-hundred percent (100%) of Global Regulatory Costs and Global R&D Costs for
Global Development Activities for such Co-Co Licensed Product that occur prior
to the ALN-AT3 Global R&D Cost Opt-In Date, except for amounts specified in
clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(c) The Global R&D Costs to be shared by the Parties pursuant to Sections
2.3.1.2(a) and 2.3.1.2(b) above shall only include amounts that are within one
or more of the following four (4) categories:

(i) [***]

(ii) [***]

(iii) [***]

(iv) [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) For clarity, Global Regulatory Costs and Global R&D Costs to be shared by
the Parties pursuant to Section 2.3.1.2(a) and Section 2.3.1.2(b) shall exclude
any amounts paid after the Global R&D Cost Opt-In Date to Third Parties with
respect to services rendered or materials procured in connection with the
conduct of any Clinical Study or other Development activity that, in either
case, is completed prior to the Global R&D Cost Opt-In Date.

(e) Global R&D Costs and Global Regulatory Costs for each Co-Co Licensed Product
shall initially be borne by the Party incurring the cost or expense. Each Party
will calculate and maintain records of Global R&D Costs and Global Regulatory
Costs incurred by it and its Affiliates with respect to each Co-Co Licensed
Product and, within [***] days following the end of each Calendar Quarter, each
Party shall submit to the other a report detailing the Global R&D Costs and
Global Regulatory Costs incurred by it and its Affiliates during such Calendar
Quarter, and, if requested, reasonable supporting documentation will be provided
(a “Global R&D Costs Report”). In addition, each Party shall use good faith
efforts to notify the other Party of any material Global R&D Costs and Global
Regulatory Costs incurred by such Party during such Calendar Quarter within
[***] days after the end of such Calendar Quarter. The Party that incurs more
than its share of the total actual Global R&D Costs and Global Regulatory Costs
with respect to a Co-Co Licensed Product during any Calendar Quarter shall be
paid by the other Party an amount of cash sufficient to reconcile to its agreed
percentage of Global R&D Costs and Global Regulatory Costs for such Co-Co
Licensed Product, which payment shall be made within [***] days after delivery
of the Global R&D Cost Reports for such Calendar Quarter. Notwithstanding the
foregoing, if following receipt of a Global R&D Costs Report a Party (the
“Disputing Party”) disputes any Global R&D Costs or Global Regulatory Costs
under such Global R&D Costs Report, it shall have [***] days to notify the other
Party (the “Non-Disputing Party”). Upon receiving such notice from the Disputing
Party, the Non-Disputing Party shall, at the reasonable request of the Disputing
Party, provide to the Disputing Party supporting documentation relating to any
such disputed Global R&D Costs or Global Regulatory Costs. The Parties agree to
use reasonable efforts to resolve any such dispute as soon as reasonably
practicable, and any undisputed portion of Global R&D Costs or Global Regulatory
Costs in such Global R&D Costs Report shall be paid within [***] days after
delivery of such Global R&D Costs Report. Once the Parties have resolved such
dispute, any disputed amounts still owed by either Party will be paid within
[***] days of resolution of such dispute.

(f) [***]

(g) Notwithstanding anything to the contrary in these Co-Co License Terms, the
Parties shall not share Global R&D Costs incurred in a Calendar Year with
respect to Global Development Activities for a Co-Co Licensed Product to the
extent such Global R&D Costs exceed [***] of the amounts included in the final
[***] Budget that was applicable to such Current Calendar Year (the amount in
excess of such [***] limit is the “Excess Global R&D Costs”). One hundred
percent (100%) of any Excess Global R&D Costs for such Co-Co Licensed Product
will be borne by the Party that incurred such Excess Global R&D Costs.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

2.3.2. Genzyme Development. Except with respect to Global R&D Costs (which shall
be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)),
Genzyme shall be responsible for one hundred percent (100%) of all costs and
expenses incurred with respect to Development activities that are conducted by
Genzyme pursuant to any Genzyme Territory Development Plan. Genzyme will conduct
all Development of each Co-Co Licensed Product for the Genzyme Territory solely
in accordance with the applicable Global Development Plan and Genzyme Territory
Development Plan, as such Global Development Plan and Genzyme Territory
Development Plan may be amended in accordance with these Co-Co License Terms,
and in sound scientific manner and in compliance with applicable Law.

2.3.3. Alnylam Development. Alnylam will conduct all Development of each Co-Co
Licensed Product for the Co-Co Territory solely in accordance with the
applicable Global Development Plan, as such Global Development Plan may be
amended in accordance with these Co-Co License Terms, and in sound scientific
manner and in compliance with applicable Law.

2.4. Diligence.

2.4.1. Genzyme Diligence. With respect to each Co-Co Licensed Product, Genzyme
will use Commercially Reasonable Efforts to [***].

2.4.2. Alnylam Diligence. With respect to each Co-Co Licensed Product, Alnylam
will use Commercially Reasonable Efforts to (a) Develop such Co-Co Licensed
Product and obtain Regulatory Approval therefor in (i) each Co-Co Territory MMC,
and (ii) any other country(ies) within the Co-Co Territory where the PJSC
determines that it is commercially reasonable to seek Regulatory Approval
(taking into account all relevant factors as provided in the definition of
Commercially Reasonable Efforts); and (b) perform the Global Development
Activities allocated to it under the Global Development Plan for such Co-Co
Licensed Product in accordance with the Global Development Plan.

2.5. Records; Reports; Information Sharing.

2.5.1. Development Activities Reports. Each Party will periodically provide to
the PJSC responsible for a Co-Co Licensed Product, but in no event less than on
a Calendar Quarter basis, or more frequently as reasonably requested by the
other Party, an update regarding Development activities conducted by or on
behalf of such Party with respect to such Co-Co Licensed Product, as well as any
Secondary Indication Studies and Post-Marketing Studies conducted by or on
behalf of such Party with respect to such Co-Co Licensed Product. The Parties
will periodically report to the PJSC responsible for a Co-Co Licensed Product,
but in no event less than on a Calendar Quarter basis, regarding their
respective activities conducted under the Global Development Plan for such Co-Co
Licensed Product. In addition, each Party will promptly share with the other
Party all material developments and information that it comes to possess
relating to the Development of any Co-Co Licensed Products, including Safety
Concerns and study reports and data generated from Clinical Studies of such
Co-Co Licensed Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

2.5.2. Scientific Records. Each Party will maintain scientific records, in
sufficient detail and in sound scientific manner appropriate for patent and
regulatory purposes, which will fully and properly reflect all work done and
results achieved in the performance of the Development activities and Secondary
Indication Studies with respect to Co-Co Licensed Products by such Party.

2.5.3. Information Exchange and Development Assistance. Until the expiration or
termination of the final Global Development Plan, upon the reasonable request of
the other Party, each Party shall provide to the other Party, without additional
compensation (except as provided in Section 6.5 (Transfer of Manufacturing
Know-How) of the Master Agreement) and in a commercially reasonable format,
Know-How Controlled by such Party and/or its Related Parties that is licensed to
the other Party under these Co-Co License Terms (i.e., Know-How included in
Genzyme Technology for Genzyme and Know-How included in Alnylam Technology for
Alnylam) to the extent that it is reasonably necessary or useful for Developing
a Co-Co Licensed Product in the requesting Party’s Territory or for obtaining or
maintaining Regulatory Approval for a Co-Co Licensed Product in the requesting
Party’s Territory, including copies of (a) all scientific information and data
related to such Co-Co Licensed Product (including all data made, collected or
otherwise generated in the conduct of any pre-clinical studies, Clinical
Studies, Secondary Indication Studies or early access/named patient programs for
the Co-Co Licensed Products, as well as CMC information), and (b) protocols and
investigator brochures, in each case, that are reasonably necessary for the
other Party (or its Related Parties) to perform its obligations or exploit its
rights under these Co-Co License Terms with respect to such Co-Co Licensed
Product. Notwithstanding the foregoing, Genzyme shall have no obligation to
transfer or disclose to Alnylam any Know-How included in the Genzyme
Manufacturing IP; provided, however, that if Genzyme elects, in its sole
discretion, to transfer or disclose any such Know-How to Alnylam in writing, it
shall be “Genzyme Disclosed Manufacturing Know-How” under these Co-Co License
Terms and licensed to Alnylam in accordance with Section 7.2.3 (License to
Genzyme Disclosed Manufacturing Know-How).

2.5.4. Personnel. Each Party may request, through the PJSC or the other Party’s
CLP Alliance Manager responsible for a Co-Co Licensed Product, that the other
Party reasonably make available for consultation regarding the Development of
such Co-Co Licensed Product certain of its employees engaged in Development
activities and Secondary Indication Studies with respect to such Co-Co Licensed
Product. The PJSC or the CLP Alliance Managers responsible for a Co-Co Licensed
Product will reasonably coordinate, upon reasonable notice during normal
business hours and at their respective places of employment, consultation
between the Parties on the progress of the Development and Secondary Indication
Studies for such Co-Co Licensed Product.

2.5.5. Confidentiality. All information exchanged by the Parties under this
Section 2.5 will be deemed to be Confidential Information of the disclosing
Party and maintained in accordance with Section 7 of the Master Agreement
(Confidentiality and Publication).

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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2.6. Third Parties.

2.6.1. Use of Third Parties. The Parties shall be entitled to utilize the
services of Third Parties to perform their respective Development and
Manufacturing activities under these Co-Co License Terms, provided that (a) each
Party shall require that such Third Party operates in a manner consistent with
these Co-Co License Terms, (b) each Party shall remain at all times fully liable
for its respective responsibilities and (c) the Parties will make reasonable
efforts to share, through the PJSC, information regarding any prior experience
with specific CROs that are anticipated to be engaged to perform work under the
Global Development Plan. Each Party shall require that any Third Party agreement
entered into pursuant to this Section 2.6.1 include confidentiality and non-use
provisions that are no less stringent than those set forth in Section 7 of the
Master Agreement (Confidentiality and Publication) and shall obtain ownership
of, and/or a fully sublicensable license under and to, any Know-How and Patent
Rights that are developed by such Third Party in the performance of such
agreement and are reasonably necessary or useful to Develop, Manufacture and/or
Commercialize Co-Co Licensed Products in the Field. The Party utilizing the
services of a Third Party service provider shall be solely responsible for
direction of and communications with such Third Party, but such Party shall
provide the other Party with reasonably detailed updates regarding any such
activities from time to time.

2.6.2. [***].

2.7. [***].

3. REGULATORY MATTERS

3.1. Regulatory Filings and Interactions in the Genzyme Territory.

3.1.1. Ownership of Regulatory Filings.

3.1.1.1. Genzyme will own all INDs, NDAs and related regulatory documentation
submitted to any Regulatory Authority in the Genzyme Territory with respect to
any Co-Co Licensed Product. At Genzyme’s request following the Implementation
Date for a Co-Co Licensed Product, Alnylam will promptly assign and transfer to
Genzyme all INDs, NDAs and other regulatory documentation submitted to any
Regulatory Authority in the Genzyme Territory with respect to such Co-Co
Licensed Product that is in the possession or control of Alnylam, and each Party
will submit all filings, letters and other documentation necessary to effect
such assignment and transfer to the applicable Regulatory Authority no later
than [***] days after such request for such Co-Co Licensed Product, in each
case, excluding any drug master files maintained by or on behalf of Alnylam,
which shall be and remain Alnylam’s sole responsibility. Alnylam hereby appoints
Genzyme as Alnylam’s agent for all matters related to each Co-Co Licensed
Product involving Regulatory Authorities in the Genzyme Territory during the
period beginning on the Implementation Date for such Co-Co Licensed

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Product and ending on the date that the transfer of all INDs, NDAs and related
regulatory documents filed with or submitted to any Regulatory Authority in the
Genzyme Territory that relate to such Co-Co Licensed Product becomes effective,
and Genzyme hereby accepts such appointment, excluding any drug master files
maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole
responsibility.

3.1.1.2. Notwithstanding the foregoing, for every Clinical Study conducted under
a Global Development Plan, Alnylam will draft the protocol, develop the IND
strategy, and file INDs globally, including in the Genzyme Territory, after
input and review by Genzyme and Alnylam will use reasonable efforts to address
any concerns raised by Genzyme in connection with such activities. Unless
otherwise agreed by the Parties, on a country-by-country basis, following the
acceptance or approval of the IND and the first dosing of the first patient in
the first Phase III Study of the relevant Co-Co Licensed Product in such
country, Alnylam will assign the IND in such country, as set forth in
Section 3.1.1.1, in the Genzyme Territory to Genzyme and from that point
forward, Genzyme will be primarily responsible for the related regulatory
activities with respect thereto in its Territory. [***]

3.1.2. Responsibilities for Regulatory Matters. Pursuant to the Global
Development Plan for a Co-Co Licensed Product and, except as otherwise provided
in such Global Development Plan, Genzyme will be solely responsible for all
regulatory matters relating to such Co-Co Licensed Product in the Genzyme
Territory, including (i) overseeing, monitoring and coordinating all regulatory
actions, communications and filings with, and submissions to, each Regulatory
Authority in the Genzyme Territory with respect to such Co-Co Licensed Product;
(ii) interfacing, corresponding and meeting with each Regulatory Authority in
the Genzyme Territory with respect to such Co-Co Licensed Product; and
(iii) seeking and maintaining all regulatory filings in the Genzyme Territory
with respect to such Co-Co Licensed Product, excluding any drug master files
maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole
responsibility.

3.1.3. Communications with Regulatory Authorities. Genzyme will promptly (and in
any event no later than [***] days) notify the Alnylam representatives on the
PJSC responsible for a Co-Co Licensed Product in writing, including a brief
description in English, of the principal issues raised in any material
communication with any Regulatory Authority in the Genzyme Territory with
respect to such Co-Co Licensed Product. Upon Alnylam’s reasonable request after
receiving a notice from Genzyme in accordance with the immediately preceding
sentence, Genzyme will provide to Alnylam: (i) at Genzyme’s expense, a summary
translation of the applicable material communication in English; (ii) at
Genzyme’s expense, complete copies of the original correspondence with the
applicable Regulatory Authority in their native language; or (iii) at Alnylam’s
expense, a full translation of the applicable material communication in English,
in each case (i) through (iii) within a reasonable period of time following such
request. For purposes of this Section 3.1.3, “material communication” will
include any meetings with

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Regulatory Authorities, or questions or concerns from Regulatory Authorities,
regarding significant issues, such as key product quality attributes (e.g.,
purity), safety findings affecting the platform (e.g., Serious Adverse Events,
emerging safety signals), clinical or nonclinical findings affecting patient
safety or lack of efficacy, or receipt or denial of Regulatory Approval.

3.1.4. Meetings with Regulatory Authorities. Genzyme shall provide Alnylam with
reasonable advance notice of all substantive meetings with Regulatory
Authorities in the Genzyme Territory pertaining to each Co-Co Licensed Product,
or with as much advance notice as practicable under the circumstances. Genzyme
shall use reasonable efforts, to the extent reasonably practicable, to permit
Alnylam to have, at Alnylam’s expense, mutually acceptable representatives of
Alnylam attend, solely as a non-participating observers, material, substantive
meetings (including pre-IND and end of Phase II Study meetings) with Regulatory
Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product;
provided, however, that Genzyme shall not be obligated to change or re-schedule
any such meeting in order to accommodate the schedule of Alnylam’s
representatives. Prior to the acceptance or approval of the IND and the first
dosing of the first patient in the first Phase III Study of a Co-Co Licensed
Product in a country in the Genzyme Territory, Alnylam shall provide Genzyme
with reasonable advance notice of all substantive meetings with Regulatory
Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product,
or with as much advance notice as practicable under the circumstances. Alnylam
shall use reasonable efforts, to the extent reasonably practicable, to permit
Genzyme to have, at Genzyme’s expense, mutually acceptable representatives of
Genzyme attend, as full and equal participants, material, substantive meetings
(including pre-IND and end of Phase II Study meetings) with Regulatory
Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product.

3.1.5. Submissions. With respect to each Co-Co Licensed Product, Genzyme shall
provide Alnylam with prompt written notice of each of the following events (but
in any event within [***] days) after the occurrence of such event in the
Genzyme Territory: (i) the filing of any IND for such Co-Co Licensed Product;
and (ii) the submission of any filings or applications for Regulatory Approval
(including orphan drug applications and designations) of such Co-Co Licensed
Product to any Regulatory Authority; provided, however, that in all
circumstances, Genzyme shall inform Alnylam of such event prior to public
disclosure of such event by Genzyme.

3.2. Regulatory Filings and Interactions in the Co-Co Territory.

3.2.1. Ownership of Regulatory Filings. Alnylam will own all INDs, NDAs and
related regulatory documentation submitted to any Regulatory Authority in the
Co-Co Territory with respect to any Co-Co Licensed Product.

3.2.2. Responsibilities for Regulatory Matters. Pursuant to the Global
Development Plan for a Co-Co Licensed Product and, except as otherwise provided
in such Global Development Plan, Alnylam will be primarily responsible for all
regulatory matters relating to such Co-Co Licensed Product in the Co-Co
Territory, including (i) overseeing, monitoring and coordinating all regulatory
actions, communications and filings with, and

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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submissions to, each Regulatory Authority in the Co-Co Territory with respect to
such Co-Co Licensed Product; (ii) interfacing, corresponding and meeting with
each Regulatory Authority in the Co-Co Territory with respect to such Co-Co
Licensed Product; and (iii) seeking and maintaining all regulatory filings in
the Co-Co Territory with respect to such Co-Co Licensed Product; provided,
however, that Alnylam and Genzyme may have roles of varying responsibility for
such activities in respect of the Co-Co Licensed Products in the Co-Co Territory
as is set forth in the applicable Global Development Plan.

3.2.3. Communications with Regulatory Authorities. Alnylam will notify the
Genzyme representatives on the PJSC responsible for a Co-Co Licensed Product in
writing, including a brief description in English, of the principal issues
raised in any material communication with any Regulatory Authority in the Co-Co
Territory with respect to such Co-Co Licensed Product within [***] days after
receipt of such material communication. Alnylam will allow Genzyme a reasonable
opportunity to review and comment on Alnylam’s proposed response to any such
material communications in advance of the transmission of any such response, and
Alnylam will reasonably consider all comments timely provided by Genzyme in
connection therewith. Upon Genzyme’s reasonable request after receiving a notice
from Alnylam in accordance with the immediately preceding sentence, Alnylam will
provide to Genzyme: (i) at Alnylam’s expense, a summary translation of the
applicable material communication in English; (ii) at Alnylam’s expense,
complete copies of the original correspondence with the applicable Regulatory
Authority in their native language; or (iii) at Genzyme’s expense, a full
translation of the applicable material communication in English, in each case
(i) through (iii) within a reasonable period of time following such request. For
purposes of this Section 3.2.3, “material communication” will include any
meetings with Regulatory Authorities, or questions or concerns from Regulatory
Authorities, regarding significant issues, such as key product quality
attributes (e.g., purity), safety findings affecting the platform (e.g., Serious
Adverse Events, emerging safety signals), clinical or nonclinical findings
affecting patient safety, lack of efficacy, or receipt or denial of Regulatory
Approval.

3.2.4. Meetings with Regulatory Authorities. Alnylam shall provide Genzyme with
reasonable advance notice of all substantive meetings with Regulatory
Authorities in the Co-Co Territory pertaining to each Co-Co Licensed Product, or
with as much advance notice as practicable under the circumstances. Alnylam
shall use Commercially Reasonable Efforts, to the extent reasonably practicable,
to permit Genzyme to have, at Genzyme’s expense, mutually acceptable
representatives of Genzyme attend the following: (i) solely as non-participating
observers, material, substantive meetings (including pre-IND and end of Phase II
Study meetings) with Regulatory Authorities in the Co-Co Territory pertaining to
such Co-Co Licensed Product, and (ii) any internal Alnylam meetings held in
preparation for such material, substantive meetings with Regulatory Authorities
in the Co-Co Territory.

3.2.5. Submissions. With respect to each Co-Co Licensed Product, Alnylam will
allow Genzyme a reasonable opportunity to review and comment on all regulatory
filings and other submissions to Regulatory Authorities or other Governmental
Authorities in the Co-Co Territory in advance of the submission of any such
filing, and Alnylam will reasonably consider

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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all comments timely provided by Genzyme in connection therewith. In addition,
Alnylam shall provide Genzyme with prompt written notice of each of the
following events (but in any event within [***] days) after the occurrence of
such event in the Co-Co Territory: (i) the filing of any IND for such Co-Co
Licensed Product; (ii) the submission of any filings or applications for
Regulatory Approval (including orphan drug applications and designations) of
such Co-Co Licensed Product to any Regulatory Authority; and (iii) receipt or
denial of Regulatory Approval for such Co-Co Licensed Product; provided,
however, that in all circumstances, Alnylam shall inform Genzyme of such event
prior to public disclosure of such event by Alnylam.

3.3. EMA Regulatory Strategy. Within [***] year before the anticipated MAA
filing for a Co-Co Licensed Product, the PJSC will determine an EMA regulatory
strategy for such Co-Co Licensed Product pursuant to which the PJSC will
determine (a) whether Alnylam will seek Regulatory Approval for such Co-Co
Licensed Product in the EU using the EMA centralized or a national authorization
procedure and (b) whether Genzyme will file a duplicate license with respect to
any MAA held by Alnylam in the Co-Co Territory [***]. In determining the EMA
regulatory strategy, the Parties agree to reasonably consider in good faith each
Party’s interests. In the event that Genzyme files a duplicate license in the
Genzyme Territory, Alnylam will coordinate communications with EMA, and provide
support to enable Genzyme to efficiently obtain such duplicate license to
provide for marketing in Genzyme countries under a separate, Genzyme trade name,
to the extent not inconsistent with the Global Commercial Strategy or Global
Branding Strategy for such Co-Co Licensed Product.

3.4. Costs of Regulatory Affairs. Except as provided in Sections 2.3 (Joint
Responsibilities for Development Activities and Costs) and 3.1.1.2 (Ownership of
Regulatory Filings), each Party shall be responsible for all costs and expenses
incurred in connection with applying for, obtaining and maintaining Regulatory
Approval with respect to Co-Co Licensed Products, and related regulatory affairs
activities.

3.5. Right of Reference. Each Party hereby grants to the other Party, and at the
request of the other Party will grant to the other Party’s Related Parties, a
“Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any
successor rule or analogous Law recognized outside of the United States), to,
and a right to copy, access, and otherwise use, all information and data
(including all CMC information as well as data made, collected or otherwise
generated in the conduct of any Clinical Studies or Secondary Indication Studies
or early access/named patient programs for the Co-Co Licensed Products) included
in or used in support of any regulatory filing, Regulatory Approval, drug master
file or other regulatory documentation (including orphan drug applications and
designations) owned or controlled by such Party or its Related Parties that
relates to (a) any Co-Co Licensed Product or (b) with respect to such
information and data provided to Genzyme, the siRNA Controlled by Alnylam and
known as ALN-TTR01, to the extent necessary or useful to obtain Regulatory
Approval of a Co-Co Licensed Product in the Genzyme Territory, and such Party
shall provide a signed statement to this effect, if requested by the other
Party, in accordance with 21 C.F.R. § 314.50(g)(3) (or any successor or
analogous Law outside of the United States). In addition, upon request of either
Party (on behalf of itself or a Sublicensee), the other Party shall obtain and

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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provide to the requesting Party certificates or other formal or official
attestations concerning the regulatory status of the Co-Co Licensed Products in
the Genzyme Territory or the Co-Co Territory, as applicable (e.g., Certificates
of Free Sale, Certificates for Export, Certificates to Foreign Governments).
Notwithstanding anything to the contrary in these Co-Co License Terms, neither
Party shall withdraw or inactivate any regulatory filing that the other Party
references or otherwise uses pursuant to this Section 3.5.

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

4.1. Responsibility, Cost and Diligence.

4.1.1. Global Commercial Strategy. For each Co-Co Licensed Product, the key
Commercialization principles will be set forth in a written summary of the
global Commercialization strategy for such Co-Co Licensed Product (each, a
“Global Commercial Strategy”). Alnylam shall provide the initial draft of such
Global Commercial Strategy to the PJSC responsible for the applicable Co-Co
Licensed Product within [***] days after the Implementation Date for such Co-Co
Licensed Product, and within [***] days after provision, such PJSC shall review,
update and approve such Global Commercial Strategy. The PJSC for such Co-Co
Licensed Product will update and amend the Global Commercial Strategy not later
than the initiation of the first Phase III Study for such Co-Co Licensed
Product, and then annually thereafter. Amendments to any Global Commercial
Strategy will become effective following review and approval by the applicable
PJSC. In no event, however, may any Global Commercial Strategy be amended with
the result that it fails to satisfy the requirements for Commercialization of
Co-Co Licensed Products set forth in this Section 4.

4.1.2. Co-Co Territory. The PJSC will lead responsibility for all
Commercialization activities relating to Co-Co Licensed Products in the Field in
the Co-Co Territory. The Parties, under the direction of the PJSC, will
participate in the planning and conduct of such Commercialization activities as
and to the extent set forth in these Co-Co License Terms, including without
limitation, Section 4.2 (Co-Co Territory Commercialization).

4.1.3. Genzyme Territory. Genzyme shall be solely responsible, at its expense,
for all Commercialization activities relating to Co-Co Licensed Products in the
Field in the Genzyme Territory.

4.1.4. Genzyme Commercial Diligence. Genzyme shall use Commercially Reasonable
Efforts to [***].

4.2. Co-Co Territory Commercialization.

4.2.1. Co-Co Territory Commercialization Plan. For each Co-Co Licensed Product,
the Commercialization activities that are necessary or useful to be undertaken
for such Co-Co Licensed Product in the Co-Co Territory will be set forth in
reasonable detail in a written work plan (each, a “Co-Co Territory
Commercialization Plan”). Each Co-Co Territory Commercialization Plan must, at
all times, include a detailed description of the S&M Activities

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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to be undertaken in each country in the Co-Co Territory with respect to the
applicable Co-Co Licensed Product during the then-current Calendar Year and the
next Calendar Year. Each Co-Co Territory Commercialization Plan shall be
consistent with the requirements of the applicable Global Commercialization
Strategy, as such Global Commercialization Strategy may be updated as reasonably
necessary. Any amendment to a Global Commercialization Strategy shall take into
account the then-current deployment of resources and time required to realign
resources consistent with the Global Commercialization Strategy in a reasonable
manner, and with this Section 4.2.1. The Commercialization Activities set forth
in each Co-Co Territory Commercialization Plan will at all times be designed to
be in compliance with all applicable Laws and in accordance with professional
and ethical standards customary in the pharmaceutical industry.

4.2.1.1. ALN-TTRsc Co-Co Territory Commercialization Plan. Within [***] year
after the Effective Date, Alnylam will provide a draft of the initial Co-Co
Territory Commercialization Plan for ALN-TTRsc to the PJSC, and within [***]
days thereafter, the PJSC will review, update and approve such Co-Co Territory
Commercialization Plan and it will be attached hereto as Schedule 4.2-1.

4.2.1.2. ALN-AT3 Co-Co Territory Commercialization Plan. The initial Co-Co
Territory Commercialization Plan for ALN-AT3 will be prepared and approved by
the PJSC no later than [***] years prior to the anticipated date of the First
Commercial Sale of ALN-AT3 in any country in the Co-Co Territory and, upon
approval, it will be attached hereto as Schedule 4.2-2.

4.2.1.3. Allocation of S&M Activities. Promptly following the approval of any
Co-Co Territory Commercialization Plan in accordance with this Section 4.2.1 or
Section 4.2.4, the Parties shall allocate responsibility for each S&M Activity
to be performed in the next Calendar Year between the Parties in an equitable
manner mutually agreed by the Parties, which allocation shall be made on an
activity-by-activity or S&M FTE-by-S&M FTE basis, as applicable, and subject to
the following:

(a) each Party will have the right to provide up to [***] in each country in the
Co-Co Territory in such Calendar Year; and

(b) [***]

4.2.2. Diligence. If the PJSC agrees upon the allocation of responsibility for
the S&M Activities in a Co-Co Territory Commercialization Plan [***].

4.2.3. Co-Co Territory Commercialization Budget. Each Co-Co Territory
Commercialization Plan will contain a budget for the S&M Activities (and no
other activities) to be performed during the then-current Calendar Year with
respect to the applicable Co-Co Licensed Product in the Co-Co Territory (a
“Co-Co Territory Commercialization Budget”), which budget will allocate
expenditures equitably across the countries in the Co-Co Territory,

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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taking into account the allocation of activities described in Section 4.2.1.3
(Allocation of S&M Activities) and the then-current and future commercial
opportunities for such Co-Co Licensed Product. Each Co-Co Territory
Commercialization Budget will be updated annually by the PJSC responsible for
the applicable Co-Co Licensed Product in accordance with Section 4.2.4 (Managing
and Amending Co-Co Territory Commercialization Plans and Co-Co Territory
Commercialization Budgets). The initial Co-Co Territory Commercialization Budget
for a Co-Co Licensed Product, and each update thereto, will be prepared by the
PJSC [***]. Alnylam will enter such Co-Co Commercialization Budget in a template
that the Parties agree is efficient for both Parties to communicate such
information. [***]

4.2.4. Managing and Amending Co-Co Territory Commercialization Plans and Co-Co
Territory Commercialization Budgets. For each Co-Co Licensed Product, Alnylam
will update and amend, and the PJSC will approve, the applicable Co-Co Territory
Commercialization Plan from time-to-time as it deems necessary and, until such
time as no further S&M Activities are occurring or expected to occur with
respect to such Co-Co Licensed Product, the Co-Co Territory Commercialization
Plan will be updated as follows:

(a) No later than [***] of each Calendar Year, Alnylam shall prepare, and the
applicable PJSC will approve, an updated draft of the Co-Co Territory
Commercialization Plan, which shall contain a proposed Co-Co Territory
Commercialization Budget covering the next Calendar Year. The proposed Co-Co
Territory Commercialization Budget will satisfy the requirements set forth in
Section 4.2.3 (Co-Co Territory Commercialization Budget).

(b) No later than [***] of each Calendar Year, Alnylam shall prepare, and the
applicable PJSC will review and tentatively approve an updated Co-Co Territory
Commercialization Plan and Co-Co Territory Commercialization Budget for such
Co-Co Licensed Product, and such updated Co-Co Territory Commercialization Plan
and Co-Co Territory Commercialization Budget will become effective upon such
tentative approval by the PJSC, provided that the Parties acknowledge and agree
that each Party’s internal process for receiving final approval of such Co-Co
Territory Commercialization Plan and Co-Co Territory Commercialization Budget
from its Board of Directors may occur after [***] (but, in any event, before
[***]) and Co-Co Territory Commercialization Plan and Co-Co Territory
Commercialization Budget will not become final unless and until such approvals
are obtained. In no event may any Co-Co Territory Commercialization Plan be
amended with the result that it fails to satisfy the requirements for Co-Co
Territory Commercialization Plans set forth in Section 4.2.1 (Co-Co Territory
Commercialization Plan).

4.2.5. Responsibility for Co-Co Territory Commercialization Costs. With respect
to each Co-Co Licensed Product, unless otherwise agreed to by the Parties in
writing [***]. On the first day of each Calendar Year, the PJSC responsible for
a Co-Co Licensed Product will determine the total S&M Costs allocated to each
Party for such Calendar Year under the applicable Co-Co Territory
Commercialization Budget, which S&M Costs shall be calculated by [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.2.6. Verification. With respect to each Co-Co Licensed Product, promptly
following the end of each Calendar Year, the Head of the Rare Disease Business
of Genzyme and an appropriate officer of Alnylam shall certify to one another in
writing whether or not such Party has spent the S&M Costs allocated to such
Party in the applicable Co-Co Territory Commercialization Budget during such
Calendar Year in performing the S&M Activities allocated to such Party in the
applicable Co-Co Territory Commercialization Plan. If either Party did not spend
all of the S&M Costs or perform all of the S&M Activities allocated to such
Party in the applicable Co-Co Territory Commercialization Plan, then such Party
shall pay the other Party an amount equal to [***] of the difference between the
S&M Costs and S&M Activities allocated to such Party in the applicable Co-Co
Territory Commercialization Plan and the S&M Costs and S&M Activities certified
as being spent or performed by such Party. The certification mechanism and
true-up payment provided for in this Section 4.2.6 shall be in lieu of auditing
the Parties’ S&M Costs and S&M Activities for Co-Co Licensed Products in the
Co-Co Territory.

4.3. Genzyme Territory Commercialization Plan. No less than [***] months in
advance of the reasonably expected first Regulatory Approval in the Genzyme
Territory with respect to a Co-Co Licensed Product, and on an annual basis
thereafter, Genzyme shall prepare and deliver to the PJSC responsible for such
Co-Co Licensed Product for review a reasonable written plan that summarizes the
Commercialization activities to be undertaken with respect to such Co-Co
Licensed Product in the Genzyme Territory in the next Calendar Year and, to the
extent commercially reasonable, Genzyme’s plans to obtain further Regulatory
Approvals and Commercialize such Co-Co Licensed Product in countries in the
Genzyme Territory in which Genzyme is not then Commercializing such Co-Co
Licensed Product, and the dates by which such activities are targeted to be
accomplished (the “Genzyme Territory Commercialization Plan”). Each Genzyme
Territory Commercialization Plan shall be consistent with the requirements of
the initial Global Commercialization Strategy approved by the PJSC pursuant to
Section 4.1.1 (Global Commercial Strategy) or the most recently approved by the
PJSC without the use of tie-break authority pursuant to Section 5.7.3
(Tie-Breaking). The Genzyme Territory Commercialization Plan for a Co-Co
Licensed Product shall subsequently be updated and modified by Genzyme, from
time to time at its discretion and no less frequently than once per Calendar
Year, based upon, among other things, Genzyme’s Commercialization activities
with respect to such Co-Co Licensed Product in the Genzyme Territory, a copy of
which updated plan Genzyme will provide to the PJSC responsible for such Co-Co
Licensed Product. [***].

4.4. Advertising and Promotional Materials.

4.4.1. Global Branding. Alnylam shall have the right, from time to time during
the Term, to develop (and thereafter to modify and update) a global branding
strategy (including global positioning, colors and other visual branding
elements) for each Co-Co Licensed Product for use in the Field throughout the
world (the “Global Branding Strategy”), which the PJSC responsible for such
Co-Co Licensed Product shall, in accordance with Sections 5.6 (PJSC

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Commercialization Responsibilities) and 5.7 (PJSC Decision-Making), review and
approve, and which the Parties shall, following such review and approval,
implement. Alnylam will submit the Global Branding Strategy for a Co-Co Licensed
Product to the PJSC responsible for such Co-Co Licensed Product at least
annually (or more frequently if reasonably requested by Genzyme). Alnylam shall
consider in good faith any timely comments Genzyme may have with respect to any
Global Branding Strategy, but shall have final decision-making authority with
respect to such Global Branding Strategy. Notwithstanding the foregoing, Alnylam
shall ensure that the Global Branding Strategy complies with applicable Laws in
the Genzyme Territory, and that any branding elements selected for inclusion in
the Global Branding Strategy do not infringe any Third Party trademarks or other
intellectual property rights. If any such Global Branding Strategy infringes
Third Party trademarks or other intellectual property rights or otherwise does
not comply with applicable Law in the Genzyme Territory, Alnylam shall take
action to end such infringement or other noncompliance (including by modifying
such Global Branding Strategy) and Genzyme will not be obligated to implement
such Global Branding Strategy in the Genzyme Territory pursuant to this
Section 4.4.1 unless and until such infringement or noncompliance is ended.

4.4.2. Alnylam A&P. Alnylam will be responsible for the creation, preparation,
production, reproduction and filing with the applicable Regulatory Authorities,
of relevant written sales, promotion and advertising materials relating to each
Co-Co Licensed Product (“Promotional Materials”) for use in the Co-Co Territory.
All such Promotional Materials will be compliant with applicable Law and, if
applicable, consistent in all material respects with the Global Branding
Strategy for such Co-Co Licensed Product. Alnylam will submit representative
samples of its Promotional Materials developed by it for use in the Co-Co
Territory to the PJSC, at least annually (or more frequently if reasonably
requested by Genzyme). Alnylam shall consider in good faith any timely comments
Genzyme may have with respect to any such Promotional Materials, but shall have
final decision-making authority with respect to such Promotional Materials.
Notwithstanding the foregoing, Alnylam will incorporate any changes to
Promotional Materials requested by Genzyme in a timely fashion in cases where
Genzyme indicates that believes in good faith based on the advice of counsel
that such change is necessary to enable it to comply with any applicable Law.

4.4.3. Genzyme A&P. Genzyme will be responsible for the creation, preparation,
production, reproduction and filing with the applicable Regulatory Authorities,
of relevant Promotional Materials relating to each Co-Co Licensed Product for
use in the Genzyme Territory. All such Promotional Materials will be compliant
with applicable Law, consistent in all material respects with the Genzyme
Territory Commercialization Plan and, if applicable, consistent in all material
respects with the Global Branding Strategy for such Co-Co Licensed Product.
Genzyme will submit representative samples of its Promotional Materials
developed by it for use in the Genzyme Territory to the PJSC at least annually
thereafter (or more frequently if reasonably requested by Alnylam). Genzyme
shall consider in good faith any timely comments Alnylam may have with respect
to any such Promotional Materials, but shall have final decision-making
authority with respect to such Promotional Materials.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.4.4. Reporting Obligations.

4.4.4.1. Genzyme Territory. Genzyme shall report to the PJSC responsible for a
Co-Co Licensed Product in writing, by no later than each [***] following the
first Regulatory Approval of such Co-Co Licensed Product in the Field in the
Genzyme Territory (for the period ending December 31 of the prior Calendar
Year), summarizing in reasonable detail Genzyme’s Commercialization activities
for such Co-Co Licensed Product in the Genzyme Territory performed to date (or
updating such report for activities performed since the last such report was
given hereunder, as applicable). In addition, Genzyme shall provide Alnylam with
written notice of the First Commercial Sale of each Co-Co Licensed Product in
the Genzyme Territory within [***] days after such event; provided, however,
that in all circumstances, Genzyme shall inform Alnylam of such event prior to
public disclosure of such event by Genzyme. Genzyme shall provide such other
information to the PJSC responsible for a Co-Co Licensed Product as Alnylam may
reasonably request with respect to Commercialization of such Co-Co Licensed
Product and shall keep such PJSC reasonably informed of Genzyme’s
Commercialization activities in the Genzyme Territory with respect to such Co-Co
Licensed Product.

4.4.4.2. Co-Co Territory. Each Party shall report to the PJSC responsible for a
Co-Co Licensed Product in writing, by no later than each [***] following the
first Regulatory Approval of such Co-Co Licensed Product in the Field in the
Co-Co Territory (for the period ending December 31 of the prior Calendar Year),
summarizing in reasonable detail such Party’s Commercialization activities for
such Co-Co Licensed Product in the Co-Co Territory performed to date (or
updating such report for activities performed since the last such report was
given hereunder, as applicable). Each Party shall provide such other information
to the PJSC responsible for a Co-Co Licensed Product as the other Party may
reasonably request with respect to Commercialization of such Co-Co Licensed
Product and shall keep such PJSC reasonably informed of such Party’s
Commercialization activities in the Co-Co Territory with respect to such Co-Co
Licensed Product.

4.5. Commercialization Reporting Obligations. Each Party and its Related Parties
shall be responsible for booking sales in its Territory (for avoidance of doubt,
meaning, with respect to the Co-Co Territory, Alnylam, and with respect to the
Genzyme Territory, Genzyme). Each Party and its Related Parties may warehouse
Co-Co Licensed Products both inside and outside of such Party’s Territory,
provided that any sales with respect to such Co-Co Licensed Products are booked
in such Party’s Territory. If a Party receives any orders for any Co-Co Licensed
Product in the other Party’s Territory, it shall refer such orders to the other
Party, to the extent it is not prohibited from doing so under applicable Law.
Moreover, each Party and its Related Parties shall be solely responsible for
handling all returns of any Co-Co Licensed Product sold in its Territory, as
well as all aspects of Co-Co Licensed Product order processing, invoicing and
collection, distribution, inventory and receivables of Co-Co Licensed Products
sold in its Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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4.6. Recalls, Market Withdrawals or Corrective Actions. In the event that any
Regulatory Authority issues or requests a recall or takes a similar action in
connection with a Co-Co Licensed Product in the Co-Co Territory or Genzyme
Territory, or in the event either Party determines that an event, incident or
circumstance has occurred that may result in the need for a recall or market
withdrawal of a Co-Co Licensed Product in the Co-Co Territory or Genzyme
determines that an event, incident or circumstance has occurred that may result
in the need for a recall or market withdrawal of a Co-Co Licensed Product in the
Genzyme Territory, the Party notified of such recall or similar action, or the
Party that desires such recall or similar action, shall within [***] hours
notify the other Party’s CLP Alliance Manager and PJSC representatives thereof
by telephone or e-mail. The Parties shall mutually agree whether to conduct a
recall of a Co-Co Licensed Product in the Co-Co Territory and the manner in
which any such recall shall be conducted (except in the case of a government
mandated recall, when the Party subject to such mandate may act without such
advance notice but shall notify the other Party as soon as possible). Genzyme
shall determine whether to conduct a recall of a Co-Co Licensed Product in the
Genzyme Territory and the manner in which any such recall shall be conducted
(except in the case of a government mandated recall, when Genzyme may act
without such advance notice but shall notify Alnylam as soon as possible).
Except as may be otherwise agreed by the Parties, each Party shall share equally
the expense of any such recall in the Co-Co Territory and Genzyme shall bear the
expense of any such recall in the Genzyme Territory. Each Party will make
available all of its pertinent records that may be reasonably requested by the
other Party in order to effect a recall of a Co-Co Licensed Product in the Co-Co
Territory or Genzyme Territory. The Parties’ rights and obligations under this
Section 4.6 shall be subject to the terms of any supply agreement(s) entered
into between the Parties and, in the event of any conflict between the
provisions of any such supply agreement and this Section 4.6, the provisions of
such supply agreement shall govern.

4.7. Export Monitoring.

4.7.1. [***]

4.7.2. [***]

5. COLLABORATION MANAGEMENT

5.1. Product Joint Steering Committee. The Parties shall establish a product
joint steering committee (a “PJSC”) to facilitate the Co-Co Collaboration with
respect to each Co-Co Licensed Product as follows:

5.1.1. Composition of the Product Joint Steering Committee. The Development and
Commercialization of each Co-Co Licensed Product pursuant to the Co-Co
Collaboration will be conducted under the oversight of a PJSC, which shall be
comprised of three (3) representatives of each Party. The PJSC for ALN-TTRsc
shall be established as of the

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Effective Date. Each Party shall appoint its respective representatives to each
PJSC from time to time following the Implementation Date for ALN-AT3, and may
substitute one or more of its representatives on any PJSC, in its sole
discretion, effective upon notice to the other Party of such change. Each Party
shall have at least one representative on each PJSC who is a senior employee
(vice president level or above), and all representatives on each PJSC shall have
appropriate expertise, seniority, decision-making authority and ongoing
familiarity with the Co-Co Collaboration and the applicable Co-Co Licensed
Product. Unless otherwise agreed by the Parties, each Party’s representatives on
any PJSC must be employees of such Party or any of its Affiliates. For the
avoidance of doubt, the same representatives from each Party may serve on the
PJSC for more than one Co-Co Licensed Product. Additional representatives or
consultants may from time to time, by mutual consent of the Parties, be invited
to attend PJSC meetings, subject to such representatives and consultants
undertaking confidentiality obligations, whether in a written agreement or by
operation of law, no less stringent than the requirements of Section 7 of the
Master Agreement (Confidentiality and Publication).

5.1.2. PJSC Chairperson. The chairperson of each PJSC shall rotate every twelve
(12) months between a PJSC representative of Alnylam and a PJSC representative
of Genzyme. The initial chairperson of each PJSC shall be a representative of
Alnylam. Each PJSC chairperson’s responsibilities shall include chairing
meetings, including ensuring that objectives for each meeting are set and
achieved.

5.2. Appointment of Subcommittees, Project Teams and CLP Alliance Managers. Each
PJSC shall be empowered to create such subcommittees and project teams as it may
deem appropriate or necessary, such as for specific oversight of Development,
Manufacturing, Commercialization or intellectual property issues relating to the
Co-Co Licensed Product for which such PJSC is responsible. Each such project
team created by a PJSC shall report to such PJSC, which shall have authority to
approve or reject recommendations or actions proposed by such project team,
subject to these Co-Co License Terms. For the avoidance of doubt, the same
representatives from each Party may serve on the project team for more than one
Co-Co Licensed Product. Each Party will designate an alliance manager for each
Co-Co Licensed Product (each, a “CLP Alliance Manager”) to serve as a primary
point of contact for the other Party with respect to all activities under the
CLP Collaboration related to such Co-Co Licensed Product. Each CLP Alliance
Manager’s responsibilities shall include (a) scheduling meetings of the PJSC at
least once per Calendar Quarter, but more frequently if the PJSC determines it
necessary; (b) setting agendas for PJSC meetings with solicited input from the
CLP Alliance Manager for the other Party and other members of the PJSC; and
(c) coordinating the delivery of draft minutes to the PJSC for review and final
approval. Beginning with Alnylam’s CLP Alliance Manager, such responsibilities
shall alternate between the CLP Alliance Managers from each Party on a
meeting-by-meeting basis after each meeting of the applicable committee. Each
Party may change any of its CLP Alliance Managers at any time in its sole
discretion with written notice to the other Party, provided that each CLP
Alliance Manager will be individually identified at all times and will have such
experience, authority, responsibility and accountability as is reasonably
sufficient to enable such person to fulfill his or her responsibilities as a CLP
Alliance Manager under these Co-Co License Terms on behalf of the applicable
Party.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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5.3. PJSC Meetings. Each PJSC shall meet in accordance with a schedule
established by mutual written agreement of the Parties, but no less frequently
than once per Calendar Quarter during the Term, with the location for such
meetings alternating between Alnylam and Genzyme facilities (or such other
locations as are mutually agreed by the Parties). Alternatively, a PJSC may meet
by means of teleconference, videoconference or other similar communications
equipment, but at least two (2) meetings of such PJSC per Calendar Year shall be
conducted in person. All proceedings for each PJSC shall take place in English.
Where the membership of a PJSC for a Co-Co Licensed Product is the same as one
or more other PJSCs for the other Co-Co Licensed Product, such PJSCs may have a
single meeting to discuss each Co-Co Licensed Product for which they have
responsibility. Each Party shall bear its own expenses relating to attendance at
such meetings by its representatives.

5.4. PJSC Minutes. A CLP Alliance Manager shall be appointed secretary for each
meeting of each PJSC and shall prepare minutes of the meeting, which shall
provide a description in reasonable detail of the discussions held at the
meeting and a list of any actions, decisions or determinations approved by such
PJSC. Within [***] days after each meeting, the drafting CLP Alliance Manager
shall provide the draft minutes to the other CLP Alliance Manager for review and
comment. The drafting CLP Alliance Manager shall reasonably consider all
comments from the other CLP Alliance Manager within [***] days. The drafting CLP
Alliance Manager shall prepare and submit revised minutes for approval within
[***] days after receipt of such comments or upon expiration of such [***] day
period.

5.5. PJSC Development Responsibilities. Each PJSC shall have the following
responsibilities with respect to the Development of the Co-Co Licensed Product
for which it is responsible:

5.5.1. reviewing, commenting on and approving updates and amendments to the
Global Development Strategy for such Co-Co Licensed Product in accordance with
Section 2.2.2.3 (Managing and Amending Global Development Plans and Global
Development Budgets);

5.5.2. reviewing, commenting on and approving updates and amendments to the
Global Development Plan for such Co-Co Licensed Product in accordance with
Section 2.2.2.3 (Managing and Amending Global Development Plans and Global
Development Budgets);

5.5.3. monitoring the implementation of the Global Development Plan for such
Co-Co Licensed Product, including the Global Development Activities set forth in
such Global Development Plan;

5.5.4. reviewing, commenting on and approving the design of any Phase III Study
for such Co-Co Licensed Product;

5.5.5. monitoring any Clinical Study included in such Global Development
Activities (a “Global Clinical Study”) performed by a CRO retained by a Party to
perform such Global Clinical Study, against the criteria and timelines in such
Global Development Plan;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

5.5.6. reviewing, commenting on and approving the initial Genzyme Territory
Development Plan for such Co-Co Licensed Product in accordance with
Section 2.2.3 (Genzyme Territory Development Plan);

5.5.7. reviewing, commenting on and approving updates and amendments to the
Genzyme Territory Development Plan in accordance with Section 2.2.3 (Genzyme
Territory Development Plan), and providing Genzyme with feedback regarding the
same;

5.5.8. reviewing and discussing updates provided by each Party regarding the
Development of such Co-Co Licensed Product in either Territory in accordance
with Section 2.5.1 (Development Activities Reports), and providing each Party
with feedback regarding the same;

5.5.9. monitoring and coordinating Development activities in the Genzyme
Territory and the Co-Co Territory for such Co-Co Licensed Product, and
regulatory and pharmacovigilance requirements and matters;

5.5.10. reviewing and discussing updates provided by each Party regarding any
Global Development Activities in accordance with the Global Development Plan for
such Co-Co Licensed Product (including the Global Development Budget);

5.5.11. overseeing any manufacturing and supply relationship between the Parties
with respect to the Manufacture of such Co-Co Licensed Product for Development
activities (subject to the provisions of the CLP Clinical Supply Agreement);

5.5.12. approving a global list of clinical sites for each Global Clinical Study
for such Co-Co Licensed Product;

5.5.13. approving the appointment of the global CRO to manage any Phase II Study
or Phase III Study for such Co-Co Licensed Product; and

5.5.14. performing such other activities as the Parties agree in writing shall
be the responsibility of such PJSC or that are otherwise assigned to such PJSC
under these Co-Co License Terms.

5.6. PJSC Commercialization Responsibilities. Each PJSC shall have the following
responsibilities with respect to the Commercialization of the Co-Co Licensed
Product for which it is responsible, to the extent permissible under applicable
Laws:

5.6.1. reviewing, commenting on and approving updates and amendments to the
Global Commercial Strategy for such Co-Co Licensed Product in accordance with
Section 4.1.1 (Global Commercial Strategy);

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

5.6.2. reviewing and discussing reports and information provided by each Party
regarding the Commercialization of such Co-Co Licensed Product in both
Territories in accordance with Section 4.5 (Commercialization Reporting
Obligations);

5.6.3. reviewing, commenting on and approving any Global Branding Strategy
developed by Alnylam for such Co-Co Licensed Product in accordance with
Section 4.4.1 (Global Branding);

5.6.4. reviewing, commenting on and approving the Genzyme Territory
Commercialization Plan for such Co-Co Licensed Product and updates thereto
provided by Genzyme to the extent provided in Section 4.3 (Genzyme Territory
Commercialization Plan);

5.6.5. reviewing, commenting on and approving the Co-Co Territory
Commercialization Plan for such Co-Co Licensed Product and updates thereto
provided by Genzyme to the extent provided in Section 4.2 (Co-Co Territory
Commercialization Plan);

5.6.6. reviewing, commenting on and discussing Promotional Material for such
Co-Co Licensed Product of both Parties in accordance with Sections 4.4.2
(Alnylam A&P) and 4.4.3 (Genzyme A&P);

5.6.7. providing a forum for the Parties to discuss the Commercialization of
such Co-Co Licensed Product in the Field worldwide, including coordination
regarding Co-Co Licensed Product positioning and messaging, key opinion leader
relationship management, medical affairs, and marketing and selling materials;

5.6.8. providing a forum for the Parties to discuss collaborating on commercial
activities with respect to such Co-Co Licensed Product that can be leveraged for
both Territories and how the Parties would share the costs of such mutually
agreed joint Commercialization activities;

5.6.9. overseeing any manufacturing and supply relationship between the Parties
with respect to the Manufacture of such Co-Co Licensed Product for
Commercialization activities (subject to the provisions of the CLP Commercial
Supply Agreement); and

5.6.10. performing such other activities as the Parties agree in writing shall
be the responsibility of such PJSC or that are otherwise assigned to such PJSC
under these Co-Co License Terms.

5.7. PJSC Decision-Making.

5.7.1. PJSC Decisions. With respect to decisions of each PJSC, the
representatives of each Party on such PJSC shall have collectively one vote on
behalf of such Party. For each meeting of a PJSC, at least two
(2) representatives of each Party shall constitute a quorum. Action on any
matter may be taken at a meeting, by teleconference, videoconference or by
written agreement. Each PJSC shall attempt to resolve any and all disputes
before it for decision by consensus. [***]. For the avoidance of doubt, the
phrase “approval by the PJSC” and similar phrases used in these Co-Co License
Terms shall mean approval in accordance with this Section 5.7 (PJSC
Decision-Making), including [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

5.7.2. Escalation. If a PJSC is unable to reach a consensus with respect to any
dispute for a period in excess of [***] days, then the dispute shall be
submitted to the AJSC (as defined in the Master Agreement) at a meeting or
meetings (whether in-person or by teleconference or videoconference). During
such meeting(s), each Party shall provide analysis to support its position with
respect to such dispute. If the dispute is still unresolved after a further
[***] days, such dispute shall be [***].

5.7.3. [***]. If a PJSC dispute cannot be resolved under Section 5.7.2
(Escalation), then, subject to Sections 5.7.4 ([***]) and 5.7.5 (No Deciding
Vote):

5.7.3.1. [***]

5.7.3.2. [***]

5.7.3.3. [***]

[***]

5.7.4. [***]

5.7.4.1. [***]r

5.7.4.2. [***]

[***]

5.7.5. [***]

5.7.5.1. [***]

5.7.5.2. [***]

5.7.5.3. [***]

5.7.5.4. [***]

5.7.5.5. [***]

5.8. Term of PJSC. With respect to each Co-Co Licensed Product, after the [***]
of the Implementation Date for such Co-Co Licensed Product, Alnylam shall have
the right, but not the obligation, to continue its participation on the PJSC
responsible for such Co-Co Licensed Product.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

6. MANUFACTURE AND SUPPLY OF CO-CO LICENSED PRODUCTS

6.1. Supply Agreements. The Manufacturing of each Co-Co Licensed Product,
including ALN-TTRsc, will be addressed in the Master Agreement and breach of
such Manufacturing terms as applied to a Co-Co Licensed Product shall be treated
as a breach under this Agreement, and not under the Master Agreement.

7. LICENSES

7.1. License Grants to Genzyme.

7.1.1. Development License. On a Co-Co Licensed Product-by-Co-Co Licensed
Product basis, subject to the provisions of these Co-Co License Terms (including
Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Clinical Supply
Agreement, effective upon the Implementation Date for such Co-Co Licensed
Product, Alnylam hereby grants Genzyme (i) a non-transferable (except as
provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam)
license under Alnylam Technology to Develop such Co-Co Licensed Product in the
Field in the Genzyme Territory and Co-Co Territory, in each case (x) solely as
and to the extent provided in any approved Genzyme Territory Development Plan or
any Global Development Plan and (y) solely for Regulatory Approval and
Commercialization in the Genzyme Territory; and (ii) a non-transferable,
non-sublicensable, co-exclusive (with Alnylam) license under Alnylam Technology
to Develop such Co-Co Licensed Product in the Field for Regulatory Approval and
Commercialization in the Co-Co Territory, solely as and to the extent provided
in any approved Global Development Plan. Notwithstanding the foregoing:
(a) Alnylam retains the right under the Alnylam Technology to Develop each Co-Co
Licensed Product in the Field anywhere in the world for Regulatory Approval and
Commercialization by Genzyme in the Genzyme Territory, in accordance with the
Global Development Plan for such Co-Co Licensed Product and (b) Alnylam retains
the co-exclusive right (with Genzyme) under the Alnylam Technology to Develop
such Co-Co Licensed Product anywhere in the world for Commercialization in the
Co-Co Territory.

7.1.2. Commercialization License. On a Co-Co Licensed Product-by-Co-Co Licensed
Product basis, subject to the provisions of these Co-Co License Terms (including
Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Commercial Supply
Agreement, effective upon the Implementation Date for such Co-Co Licensed
Product, Alnylam hereby grants Genzyme (i) a non-transferable (except as
provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable
(subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam)
license under Alnylam Technology to Commercialize such Co-Co Licensed Products
in the Field in the Genzyme Territory and (ii) a non-transferable,
non-sublicensable, co-exclusive (with Alnylam) license under Alnylam Technology
to Commercialize such Co-Co Licensed Product in the Field in the Co-Co
Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

The license granted under the foregoing clause (i) shall be royalty-bearing for
the Royalty Term applicable to each Co-Co Licensed Product in each country in
the Genzyme Territory, and, after the Royalty Term applicable to such Co-Co
Licensed Product in such country, shall convert to a fully-paid, exclusive,
perpetual license to Commercialize such Co-Co Licensed Product in the Field in
such country in the Genzyme Territory.

7.1.3. Manufacturing Licenses. On a Co-Co Licensed Product-by-Co-Co Licensed
Product basis, subject to the provisions of these Co-Co License Terms (including
Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Clinical Supply
Agreement and Co-Co Commercial Supply Agreement, effective upon the
Implementation Date for such Co-Co Licensed Product, Alnylam hereby grants
Genzyme (i) a non-transferable (except as provided in Section 13.1 of the Master
Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing
Terms)), worldwide, non-exclusive license under Alnylam Technology to
Manufacture such Co-Co Licensed Product inside or outside the Genzyme Territory
solely for Development or Commercialization in the Genzyme Territory and, to the
extent permitted pursuant to Section 2.3.2 (Genzyme Development), for
Development in the Co-Co Territory for the purpose of obtaining Regulatory
Approval and Commercialization in the Genzyme Territory and (ii) a
non-transferable, non-sublicensable, non-exclusive license under Alnylam
Technology to Manufacture such Co-Co Licensed Product inside or outside the
Genzyme Territory for Development and Commercialization in the Co-Co Territory
solely as and to the extent required for Genzyme to act as a second source
Manufacturer as described in Section 6 of the Master Agreement (Manufacture and
Supply of the Collaboration Products) or to Manufacture Co-Co Licensed Products
on the terms and conditions set forth in the Co-Co Supply Agreements.
Notwithstanding the foregoing exclusive license: Alnylam retains the exclusive
right under the Alnylam Technology, with the right to grant licenses through
multiple tiers without restriction, to Manufacture Co-Co Licensed Products
anywhere in the world (a) for Development and Commercialization in the Co-Co
Territory and, to the extent permitted pursuant to Section 2 (Development
Collaboration) for Development in the Genzyme Territory, and (b) to supply
Genzyme pursuant to the Co-Co Supply Agreements to be agreed by the Parties
pursuant to Section 6.1 (Supply Agreements).

7.1.4. Sublicensing Terms.

(a) Genzyme shall have the right to sublicense any of its rights under
(i) Section 7.1.1 (Development License), (ii) the license granted in clause
(i) (but not clause (ii)) of Section 7.1.2 (Commercialization License), and
(iii) Section 7.1.3 (Manufacturing License) to any of its Affiliates or to any
Third Party (which sublicensed rights may be further sublicensable through
multiple tiers) without the prior consent of Alnylam, subject to the
requirements of this Section 7.1.4. [***]

(b) Each sublicense granted by Genzyme pursuant to this Section 7.1.4 shall be
subject and subordinate to the provisions of these Co-Co License Terms and shall
contain terms and conditions consistent with those in these Co-Co License Terms.
Genzyme shall promptly provide Alnylam with a copy of the fully executed
sublicense

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

agreement covering any sublicense granted hereunder (which copy may be redacted
to remove terms and conditions which are not necessary to monitor compliance
with this Section 7.1.4), and each such sublicense agreement shall contain the
following provisions: (i) a requirement that the Sublicensee comply with the
confidentiality and non-use provisions of Section 7 of the Master Agreement
(Confidentiality and Publication) with respect to Alnylam’s Confidential
Information; (ii) if such sublicense agreement contains a sublicense of Co-Co
Licensed Product Commercialization rights, such sublicense agreement shall also
contain the following provisions: (x) a requirement that the Sublicensee submit
applicable sales or other reports to Genzyme to the extent necessary or relevant
to the reports required to be made or records required to be maintained under
these Co-Co License Terms; and (y) the audit requirement set forth in
Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the
Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the terms of any sublicense
by any Genzyme Sublicensee, compliance with which is necessary for Genzyme’s
compliance with the provisions of these Co-Co License Terms, Genzyme shall
promptly notify Alnylam of the particulars of the same and use Commercially
Reasonable Efforts to cause the Sublicensee to comply with all the terms of the
sublicense necessary for Genzyme’s compliance with the provisions of these Co-Co
License Terms. [***] Notwithstanding any sublicense, Genzyme shall remain
primarily liable to Alnylam for the performance of all of Genzyme’s obligations
under, and Genzyme’s compliance with all provisions of, these Co-Co License
Terms.

7.1.5. Back-Up Products. Subject to Sections 13.2 (Future Acquisition of a Party
or its Business), 13.3.1 (Acquired Programs) and 13.3.2 (Acquired Programs),
Alnylam hereby grants to Genzyme a series of exclusive options (each, a “Back-Up
Option”), under each of which Genzyme shall have the right, but not the
obligation, to take a license on the terms set forth in these Co-Co License
Terms, to any siRNA that targets the same Licensed Target as a Co-Co Licensed
Product (a “Back-Up Product”) and for which Alnylam has determined the GLP
toxicology studies will be conducted during the Back-Up Option Period. Genzyme
may exercise the Back-Up Option with respect to such Back-Up Product by
delivering written notice to Alnylam at any time during the Back-Up Option
Period (the “Back-Up Option Exercise Notice”). Upon delivery of the Back-Up
Option Exercise Notice to Alnylam, the applicable Back-Up Product shall
automatically be deemed to be a Co-Co Licensed Product for all purposes under
the Collaboration Agreement and the license from Alnylam to Genzyme for such
Co-Co Licensed Product shall automatically, with no further action by any Party,
go into full force and effect and all obligations of Alnylam and Genzyme set
forth in these Co-Co License Terms, including the payment obligations set forth
herein, shall become the binding obligations of the applicable Party in respect
of such Co-Co Licensed Product. Upon the expiration of the Back-Up Option
Period, all Back-Up Options not previously exercised shall automatically
terminate.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

7.2. License Grants to Alnylam.

7.2.1. Commercialization License in the Co-Co Territory. Genzyme hereby grants
Alnylam a non-transferable (except as provided in Section 13.1 of the Master
Agreement (Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing
Terms)), non-exclusive, royalty-free license under Genzyme Collaboration IP to
Develop and Commercialize Co-Co Licensed Products in the Field in the Co-Co
Territory.

7.2.2. License to Improvement Manufacturing Patent Rights. Subject to the
provisions of these Co-Co License Terms, Genzyme hereby grants Alnylam a
non-transferable (except as provided in Section 13.1 of the Master Agreement
(Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing Terms)),
worldwide, non-exclusive license under the Improvement Manufacturing Patent
Rights, to Manufacture (a) Alnylam Developed siRNA Products targeting any human
gene; and (b) Co-Co Licensed Products for Commercialization in the Co-Co
Territory, Development in either the Co-Co Territory or Genzyme Territory in
accordance with the Global Development Plan for such Co-Co Licensed Product, and
for sale to Genzyme under any Co-Co Clinical Supply Agreement or Co-Co
Commercial Supply Agreement.

7.2.3. License to Genzyme Disclosed Manufacturing Know-How. Subject to the
provisions of these Co-Co License Terms, Genzyme hereby grants Alnylam a
non-transferable (except as provided in Section 13.1 of the Master Agreement
(Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing Terms)),
worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing
Know-How to Manufacture Co-Co Licensed Products for Commercialization in the
Co-Co Territory, Development in either the Co-Co Territory or Genzyme Territory
in accordance with the Global Development Plan for such Co-Co Licensed Product,
and for sale to Genzyme under any Co-Co Clinical Supply Agreement or Co-Co
Commercial Supply Agreement.

7.2.4. Sublicensing Terms.

(a) Alnylam shall have the right to sublicense any of its rights under
Section 7.2.1 (Commercialization License in the Co-Co Territory), 7.2.2 (License
to Improvement Manufacturing Patent Rights) and 7.2.3 (License to Genzyme
Disclosed Manufacturing Know-How) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 7.2.4 shall be
subject and subordinate to the provisions of these Co-Co License Terms and shall
contain terms and conditions consistent with those in these Co-Co License Terms.
Alnylam shall promptly provide Genzyme with a copy of the fully executed
sublicense agreement covering any sublicense granted hereunder (which copy may
be redacted to remove terms and conditions which are not necessary to monitor
compliance with this Section 7.2.4), and each such sublicense agreement shall
contain the following provisions: (i) a requirement that the Sublicensee comply
with the confidentiality and non-use provisions of Section 7 of the Master
Agreement (Confidentiality and Publication) with respect to Genzyme’s
Confidential Information and (ii) a requirement that the Sublicensee comply with
the applicable provisions under any Genzyme In-License.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

(c) If Alnylam becomes aware of a material breach of any sublicense by any
Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance
with the provisions of these Co-Co License Terms, Alnylam shall promptly notify
Genzyme of the particulars of the same and use Commercially Reasonable Efforts
to cause the Sublicensee to comply with all the terms of the sublicense
necessary for Alnylam’s compliance with the provisions of these Co-Co License
Terms. [***] Notwithstanding any sublicense, Alnylam shall remain primarily
liable to Genzyme for the performance of all of Alnylam’s obligations under, and
Alnylam’s compliance with all terms and conditions of, these Co-Co License
Terms.

7.3. Joint Collaboration IP. Subject to the rights and licenses granted to, and
the obligations (including royalty obligations) of, each Party under these Co-Co
License Terms, either Party is entitled to practice Joint Collaboration IP for
all purposes on a worldwide basis and license Joint Collaboration IP without
consent of and without a duty of accounting to the other Party. Each Party will
grant and hereby does grant all permissions, consents and waivers with respect
to, and all licenses under, the Joint Collaboration IP, throughout the world,
necessary to provide the other Party with such rights of use and exploitation of
the Joint Collaboration IP, and will execute documents as necessary to
accomplish the foregoing.

7.4. In-Licenses.

All licenses and other rights granted to Genzyme under this Section 7 are
subject to the rights and obligations of Alnylam under the Alnylam In-Licenses.
All licenses and other rights granted to Alnylam under this Section 7 are
subject to the rights and obligations of Genzyme under the Genzyme In-Licenses.
Each Party shall comply with all applicable terms and conditions of the
In-Licenses, and shall perform and take such actions as may be required to allow
the Party that is party to such In-License to comply with its obligations
thereunder, including obligations relating to sublicensing, patent matters,
confidentiality, reporting, audit rights, indemnification and diligence. Without
limiting the foregoing, each Party shall prepare and deliver to the other Party
any additional reports required under the applicable In-Licenses and requested
by such other Party, in each case sufficiently in advance to enable the Party
that is party to such In-License to comply with its obligations under the
applicable In-Licenses. Each Party agrees, upon the other Party’s request, to
provide the other Party with copies of any In-Licenses to which it is a party.
Confidential Information of the providing Party or its counterparty may be
redacted from such copies, except to the extent that such information is
required in order to enable the other Party to comply with its obligations to
the providing Party under these Co-Co License Terms with respect to such
In-License or in order to enable the providing Party to ascertain compliance
with the provisions of these Co-Co License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

7.5. Bankruptcy. All rights and licenses granted under or pursuant to these
Co-Co License Terms by a Party to the other, including those set forth in
Sections 7.1 (License Grants to Genzyme), 7.2 (License Grants to Alnylam), and
3.5 (Right of Reference), are and shall otherwise be deemed to be, for purposes
of Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to
“intellectual property” as defined under Section 101 of the U.S. Bankruptcy
Code. The Parties agree that the Parties and their respective Sublicensees, as
sublicensees of such rights under these Co-Co License Terms, shall retain and
may fully exercise all of their rights and elections under the U.S. Bankruptcy
Code and any foreign counterpart thereto. The Parties further agree that upon
commencement of a bankruptcy proceeding by or against a Party (the “Bankrupt
Party”) under the Bankruptcy Code, the other Party (the “Non-Bankrupt Party”)
will be entitled to a complete duplicate of, or complete access to (as the
Non-Bankrupt Party deems appropriate), all such intellectual property and all
embodiments of such intellectual property. Such intellectual property and all
embodiments of such intellectual property will be promptly delivered to the
Non-Bankrupt Party (a) upon any such commencement of a bankruptcy proceeding and
upon written request by the Non-Bankrupt Party, unless the Bankrupt Party elects
to continue to perform all of its obligations under these Co-Co License Terms,
or (b) if not delivered under (a) above, upon the rejection of these Co-Co
License Terms by or on behalf of the Bankrupt Party and upon written request by
the Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to
Genzyme a right of access to and to obtain possession of (i) copies of research
data, (ii) laboratory samples, (iii) samples of Co-Co Licensed Product,
(iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related
to clinical trials, (vii) regulatory filings and approvals, (viii) rights of
reference in respect of regulatory filings and approvals, (ix) pre-clinical
research data and results, and (x) marketing, advertising and promotional
materials, all of which (in clauses (i) through (x)) constitute “embodiments” of
intellectual property pursuant to Section 365(n) of the Bankruptcy Code and
(xi) all other embodiments of such intellectual property, and in respect of each
of the foregoing clauses (i) through (xi), solely for the purpose of the
exercise of Genzyme’s rights and licenses under these Co-Co License Terms,
whether any of the foregoing are in Alnylam’s possession or control or in the
possession and control of Third Parties. The Bankrupt Party (in any capacity,
including debtor-in-possession) and its successors and assigns (including any
trustee) agree not to interfere with the exercise by the Non-Bankrupt Party or
its Related Parties of its rights and licenses to such intellectual property and
such embodiments of intellectual property in accordance with these Co-Co License
Terms, and agrees to assist the Non-Bankrupt Party and its Related Parties in
obtaining such intellectual property and such embodiments of intellectual
property in the possession or control of Third Parties as are reasonably
necessary or desirable for the Non-Bankrupt Party to exercise such rights and
licenses in accordance with these Co-Co License Terms. The foregoing provisions
are without prejudice to any rights the Non-Bankrupt Party may have arising
under the Bankruptcy Code or other Laws.

7.6. No Other Rights. Except as otherwise expressly provided in these Co-Co
License Terms, under no circumstances shall a Party, as a result of these Co-Co
License Terms, obtain any ownership interest or other right in any Know-How,
Patent Rights or other intellectual property rights of the other Party,
including items owned, controlled or developed by the other Party, or provided
by the other Party to the receiving Party at any time pursuant to these Co-Co
License Terms.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

8. FINANCIAL TERMS FOR GENZYME TERRITORY

8.1. Development Milestone Fees. Genzyme shall provide Alnylam with written
notice of the achievement by Genzyme or any of its Related Parties of any
development milestone event set forth below in this Section 8.1 and Alnylam
shall provide Genzyme with written notice of the achievement by Alnylam or any
of its Related Parties of any development milestone event set forth below in
this Section 8.1, in each case within [***] days after such event has occurred;
provided, however, that the notifying Party shall inform the other Party of such
event prior to any public disclosure of such event by the notifying Party.
Alnylam shall invoice Genzyme within [***] days of receipt of such written
notice by either Party, and Genzyme shall remit the associated development
milestone payment within [***] days of the receipt of such invoice. Each
development milestone payment by Genzyme to Alnylam hereunder shall be payable
only once with respect to each Co-Co Licensed Product, regardless of the number
of times a development milestone event is achieved with respect to such Co-Co
Licensed Product.

8.1.1. Development Milestones for ALN-TTRsc. Genzyme shall pay Alnylam the
following amounts upon achievement of the following development milestone events
with respect to ALN-TTRsc:

 

Development Milestone Event

   Development Milestone Payment  

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

8.1.2. Development Milestones for ALN-AT3. Genzyme shall pay Alnylam the
following amounts upon achievement of the following development milestone events
with respect to ALN-AT3:

 

Development Milestone Event

   Development Milestone Payment  

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

8.2. Royalties.

8.2.1. Royalties Payable on Co-Co Licensed Products. Subject to the provisions
these Co-Co License Terms, Genzyme shall pay to Alnylam royalties on annual Net
Sales by Genzyme and its Related Parties of each Co-Co Licensed Product in the
Genzyme Territory, as follows:

 

Calendar Year

Net Sales of a Co-Co Licensed Product in

the Genzyme Territory

   Royalty
(as a percentage of Net Sales of such Co-Co
Licensed Product)  

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

     [***]   

[***]

[***]

Royalties on annual Net Sales of a Co-Co Licensed Product shall be paid at the
rate applicable to the portion of Net Sales within each of the Net Sales levels
above during such Calendar Year.

8.2.2. Royalty Term. Subject to Section 8.2.6 (Royalty Floor), the period during
which the royalties set forth in Section 8.2.1 (Royalties Payable on Co-Co
Licensed Products) shall be payable, on a Co-Co Licensed Product-by-Co-Co
Licensed Product and country-by-country basis, shall commence with the First
Commercial Sale of a Co-Co Licensed Product in a country and continue until the
latest of (a) the expiration of the last Valid Claim of [***] in the country of
sale; (b) the expiration of Regulatory Exclusivity for such Co-Co Licensed
Product in such country; or (c) subject to the last sentence of this
Section 8.2.2, the [***] anniversary of the First Commercial Sale of such Co-Co
Licensed Product in such country (each such period, a “Royalty Term”). [***].

8.2.3. Third Party Royalty Offsets. Genzyme shall be permitted to reduce any
royalties payable under Section 8.2.1 (Royalties Payable on Co-Co Licensed
Products) for a Co-Co Licensed Product by [***].

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

8.2.4. [***].

8.2.5. [***].

8.2.6. Royalty Floor. Anything in these Co-Co License Terms to the contrary
notwithstanding, in no event during the applicable Royalty Term for a Co-Co
Licensed Product in a country of the Genzyme Territory shall the royalties
payable to Alnylam hereunder for such Co-Co Licensed Product in such country for
any Calendar Quarter be reduced [***] In-Licenses).

8.2.7. Validation Information. At Genzyme’s request, Alnylam will provide
Genzyme with such information as Genzyme may reasonably request to validate the
amount of the royalty floor described in Section 8.2.6 (Royalty Floor).

9. FINANCIAL TERMS FOR CO-CO TERRITORY

9.1. [***].

9.2. Third Party License Payments Paid By Genzyme. Genzyme shall provide Alnylam
with written notice of any Third Party License Payments made by Genzyme with
respect to a Co-Co Licensed Product in the Co-Co Territory. [***].

10. REPRESENTATIONS, WARRANTIES AND COVENANTS

10.1. Representations and Warranties of Alnylam. Except as provided in the
Disclosure Schedule to this Section 10.1 (which Disclosure Schedule with respect
to ALN-TTRsc is attached hereto as Schedule 10.1-1 and with respect to ALN-AT3
will be provided by Alnylam to Genzyme as part of the Option Data Package for
ALN-AT3), Alnylam represents and warrants to Genzyme that, with respect to
ALN-AT3, as of the Implementation Date, and, with respect to ALN-TTRsc, as of
the Execution Date:

10.1.1. Alnylam is the sole and exclusive owner of, or otherwise Controls
pursuant to an Alnylam In-License, the Alnylam Technology, and all of the
Alnylam Technology licensed to Genzyme hereunder in the Genzyme Territory and
the Co-Co Territory that is solely and exclusively owned by Alnylam is free and
clear of liens, charges or encumbrances other than licenses granted to Third
Parties that are not inconsistent with the rights and licenses granted to
Genzyme under these Co-Co License Terms.

10.1.2. Alnylam has sufficient legal and/or beneficial title and ownership of,
or sufficient license rights under, the Alnylam Technology to grant the licenses
to such Alnylam Technology granted to Genzyme pursuant to these Co-Co License
Terms.

10.1.3. (a) Schedule 1.2.14 and Schedule 1.2.19 collectively set forth a
complete and accurate list of the Alnylam Patents owned, either solely or
jointly, by Alnylam, and to Alnylam’s knowledge, Schedule 1.2.14 and Schedule
1.2.19 collectively set forth a complete and accurate list of the Alnylam
Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to
Alnylam’s knowledge, each issued Alnylam Patent remains in full force and effect
and

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

(c) Alnylam or its Affiliates have timely paid all filing and renewal fees
payable with respect to such Alnylam Patents for which Alnylam controls
prosecution and maintenance. Schedule 1.2.14 and Schedule 1.2.19 indicate
whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by
Alnylam and one or more Third Parties, or is licensed to Alnylam. For each
Alnylam Patent that is owned, but not owned exclusively, by Alnylam, or that is
licensed to Alnylam, Schedule 1.2.14 and Schedule 1.2.19 identify the Third
Party owner(s) and, if applicable, the Alnylam In-License pursuant to which
Alnylam Controls such Alnylam Patent. For each Alnylam Product-Specific Patent
that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.19
indicates the non-exclusive nature of the license. For each Alnylam Core
Technology Patent family (other than Patent Rights licensed from Isis
Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to
Alnylam, Schedule 1.2.14 indicates the non-exclusive nature of the license.
Alnylam is the sole and exclusive owner of all Patent Rights identified in
Schedule 1.2.14 and Schedule 1.2.19 as being owned exclusively by Alnylam and
Controls all other Patent Rights identified on such schedules.

10.1.4. To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or,
upon issuance, will be, valid and enforceable patents and no Third Party has
challenged or threatened to challenge the scope, validity or enforceability of
any Alnylam Product-Specific Patent (including, by way of example, through
opposition or the institution or written threat of institution of interference,
nullity or similar invalidity proceedings before the United States Patent and
Trademark Office or any analogous foreign Governmental Authority).

10.1.5. Alnylam has complied with all applicable Laws, including any duties of
candor to applicable patent offices, in connection with the filing, prosecution
and maintenance of the Alnylam Patent Rights.

10.1.6. Alnylam owns or Controls all Know-How that is or has been used by
Alnylam in the Development and Manufacture of such Co-Co Licensed Product, and
has sufficient legal or beneficial title and ownership of, or sufficient license
rights under such Know-How to transfer Know-How to Genzyme as provided in
Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

10.1.7. Alnylam Controls all Know-How and Patent Rights licensed to Alnylam
under the Existing Alnylam In-Licenses that is necessary or useful for Genzyme
to Develop, Manufacture and/or Commercialize such Co-Co Licensed Product in the
Field in the Genzyme Territory and the Co-Co Territory. Without limiting the
generality of the foregoing, Alnylam has obtained all necessary consents and
fulfilled all necessary conditions, if any, to sublicense to Genzyme under these
Co-Co License Terms such Know-How and Patent Rights licensed to Alnylam under
Existing Alnylam In-Licenses.

10.1.8. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach
or default under any existing Alnylam In-License, and neither Alnylam nor its
Affiliates have received any written notice of breach or default with respect to
any existing Alnylam In-License.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

10.1.9. Alnylam has obtained from all inventors of Alnylam Technology owned by
Alnylam valid and enforceable agreements assigning to Alnylam each such
inventor’s entire right, title and interest in and to all such Alnylam
Technology.

10.1.10. To Alnylam’s knowledge, the use, Development, Manufacture or
Commercialization by Alnylam or Genzyme (or their respective Related Parties) of
such Co-Co Licensed Product as formulated and manufactured as of the Effective
Date, or as intended to be formulated and manufactured as of the Effective Date
(a) does not and will not infringe any issued patent of any Third Party and
(b) will not infringe the claims of any published Third Party patent application
when and if such claims were to issue in their current form.

10.1.11. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry,
investigation or other legal action of any nature, civil, criminal, regulatory
or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or
any of its Affiliates or (b) judgment or settlement against or owed by Alnylam
or any of its Affiliates, in each case in connection with the Alnylam Technology
or such Co-Co Licensed Product.

10.1.12. For each Co-Co Licensed Product, other than ALN-TTRsc, Schedule
10.1.12(a) (Existing Alnylam In-Licenses) sets forth a complete and accurate
list of all agreements between Alnylam and a Third Party entered into prior to
the Implementation Date for a Co-Co Licensed Product pursuant to which Alnylam
Controls Know-How or Patent Rights that are necessary or useful to Develop,
Manufacture or Commercialize such Co-Co Licensed Product in the Field other than
Additional Alnylam In-Licenses. [***]. For the sake of clarity, representations
and warranties similar to those made pursuant to this Section 10.1.12 with
respect to Regional Licensed Products other than ALN-TTRsc are made with respect
to ALN-TTRsc in the Master Agreement.

10.2. Representations and Warranties of Genzyme. Except as disclosed in
Genzyme’s Option Exercise Notice for a Co-Co Licensed Product, Genzyme
represents and warrants to Alnylam as of the Implementation Date that it is not
a party to any agreement with a Third Party under which it Controls Know-How or
Patent Rights that are sublicensed to Alnylam under these Co-Co License Terms
with respect to such Co-Co Licensed Product.

10.3. Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE CO-CO
LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF
ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY
TECHNOLOGY, CO-CO LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT
MATTER OF THESE CO-CO LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES
OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH
RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY
REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR
COMMERCIALIZATION OF ANY CO-CO LICENSED PRODUCT PURSUANT TO THESE CO-CO LICENSE
TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY
CO-CO LICENSED PRODUCT WILL BE ACHIEVED.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

10.4. Certain Covenants.

10.4.1. [***].

10.4.1.1. [***]

 

  (i) [***]

 

  (ii) [***]

 

  (iii) [***]

10.4.1.2. [***]

 

  (i) [***]

 

  (ii) [***]

 

  (iii) [***]

10.4.1.3. [***]

 

  (i) [***]

 

  (ii) [***]

 

  (iii) [***]

10.4.1.4. [***]

10.4.2. No Third Party Collaboration Agreements in the Co-Co Territory. During
the Term, Alnylam shall not enter into any agreement with any Third Party
granting it rights to Develop or Commercialize any Co-Co Licensed Product in the
Field in any portion of the Co-Co Territory except for the benefit, and at the
direction, of Alnylam.

10.4.3. Compliance. Each Party and its Related Parties shall conduct the Co-Co
Collaboration and the Development, Manufacture and Commercialization of the
Co-Co Licensed Products in accordance with all Laws, including current
governmental regulations concerning Good Laboratory Practices (as defined in the
Master Agreement), good clinical practices and good manufacturing practices. In
addition, if either Party is or becomes subject to a legal obligation to a
Regulatory Authority or other Governmental Authority (such as a corporate
integrity agreement or settlement agreement with a Governmental Authority), then
the other Party shall perform such activities as may be reasonably requested by
the obligated Party to enable the obligated Party to comply with its legal
obligation to such Regulatory Authority with respect to the Co-Co Licensed
Products.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

10.4.4. Conflicting Transactions. During the Term, Alnylam shall not
(a) transfer or assign any of its rights, title or interests in the Alnylam
Technology other than as part of a transaction pursuant to which these Co-Co
License Terms are also assigned and assumed in accordance with Section 13.1 of
the Master Agreement (Assignment), or (b) enter into any agreement granting a
license or other right under the Alnylam Technology that is inconsistent with
the provisions of these Co-Co License Terms.

10.4.5. Governmental Authority. If any of the Alnylam Technology is subject to
any funding arrangement with any Governmental Authority, at Genzyme’s reasonable
request, Alnylam will reasonably cooperate in seeking a waiver or other
modification to such funding arrangement with respect to such Alnylam
Technology.

11. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

11.1. Inventorship. Inventorship for inventions and discoveries first made
during the course of the performance of activities pursuant to these Co-Co
License Terms shall be determined in accordance with United States patent Laws
for determining inventorship.

11.2. Ownership. Alnylam shall own the entire right, title and interest in and
to all inventions and discoveries (and Patent Rights claiming patentable
inventions therein) first made or discovered solely by employees or consultants
of Alnylam or acquired solely by Alnylam in the course of conducting the
Collaboration. Genzyme shall own the entire right, title and interest in and to
all inventions and discoveries (and Patent Rights claiming patentable inventions
therein) first made or discovered solely by employees or consultants of Genzyme
or acquired solely by Genzyme in the course of conducting the Collaboration. The
Parties shall jointly own any inventions and discoveries (and Patent Rights
claiming patentable inventions therein) first made or discovered jointly in the
course of conducting the Collaboration.

11.3. Prosecution and Maintenance of Patent Rights.

11.3.1. IP Committee. The Parties agree that the IP Committee created pursuant
to Section 5.3 of the Master Agreement (IP Committee) shall be responsible for
overseeing and effecting the information sharing and consulting provisions under
this Section 11.3.

11.3.2. Genzyme Technology.

(a) Subject to Section 11.3.2(b) below, Genzyme has the sole responsibility to,
at Genzyme’s discretion and at Genzyme’s sole cost and expense, file, prosecute,
and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Genzyme Technology (other than Joint
Collaboration IP), in Genzyme’s name.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

(b) In the event that Genzyme elects not to seek or continue to seek or maintain
patent protection on any Genzyme Collaboration IP in the Co-Co Territory,
Genzyme shall notify Alnylam at least [***] days before any such Patent Rights
would become abandoned, no longer available or otherwise forfeited, and subject
to the terms and conditions of any applicable Genzyme In-License, Alnylam shall
have the right (but not the obligation), at its sole cost and expense, to seek,
prosecute and maintain in any country patent protection on such Genzyme
Collaboration IP in the name of Genzyme. Genzyme shall use Commercially
Reasonable Efforts to make available to Alnylam its authorized attorneys, agents
or representatives, and/or such of its employees as are reasonably necessary to
assist Alnylam in obtaining and maintaining the patent protection described
under this Section 11.3.2(b). Genzyme shall sign or use Commercially Reasonable
Efforts to have signed all legal documents as are reasonably necessary to file
and prosecute such patent applications or to obtain or maintain such patents.

11.3.3. Alnylam Technology. The following will apply with respect to Alnylam
Patent Rights during the Term, [***].

(a) Subject to Section 11.3.3(c) below, Alnylam has the sole responsibility to,
at Alnylam’s discretion and at Alnylam’s sole cost and expense, file, conduct
prosecution, and maintain (including the defense of any interference or
opposition proceedings), all Patent Rights comprising Alnylam Technology (other
than Joint Collaboration IP), in Alnylam’s name. Notwithstanding the foregoing,
Alnylam shall file such Alnylam Product-Specific Patents in the Genzyme Patent
Jurisdictions (as defined in the Master Agreement) and shall use commercially
reasonable efforts to prosecute and maintain such Patent Rights in the Genzyme
Patent Jurisdictions and shall timely pay all filing and renewal fees payable
with respect thereto.

(b) Notwithstanding the foregoing Section 11.3.3(a), Alnylam shall consult with
Genzyme, including through the IP Committee, on its strategy for the
preparation, filing, prosecution, and maintenance of all Alnylam
Product-Specific Patents in the Genzyme Territory and the Co-Co Territory.
Alnylam shall furnish to Genzyme, via electronic mail or such other method as
mutually agreed by the Parties, copies of proposed filings and documents
received from outside counsel in the course of such filing, prosecution or
maintenance of and/or copies of documents filed with the relevant patent offices
with respect to Alnylam Product-Specific Patents and such other documents
directly related to the prosecution and maintenance of Alnylam Product-Specific
Patents reasonably necessary for Genzyme to exercise its rights under this
Section 11.3.3(b), and as applicable in sufficient time prior to filing such
document or making any payment due thereunder to allow for review and comment by
Genzyme and shall consider in good faith timely comments from Genzyme thereon.
Alnylam shall furnish to Genzyme, via electronic mail or such other method as
mutually agreed by the Parties, copies of documents received from outside
counsel in the course of filing, prosecution or maintenance of and/or copies of
documents filed with the relevant national patent offices with respect to the
filing, prosecution, and maintenance of Alnylam Core Technology Patents within a
reasonable period of time after the receipt and/or filing of such documents.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(c) In the event that Alnylam elects not to seek or continue to seek or maintain
patent protection on any Alnylam Product-Specific Patent in the Genzyme
Territory or the Co-Co Territory, Alnylam shall notify Genzyme at least [***]
days before any such Patent Rights would become abandoned, no longer available
or otherwise forfeited, and subject to the provisions of any applicable Alnylam
In-License, Genzyme shall have the right (but not the obligation), at its sole
cost and expense, to seek, prosecute and maintain in any country patent
protection on such Alnylam Product-Specific Patent in the Genzyme Territory. If
Genzyme exercises such right, Alnylam shall thereafter and hereby does assign
all right, title and interest in and to such Alnylam Product-Specific Patent
Rights to Genzyme. Alnylam shall use Commercially Reasonable Efforts to make
available to Genzyme its authorized attorneys, agents or representatives, and/or
such of its employees as are reasonably necessary to assist Genzyme in obtaining
and maintaining the patent protection described under this Section 11.3.3(c).
Alnylam shall sign or use Commercially Reasonable Efforts to have signed all
legal documents as are reasonably necessary to file and prosecute such patent
applications or to obtain or maintain such patents.

(d) [***]

11.3.4. Joint Collaboration IP.

(a) [***]shall have the first right to, at [***]discretion, file, prosecute and
maintain (including the defense of any interference or opposition proceedings),
all Patent Rights comprising Joint Collaboration IP, in the names of both
Alnylam and Genzyme. [***]shall consult with [***] on the filing, prosecution
and maintenance of all such Patent Rights. Each Party shall sign, or use
Commercially Reasonable Efforts to have signed, all legal documents as are
reasonably necessary to file and prosecute patent applications or to obtain or
maintain patents in respect of such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish [***], via electronic mail or such other method as
mutually agreed by the Parties, copies of documents received from outside
counsel in the course of such filing, prosecution or maintenance of Joint
Collaboration IP and/or copies of documents relevant to such preparation,
filing, prosecution, and maintenance in sufficient time prior to filing such
document or making any payment due thereunder to allow for review and comment by
[***] and shall consider in good faith timely comments from [***] thereon.
Alnylam shall furnish to[***], via electronic mail or such other method as
mutually agreed by the Parties, copies of such documents as filed in the
relevant patent offices.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(c) In the event that [***] elects not to file or continue to prosecute or
maintain patent protection on any Joint Collaboration IP, [***] shall have the
right (but not the obligation) to file, prosecute and maintain Patent Rights
comprising Joint Collaboration IP in the names of both Alnylam and Genzyme. If
Genzyme exercises such right, [***] shall use Commercially Reasonable Efforts to
make available to [***] its authorized attorneys, agents or representatives,
and/or such of its employees as are reasonably necessary to assist [***] in
obtaining and maintaining the patent protection described under this
Section 11.3.4(c). [***] shall sign or use Commercially Reasonable Efforts to
have signed all legal documents as are reasonably necessary to file and
prosecute such patent applications or to obtain or maintain such patents.

(d) The Parties shall share equally the out-of-pocket patent filing, prosecution
and maintenance expenses incurred with respect to Patent Rights comprising Joint
Collaboration IP.

11.3.5. Patent Miscellaneous. Each Party hereby agrees: (a) to make its
employees, agents and consultants reasonably available to the other Party (or to
the other Party’s authorized attorneys, agents or representatives), to the
extent reasonably necessary to enable such Party to undertake patent
prosecution; (b) to provide the other Party with copies of all material
correspondence pertaining to prosecution with the patent offices; (c) to
cooperate, if necessary and appropriate, with the other Party in gaining patent
term extensions wherever applicable to Patent Rights licensed under these Co-Co
License Terms; and (d) to endeavor in good faith to coordinate its efforts with
the other Party to minimize or avoid interference with the prosecution and
maintenance of the other Party’s patent applications.

11.3.6. [***].

11.3.6.1. [***]

11.3.6.2. [***]

11.3.6.3. [***]

11.4. Third Party Infringement.

11.4.1. Notices. Each Party shall promptly report in writing to the other Party
any (a) known or suspected infringement of any Alnylam Technology, Genzyme
Technology or Joint Collaboration IP or (b) unauthorized use or misappropriation
of any Confidential Information or Know-How of a Party by a Third Party of which
it becomes aware, in each case to the extent such infringing, unauthorized or
misappropriating activities involve, as to a Co-Co Licensed Product, a competing
product in the Field (a “Competitive Infringement”), and shall provide the other
Party with all available evidence of such infringement, unauthorized use or
misappropriation.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.4.2. Rights to Enforce.

(a) Genzyme Technology. Subject to the provisions of any In-License, Genzyme
shall have the sole and exclusive right to initiate an infringement or other
appropriate suit (an “Infringement Action”) anywhere in the world against any
Third Party as to any infringement, or suspected infringement, of any Patent
Rights, or as to any use or suspected use without proper authorization of any
Know-How comprising Genzyme Patent Rights, Genzyme Know-How or Genzyme
Collaboration IP. Genzyme will consider in good faith any request from Alnylam
to initiate an Infringement Action against any Third Party with respect to
Competitive Infringement in the Co-Co Territory of Genzyme Patent Rights,
Genzyme Know-How or Genzyme Collaboration IP licensed to Alnylam under Section 7
(Licenses); provided, however, that Genzyme shall not be required to initiate
any such Infringement Action or permit Alnylam to initiate any such Infringement
Action.

(b) Alnylam Technology.

 

  (i) Genzyme Territory. Subject to the provisions of any In-License, Genzyme
shall have the first right to initiate an Infringement Action anywhere in the
world against any Third Party with respect to any Competitive Infringement in
the Genzyme Territory of any Alnylam Product-Specific Patent, Joint
Collaboration IP or Alnylam Collaboration IP, or, with Alnylam’s prior written
consent, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam will
consider in good faith any request from Genzyme to initiate an Infringement
Action against any Third Party with respect to a Competitive Infringement in the
Genzyme Territory of any Alnylam Core Technology Patent Right or Alnylam
Know-How; provided, however, that Alnylam shall not be required to initiate any
such Infringement Action or permit Genzyme to initiate any such Infringement
Action.

 

  (ii) Co-Co Territory. Subject to the provisions of any In-License, Alnylam
shall have the first right to initiate an Infringement Action anywhere in the
world against any Third Party with respect to any Competitive Infringement in
the Co-Co Territory of any Alnylam Product-Specific Patent, Joint Collaboration
IP, Alnylam Collaboration IP, Alnylam Core Technology Patent or Alnylam
Know-How. Alnylam will consider in good faith any request from Genzyme to
initiate an Infringement Action against any Third Party with respect to such
Competitive Infringement in the Co-Co Territory; provided, however, that Alnylam
shall not be required to initiate any such Infringement Action.

 

  (c) Step-In Rights.

 

  (i)

Alnylam Step-In Right for Alnylam Technology in Genzyme Territory. If within
[***] days (or such shorter period of time as required by applicable Law to
avoid loss of material enforcement rights) after Genzyme’s receipt

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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  of a notice of a Competitive Infringement with respect to any Alnylam
Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any
Infringement Action against such Competitive Infringement in the Genzyme
Territory, Alnylam may in its sole discretion, bring and control any
Infringement Action in connection therewith at its sole cost and expense.

 

  (ii) Genzyme Step-In Right for Alnylam Technology in Co-Co Territory. If
within [***] days (or such shorter period of time as required by applicable Law
to avoid loss of material enforcement rights) after Alnylam’s receipt of a
notice of a Competitive Infringement with respect to any Alnylam
Product-Specific Patent, Joint Collaboration IP or Alnylam Collaboration IP,
Alnylam does not initiate any Infringement Action against such Competitive
Infringement in the Co-Co Territory, Genzyme may in its sole discretion, bring
and control any Infringement Action in connection therewith at its sole cost and
expense.

 

  (iii) [***]

11.4.3. Procedures; Expenses and Recoveries. The Party having the right to
initiate any Infringement Action under Section 11.4.2 (Rights to Enforce) above
shall have the sole and exclusive right to select counsel for any such
Infringement Action and shall pay all expenses of the suit, including attorneys’
fees and court costs and reimbursement of the other Party’s reasonable Co-Co
Out-of-Pocket Costs in rendering assistance requested by the initiating Party.
If required under applicable Law in order for the initiating Party to initiate
and/or maintain such Infringement Action, or if either Party is unable to
initiate or prosecute such Infringement Action solely in its own name or it is
otherwise advisable to obtain an effective legal remedy, in each case, the other
Party shall join as a party to the Infringement Action and will execute and
cause its Affiliates to execute all documents necessary for the initiating Party
to initiate litigation to prosecute and maintain such action. In addition, at
the initiating Party’s request, the other Party shall provide reasonable
assistance to the initiating Party in connection with an Infringement Action at
no charge to the initiating Party except for reimbursement by the initiating
Party of reasonable Co-Co Out-of-Pocket Costs incurred in rendering such
assistance. The non-initiating Party shall have the right to participate and be
represented in any such Infringement Action by its own counsel at its own
expense. If the Parties obtain from a Third Party, in connection with such
Infringement Action, any damages, license fees, royalties or other compensation
(including any amount received in settlement of such litigation), after payment
of any amounts required under any In-Licenses, the remaining amounts shall be
allocated in all cases as follows:

(a) first, to reimburse each Party for all expenses of the Infringement Action
incurred by the Parties, including attorneys’ fees and disbursements, court
costs and other litigation expenses;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

(b) second, [***] of the balance to be paid to the Party initiating the
Infringement Action, with respect to Infringement Actions in the Genzyme
Territory, and [***] of the balance to be paid to the Party initiating the
Infringement Action, with respect to Infringement Actions in the Co-Co
Territory; and

(c) third, the remainder to the other Party.

Notwithstanding the foregoing, in the event that Alnylam elects to itself assert
an Alnylam Core Technology Patent against a Competitive Infringement in the
Genzyme Territory, the Parties shall each be entitled to [***] of the balance of
any recovery therefrom after reimbursement of expenses as described in clause
(i) above. In addition, with respect to Infringement Actions brought in the
Co-Co Territory, the Parties shall share evenly the expenses of the suit,
including attorneys’ fees of each Party, court costs, and both Parties’
reasonable Co-Co Out-of-Pocket expenses in rendering assistance related to the
Infringement Action (“Litigation Expenses”). For such Infringement Actions
brought in the Co-Co Territory, Litigation Expenses shall initially be borne by
the Party incurring the expense. Each Party will calculate and maintain records
of Litigation Expenses incurred by it and its Affiliates with respect to any
such Infringement Action, and, within thirty (30) days following the end of each
Calendar Quarter, each Party shall submit to the other a report detailing the
Litigation Expenses incurred by it and its Affiliates during such Calendar
Quarter. Unless otherwise agreed by the Parties, the Party that incurs more than
its share of the total Litigation Expenses with respect to such an Infringement
Action in the Co-Co Territory during any Calendar Quarter shall be paid by the
other Party an amount of cash sufficient to reconcile to its fifty percent
(50%) share of Litigation Expenses.

11.5. Patent Term Extensions.

11.5.1. Retained Alnylam Product-Specific Patent Rights. Subject to the
provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable
Efforts to obtain all available supplementary protection certificates (“SPCs”)
and other extensions of Alnylam Product-Specific Patents in the Genzyme
Territory[***]. If more than one Alnylam Product-Specific Patent is eligible for
extension or patent term restoration in the Genzyme Territory, Genzyme will
determine, in its sole discretion, a strategy that will be designed to maximize
patent protection and commercial value for the Co-Co Licensed Product, and the
Parties, subject to the provisions of any In-License, will seek patent term
extensions, restorations and SPCs for Alnylam Product-Specific Patents in the
Genzyme Territory in accordance with that strategy. Where required under
national law, and subject to the other requirements of this Section 11.5,
Alnylam will make the filings for such extensions, restorations and SPCs for
Alnylam Product-Specific Patents in the Genzyme Territory as directed by
Genzyme.

11.5.2. Further Assurances for SPCs. Each Party will execute such authorizations
and other documents and take such other actions as may be reasonably requested
by the other Party to obtain any such extensions, restorations and SPCs for
Alnylam Product-Specific Patents in the Genzyme Territory, in accordance with
this Section 11.5.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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11.6. Common Interest. All information exchanged between the Parties’
representatives regarding the preparation, filing, prosecution, maintenance, or
enforcement of the Patent Rights under this Section 11 will be deemed
Confidential Information. In addition, the Parties acknowledge and agree that,
with regard to such preparation, filing, prosecution, maintenance, and
enforcement of the Patents Rights under this Section 11, the interests of the
Parties as collaborators and licensor and licensee are to obtain the strongest
patent protection possible, and as such, are aligned and are legal in nature.
The Parties agree and acknowledge that they have not waived, and nothing in
these Co-Co License Terms constitutes a waiver of, any legal privilege
concerning the Patents Rights under this Section 11, including privilege under
the common interest doctrine and similar or related doctrines.

11.7. Trademarks.

(a) Each Party has the right to use any trademark it owns or controls for Co-Co
Licensed Products in its Territory at its sole discretion, and each Party and
its Affiliates shall retain all right, title and interest in and to its and
their respective corporate names and logos.

(b) Genzyme will develop and propose, and the PJSC shall review and comment on,
one or more Product Trademark(s) for use by Genzyme and its Related Parties
throughout the Genzyme Territory. Such Product Trademark(s) considered by the
PJSC may include, in Genzyme’s sole discretion, the Product Trademark(s)
developed and/or used by Alnylam with respect to the Commercialization of Co-Co
Licensed Products in the Co-Co Territory (the “Alnylam Trademarks”), but may not
include other trademarks owned or controlled by Alnylam. Any Product
Trademark(s) (other than the Alnylam Trademarks) that are used by Genzyme to
promote and sell Co-Co Licensed Products in the Genzyme Territory are
hereinafter referred to as the “Genzyme Trademarks.” Alnylam (or its Related
Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all
goodwill associated therewith, throughout the Co-Co Territory and the Genzyme
Territory. Genzyme (or its Related Parties, as appropriate) shall own all rights
to Genzyme Trademarks and all goodwill associated therewith, throughout the
Genzyme Territory. Alnylam shall also own rights to any Internet domain names
incorporating the applicable Alnylam Trademarks or any variation or part of such
Alnylam Trademarks used as its URL address or any part of such address; and
Genzyme shall also own rights to any Internet domain names incorporating the
applicable Genzyme Trademarks or any variation or part of such Genzyme
Trademarks used as its URL address or any part of such address.

(c) If Genzyme determines to use Alnylam Trademarks to promote and sell any
Co-Co Licensed Product in the Genzyme Territory, then Alnylam and Genzyme shall
enter into a separate trademark license agreement containing commercially
reasonable and customary terms pursuant to which Alnylam will grant Genzyme an
exclusive, royalty-free license to use the applicable Alnylam Trademark(s) to
Commercialize Co-Co Licensed Products in the Genzyme Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) In the event either Party becomes aware of any infringement of any Product
Trademark by a Third Party, such Party shall promptly notify the other Party and
the Parties shall consult with each other and jointly determine the best way to
prevent such infringement, including by the institution of legal proceedings
against such Third Party.

(e) For the avoidance of doubt, neither Party shall have any right to use the
other Party’s or the other Party’s Affiliates’ corporate names or logos in
connection with Commercialization of Co-Co Licensed Products.

11.8. Cooperative Research and Technology (CREATE) Act Acknowledgment. It is the
intention of the Parties that these Co-Co License Terms are a “joint research
agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

12. TERM AND TERMINATION

12.1. Term. These Co-Co License Terms shall be effective as of the Effective
Date and, unless terminated earlier pursuant to Section 12.2 (Termination
Rights), these Co-Co License Terms shall continue in effect on a Co-Co Licensed
Product-by-Co-Co Licensed Product and country-by-country basis until no further
payments are due under Section 8 (Financial Terms for Genzyme Territory) or
Section 9 (Financial Terms for Co-Co Territory) of these Co-Co License Terms
(“Term”). Upon expiration of the Royalty Term for any particular Co-Co Licensed
Product, all licenses of the Parties under Section 7 (Licenses) with respect to
such Co-Co Licensed Product then in effect shall become fully paid-up, perpetual
licenses.

12.2. Termination Rights. These Co-Co License Terms may be terminated by the
Parties only as set forth in this Section 12.2.

12.2.1. Termination for Convenience. Subject to the remainder of this Article
12, Genzyme shall have the right to terminate these Co-Co License Terms with
respect to any particular Co-Co Licensed Product as follows:

(a) After initiation of the first Phase II Study for such Co-Co Licensed Product
and prior to completion of such Phase II Study for such Co-Co Licensed Product,
Genzyme shall have the right to terminate these Co-Co License Terms with respect
to such Co-Co Licensed Product upon sixty (60) days prior written notice in the
event that a Safety Concern occurs, provided that in the event of such
termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and
Global Regulatory Costs incurred through the effective date of termination (not
to exceed [***]) to wind down any ongoing Phase II Studies with respect to such
Co-Co Licensed Product in an efficient manner consistent with patient safety,
applicable Law and ethical standards.

(b) After initiation of the first Phase II Study for such Co-Co Licensed Product
and prior to completion of such Phase II Study for such Co-Co Licensed Product,
Genzyme shall have the right to terminate these Co-Co License Terms with respect
to

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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such Co-Co Licensed Product for any reason upon written notice (in which case,
such termination shall become effective immediately upon Alnylam’s receipt of
notice of such termination), provided that in the event of such termination
Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory
Costs incurred in any ongoing Phase II Studies for such Co-Co Licensed Product
(not to exceed [***].

(c) Within sixty (60) days of Genzyme’s receipt of the Phase 3 Budget and End of
Phase II Package, Genzyme shall have the right to terminate these Co-Co License
Terms with respect to such Co-Co Licensed Product upon written notice to Alnylam
(in which case, such termination shall become effective immediately upon
Alnylam’s receipt of notice of such termination), provided that in the event of
such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and
Global Regulatory Costs incurred through the effective date of termination (not
to exceed [***].

(d) After initiation of the first Phase III Study for such Co-Co Licensed
Product and prior to completion of such Phase III Study for such Co-Co Licensed
Product, Genzyme shall have the right to terminate these Co-Co License Terms
with respect to such Co-Co Licensed Product upon sixty (60) days prior written
notice in the event that a Safety Concern occurs, provided that in the event of
such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and
Global Regulatory Costs incurred through the effective date of termination (not
to exceed [***]) to wind down any ongoing Clinical Studies with respect to such
Co-Co Licensed Product in an efficient manner consistent with patient safety,
applicable Law and ethical standards.

(e) After initiation of the first Phase III Study for such Co-Co Licensed
Product and Genzyme’s payment of the Phase III Study initiation milestone
payment described in Section 8.1.1(i) (Development Milestones for ALN-TTRsc) or
8.1.2(i) (Development Milestones for ALN-AT3), Genzyme shall have the right to
terminate these Co-Co License Terms with respect to such Co-Co Licensed Product
at any time upon sixty (60) days prior written notice to Alnylam, provided that
in the event of such termination Genzyme shall pay to Alnylam [***] of the
Global R&D Costs and Global Regulatory Costs incurred in conducting any ongoing
Phase III Study with respect to such Co-Co Licensed Product through filing of
the first NDA with respect to such Co-Co Licensed Product (not to[***]).

(f) After completion of the first Phase III Study for such Co-Co Licensed
Product, Genzyme shall have the right to terminate these Co-Co License Terms
with respect to such Co-Co Licensed Product at any time upon sixty (60) days
prior written notice to Alnylam.

12.2.2. Termination for Cause. These Co-Co License Terms may be terminated with
respect to any particular Co-Co Licensed Product at any time during the Term
upon written notice by either Party if (a) the other Party is in material breach
of its obligations hereunder with respect to such Co-Co Licensed Product and (b)
the other Party has not cured such breach within thirty (30) days in the case of
a payment breach, or within ninety (90) days in the case of all

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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other breaches, after notice requesting cure of the breach; provided, however,
that if any breach other than a payment breach is not reasonably curable within
ninety (90) days and if a Party is making a bona fide effort to cure such
breach, such termination shall be delayed for a time period to be agreed by both
Parties, not to exceed an additional ninety (90) days, in order to permit such
Party a reasonable period of time to cure such breach; and provided, further,
that in the event that the breach relates to a dispute between the Parties
regarding Genzyme’s obligations to use Commercially Reasonable Efforts in
Developing or Commercializing such Co-Co Licensed Product and Genzyme disputes
whether it has breached such obligation or whether such breach gives Alnylam the
right to terminate these Co-Co License Terms with respect to such Co-Co Licensed
Product and initiates a legal action against Alnylam to resolve such dispute
within the foregoing sixty (60) day cure period, then these Co-Co License Terms
shall not terminate during the pendency of such legal action, provided that if
(i) Genzyme is found, in an unappealable decision by a court of competent
jurisdiction or an appealable decision of a court of competent jurisdiction that
has not been appealed in the time allowed for an appeal in such legal action, to
have materially breached these Co-Co License Terms with respect to such Co-Co
Licensed Product, or (ii) Genzyme admits in such legal action or settlement
thereof that it has materially breached these Co-Co License Terms with respect
to such Co-Co Licensed Product, then these Co-Co License Terms shall terminate
immediately with respect to such Co-Co Licensed Product following the Parties’
receipt of such decision or immediately following such admission, as applicable.

12.2.3. Challenges of Patent Rights. If, during the Term, Genzyme or any of its
Affiliates (a) commences or participates in any action or proceeding (including
any patent opposition or re-examination proceeding), or otherwise asserts any
claim, challenging or denying the validity or enforceability of any Alnylam
Product-Specific Patent or any claim thereof or (b) actively assists any other
Person or entity in bringing or prosecuting any action or proceeding (including
any patent opposition or re-examination proceeding) challenging or denying the
validity or enforceability of any Alnylam Product-Specific Patent for a Co-Co
Licensed Product or any claim thereof (each of (a) and (b), a “Patent
Challenge”), then, to the extent permitted by the applicable Laws, Alnylam shall
have the right, exercisable within sixty (60) days following receipt of notice
regarding such Patent Challenge, in its sole discretion, to give notice to
Genzyme that Alnylam may terminate these Co-Co Licensed Terms with respect to
the Co-Co Licensed Product Covered by the Alnylam Product-Specific Patent that
is the subject of the Patent Challenge (which termination will be effective
ninety (90) days following such notice (or such longer period as Alnylam may
designate in such notice)), and, unless Genzyme or such Affiliate withdraws or
causes to be withdrawn all such challenge(s) (or in the case of ex-parte
proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or
Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to
be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any
other party to such Patent Challenge and, to the extent Genzyme or a Genzyme
Affiliate is a party to such Patent Challenge, it withdraws from such Patent
Challenge) within such ninety (90)-day period, Alnylam will have the right to
terminate these Co-Co License Terms with respect to such Co-Co Licensed Product
by providing written notice thereof to Genzyme. The foregoing sentence shall not
apply with respect to (i) any Alnylam Product-Specific Patent that Alnylam first
asserts against Genzyme or any of its

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Affiliates where the Patent Challenge is made in defense of such assertion or
(ii) any Patent Challenge commenced by a Third Party that, after the Effective
Date, acquires or is acquired by Genzyme or its Affiliates or its or their
business or assets, whether by stock purchase, merger, asset purchase or
otherwise, but only with respect to Patent Challenges commenced prior to the
closing of such acquisition.

12.2.4. Abandonment of Development. At any time on or after [***], either Party
may terminate these Co-Co License Terms in their entirety (i.e., with respect to
all Co-Co Licensed Products) if (a) no Co-Co Licensed Product has received
Regulatory Approval anywhere in the Genzyme Territory, (b) no Co-Co Licensed
Product is being Developed for the Genzyme Territory, (c) no Global Development
Plan or Genzyme Territory Development Plan is in effect for any Co-Co Licensed
Product, provided that if Genzyme provides Alnylam with a good faith Genzyme
Territory Development Plan pursuant to Section 2.2.3 (Genzyme Territory
Development Plan) during the termination notice period set forth below in this
Section 12.2.4, then the condition set forth in this clause (c) shall be deemed
not satisfied at such time and the applicable termination notice shall be deemed
not to have effect, and (d) the absence of Development in the Genzyme Territory
or a good faith Genzyme Territory Development Plan is not the result of a breach
by the Party seeking to terminate these Co-Co License Terms of its obligations
under Section 2.4 (Diligence). In order to terminate these Co-Co License Terms
pursuant to this Section 12.2.4, the terminating Party must provide at least six
(6) months’ prior written notice to the other Party referencing this
Section 12.2.4 and specifying a termination date on or after [***], provided
that, with respect to any such termination by Alnylam, such notice must also
include an update regarding the current status of Alnylam’s Development
activities with respect to Co-Co Licensed Products.

12.3. Effect of Termination.

12.3.1. Effects of Termination by Genzyme for Cause. Without limiting any other
legal or equitable remedies that either Party may have, if these Co-Co License
Terms are terminated by Genzyme with respect to any particular Co-Co Licensed
Product pursuant to Section 12.2.2 (Termination for Cause), then:

(a) these Co-Co License Terms shall continue to survive in all respects with
respect to all Co-Co Licensed Products other than the terminated Co-Co Licensed
Product;

(b) all license grants in these Co-Co License Terms with respect to the
terminated Co-Co Licensed Product from either Party to the other shall
immediately terminate;

(c) the Back-Up Option shall terminate with respect to all Back-Up Products for
the terminated Co-Co Licensed Product; provided, however, that such Back-Up
Products shall, as of such date, be considered Option Products for the purposes
of the Master Agreement, and the Options granted under the Master Agreement to
siRNA that targets the same gene as the terminated Co-Co Licensed Product shall
again apply in accordance with the terms and conditions set forth in the Master
Agreement;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all Regulatory Approvals and pricing
and reimbursement approvals relating to the Development, Manufacture or
Commercialization of the terminated Co-Co Licensed Product, and (ii) copies of
all non-clinical and clinical data and material regulatory correspondence
relating to the terminated Co-Co Licensed Product, provided that Alnylam shall
reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme
in connection with such transfer;

(e) Genzyme will assign and transfer to Alnylam all rights, title and interests
in and to any Alnylam Product-Specific Patents that relate solely to the
terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to
Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme),
provided that Alnylam shall reimburse Genzyme for any reasonable out-of-pocket
expenses incurred by Genzyme in connection with such assignment and transfer. In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme; and

(f) each Party shall promptly pay any amounts owed to the other Party as of the
effective date of such termination.

12.3.2. Effects of Termination by Alnylam for Cause or by Genzyme for
Convenience. Without limiting any other legal or equitable remedies that either
Party may have, if these Co-Co License Terms are terminated with respect to any
particular Co-Co Licensed Product by Genzyme pursuant to Section 12.2.1
(Termination for Convenience) or by Alnylam under Section 12.2.2 (Termination
for Cause) or Section 12.2.3 (Challenges of Patent Rights), then:

(a) these Co-Co License Terms shall continue to survive in all respects with
respect to all Co-Co Licensed Products other than the terminated Co-Co Licensed
Product;

(b) all licenses granted by Alnylam to Genzyme in these Co-Co License Terms with
respect to the terminated Co-Co Licensed Product shall immediately terminate;

(c) the Back-Up Option shall terminate with respect to all Back-Up Products for
the terminated Co-Co Licensed Product and such Back-Up Products shall be treated
as Option Products for which Genzyme has not exercised an Option for purposes of
Section 3.5 of the Master Agreement;

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(d) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product Specific Patents that relate solely to the
terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to
Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme;

(e) Genzyme will grant to Alnylam, effective upon the effective date of
termination and subject to the provisions of any applicable Genzyme In-License,
a non-transferable, sublicensable (on terms consistent with Section 7.2.4
(Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any
Genzyme Collaboration IP and Genzyme Patent Rights that Cover the terminated
Co-Co Licensed Product, in the form that such terminated Co-Co Licensed Product
exists on the effective date of termination (the “Reverted Co-Co Licensed
Product”), solely to the extent necessary to Develop and Commercialize the
Reverted Co-Co Licensed Product in the Field in the Genzyme Territory.
Notwithstanding the foregoing, if (i) any Patent Rights that Cover the Reverted
Co-Co Licensed Product are Controlled by Genzyme pursuant to a Genzyme
In-License and (ii) such Genzyme In-License cannot be assigned to Alnylam or
does not relate exclusively to the Reverted Co-Co Licensed Product, Genzyme
shall promptly disclose any payment obligations under such Genzyme In-License to
Alnylam and such Genzyme Patent Rights shall be subject to the license granted
in this Section 12.3.2(e) only if Alnylam agrees in writing to (A) reimburse
Genzyme for one hundred percent (100%) of any amounts that become payable under
such Genzyme In-License as a result of Alnylam’s exercise of the license granted
in this Section 12.3.2(e), (B) comply with all applicable terms and conditions
of such Genzyme In-License and (C) perform and take such actions as may be
required to allow Genzyme to comply with its obligations under such Genzyme
In-License.

(f) The license grants to Alnylam in Section 7.2 (License Grants to Alnylam)
shall survive and shall be expanded to include the Genzyme Territory with
respect to the Reverted Co-Co Licensed Product.

(g) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all governmental or regulatory
correspondence, conversation logs, filings and approvals (including all
Regulatory Approvals and pricing and reimbursement approvals) solely relating to
the Development, Manufacture or Commercialization of the Reverted Co-Co Licensed
Product, (ii) copies of all data, reports, records and materials, and other
sales and marketing related information in Genzyme’s possession or Control, to
the extent that such data, reports, records, materials or other information
relate to the Development, Manufacture or Commercialization of the Reverted
Co-Co Licensed Product, including all non-clinical and clinical data relating to
the Reverted Co-Co Licensed Product, and customer lists and customer contact
information and all adverse event data relating to the Reverted Co-Co Licensed
Product in Genzyme’s possession or Control, provided that for a period of [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

months after the effective date of termination with respect to such Reverted
Co-Co Licensed Product, Genzyme shall use Commercially Reasonable Efforts to
obtain for Alnylam the right to access all such data, reports, records,
materials, and other sales and marketing related information related to the
Reverted Co-Co Licensed Product, and (iii) all records and materials in
Genzyme’s possession or Control containing Confidential Information of Alnylam
solely relating to the Reverted Co-Co Licensed Product. In addition, Genzyme
shall appoint Alnylam as Genzyme’s and/or Genzyme’s Related Parties’ agent for
all matters related to the Reverted Co-Co Licensed Product involving Regulatory
Authorities in the Genzyme Territory until all Regulatory Approvals and other
regulatory filings have been transferred to Alnylam or its designee.

(h) If the effective date of termination is after First Commercial Sale of the
Reverted Co-Co Licensed Product, then Genzyme shall appoint Alnylam as its
exclusive distributor of the Reverted Co-Co Licensed Product in the Genzyme
Territory and grant Alnylam the right to appoint sub-distributors, until such
time as all Regulatory Approvals in the Genzyme Territory have been transferred
to Alnylam or its designee.

(i) If Genzyme or its Related Parties are Manufacturing finished product with
respect to the Reverted Co-Co Licensed Product on the effective date of
termination, at Alnylam’s option, Genzyme or its Related Parties shall supply
such finished product to Alnylam in the Genzyme Territory on terms no less
favorable than those on which Genzyme supplied such finished product prior to
such termination to its most favored distributor in the Genzyme Territory, until
the earlier of (i) such time as all Regulatory Approvals in the Genzyme
Territory solely related to the Reverted Co-Co Licensed Product have been
transferred to Alnylam or its designee, Alnylam has obtained all necessary
manufacturing approvals and Alnylam has procured or developed its own source of
such finished product supply or (ii) [***] months following the effective date
of such termination.

(j) If Alnylam so requests, and to the extent permitted under Genzyme’s
obligations to Third Parties on the effective date of termination, Genzyme shall
transfer to Alnylam any Third Party agreements relating solely and exclusively
to the Development, Manufacture or Commercialization of the Reverted Co-Co
Licensed Product to which Genzyme is a party (including any Genzyme In-License),
subject to any required consents of such Third Party, which Genzyme shall use
Commercially Reasonable Efforts to obtain promptly.

(k) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and
its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s)
(but not any Genzyme house marks or any trademark containing the word “Genzyme”
owned by Genzyme and used for the Reverted Co-Co Licensed Product in the Field
in the Genzyme Territory) owned by Genzyme and used solely and exclusively for
the Reverted Co-Co Licensed Product in the Field in the Genzyme Territory.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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(l) Genzyme shall transfer to Alnylam any inventory of the Reverted Co-Co
Licensed Products Controlled by Genzyme or its Affiliates as of the termination
date at the actual price paid by Genzyme for such supply.

(m) Genzyme shall provide any other assistance reasonably requested by Alnylam
for the purpose of allowing Alnylam or its designee to proceed expeditiously
with the Development, Manufacture and Commercialization of the Reverted Co-Co
Licensed Product in the Genzyme Territory, provided that Genzyme’s obligations
under this clause (m) of Section 12.3.2 shall expire [***] months after the
effective date of termination of such Reverted Co-Co Licensed Product.

(n) Genzyme shall execute all documents and take all such further actions as may
be reasonably requested by Alnylam in order to give effect to the foregoing
clauses.

12.3.3. Effects of Termination for Abandonment of Development. If these Co-Co
License Terms are terminated in their entirety (i.e., with respect to all Co-Co
Licensed Products) by either Party pursuant to Section 12.2.4 (Abandonment of
Development), then the license granted to Alnylam under Section 7.2.2 (License
to Improvement Manufacturing Patent Rights) shall survive and all other licenses
granted in these Co-Co License Terms from either Party to the other shall
immediately terminate and:

(a) the Back-Up Option shall terminate with respect to all Back-Up Products for
the terminated Co-Co Licensed Products ;

(b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s
designee (i) possession and ownership of all Regulatory Approvals and pricing
and reimbursement approvals relating to the Development, Manufacture or
Commercialization of the terminated Co-Co Licensed Product, and (ii) copies of
all non-clinical and clinical data and material regulatory correspondence
relating to the terminated Co-Co Licensed Product;

(c) Genzyme will assign and transfer to Alnylam, all rights, title and interests
in and to any Alnylam Product Specific Patents that relate solely to the
terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to
Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In
such event, Genzyme will execute and deliver a patent assignment relating to
such Alnylam Product-Specific Patents in the same form used to assign such
Patent Rights to Genzyme; and

(d) each Party shall promptly pay any amounts owed to the other Party as of the
effective date of such termination.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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12.4. Fundamental Breach of Alnylam’s Development Obligations. Without limiting
Genzyme’s rights under Section 12.2.2 (Termination for Cause) with respect to
other material breaches, in the event that Alnylam commits a Fundamental Breach
of its Development obligations under Section 2.4.2 (Alnylam Diligence) with
respect to any particular Co-Co Licensed Product, and Genzyme does not terminate
these Co-Co License Terms in their entirety (i.e., with respect to all Co-Co
Licensed Products) or with respect to such Co-Co Licensed Product for cause
pursuant to Section 12.2.2 (Termination for Cause), then Genzyme may elect to
receive the following remedies for such Fundamental Breach:

12.4.1. Genzyme’s obligation to pay development milestone fees under Section 8.1
(Development Milestone Fees) with respect to such Co-Co Licensed Product shall
automatically terminate;

12.4.2. Genzyme will receive a credit, which Genzyme may offset against
royalties and other amounts payable under these Co-Co License Terms due to
Alnylam with respect to such Co-Co Licensed Product pursuant to Section 8
(Financial Terms for Genzyme Territory), in an amount equal to one hundred fifty
percent (150%) of all costs and expenses (i) incurred by Genzyme to Develop such
Co-Co Licensed Product for the Genzyme Territory that are in excess of the costs
budgeted by Genzyme in connection with the Genzyme Territory Development Plan
for such Co-Co Licensed Product in effect at the time of Alnylam’s Fundamental
Breach of Section 2.4.2 (Alnylam Diligence) with respect to such Co-Co Licensed
Product and (ii) are incurred by Genzyme as a direct consequence of Alnylam’s
Fundamental Breach of Section 2.4.2 (Alnylam Diligence) with respect to such
Co-Co Licensed Product;

12.4.3. Genzyme may, in its discretion, terminate any or all of the following
provisions of these Co-Co License Terms (or any subsection thereof) with respect
to such Co-Co Licensed Product: Section 3.1.4 (Meetings with Regulatory
Authorities), Section 4.1.2 (Co-Co Territory), Section 4.2.1 (Co-Co Territory
Commercialization Plan), Section 4.3 (Genzyme Territory Commercialization Plan),
Section 4.4 (Advertising and Promotional Materials), Section 4.5
(Commercialization Reporting Obligations) and Section 5 (Collaboration
Management); and

12.4.4. Without limiting Genzyme’s remedies under these Co-Co License Terms or
otherwise with respect to breaches of Alnylam’s Development obligations under
clause (a) of Section 2.4.2 (Alnylam Diligence) other than Fundamental Breaches,
if Genzyme elects to receive the remedies set forth in this Section 12.4 with
respect to a Fundamental Breach of its Development obligations under clause
(a) of Section 2.4.2 (Alnylam Diligence) with respect to any Co-Co Licensed
Product, such remedies shall be Genzyme’s sole and exclusive remedies with
respect to such Fundamental Breach and Genzyme shall have no right to seek any
further remedies or damages against Alnylam and its Affiliates with respect to
such Fundamental Breach by Alnylam of clause (a) of Section 2.4.2 (Alnylam
Diligence).

12.5. Effect of Expiration or Termination; Survival. Any expiration or
termination of these Co-Co License Terms (a) shall not relieve the Parties of
any obligation accruing prior to such expiration or termination and (b) shall be
without prejudice to the rights of either Party against the other accrued or
accruing under these Co-Co License Terms prior to expiration or termination,
including the obligation to pay royalties for any Co-Co Licensed Product sold
prior to such expiration or termination. The following provisions shall survive
any expiration or

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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termination of these Co-Co License Terms in their entirety (i.e., with respect
to all Co-Co Licensed Products) and, if these Co-Co License Terms expire or are
terminated with respect to any particular Co-Co Licensed Product, shall survive
with respect to such Co-Co Licensed Product: (a) Sections 1 (Definitions), 9
(Financial Terms for Co-Co Territory), 10.3 (Warranty Disclaimer), 11.1
(Inventorship), 11.2 (Ownership), 12.3 (Effect of Termination), 12.5 (Effect of
Termination or Expiration; Survival), Section 13 (Performance by Affiliates) of
these Co-Co License Terms and (b) Sections 1 (Definitions), 7 (Confidentiality
and Publication), 10 (Indemnification; Limitation of Liability; Insurance), 12
(Term and Termination) and 13 (Miscellaneous) of the Master Agreement.
Section 8.2.6 (Royalty Floor) shall survive any termination or expiration of
these Co-Co License Terms with respect to any Co-Co Licensed Product for
royalties accruing prior to such termination or expiration. Section 9 of the
Master Agreement (Royalty Reports; Payments; Audit) will survive for so long as
any royalties are due under these Co-Co License Terms plus three (3) years.
Except as otherwise set forth in this Section 12 or elsewhere in these Co-Co
License Terms, upon termination or expiration of these Co-Co License Terms in
their entirety, all rights and obligations of the Parties under these Co-Co
License Terms shall cease, but, for clarity, expiration or termination of these
Co-Co License Terms in their entirety (i.e., with respect to all Co-Co Licensed
Products) shall not result in the termination or expiration of the Master
Agreement or any other License Terms. Upon termination or expiration of these
Co-Co License Terms with respect to any particular Co-Co Licensed Product, all
rights and obligations of the Parties under these Co-Co License Terms with
respect to such Co-Co Licensed Product shall cease except as otherwise set forth
in this Section 12 or elsewhere in these Co-Co License Terms, but, for clarity,
such termination or expiration shall not affect the Parties’ rights and
obligations under these Co-Co License Terms with respect to the other Co-Co
Licensed Product.

13. PERFORMANCE BY AFFILIATES

13.1. Use of Affiliates. Each Party acknowledges and accepts that the other
Party may exercise its rights and perform its obligations under these Co-Co
License Terms either directly or through one or more of its Affiliates. A
Party’s Affiliates will have the benefit of all rights (including all licenses)
of such Party under these Co-Co License Terms. Accordingly, in these Co-Co
License Terms “Genzyme” will be interpreted to mean “Genzyme and/or its
Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its
Affiliates” where necessary to give each Party’s Affiliates the benefit of the
rights provided to such Party in these Co-Co License Terms; provided, however,
that in any event each Party will remain responsible for the acts and omissions,
including financial liabilities, of its Affiliates.

13.2. Future Acquisition of a Party or its Business. [***]

13.3. Acquired Programs.

13.3.1. [***]

13.3.2. [***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

13.3.3. For clarity, upon the closing of the acquisition of the stock and/or
assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp.,
all relevant acquired intellectual property rights acquired in such transaction
that may be Controlled by Alnylam (without any further action by Alnylam or
Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of
these Co-Co License Terms.

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 1.2.14-1

ALNYLAM CORE TECHNOLOGY PATENTS FOR ALN-TTRsc

See attached.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 1.2.19-1

ALNYLAM PRODUCT-SPECIFIC PATENTS FOR ALN-TTRsc

See attached.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Schedule 2.2.2.1-1

GLOBAL DEVELOPMENT STRATEGY FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.2.1.)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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Schedule 2.2.2-1

GLOBAL DEVELOPMENT PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.2.)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Schedule 2.2.3-1

GENZYME TERRITORY DEVELOPMENT PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.3.)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-83-

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CO-CO LICENSE TERMS

 

Schedule 2.7

TTRSC/02 ARBITRATION CRITERIA

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Schedule 4.2-1

CO-CO TERRITORY COMMERCIALIZATION PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 4.2.)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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CO-CO LICENSE TERMS

 

Schedule 10.1-1

DISCLOSURE SCHEDULE

See attached.

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-86-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 2 pages were omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

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--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

Schedule 10.1.12

(A) EXISTING ALNYLAM IN-LICENSES

(To be attached)

(B) ADDITIONAL ALNYLAM IN-LICENSES

(To be attached)

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-88-

--------------------------------------------------------------------------------

CO-CO LICENSE TERMS

 

Schedule 10.4.1.4

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 1 page was omitted.

[***]

 

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH
“[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE
SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE
ACT OF 1934.

-89-