exv10w39






Exhibit 10.39




Execution Version




Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Asterisks denote omissions.




COLLABORATION AGREEMENT



BY AND AMONG



ALNYLAM PHARMACEUTICALS, INC.



AND



F. HOFFMANN-LA ROCHE LTD



AND



HOFFMANN-LA ROCHE INC.



 









 





TABLE OF CONTENTS




	 	 	 	 	 
	 	 	Page
	ARTICLE I DEFINITIONS
	 	 	1	 
	 
	 	 	 	 
	ARTICLE II MANAGEMENT OF COLLABORATIVE ACTIVITIES
	 	 	1	 
	 
	 	 	 	 
	Section 2.1 Joint Steering Committee
	 	 	1	 
	Section 2.2 Joint Commercialization Team
	 	 	3	 
	Section 2.3 Appointment of Subcommittees, Project Teams and Alliance Managers
	 	 	5	 
	Section 2.4 JSC and JCT Decisions by Consensus
	 	 	5	 
	Section 2.5 JSC or JCT Deadlocks; Dispute Resolution; Decision-Making Authority
	 	 	5	 
	 
	 	 	 	 
	ARTICLE III LICENSE GRANTS; EXCLUSIVITY
	 	 	7	 
	 
	 	 	 	 
	Section 3.1 License Grants to Roche
	 	 	7	 
	Section 3.2 License Grants to Alnylam
	 	 	10	 
	Section 3.3 Sublicensing Terms
	 	 	11	 
	Section 3.4 Third Party Contractors
	 	 	11	 
	Section 3.5 Retained Rights
	 	 	11	 
	Section 3.6 No Implied Licenses
	 	 	11	 
	Section 3.7 Exclusivity Covenant
	 	 	11	 
	 
	 	 	 	 
	ARTICLE IV COLLABORATION OVERVIEW; DEVELOPMENT OF LICENSED PRODUCT(S); OPT-OUT RIGHTS
	 	 	13	 
	 
	 	 	 	 
	Section 4.1 Collaboration Overview
	 	 	13	 
	Section 4.2 Joint Research Plan; Amendments
	 	 	13	 
	Section 4.3 Selection of Program Targets
	 	 	13	 
	Section 4.4 Selection of Development Candidate
	 	 	14	 
	Section 4.5 Development Plan; Amendments
	 	 	15	 
	Section 4.6 Exchange of Know-How
	 	 	15	 
	Section 4.7 Records and Reports
	 	 	16	 
	Section 4.8 Development Costs
	 	 	16	 
	Section 4.9 Opt-Out Right
	 	 	16	 
	 
	 	 	 	 
	ARTICLE V COMMERCIALIZATION
	 	 	18	 
	 
	 	 	 	 
	Section 5.1 Commercialization Activities
	 	 	18	 
	Section 5.2 Commercialization Costs
	 	 	18	 
	Section 5.3 Commercialization Plan
	 	 	19	 
	 
	 	 	 	 
	ARTICLE VI MANUFACTURE AND SUPPLY
	 	 	19	 
	 
	 	 	 	 
	Section 6.1 Pre-Candidate Selection Supply
	 	 	19	 






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	 	 	Page
	Section 6.2 Supply for IND-Enabling Studies and Clinical Studies
	 	 	19	 
	Section 6.3 Supply Agreement
	 	 	20	 
	Section 6.4 Transition of Manufacturing Responsibilities to Continuing Party
	 	 	21	 
	Section 6.5 Backup Manufacturing Rights
	 	 	22	 
	Section 6.6 Technical Regulatory Documentation
	 	 	22	 
	Section 6.7 Auditing Rights
	 	 	22	 
	 
	 	 	 	 
	ARTICLE VII REGULATORY MATTERS
	 	 	23	 
	 
	 	 	 	 
	Section 7.1 Regulatory Filings
	 	 	23	 
	Section 7.2 Product Complaints; Pharmacovigilance
	 	 	24	 
	Section 7.3 Product Withdrawals and Recalls
	 	 	24	 
	Section 7.4 Regulatory Compliance
	 	 	24	 
	Section 7.5 Debarment
	 	 	24	 
	 
	 	 	 	 
	ARTICLE VIII DILIGENCE
	 	 	25	 
	 
	 	 	 	 
	Section 8.1 General
	 	 	25	 
	Section 8.2 Development and Commercialization
	 	 	26	 
	 
	 	 	 	 
	ARTICLE IX FINANCIAL PROVISIONS
	 	 	26	 
	 
	 	 	 	 
	Section 9.1 Event Payments
	 	 	26	 
	Section 9.2 Profit-sharing and sharing of Commercialization Costs
	 	 	29	 
	Section 9.3 Royalties
	 	 	30	 
	Section 9.4 Withholding Taxes
	 	 	36	 
	Section 9.5 Financial Records
	 	 	36	 
	Section 9.6 Audits
	 	 	36	 
	Section 9.7 Late Payments
	 	 	37	 
	 
	 	 	 	 
	ARTICLE X INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS
	 	 	37	 
	 
	 	 	 	 
	Section 10.1 Inventorship
	 	 	37	 
	Section 10.2 Ownership of Collaboration IP
	 	 	37	 
	Section 10.3 Prosecution and Maintenance of Patent Rights
	 	 	38	 
	Section 10.4 Third Party Infringement
	 	 	40	 
	Section 10.5 Claimed Infringement; Third Party Challenges to Patent Rights
	 	 	42	 
	Section 10.6 Third Party Technology
	 	 	43	 
	Section 10.7 Patent Marking
	 	 	44	 
	Section 10.8 Product Labeling
	 	 	44	 
	 
	 	 	 	 
	ARTICLE XI CONFIDENTIALITY
	 	 	44	 
	 
	 	 	 	 
	Section 11.1 Confidential Information
	 	 	44	 
	Section 11.2 Employee and Advisor Obligations
	 	 	45	 
	Section 11.3 Publicity
	 	 	46	 
	Section 11.4 Publications
	 	 	46	 
	Section 11.5 Clinical Trial Registry
	 	 	46	 






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	 	 	Page
	ARTICLE XII REPRESENTATIONS AND WARRANTIES
	 	 	47	 
	 
	 	 	 	 
	Section 12.1 Mutual Representations and Warranties
	 	 	47	 
	Section 12.2 Representations and Warranties of Alnylam
	 	 	47	 
	Section 12.3 Representations and Warranties of Roche
	 	 	48	 
	Section 12.4 No Warranties
	 	 	48	 
	 
	 	 	 	 
	ARTICLE XIII INDEMNIFICATION; INSURANCE
	 	 	49	 
	 
	 	 	 	 
	Section 13.1 Indemnification by Roche
	 	 	49	 
	Section 13.2 Indemnification by Alnylam
	 	 	49	 
	Section 13.3 Product Liability Claims
	 	 	50	 
	Section 13.4 Claims for Indemnification with respect to Third Parties
	 	 	50	 
	Section 13.5 Insurance
	 	 	51	 
	 
	 	 	 	 
	ARTICLE XIV TERM AND TERMINATION
	 	 	51	 
	 
	 	 	 	 
	Section 14.1 Term
	 	 	51	 
	Section 14.2 Termination for Cause
	 	 	51	 
	Section 14.3 Termination for Patent Challenge
	 	 	52	 
	Section 14.4 Termination At Will
	 	 	52	 
	Section 14.5 Effects of Termination
	 	 	54	 
	Section 14.6 Effect of Expiration or Termination; Survival
	 	 	59	 
	 
	 	 	 	 
	ARTICLE XV MISCELLANEOUS
	 	 	59	 
	 
	 	 	 	 
	Section 15.1 Choice of Law
	 	 	59	 
	Section 15.2 Notices
	 	 	59	 
	Section 15.3 Severability
	 	 	60	 
	Section 15.4 Interpretation
	 	 	61	 
	Section 15.5 Integration
	 	 	61	 
	Section 15.6 Independent Contractors; No Agency
	 	 	61	 
	Section 15.7 Assignment; Successors
	 	 	61	 
	Section 15.8 Execution in Counterparts; Facsimile Signatures
	 	 	62	 
	Section 15.9 Waivers
	 	 	62	 
	Section 15.10 No Consequential or Punitive Damages
	 	 	62	 
	Section 15.11 Actions of Affiliates
	 	 	62	 
	Section 15.12 Expenses
	 	 	62	 
	Section 15.13 No Third Party Beneficiaries
	 	 	62	 
	Section 15.14 Bankruptcy
	 	 	63	 
	Section 15.15 Change of Control
	 	 	63	 






-iii-









 






	 	 	 
	EXHIBITS	 	 
	EXHIBIT A

	 	Definitions
	EXHIBIT B-1

	 	Certain Alnylam Pre-Existing Alliance Agreements
	EXHIBIT B-2

	 	Certain Listed Alnylam Third Party Agreements
	EXHIBIT B-3

	 	Manufacturing Agreements
	EXHIBIT C

	 	Joint Research Plan
	EXHIBIT D

	 	Supply Agreement Term Sheet
	EXHIBIT E

	 	Financial Appendix
	EXHIBIT F

	 	Press Release
	EXHIBIT G

	 	Baseball Arbitration Provisions







-iv-











 





COLLABORATION AGREEMENT




     This Collaboration Agreement (this “Agreement”) is entered into as of the
29th day of October 2009 (the “Effective Date”), by and among F. Hoffmann-La
Roche Ltd, a Swiss corporation (“Roche Basel”), having a place of business at
Grenzacherstrasse 124, CH-4070 Basel, Switzerland, and Hoffmann-La Roche Inc., a New Jersey
corporation (“Roche Nutley”), having a place of business at 340 Kingsland Street, Nutley,
New Jersey 07110, U.S.A. (Roche Basel and Roche Nutley, collectively, “Roche”), and Alnylam
Pharmaceuticals, Inc., a Delaware corporation, having a place of business at 300 Third Street, 3rd
Floor, Cambridge, Massachusetts 02142, U.S.A. (“Alnylam”).



INTRODUCTION




     WHEREAS, Alnylam and Roche are parties to a License and Collaboration Agreement dated as of
July 8, 2007, as supplemented by the letter agreement dated May 29, 2009 between the Parties (the
“LCA”), pursuant to which Alnylam granted to Roche certain non-exclusive licenses to
Alnylam’s proprietary RNAi platform technology;



     WHEREAS, pursuant to the LCA, Alnylam and Roche have agreed to pursue a collaboration
regarding the Discovery and Development of potential RNAi Compounds directed to certain Targets
through at least initiation of IND-Enabling Studies; and



     WHEREAS, Alnylam and Roche desire to undertake a collaboration regarding an RNAi Product
initially directed to the [**], and to apply Alnylam’s proprietary lipid nanoparticle (LNP)
technology, Roche’s proprietary dynamic polyconjugate (DPC) technology and other relevant
technologies to such collaboration, on the terms and conditions of this Agreement.



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



ARTICLE I




DEFINITIONS


The definitions are set forth on Exhibit A.




ARTICLE II




MANAGEMENT OF COLLABORATIVE ACTIVITIES



     Section 2.1 Joint Steering Committee. The Parties hereby establish a joint committee
to facilitate the Collaboration as follows:



          (a) Composition of the Joint Steering Committee. The Discovery and Development
elements of the Collaboration shall be conducted under the direction of a joint steering committee
(the “JSC”) comprised of three (3) named representatives of Roche and three (3) named
representatives of Alnylam or such other number of representatives as the Parties may from time to
time mutually agree. Each Party shall appoint its respective representatives to the





 









 







JSC from time
to time, and 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 JSC
representative who is a senior employee (vice president level or above), and all JSC
representatives shall have appropriate expertise and ongoing familiarity with the Collaboration.
Each Party’s respective representatives to the Joint Future Technology Committee may initially
serve as such Party’s representatives to the JSC hereunder. Additional representatives or
consultants may from time to time, by mutual consent of the Parties, be invited to attend JSC
meetings, provided such representatives’ and consultants are subject to written obligations that
are no less stringent than the confidentiality obligations and restrictions on use set forth in
Article IX. All proceedings for the JSC shall take place in English. Each Party shall bear its
own expenses relating to attendance at such meetings by its representatives.




          (b) JSC Chairperson. The chairperson of the JSC (the “JSC Chairperson”) shall
rotate every twelve (12) months between Alnylam and Roche. The chairman of the Joint Future
Technology Committee may serve as the initial JSC Chairperson. The JSC Chairperson’s
responsibilities shall include (i) scheduling meetings at least [**] per Calendar Quarter, but more
frequently if the JSC determines it necessary; (ii) setting agendas for meetings with solicited
input from other members; and (iii) confirming and delivering minutes to the JSC for review and
final approval.




          (c) Meetings; Minutes. The first JSC meeting shall be held within [**] days after the
Effective Date, and the JSC shall meet in accordance with a schedule established by mutual
agreement of the Parties, but no less frequently than [**] each Calendar Quarter, with the location
for such meetings alternating between Alnylam facilities in Massachusetts and Roche facilities in
the U.S. (or such other locations as are determined by the JSC). Alternatively, the JSC may meet
by means of teleconference, videoconference or other similar communications equipment, but at least
[**] meetings per Calendar Year shall be conducted in person. A secretary shall be appointed for
each meeting and shall prepare minutes of the meeting, it being understood that the secretary and
the JSC Chairperson shall not be representatives of the same
Party (that is, if the JSC Chairperson is a representative of Roche, the secretary shall be a
representative of Alnylam, and vice versa).




          (d) JSC Responsibilities. The JSC shall have the following responsibilities with
respect to the Collaboration, unless and until either Party exercises its Opt-Out Right or the JSC
otherwise dissolves:




               (i) reviewing, proposing to the Parties, and deciding, as necessary, (A) each annual update to
the Joint Research Plan or the Development Plan, as applicable (with the goal of finalizing such
annual update by [**] of each Calendar Year), and (B) any modifications to the Joint Research Plan
or the Development Plan, as applicable, in each case excluding any budgets;



               (ii) regularly assessing, and updating the Parties as necessary on, the progress of the
Parties in their conduct of the Joint Research Plan or the Development Plan, as applicable, against
the timelines contained therein;



-2-









 





               (iii) reviewing relevant data generated during the course of the Program and advising the
Parties on general Development strategy and issues of priority;



               (iv) coordinating the Parties’ efforts in the Discovery or Development of the Licensed
Product(s) in the Field in the Territory, including regulatory matters;



               (v) establishing procedures for the calculation and maintenance of Development Costs incurred
by each Party consistent with the guidelines set forth on Exhibit E;



               (vi) review, discuss and coordinate the scientific presentation and publication strategy
relating to Licensed Products in the Field in the Territory prior to First Commercial Sale; and



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



     For purposes of clarity, (I) it is expected that with respect to the sharing of information
regarding the Licensed Product(s), each Party will, through the JSC and through regular
communication between each Party’s designated Alliance Manager (if the JSC remains in place), keep
the other Party promptly informed at a reasonably detailed level about all activities related to
the Discovery, Development, Manufacture and Commercialization of the Licensed Product(s) in the
Field in each of the Major Market Countries and the rest of the Territory, and will promptly
provide information reasonably requested of such Party by the other Party related thereto, and (II)
the JSC shall have the authority to update or modify the Joint Research Plan or the Development
Plan (in each case, excluding the budget), and to determine the allocation of resources among the
various items set forth in the Joint Research Plan or Development Plan budget, provided
that the JSC does not alter the overall budget or either Party’s overall financial
obligations under the Joint Research Plan or Development Plan, as applicable.



          (e) Dissolution of JSC. The JSC shall be dissolved (i) if at the time of the First
Commercial Sale of Licensed Product in the Territory there is no further Development
contemplated for any Licensed Products for any indication beyond the indication approved on
First Commercial Sale, or (ii) at such time as any exercise by either Party of its Opt-Out Right
becomes effective under Section 4.9, in which case the JSC shall be dissolved solely with respect
to the Opt-Out Product(s); provided that, after August 9, 2012, Alnylam shall have
the right, but shall not be obligated, to participate on the JSC. If Alnylam elects not to
participate in the JSC, then Roche shall have the right to make all decisions related to the
Discovery and Development of Licensed Products under the Collaboration, subject to Section 2.5(d),
Roche’s diligence obligations under Article VIII, and other applicable terms and conditions of this
Agreement.




     Section 2.2 Joint Commercialization Team.



          (a) Establishment of JCT. Commencing with the earlier of (x) initiation of the first
Phase III Study of Licensed Product, and (y) the date [**] prior to the anticipated launch of the
first Licensed Product in the Territory, unless and until either Party exercises its Opt-Out Right,
the Parties will establish a joint commercialization team (“JCT”) to coordinate the
Commercialization of the Licensed Product(s) in the United States. The provisions of Sections
2.1(a) (with each Party’s respective representatives to the JSC initially serving as such Party’s




-3-









 







representatives to the JCT hereunder), 2.1(b) (with the chairman of the JSC serving as the initial
JCT chairperson), 2.1(c) and 2.4 relating to the operation of the JSC shall also apply to the JCT.




          (b) Dissolution of the JCT. The JCT shall be dissolved solely with respect to the
applicable Opt-Out Products upon the effective date of either Party’s exercise of its Opt-Out
Right; provided, however, that after August 9, 2012, Alnylam shall have the
right, but not the obligation, to participate on the JCT. If Alnylam elects not to participate in
the JCT, then Roche shall have the right to make all decisions related to the Commercialization of
Licensed Products in the U.S. under the Collaboration, subject to Section 2.5(d), Roche’s diligence
obligations under Article VIII, and other applicable terms and conditions of this Agreement.




          (c) JCT Responsibilities. The responsibilities of the JCT shall include:




               (i) reviewing, commenting on and advising the Parties on the initial Commercialization Plan;



               (ii) reviewing, proposing to the Parties, and deciding, as necessary, (A) each annual update
to the Commercialization Plan (with the goal of finalizing such annual update by [**] of each
Calendar Year), and (B) any modifications to the Commercialization Plan, in each case excluding any
budgets;



               (iii) regularly assessing, and updating the Parties as necessary on, the progress of the
Parties in their conduct of the Commercialization Plan against the timelines contained therein;



               (iv) advising the Parties on general Commercialization strategy and issues of priority;



               (v) coordinating the Parties’ efforts in the Commercialization of the Licensed Product(s) in
the Field in the Territory, including regulatory matters;



               (vi) coordinating with the JSC regarding Development matters as necessary or appropriate to
Commercialization of the Licensed Product(s) in the United States;



               (vii) performing such other activities as the Parties agree in writing shall be the
responsibility of the JCT;



               (viii) coordinate the Parties’ efforts with respect to the initiation and conduct of any
Post-Approval Studies proposed to be conducted for Licensed Product(s) in the United States;



               (ix) review, discuss and coordinate the scientific presentation and publication strategy
relating to Licensed Product(s) in the Field in the Territory following First Commercial Sale; and



               (viii) attempting to resolve any and all disputes within the JCT’s purview relating to the
Commercialization of the Licensed Product(s) by consensus pursuant to Section 2.5.



-4-









 





          (d) Limitations on JCT Authority. For purposes of clarity, the JCT shall have the
authority to update or modify the Commercialization Plan (in each case, excluding the budget), and
to determine the allocation of resources among the various items set forth in the Commercialization
Plan budget, provided that the JCT does not alter the overall budget for the United
States or either Party’s overall financial obligations under the Commercialization Plan.




     Section 2.3 Appointment of Subcommittees, Project Teams and Alliance Managers. The
JSC shall be empowered to create such subcommittees of itself and project teams as it may deem
appropriate or necessary. Each such subcommittee and project team shall report to the JSC, which
shall have authority to approve or reject recommendations or actions proposed thereby subject to
the terms of this Agreement. Each Party shall also designate an alliance manager (each, an
“Alliance Manager”), who shall be responsible for the day-to-day coordination of the
Collaboration and will serve to facilitate communication between the Parties. Each Party may
change its designated Alliance Manager from time to time upon written notice to the other Party.
Among the subcommittees contemplated, it is expected that the JSC will establish a joint project
development team (“JPDT”) to share information through regular communications regarding the
Development of Licensed Product(s) in the Territory, a joint finance team (“JFT”) regarding
cost sharing and budgeting, and other joint teams as necessary regarding Manufacturing, patent and
other matters. After August 9, 2012, Alnylam shall have the right, but not the obligation, to
participate on any of the subcommittees contemplated in this Section 2.3.



     Section 2.4 JSC and JCT Decisions by Consensus. Decisions within the purview of the
JSC or, if applicable, the JCT shall be made by consensus, with the representatives of each Party
collectively having one vote on behalf of such Party. For each meeting of the JSC or, if
applicable, the JCT 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, as may be mutually agreed by the Parties.



     Section 2.5 JSC or JCT Deadlocks; Dispute Resolution; Decision-Making Authority.



          (a) The JSC (or, if applicable, the JCT) shall attempt to resolve any and all disputes over
any matter that is within such committee’s purview relating to the Collaboration by consensus.




          (b) If the JSC (or, if applicable, the JCT) is unable to reach a consensus with respect to a
dispute within such committee’s purview, then the dispute shall be submitted to escalating levels
of Alnylam and Roche senior management for review. If such dispute cannot be resolved despite
escalation, then the Executive Officers of Alnylam and Roche shall attempt to resolve such dispute.




          (c) If, despite the Executive Officers’ efforts to resolve a dispute pursuant to clause (b),
the Executive Officers cannot reach an agreement regarding such dispute within [**] days after
submission to them for resolution, then:




               (i) unless either Party has exercised its Opt-Out Right hereunder, if the dispute relates to
the Development of the Licensed Product(s) prior to First Phase II



-5-









 




Completion, then [**] shall have
the final decision-making authority over operational matters related to any Clinical Study
conducted by [**];




               (ii) unless either Party has exercised its Opt-Out Right hereunder, [**] shall have final
decision-making authority over Development and Commercialization activities that are specific to
the ROW Territory so long as such decision does not materially negatively affect Development and
Commercialization activities that are specific to the U.S.;



               (iii) the Party that is responsible for booking sales in the U.S. shall have final
decision-making authority over (A) the price and commercial terms of Licensed Product(s) in the
U.S., (B) a policy governing the handling of all returns, recalls, order processing, invoicing and
collection, distribution, and inventory and receivables for Licensed Product(s) in the U.S., (C)
(1) any label or other written, printed or graphic matter upon (aa) any container or wrapper
utilized with Licensed Product(s) in the U.S. or (bb) any written material accompanying any
container or wrapper utilized with Licensed Product(s) in the U.S. including package inserts, and
(2) any communication or program associated with the promotion of Licensed Product(s) in the U.S.,
including such communications and programs that (aa) specifically identify or describe Licensed
Product(s) or (bb) otherwise support Licensed Product(s) or raise awareness of the Field, and (D)
whether or not to recall or withdraw Licensed Product(s) in the U.S.; provided,
however, that, such Party shall have the obligation to give due consideration to
any recommendations or opinions offered by the other Party, consistent with the principle of
setting the wholesale price of Licensed Product(s) to its maximum potential without regard to its
effect on other products, to the extent permitted by applicable Laws; and



               (iv) if the dispute does not fall within clause (i), (ii) or (iii) above, then neither Party
may implement any activities that would result from resolution of the matter until consent of the
other Party is achieved; it being understood that, in the event that either Party exercises its
Opt-Out Right, the Continuing Party shall have final decision-making authority with respect the
Discovery, Development, Commercialization and Manufacture of the Opt-Out Product(s), subject to
Section 2.5(d), the Continuing Party’s diligence obligations under Article VIII, and other
applicable terms and conditions of this Agreement.



          (d) Notwithstanding anything in this Agreement to the contrary, in no event may the JSC, the
JCT or either Party have the unilateral right to amend any term of this Agreement. In addition, in
no event shall either Party have the unilateral right to:




               (i) increase the other Party’s obligations or reduce the other Party’s rights under this
Agreement in connection with the Program Target(s) or Licensed Product(s), including any obligation
to devote additional personnel or financial resources to a specific activity or project to be
conducted by the other Party under the Joint Research Plan, Development Plan, or Commercialization
Plan as applicable;



               (ii) determine whether the events required for the payment of any event payments hereunder
have occurred;



               (iii) determine whether a Party has fulfilled or breached any of its obligations under this
Agreement;



-6-









 





               (iv) make a decision that is expressly stated in this Agreement to require the other Party’s
approval or consent, or the mutual agreement of the Parties; or



               (v) otherwise expand such Party’s rights or reduce such Party’s obligations under this
Agreement in connection with the Program Target(s) or Licensed Product(s).



ARTICLE III




LICENSE GRANTS; EXCLUSIVITY



     Section 3.1 License Grants to Roche. Subject to the terms and conditions of this
Agreement and to Alnylam Third Party Obligations:



          (a) License During the Research Term. Alnylam hereby grants to Roche an exclusive,
non-royalty-bearing right and license, with the right to grant sublicenses as set forth in Section
3.1(d), under Alnylam’s rights to the Alnylam Technology, to perform the activities assigned to
Roche under the Joint Research Plan in the Field in the Territory during the Research Term.




          (b) License if Alnylam has not Opted-Out. Unless Alnylam exercises its Opt-Out Right
(in which case Section 3.1(c) shall apply), subject to Alnylam’s retained rights under Section 3.5,
Alnylam hereby grants to Roche an exclusive right and license, with the right to grant sublicenses
as set forth in Section 3.1(d), under Alnylam’s rights to the Alnylam Technology, to Develop,
Manufacture and Commercialize the Licensed Product(s) in the Field in the Territory. Such license
shall be (i) subject to event payments pursuant to Section 9.1 and shall be royalty-bearing for the
Royalty Term of each Licensed Product in each country of the ROW Territory as set forth in Section
9.3(a), and (ii) subject to the Parties’ rights and obligations with respect to sharing of Profits
and costs in the United States as set forth in Section 4.8 and Section 9.2.




          (c) License if Alnylam Opts-Out. If Alnylam exercises its Opt-Out Right, Alnylam
hereby grants to Roche an exclusive right and license, with the right to grant sublicenses as set
forth in Section 3.1(d), under Alnylam’s rights to the Alnylam Technology as has been incorporated
into, or has been used in or (as documented in the Joint Research Plan, the Development Plan or the
Commercialization Plan, or any approved JSC or JCT minutes, as applicable) has been intended for
use in, the Development, Manufacture or Commercialization of the Licensed Product(s) under this
Agreement as of the effective date of Alnylam’s exercise of such Opt-Out Right, to Develop,
Manufacture and Commercialize such Licensed Product(s) in the Field in the Territory. Such license
shall be subject to event payments pursuant to Section 9.1 and shall be royalty-bearing for the
Royalty Term of each Licensed Product in each country of the Territory as set forth in Section
9.3(b).






-7-









 








          (d) Roche Sublicense Rights.




               (i) Roche shall have the right to grant sublicenses under the licenses granted to it pursuant
to Sections 3.1(a), 3.1(b) and 3.1(c), and the right to grant licenses of its rights under any
Joint Collaboration IP, to (x) an entity that is its Affiliate for so long as such entity remains
an Affiliate of Roche and complies in all material respects with the obligations of Roche under
this Agreement, or (y) to Third Party Contractors retained by Roche in accordance with Section 3.4.
Roche hereby guarantees the full payment and performance of its Affiliates under this Agreement.
In addition, Roche shall have the right to grant sublicenses under the licenses granted to it
pursuant to Sections 3.1(a), 3.1(b) and 3.1(c), and the right to grant licenses of its rights under
any Joint Collaboration IP, to Third Parties subject to the limitations of Section 3.1(d)(ii),
Section 3.1(d)(iii) and Section 3.3.



               (ii) Unless and until Alnylam has exercised its Opt-Out Right, and subject to Section
3.1(d)(iii), Roche shall not have any right to grant to any Third Party any sublicenses of its
rights and the licenses granted to it under this Agreement, or any licenses under Roche’s interest
in any Joint Collaboration IP, in each case to Discover, Develop, Manufacture and Commercialize the
Licensed Product(s) in the Field:



                    (A) for the United States, without the prior written consent of Alnylam; and



                    (B) for any of the Major EU Countries, without first notifying Alnylam of such proposed
sublicense or license, on a sublicense-by-sublicense or license-by-license basis, including the
Major EU Country(ies) proposed to be covered by the sublicense or license and any other terms as
may be reasonably requested by Alnylam to allow Alnylam to decide whether or not to pursue the
negotiation of such sublicense or license. If Alnylam notifies Roche within [**] days after
receipt of such notice from Roche that Alnylam does not want to pursue the negotiation of such
sublicense (or Alnylam is silent during such 30-day period), Roche shall be free to negotiate and
enter into a sublicense agreement with a Third Party for a period of [**] months, after the
expiration of which the terms of this Section 3.1(d)(ii)(B) shall once again apply. If Alnylam
notifies Roche within such [**]-day period that Alnylam desires to pursue such negotiations, the
Parties shall negotiate in good faith and seek to finalize commercially reasonable terms of such
sublicense or license within an additional [**] days. If the Parties are able to finalize the
terms of such sublicense within such [**]-day period, the Parties shall enter into such
agreement, either in the form of an amendment to this Agreement or a side letter, and the
Development Plan or Commercialization Plan, as the case may be, shall be updated as necessary by
mutual agreement of the Parties. If the Parties are unable to finalize the terms of such
sublicense or license within such additional [**]-day period, Roche may enter into negotiations
with a Third Party with respect to such proposed sublicense or license; provided,
however, that if the terms offered to such Third Party are more favorable in the
aggregate to such Third Party than the terms last offered to Alnylam during the [**]-day
negotiation period set forth above, and Alnylam has at least comparable relevant capabilities as
the respective sublicensee(s), then Roche shall first offer such more favorable terms to Alnylam.



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               (iii) Without limiting Section 3.1(d)(ii) above, any sublicenses granted by Roche hereunder
shall be consistent with the sublicense terms and requirements under the LCA, and Roche shall
provide Alnylam with reasonable notice of any such sublicense granted hereunder.



          (e) Certain Limitations to Licenses Granted to Roche.




               (i) The grants by Alnylam under Alnylam Technology set forth in Section 3.1 are subject to,
and are limited to the extent of, the rights that Alnylam has previously granted and is required to
grant under Alnylam Technology to Alnylam Pre-Existing Alliance Parties under the terms of the
Alnylam Pre-Existing Alliance Agreements. As and to the extent that such rights previously granted
to Alnylam Pre-Existing Alliance Parties under Alnylam Technology (whether such rights are
previously or subsequently exercised) lapse, terminate or otherwise revert to Alnylam, they shall
be automatically included in the rights under Alnylam Technology granted to Roche with respect to
the Licensed Product(s) under Sections 3.1(a), 3.1(b) and 3.1(c) without any further consideration
from Roche. For purposes of clarity, this Section 3.1(e)(i) is not intended to expand the rights
or licenses granted to Roche if Alnylam exercises its Opt-Out Right prior to August 9, 2012, nor to
expand the rights or licenses granted to Roche beyond those described in Section 3.1(c) or Section
14.5(b)(ix) (as applicable).



               (ii) Roche acknowledges that an Alnylam Pre-Existing Alliance Party may from time to time
request rights under Alnylam Technology with respect to a particular Target that Alnylam is
required, pursuant to the terms of an Alnylam Pre-Existing Alliance Agreement, to grant such rights
to such Alnylam Pre-Existing Alliance Party with respect to such Target.



               (iii) For the avoidance of doubt, the grants by Alnylam under Alnylam Technology set forth in
Sections 3.1(a), 3.1(b) and 3.1(c) include, subject to Section 3.1(f), the sublicense of Alnylam
Technology that is not owned by Alnylam. Roche’s rights and licenses under such Alnylam Technology
are limited to the rights granted by Listed Alnylam Counterparties to Alnylam under the Listed
Alnylam Third Party Agreements, and Roche shall comply, and cause its Affiliates and Licensee
Partners to comply, with those restrictions and other terms applicable to sublicensees under such
agreements, copies of which have been or will be made available to Roche, as applicable. Without
limiting the generality of the foregoing, Roche acknowledges that certain obligations are imposed
on sublicensees of certain of the sublicensed Alnylam Technology, and agrees to comply (to the
extent access to obligations and requirements have been made available to Roche in unredacted
form), and to require its Affiliates and Licensee Partners to comply, with such obligations and
requirements. Notwithstanding the foregoing, at the request of Roche, which request shall be made
within the [**] period prior to First Commercial Sale of the first Licensed Product, Alnylam shall
use commercially reasonable efforts to seek to harmonize the accounting and royalty reporting
provisions under the Listed Alnylam Third Party Agreements with the accounting and royalty
reporting provisions set forth in this Agreement.



          (f) [**] Patent Rights. Notwithstanding anything to the contrary herein, the licenses
to Alnylam Patent Rights hereunder initially shall not include licenses to Patent Rights licensed
by Alnylam or its Affiliates under the Non-Exclusive License Agreement between [**]






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and Alnylam, dated [**] (the “[**] Agreement”), which Patent Rights Roche shall have
the option, exercisable upon written notice to Alnylam at any time during the Term prior to August
9, 2012, to license solely with respect to Licensed Product(s) under this Collaboration. Upon such
election, for no additional consideration from Roche (i) the license granted to Roche under
Alnylam’s rights to Alnylam Patent Rights pursuant to Sections 3.1(a), 3.1(b) and 3.1(c) of this
Agreement shall include such Patent Rights with respect to the designated Licensed Product(s), and
(ii) the [**] Agreement shall be deemed a Listed Alnylam Third Party Agreement and Exhibit
B-2 hereof shall be amended accordingly.




     Section 3.2 License Grants to Alnylam. Subject to the terms and conditions of this
Agreement:



          (a) License During the Research Term. Roche hereby grants to Alnylam an exclusive,
non-royalty-bearing right and license, with the right to grant sublicenses as set forth in Section
3.2(d), under Roche’s rights to the Roche Technology, to perform the activities assigned to Alnylam
under the Joint Research Plan in the Field in the Territory during the Research Term.




          (b) License if Roche has not Opted-Out. Unless Roche exercises its Opt-Out Right (in
which case Section 3.2(c) shall apply), Roche hereby grants to Alnylam an exclusive right and
license, with the right to grant sublicenses as set forth in Section 3.2(d), under Roche’s rights
to the Roche Technology, to carry out Development, Commercialization and Manufacturing activities
to the extent contemplated in the Development Plan, the Commercialization Plan, the Supply
Agreement (as applicable) or as otherwise agreed by the Parties hereunder. Such license shall be
subject to the Parties’ rights and obligations with respect to sharing of Profits and costs in the
United States as set forth in Section 4.8 and Section 9.2.




          (c) License if Roche Opts-Out. If Roche exercises its Opt-Out Right, Roche hereby
grants to Alnylam an exclusive right and license, with the right to grant sublicenses as set forth
in Section 3.2(d), under Roche’s rights to the Roche Technology as has been incorporated into, or
has been used in or (as documented in the Joint Research Plan, the Development Plan or the
Commercialization Plan, or any approved JSC or JCT minutes, as applicable) has been intended for
use in, the Development, Manufacture or Commercialization of the Licensed Product(s) under this
Agreement as of the effective date of Roche’s exercise of such Opt-Out Right, to Develop,
Manufacture and Commercialize such Licensed Product(s) in the Field in the Territory. Such license
shall be subject to event payments pursuant to Section 9.1 and shall be royalty-bearing for the
Royalty Term of each Licensed Product in each country of the Territory as set forth in Section
9.3(c).




          (d) Alnylam Sublicense Rights.




               (i) Alnylam shall have the right to grant sublicenses under the licenses granted to it
pursuant to Sections 3.2(a), 3.2(b) and 3.2(c), and the right to grant licenses of its rights under
any Joint Collaboration IP, to (x) an entity that is its Affiliate for so long as such entity
remains an Affiliate of Alnylam and complies in all material respects with the obligations of
Alnylam under this Agreement, and (y) to Alnylam’s Third Party Contractors in accordance with
Section 3.4. Alnylam hereby guarantees the full payment and performance of its Affiliates under
this Agreement.



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               (ii) Unless and until Roche has exercised its Opt-Out Right, Alnylam shall not have any right
to grant to any Third Party any sublicenses of its rights and the licenses granted to it under this
Agreement, or any licenses under Alnylam’s interest in any Joint Collaboration IP, in each case to
Discover, Develop, Manufacture and Commercialize the Licensed Product(s) in the Field in the
Territory, without the prior written consent of Roche.



     Section 3.3 Sublicensing Terms.



          (a) Each sublicense agreement shall be consistent with the terms and conditions of this
Agreement. Each Party shall remain liable to the other Party for each of such Party’s (or its
Affiliate’s) sublicensees’ failure to comply with all applicable restrictions, limitations and
obligations under the sublicense agreement and this Agreement. No sublicense granted by a Party
hereunder may be assigned, transferred or further sublicensed to any Third Party without the prior
written consent of such Party.




          (b) Each Party shall provide a redacted copy of any sublicense agreement entered into by such
Party to the other Party (such redactions to exclude only the financial terms of such sublicense
and other information normally redacted from a document filed with the U.S. Securities and Exchange
Commission), (i) if such sublicense impacts upon one or more of the Major Market Countries, and
(ii) upon request by such other Party, in any country other than a Major Market Country.




     Section 3.4 Third Party Contractors. Either Party may perform its Collaboration
responsibilities hereunder through the use of Third Party Contractors; provided
that such Party shall remain primarily liable for such Party’s obligations under this
Agreement; and provided further that such Party shall ensure that any such
Third Party Contractor is under an obligation to assign, or grant an exclusive, sublicensable
license, to such Party under all Know-How, Patent Rights, and other intellectual property rights
discovered, conceived, invented or reduced to practice by such Third Party Contractor pursuant to
the conduct of such Party’s Collaboration responsibilities hereunder and related to any Program
Target, RNAi Product or Licensed Product hereunder.



     Section 3.5 Retained Rights. Notwithstanding anything in this Agreement to the
contrary, Alnylam retains all rights necessary under Alnylam Technology, and Roche retains all
rights necessary under Roche Technology, to perform such Party’s obligations and exercise such
Party’s rights under this Agreement, including conducting the activities assigned to such Party
under the Joint Research Plan, Development Plan or Commercialization Plan, as the case may be.



     Section 3.6 No Implied Licenses. Except as explicitly set forth in this Agreement,
neither Party grants to the other Party any license, express or implied, under its intellectual
property rights.



     Section 3.7 Exclusivity Covenant. Subject to Alnylam Third Party Obligations and
Section 15.15:



          (a) During the Research Term and for a period of [**] thereafter, neither Party nor such
Party’s Affiliates shall, except pursuant to this Agreement, directly or indirectly,






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conduct Development of, Manufacture or Commercialize, anywhere in the Territory, any
Competitive Product, or grant any rights to a Third Party to do any of the foregoing.




          (b) After the Research Term, during the period of Development prior to the first Regulatory
Approval in the Territory of a Licensed Product under the Program for the given Program Target(s)
to which such Licensed Product is directed, neither Party nor such Party’s Affiliates shall, except
pursuant to this Agreement, directly or indirectly, conduct Development of, Manufacture or
Commercialize, anywhere in the Territory, any Competitive Product directed to such given Program
Target(s), or grant any rights to a Third Party to do any of the foregoing. Without limiting the
foregoing exclusivity with respect to any Program Target(s) that remain in the Program, if either
Party exercises its Opt-Out Right during such period of Development prior to the first Regulatory
Approval for any Opt-Out Product(s) in the Territory and the other Party assumes the unilateral
Development and Commercialization of such Opt-Out Product(s), the opting-out Party and its
Affiliates shall not, except pursuant to this Agreement, directly or indirectly, conduct
Development in a Phase II Study of, or Commercialize, anywhere in the Territory, any Competitive
Product directed against the same Program Target(s) as the Opt-Out Product(s), or grant any rights
to a Third Party to do any of the foregoing, for a period of [**] from and after the effective date
of such opt-out.




          (c) For a period of [**] after the first Regulatory Approval in the Territory for a Licensed
Product under the Program for the given Program Target(s) to which such Licensed Product is
directed, neither Party nor such Party’s Affiliates shall, except pursuant to this Agreement,
directly or indirectly, conduct Development in a Phase III Study of, or Commercialize, anywhere in
the Territory, any Competitive Product directed to such given Program Target(s), or grant any
rights to a Third Party to do any of the foregoing. Without limiting the foregoing exclusivity
with respect to any Program Target(s) that remain in the Program, if either Party exercises its
Opt-Out Right during such period of [**] after the first Regulatory Approval for any Opt-Out
Product(s) in the Territory and the other Party assumes the unilateral Development and
Commercialization of such Opt-Out Product(s), the opting-out Party and its Affiliates shall not,
except pursuant to this Agreement, directly or indirectly, conduct Development in a Phase III Study
of, or Commercialize, anywhere in the Territory, any Competitive Product directed against the same
Program Target(s) as the Opt-Out Product(s), or grant any rights to a Third Party to do any of the
foregoing, for a period of [**] from and after the effective date of such opt-out.




          (d) For purposes of clarity, nothing in clause (a), (b) or (c) above is intended to prohibit
the Party exercising the Opt-Out Right with respect to any Opt-Out Product(s) from continuing to
Develop, Manufacture and Commercialize any Licensed Product(s) other than the Opt-Out Product(s),
or from performing its Manufacturing obligations hereunder with respect to any Opt-Out Product(s),
pursuant to, and in accordance with the terms of, this Agreement.







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ARTICLE IV




COLLABORATION OVERVIEW;

DEVELOPMENT OF LICENSED PRODUCT(S);

OPT-OUT RIGHTS



     Section 4.1 Collaboration Overview. During the Research Term, the Parties will
collaborate in the initial Discovery and Development of an RNAi Product directed to [**] or,
subject to mutual agreement of the Parties pursuant to Section 4.3 with respect to an additional
Program Target, another RNAi Product directed to both [**] and such additional Program Target, in
the Field in the Territory. Following the Research Term, subject to either Party’s exercise of its
Opt-Out Rights, the Parties will collaborate in the continued Development and Commercialization of
the Licensed Product(s); provided that the Parties will Develop the Licensed
Product(s) in the Field for the United States in accordance with the allocations of Development
responsibilities set forth in the Development Plan as amended from time-to-time in accordance with
Section 4.5; it being understood that Alnylam shall have operational responsibility for all
Licensed Product Development activities prior to and through First Phase II Completion. For
purposes of clarity, this Agreement does not contemplate the Development of multiple RNAi Products
each directed to a different Program Target under the Collaboration, unless the Parties otherwise
mutually agree to do so and mutually agree on the terms pursuant to which such Development of such
RNAi Products may be undertaken. In addition the Agreement contemplates that the Parties will
Develop the Licensed Product(s) for the U.S. and the Major EU Countries under a single global
Development Plan governing Development of the Licensed Product(s) from IND-Enabling Studies onward;
provided that none of Alnylam’s participation rights or decision-making authority
with respect to any activities under the Development Plan that are relevant for the U.S. shall be
diminished by virtue of the Development Plan covering activities for both the U.S. and ROW
Territory.



     Section 4.2 Joint Research Plan; Amendments. The initial Discovery and pre-IND
Enabling Development of the Licensed Product(s) shall be governed by the Joint Research Plan during
the Research Term. In addition to annual updates or modifications to the Joint Research Plan
decided by the JSC pursuant to Section 2.1(d), either Party may develop and submit to the JSC from
time to time proposed amendments to the Joint Research Plan (excluding any amendment to the budget,
which amendment shall require the approval of both Parties outside the JSC). Upon approval of such
proposed amendments by the JSC (subject to the limitations set forth in Section 2.1(d)), the Joint
Research Plan shall be amended accordingly.



     Section 4.3 Selection of Program Targets.



          (a) As of the Effective Date, the Parties have selected [**] as the subject of the Program to
be progressed by the Parties during the Research Term.




          (b) Prior to [**], Roche shall have the right to propose, in accordance with the remainder of
this Section 4.3, additional Targets directed to [**] until up to one (1) additional Target is
accepted by Alnylam as a Program Target pursuant to Section 4.3(d) below. Notwithstanding anything
in this Agreement to the contrary, Roche shall not have the right to propose any Blocked Target,
VEGF or KSP for inclusion as a Program Target hereunder.







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          (c) Alnylam shall submit any additional Target proposed by Roche in accordance with clause (b)
above to Novartis in accordance with Section 2.6 of the LCA. Alnylam hereby waives, and Roche
shall not be required to [**] with respect to the Target proposed by Roche pursuant to this Section
4.3 which would otherwise have been payable to Alnylam pursuant to Section 2.6 of the LCA. If
Roche submits multiple Targets simultaneously, then the Parties shall agree to present [**] to
Novartis, unless the Parties otherwise mutually agree that such [**].




          (d) Subject to Novartis’ rejection or waiver of each proposed additional Target pursuant to
clause (c) above, if Alnylam provides, in its sole discretion, written approval of such proposed
additional Target (such approval not to be unreasonably withheld by Alnylam), such Target shall be
deemed a Program Target for all purposes hereunder.




          (e) If Novartis or Alnylam (approval not to be unreasonably withheld by Alnylam) rejects any
proposed Target, Roche shall have the right to propose that an additional Target meeting the
requirements set forth in Section 4.3(b) be included in the Program. If Roche does not propose any
additional Target for inclusion as a Program Target by [**], then Roche’s right to propose an
additional Program Target pursuant to this Section 4.3 shall have no further force or effect, and
the sole subject of the Program and the Collaboration shall remain [**]. Once the first such
additional proposed Target is included in the Program, Alnylam shall have no obligation to waive,
and Roche shall thereafter be obligated to [**], unless the Parties otherwise mutually agree that
such [**] shall be waived.




          (f) For purposes of clarity, while the Parties contemplate that Roche may use Alnylam Platform
Patent Rights or Alnylam Platform Know-How under the LCA to perform activities with respect to the
Program Target during the Term, any activities conducted with respect to a Program Target shall be
conducted pursuant to this Agreement (and not pursuant to the LCA), and the terms of this Agreement
(and not the LCA) shall govern the Parties’ respective rights and obligations with respect to such
Program Target and corresponding RNAi Products and Licensed Products, including financial
obligations.




     Section 4.4 Selection of Development Candidate. During the Research Term, using the
candidate selection criteria set forth in the Joint Research Plan as a guide, each Party shall use
Diligent Efforts to conduct studies under the Program with the goal of identifying at least one (1)
RNAi Product directed to a Program Target (or, subject to Section 4.3, both Program Targets) that
are suitable for advancement as a development candidate into IND-Enabling Studies under this
Agreement. Within [**] days following the completion of activities under the Joint Research Plan,



          (a) the Parties may mutually agree on the selection of at least one (1) RNAi Product directed
to a Program Target (or both Program Targets, if applicable) as a development candidate hereunder
and on a Development Plan pursuant to which the Parties shall pursue the Development of such
development candidate under the Program, in which event the Program, and each Party’s rights and
obligations under this Agreement, shall continue as to such RNAi Product(s) and such Program
Target(s), subject to either Party’s exercise of its Opt-Out Right(s); or







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          (b) if the Parties are unable to mutually agree on the selection of at least one (1)
development candidate hereunder, or are able to mutually agree on the selection of at least one (1)
development candidate but are unable to mutually agree on a Development Plan for such development
candidate, then (i) the Parties may agree to discontinue the Program, and all Discovery and
Development activities hereunder, in which event this Agreement shall be terminated, subject to the
Parties’ mutual agreement on the terms of any necessary wind-down, or (ii) a Party may exercise its
Opt-Out Right at Candidate Selection Stage with respect to a particular RNAi Product Developed
under the Program during the Research Term pursuant to Section 4.9; provided, that,
if a Party has no bona fide interest in pursuing the Program or any RNAi Product Developed under
the Program, such Party shall have a good faith obligation to exercise its Opt-Out Right hereunder.
Notwithstanding the above, in no event shall each Party progress the same development candidate
separately because of being unable to mutually agree on a Development Plan for such development
candidate.




     Section 4.5 Development Plan; Amendments.



          (a) Within [**] days following the completion of activities under the Joint Research Plan, the
Parties shall prepare an initial Development plan (as such plan may be updated or amended from time
to time in accordance with this Agreement, the “Development Plan”) that will cover
Development activities commencing with IND-Enabling Studies through Phase I Completion with respect
to the proposed development candidate(s) under the Program, including a [**] budget for Development
Costs. Each annual update to the Development Plan shall cover Development activities through
completion of the next phase of Development and a [**] budget (or longer, if the Development
activities covered by the Development Plan extend for longer than [**]).




          (b) Unless and until either Party exercises its Opt-Out Right, in addition to annual updates
or modifications to the Development Plan decided by the JSC pursuant to Section 2.1(d), either
Party may develop and submit to the JSC from time to time proposed amendments to the Development
Plan (excluding any amendment to the budget, which amendment shall require the approval of both
Parties outside the JSC). Upon approval of such proposed amendments by the JSC (subject to the
limitations set forth in Section 2.1(d)), the Development Plan shall be amended accordingly.




     Section 4.6 Exchange of Know-How. During the Research Term, each Party shall make
available to the other Party, at no cost or expense to such other Party, such Alnylam Know-How or
Roche Know-How, as the case may be, as is requested by such other Party in connection with such
other Party’s performance of its obligations under the Joint Research Plan or in connection with
the identification, evaluation or selection of development candidates. Upon selection of the first
development candidate under this Agreement and thereafter during the Term, each Party shall make
available to the other Party, at no cost or expense to such other Party, such Alnylam Know-How or
Roche Know-How, as the case may be, as is requested by such other Party in connection with the
Discovery, Development or Commercialization of Licensed Products hereunder, including all data from
any and all clinical trials and preclinical studies and non-clinical development work for Licensed
Products that are in existence as of the completion of all activities under the Joint Research
Plan. Upon selection of the first development candidate under this Agreement and thereafter during
the Term, each Party shall promptly update the other Party




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as to Alnylam Know-How or Roche Know-How, as the case may be, that has not previously been
provided to such other Party under this Agreement, and shall promptly provide to such other Party
any such additional Alnylam Know-How or Roche Know-How, as the case may be, as may be reasonably
requested by such other Party.




     Section 4.7 Records and Reports.



          (a) Each Party will maintain scientific records, in sufficient detail and in good 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 Discovery, Development and Manufacturing
activities with respect to the Licensed Product(s) by such Party and its permitted Third Party
Contractors and permitted Licensee Partners. Each Party will [**] under this Agreement. All such
records, and the information disclosed therein, as well as all disclosures made pursuant to
Sections 2.1(d), 4.6 and 4.7(b), will be maintained in confidence by the recipient in accordance
with Article IX and will only be used for purposes of Discovery, Development, Manufacture and
Commercialization of Licensed Product(s) under this Agreement.




          (b) In addition to the other disclosure obligations set forth in this Section 4.7, at times
and in a manner to be reasonably agreed by the Parties, each Party shall [**] such disclosure.
Upon the request of either Party, the other Party shall [**] such Party; provided
that in any such case the [**]. If requested by either Party or the JSC, the Parties shall
[**] other Party. In addition to the foregoing, if required by a Regulatory Authority(ies) or if
it is reasonably necessary for a Party or its Related Party(ies) to [**] such Party. Section
4.7(b) shall apply [**].




          (c) For purposes of clarity, nothing in Section 4.6 or this Section 4.7 shall obligate a Party
to disclose any Know-How or grant any rights to the other Party that are beyond the scope of the
licenses granted to such other Party under Section 3.1, 3.2 or 14.5 (as applicable).




     Section 4.8 Development Costs. During the Research Term, each Party shall be
responsible for its own internal and out-of-pocket costs of performing activities assigned to such
Party under the Joint Research Plan. Following the Research Term, unless and until either Party
exercises its Opt-Out Right, the Parties shall each share fifty percent (50%) of Development Costs,
as calculated in accordance with the Financial Appendix (Exhibit E).



     Section 4.9 Opt-Out Right.



          (a) Exercise of Opt-Out Right.




               (i) Within [**] days after any of the following stages of Development or Commercialization of
a Licensed Product under the Program (each such stage, an “Opt-Out Point”), each Party
shall have the right, in its sole discretion, to opt-out of further Development and
Commercialization of the Licensed Product(s) under the Program, in its entirety or on a Licensed
Product-by-Licensed Product basis (each such Licensed Product, an “Opt-Out Product”), by
providing written notice to the other Party citing this Section 4.9(a):



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                    (A) [**];



                    (B) [**];



                    (C) [**];



                    (D) [**]; and



                    (E) Thereafter on [**] months prior written notice [**] annually during the [**] quarter of
the other Party’s fiscal year.



               (ii) If a Party exercise its Opt-Out Right, then the other Party may (A) assume the unilateral
Development and Commercialization of the Opt-Out Product(s), in which case such Party shall become
the Continuing Party with respect to such Opt-Out Product(s); or (B) decide not to elect to assume
such Development and Commercialization of the Opt-Out Product(s), in which case such Party shall be
deemed to have terminated this Agreement at will pursuant to Section 14.4 solely with respect to
such Opt-Out Product(s) (it being understood that the Parties shall have the right to continue to
Collaborate on the Development and Commercialization of the remaining Licensed Product(s) under the
Program subject to the terms and conditions of this Agreement).



               (iii) Notwithstanding anything in this Agreement to the contrary, in no event shall either
Party have the right to unilaterally Develop and Commercialize a Licensed Product beyond Phase I
Completion at the same time that the Parties are also Collaborating on the Development and
Commercialization of a Licensed Product in a Phase II Study or beyond hereunder.



               (iv) For purposes of clarity, (A) no exercise by a Party of its Opt-Out Right shall constitute
a breach of such Party’s obligations under this Agreement, and (B) if a Party exercises its Opt-Out
Right under this Section 4.9, then such Party shall be deemed to have opted-out of the Program, in
its entirety or with respect to the Opt-Out Product(s), as applicable, for the entire Territory,
regardless of whether any Licensed Product was being Developed under the Program for sale, or was
being sold, in a particular part of the Territory.



          (b) Effect of Opt-Out by a Party. If a Party exercises its Opt-Out Right, subject to
the Continuing Party’s right to terminate its licenses under Section 14.4 or 14.5(e), upon the
effective date of such Party’s exercise of its Opt-Out Right, the following shall occur:




               (i) The Party that exercises its Opt-Out Right hereunder shall discontinue its participation,
and shall have no further operational rights or obligations (except Manufacturing obligations
hereunder, if any), with respect to the particular Opt-Out Product(s);



               (ii) If applicable, the Parties shall perform a final reconciliation of applicable Profits,
Development Costs and Commercialization Costs (as applicable) for the Opt-Out Product(s) under the
Program pursuant to Exhibit E and neither Party shall have any further right to share in
Profits, or any further obligation to share in Development Costs or Commercialization Costs (as
applicable), with respect to such Opt-Out Product(s) pursuant to Sections 4.8 and 9.2;
provided, however, that the Party that exercises its Opt-Out Right at or
after



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First Phase II Completion shall remain responsible for its share of the costs of any Clinical
Study(ies) conducted, or committed to the conducted, by the other Party with respect to such
Opt-Out Product(s) at the time of the notice of the opt-out, through completion or earlier
termination of such Clinical Study(ies);




               (iii) If Roche is the Party opting out, the licenses granted to Roche under Section 3.1 for
the given Opt-Out Product(s) shall terminate and, if Alnylam decides to continue to unilaterally
pursue the Development and Commercialization of such Opt-Out Product(s) as the Continuing Party
hereunder, (A) the license granted to Alnylam under Section 3.2(c) for the given Opt-Out Product(s)
shall apply (subject to compliance with the financial obligations set forth therein) and (B) the
terms of Sections 14.5(a)(iv), 14.5(a)(v), 14.5(a)(vi) and 14.5(a)(x) shall apply;



               (iv) If Alnylam is the Party opting out, the licenses granted to Alnylam under Section 3.2 (or
Section 14.5(a)(ix), as the case may be) for the given Opt-Out Product(s) shall terminate, and, if
Roche decides to continue to unilaterally pursue the Development and Commercialization of such
Opt-Out Product(s) as the Continuing Party hereunder, (A) the license granted to Roche under
Section 3.1(c) (or Section 14.5(b)(ix), as the case may be) for the given Opt-Out Product(s) shall
apply (subject to compliance with the financial obligations set forth therein), and (B) the terms
of Sections 14.5(b)(iv), 14.5(b)(v), 14.5(b)(vi) and 14.5(b)(x) shall apply;



               (v) Article VI (or the Supply Agreement) and Section 3.7 shall apply in accordance with its
terms; and



               (vi) As between the Parties, the Continuing Party (if any) shall have sole right and
responsibility for the Development, Commercialization and (except to the extent that the opting-out
Party remains responsible under Article VI or the Supply Agreement) Manufacture of the Opt-Out
Product(s) in accordance with the terms of this Agreement, subject to diligence obligations
pursuant to Section 8.2, provided, that such Continuing Party no longer be bound by
the Development Plan or Commercialization Plan (as applicable).



ARTICLE V




COMMERCIALIZATION



     Section 5.1 Commercialization Activities. Subject to the terms and conditions of
this Agreement, the Commercializing Party or Commercializing Parties (as the case may be) shall be
responsible for Commercializing the Licensed Product(s) in the Field in the Territory. Where
Alnylam and Roche are both Commercializing Parties in the United States, unless otherwise mutually
agreed by the Parties, Roche shall be responsible for booking sales in the U.S., which shall
encompass setting the price and commercial terms of Licensed Product, as well as setting a policy
governing the handling of all returns, recalls, order processing, invoicing and collection,
distribution, and inventory and receivables for, Licensed Product(s) in the U.S.



     Section 5.2 Commercialization Costs. If neither Party exercises its Opt-Out Right,
then the Parties shall share in Profits and Commercialization Costs as set forth in Section 9.2;



 -18- 









 




provided, however, that each Party shall be responsible for conducting
the activities assigned to such Party under the Commercialization Plan, including all costs
thereof.




     Section 5.3 Commercialization Plan.



          (a) Unless and until either Party has exercised its Opt-Out Right, commencing no later than
[**] prior to the anticipated launch of the first Licensed Product, the Parties shall prepare and
deliver to the JCT an initial written plan and budget that describes in detail the
Commercialization activities (including pre-launch and launch activities, if applicable, but
excluding Manufacturing activities which shall be addressed as set forth in Article VI) to be
undertaken with respect to Licensed Product(s) in the United States in the next Calendar Year and
the dates by which such activities are targeted to be accomplished (as such plan may be updated or
amended from time to time in accordance with this Agreement, the “Commercialization Plan”).
The Commercialization Plan (including the budget) shall allocate activities between the Parties,
and shall contain sufficient detail with respect to Commercialization tactics and other matters to
enable the JCT to conduct a meaningful review of the Commercialization Plan. The Parties shall
seek to finalize the initial Commercialization Plan for the United States no later than [**] prior
to launch of the first Licensed Product in the United States. It is intended that the
Commercialization Plan will contemplate that the Parties will co-promote Licensed Product in the
United States in a manner that reflects each Parties’ capabilities and that is consistent with each
Parties’ promotional efforts for its own products of similar market potential. The Parties shall
negotiate in good faith a co-promotion agreement that is consistent with the terms of this
Agreement, taking into account the Parties’ respective capabilities, including terms related to
term of co-promotion activities, auditing of sales details, mechanisms to address underperformance
and failure to perform details at agreed upon levels, sales force training, and other customary
terms, with a view to finalizing and entering into such co-promotion agreement as soon as
reasonably practicable.




          (b) In addition to annual updates or modifications to the Commercialization Plan decided by
the JCT pursuant to Section 2.2(c), either Party may develop and submit to the JCT from time to
time proposed amendments to the Commercialization Plan (excluding any amendment to the budget,
which amendment shall require the approval of both Parties outside the JCT). Upon approval of such
proposed amendments by the JCT (subject to the limitations set forth in Section 2.2(d)), the
Commercialization Plan shall be amended accordingly.




ARTICLE VI




MANUFACTURE AND SUPPLY



     Section 6.1 Pre-Candidate Selection Supply. From and after the Effective Date and
before Candidate Selection Stage, each Party will be responsible for supplying its own demands for
API Bulk Drug Substance, Delivery Compound, and Formulated Bulk (as applicable) in quantities that
are sufficient for the conduct of Discovery activities as defined in the Joint Research Plan.



     Section 6.2 Supply for IND-Enabling Studies and Clinical Studies.



 -19- 









 





          (a) Subject to Section 6.3 and Section 6.4, from and after Candidate Selection Stage, the
Parties will agree on a single-source supply strategy and on which Party will be responsible for
Manufacturing supplies for IND-Enabling Studies and Clinical Studies. The responsible Party will
use Diligent Efforts, either itself or through Third Parties, to Manufacture, in accordance with
applicable cGMP, pre-clinical and clinical supply of API Bulk Drug Substance, Delivery Compound,
Formulated Bulk and Finished Product (as applicable), in quantities that are reasonably sufficient
for the conduct of Development of the Licensed Product(s) by the Parties under the Development
Plan. If either Party exercises its Opt-Out Right and such Party has been the supplying Party for
pre-clinical or clinical supply of API Bulk Drug Substance, Delivery Compound, Formulated Bulk or
Finished Product (as applicable), prior to the effective date of such opt-out, unless otherwise
mutually agreed by the Parties, such Party shall be obligated to continue to undertake such
Manufacturing until completion of the transfer of Manufacturing to the Continuing Party according
to Section 6.4, but no longer than [**], if Development is earlier than Phase I Completion, and no
longer than [**], if Development is after Phase I Completion. For purposes of clarity, upon either
Party’s exercise of its Opt-Out Right hereunder, the Continuing Party shall have the right to
Manufacture API Bulk Drug Substance, Delivery Compound, Formulated Bulk or Finished Product, by
itself (or any Related Party) or using a Third Party manufacturer.




          (b) Each Party shall pay the supplying Party the following amounts (or the Parties shall share
as Development Costs, as the case may be) for pre-clinical and clinical supply of API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product, as applicable: (i) if neither
Party has exercised its Opt-Out Right, the supplying Party’s FBMC in the United States and the
supplying Party’s FBMC in the ROW Territory, or (ii) if either Party has exercised its Opt-Out
Right, subject to the principles set forth in Paragraph 6 of Exhibit D, the supplying
Party’s FBMC plus [**] percent ([**]%) for the entire Territory. A Party’s FBMC for API Bulk Drug
Substance, Delivery Compound, Formulated Bulk and Finished Product (as applicable) supplied by such
Party to the other Party pursuant to this Section 6.2 for Development in the United States shall be
included as Development Costs.




          (c) The terms of Exhibit D hereof (the “Supply Agreement Term Sheet”) shall
govern the Manufacture and supply of API Bulk Drug Substance, Delivery Compound, Formulated Bulk
and Finished Product (as applicable) for pre-clinical and clinical Development purposes until such
time as the Parties enter into a Supply Agreement hereunder.




     Section 6.3 Supply Agreement. Subject to Section 6.4, the Parties contemplate that
upon the earlier of (a) the effective date of either Party’s exercise of its Opt-Out Right, or (b)
initiation of the first Phase II Study under the Program, the Parties shall agree to commence
discussions to finalize the terms of a supply agreement for clinical and commercial supply of API
Bulk Drug Substance, Delivery Compound, Formulated Bulk or Finished Product (as applicable) based
on the Supply Agreement Term Sheet (the “Supply Agreement”). The Parties shall use
Diligent Efforts to complete such discussions and execute the Supply Agreement within [**] after
either the exercise of a Party’s Opt-Out Right or the initiation of the first Phase II Study, as
the case may be. The transfer price for commercial supply of API Bulk Drug Substance, Delivery
Compound, Formulated Bulk or Finished Product (as applicable) shall be (i) if neither Party has
exercised its Opt-Out Right, the supplying Party’s FBMC in the United States and the supplying
Party’s FBMC plus [**] percent ([**]%) in the ROW Territory, or (ii) if either Party has



 -20- 









 




exercised its Opt-Out Right, subject to the principles set forth in Paragraph 6 of Exhibit
D, the supplying Party’s FBMC plus [**] percent ([**]%) for the entire Territory. In no event
shall any sale or transfer by the supplying Party of API Bulk Drug Substance, Delivery Compound,
Formulated Bulk or Finished Product to the other Party under this Agreement be included in the
calculation of Net Sales hereunder.




     Section 6.4 Transition of Manufacturing Responsibilities to Continuing Party.



          (a) The Parties contemplate that, at any time following the selection of a development
candidate pursuant to Section 4.4 (but in no event later than First Phase II Completion), in lieu
of Section 6.3 or 6.5, the Parties may agree to transfer responsibility for Manufacturing API Bulk
Drug Substance, Delivery Compound, Formulated Bulk and Finished Product (as applicable) to (i) one
of the Commercializing Parties as may be mutually agreed by the Parties, (ii) if either Party has
exercised its Opt-Out Right, the Continuing Party, or (iii) a Third Party manufacturer designated
by such Commercializing Party or Continuing Party, as the case may be. The undertaking of such
transfer shall not exceed a time period to be mutually agreed by the Parties.




          (b) Promptly after a decision of the Parties pursuant to Section 6.4(a) to transfer
Manufacturing of the API Bulk Drug Substance, Delivery Compound, Formulated Bulk or Finished
Product (as applicable) to the Commercializing Party or to a Third Party supplier designated by the
Commercializing Party, the other Party will transfer to the Commercializing Party or to such Third
Party supplier all documents and Manufacturing information and other Know-How Controlled by such
Party and used in the Manufacture of the API Bulk Drug Substance, Delivery Compound, Formulated
Bulk and Finished Product as of the date of such decision to transfer Manufacturing (as applicable)
(“Manufacturing Technology”).




          (c) Unless and until either Party exercises its Opt-Out Right, the costs and expenses incurred
in connection with any such transfer of Manufacturing Technology under this Section 6.4 shall be
included as Development Costs or included in the calculation of Profit, as applicable. After such
transition, unless and until either Party exercises its Opt-Out Right, the Commercializing Party’s
FBMC for API Bulk Drug Substance, Delivery Compound, Formulated Bulk and Finished Product (as
applicable) supplied for Development in the United States shall be included as Development Costs,
and the Commercializing Party’s FBMC for API Bulk Drug Substance, Delivery Compound, Formulated
Bulk and Finished Product (as applicable) supplied for Commercialization in the United States shall
be included in the calculation of Profit as set forth on Exhibit E.




          (d) From and after such time, if any, as responsibility for Manufacturing API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product is transitioned to the
Commercializing Party, the Commercializing Party shall use Diligent Efforts to Manufacture or have
Manufactured and supply sufficient quantities of the API Bulk Drug Substance, Delivery Compound,
Formulated Bulk or Finished Product (as applicable) to enable such Party (or both Parties, if
applicable) to respond on a timely basis to customer demand for the Licensed Product(s) in the
Territory.







 -21- 









 








          (e) Notwithstanding anything in this Agreement to the contrary, if, at any time prior to any
transfer of Manufacturing responsibility for a particular API Bulk Drug Substance, Delivery
Compound, Formulated Bulk or Finished Product (as applicable) to one Party hereunder, the Parties
determine by mutual agreement that the Manufacture and supply of such API Bulk Drug Substance,
Delivery Compound, Formulated Bulk or Finished Product (as applicable) by a Party to the other
Party hereunder is no longer necessary in light of the Development or Commercialization activities
and objectives under the Joint Research Plan, Development Plan or Commercialization Plan, as the
case may be, and each Party’s requirements and resources, such Party shall no longer be obligated
to Manufacture and supply such API Bulk Drug Substance, Delivery Compound, Formulated Bulk or
Finished Product (as applicable), or to undertake the transfer of Manufacturing technology or any
other Manufacturing-related obligations related to such API Bulk Drug Substance, Delivery Compound,
Formulated Bulk or Finished Product (as applicable), pursuant to this Article VI;
provided, however, that this shall not relieve either Party of any of
its other Manufacturing obligations hereunder.




     Section 6.5 Backup Manufacturing Rights. Notwithstanding any of the foregoing in
this Article VI, upon request by the purchasing Party at any time following the selection of a
development candidate pursuant to Section 4.4 hereof, and at such purchasing Party’s cost, the
supplying Party shall enable the purchasing Party to purchase API Bulk Drug Substance, Delivery
Compound, Formulated Bulk and Finished Product (as applicable) directly from the supplying Party’s
existing Third Party suppliers in such a manner that such purchasing Party shall be assured of a
secondary source of API Bulk Drug Substance, Delivery Compound, Formulated Bulk and Finished
Product (as applicable) unless and until Manufacturing responsibility is transitioned to one Party
under Section 6.3 or the supplying Party is relieved of its Manufacturing obligations pursuant to
Section 6.3(e). If a Third Party supplier for the API Bulk Drug Substance, Delivery Compound,
Formulated Bulk and Finished Product (as applicable) does not exist or has not yet been established
at the time of such request, or the purchasing Party reasonably determines that the supplying Party
is otherwise unable to procure direct supply from such secondary source (e.g., due to the Third
Party supplier’s refusal to enter into a direct supply arrangement with the purchasing Party or due
to the supplying Party’s failure to promptly undertake necessary action), the supplying Party
shall, upon the purchasing Party’s request and at the supplying Party’s cost, transfer all relevant
Manufacturing Technology Controlled by such supplying Party and used in the Manufacture of API Bulk
Drug Substance, Delivery Compound, Formulated Bulk and Finished Product (as applicable) as of the
date of such request by the purchasing Party to a Third Party designated by the purchasing Party
and reasonably acceptable to the supplying Party (such acceptance not to be unreasonably withheld,
conditioned or delayed) to enable such Third Party designated manufacturer to supply to such
purchasing Party the API Bulk Drug Substance, Delivery Compound, Formulated Bulk and Finished
Product (as applicable) as a secondary source and solely for purposes of this Agreement.



     Section 6.6 Technical Regulatory Documentation. If the supplying Party is not the
Lead Regulatory Party, then the supplying Party will be responsible for delivering all technical
documentation necessary for regulatory submissions to the Lead Regulatory Party.



     Section 6.7 Auditing Rights. In addition to the provisions of financial audits
regarding cost of API Bulk Drug Substance, Delivery Compound, Formulated Bulk and Finished Product



 -22- 









 




(FBMC) detailed in Section 9.6, both Parties grant to each other the right at any time and
from time to time, upon reasonable advance notice and during business hours, as applicable, to
inspect the manufacturing facilities of API Bulk Drug Substance, Delivery Compound, Formulated Bulk
and Finished Product, including those of all possible sub-contractors (to the extent agreed to by
such sub-contractors), which are engaged in the manufacture, preparation, shipping, processing or
warehousing for the sole purpose of reviewing the other Party’s compliance with applicable cGMP,
reasonable quality assurance/control standards and applicable EH&S regulations agreed by the
Parties in the quality agreement (cGMP agreement). Each Party shall bear its own out-of-pocket
expenses and costs related to such audit.




ARTICLE VII




REGULATORY MATTERS



     Section 7.1 Regulatory Filings.



          (a) Except as may be otherwise specified by the JSC or JCT (as applicable), or as otherwise
required for a Party to perform its obligations under this Agreement, unless and until either Party
exercises its Opt-Out Right, Roche (or its Related Parties) shall be the holder of all Regulatory
Approvals (including NDA submissions) for the Licensed Product(s) in the Territory;
provided that Alnylam shall be the holder of all INDs and IND submissions for
Licensed Product(s) in the Territory. The Party taking the lead with respect to a particular
regulatory filing hereunder (each, the “Lead Regulatory Party”) shall be Alnylam through
First Phase II Completion and Roche thereafter, unless and until either Party exercises its Opt-Out
Right, in which case the Continuing Party shall be the Lead Regulatory Party. Promptly following
First Phase II Completion (or earlier in countries for which Roche is Lead Regulatory Party),
Alnylam shall transfer to Roche all INDs and IND submissions for Licensed Product(s) in the
Territory, to the extent permitted by applicable Laws and subject to Section 7.1(c).




          (b) The Lead Regulatory Party shall have the right, with respect to regulatory activities
within its purview, to (i) oversee, monitor and coordinate all regulatory actions, communications
and filings with, and submissions to, each Regulatory Authority, (ii) be responsible for
interfacing, corresponding and meeting with each Regulatory Authority, and (iii) be responsible for
maintaining all applicable regulatory filings. The Lead Regulatory Party shall allow the other
Party’s representative(s) to attend Health Authority (“HA”) meetings with respect to a
Licensed Product, through Phase II Completion for such Licensed Product throughout the Territory
and, solely with respect to the U.S., following Phase II Completion. The Lead Regulatory Party
shall notify the other Party reasonably in advance of any such HA meeting(s) to permit the other
Party a reasonable opportunity to prepare for and attend such meeting, and shall provide the other
Party with copies of all material HA correspondence and relevant documents that the Lead Regulatory
Party either receives from, or submits to, the HA throughout the Territory with respect to a
Licensed Product.




          (c) Except as may be otherwise specified by the JSC or JCT (as applicable), or as otherwise
required for a Party to perform its obligations under this Agreement, each Party and its Related
Parties shall have the right to cross-reference all INDs, Regulatory Approvals and all other
regulatory filings filed by the other Party or such other Party’s respective Related






 -23- 









 







Parties in the Territory with respect to the Development, Manufacture or Commercialization of
the Licensed Product(s) by such Party hereunder. For purposes of clarity, following First Phase II
Completion (or earlier in countries in which Roche is the Lead Regulatory Party), it is
contemplated that Roche shall file all INDs and IND submissions directly with the appropriate
Regulatory Authorities.




     Section 7.2 Product Complaints; Pharmacovigilance.



          (a) Each Party will maintain a record of any and all complaints it receives with respect to
the Licensed Product(s), and will use Diligent Efforts to ensure that its Related Parties maintain
such records. Each Party will notify the other Party in reasonable detail of any complaint it
receives with respect to the Licensed Product(s) within sufficient time to allow the other Party
and its Related Parties to comply with any and all regulatory and other requirements imposed upon
them in any jurisdiction in which the Licensed Product(s) is being marketed or tested in Clinical
Studies or Post-Approval Studies.




          (b) In addition, each Party shall promptly notify the other Party if such Party becomes aware
of any information or circumstance that is likely to have a material adverse effect on the
Development, Manufacture or Commercialization of the Licensed Product(s) in the Territory. The
Parties agree that they will execute a separate pharmacovigilance agreement (“Pharmacovigilance
Agreement”), if legally required, specifying the procedure for the information exchange of
adverse events which may occur during the Development of the first Licensed Product in the
Territory.




     Section 7.3 Product Withdrawals and Recalls. If any Regulatory Authority (a)
threatens, initiates or advises any action against a Party or such Party’s Affiliates or Licensee
Partners to remove any Licensed Product(s) from the market in the Territory, or (b) requires or
advises a Party or such Party’s Affiliates or Licensee Partners to distribute a “Dear Doctor”
letter or its equivalent regarding use of such Licensed Product(s) in the Territory, then such
Party shall notify the other Party of such event within [**] Business Days (or sooner if required
by applicable Law) after such Party becomes aware of the action, threat, advice or requirement (as
applicable). The Party that is responsible for booking sales in the U.S. shall decide whether to
recall or withdraw such Licensed Product(s) in the U.S., and the Commercializing Party shall decide
whether to recall or withdraw such Licensed Product(s) in any other territory, at such Party’s own
cost and expense; provided, however, that the Parties will discuss in good
faith whether to recall or withdraw such Licensed Product(s), or to place a recalled or withdrawn
Licensed Product(s) back on the market, in the relevant Territory. The deciding Party shall keep
the other Party reasonably apprised of the efforts undertaken by such Party to recall or withdraw
such Licensed Product(s), or to place such Licensed Product(s) back on the market, in the relevant
Territory, and the other Party shall reasonably cooperate in such efforts.



     Section 7.4 Regulatory Compliance. Each Party agrees that in performing its
obligations under this Agreement, it shall comply in all material respects with all applicable FDA
and other current international regulatory requirements and standards, including FDA’s cGMP and
Good Clinical Practices, and comparable foreign regulatory standards, and other applicable Laws.



     Section 7.5 Debarment.



 -24- 









 





          (a) Each Party hereby certifies that it has not been debarred under the provisions of the
Generic Drug Enforcement Act of 1992, 21 U.S.C. Sec. 335a(a) and (b). If during the term of this
Agreement a Party or any of its employees engaged in the performance of activities under this
Agreement (i) becomes debarred; or (ii) receives notice of an action or threat of an action with
respect to its debarment (“Debarred Party”), at a time period when the Debarred Party is
performing activities under this Agreement (and not if such Debarred Party only has a financial
interest in the Agreement), then the Debarred Party (i) shall immediately notify the other Party,
and (ii) shall immediately cease all activities relating to this Agreement, except to the extent
permitted by applicable Laws and necessary to preserve the safety and welfare of any human subjects
in any ongoing Clinical Studies.




          (b) If a Party becomes debarred, or if a Party receives notice or otherwise becomes aware that
(i) a debarment action has been brought against such Party or any of its employees engaged in the
performance of activities under this Agreement; or (ii) such Party has been threatened with a
debarment action, in each case other than if such Party only has a financial interest in the
Agreement and is performing no activities under this Agreement, then the other Party shall have the
right to terminate this Agreement immediately upon written notice to the Debarred Party.




          (c) Each Party hereby certifies that it has not and will not use in any capacity the services
of any individual, corporation, partnership or association which has been debarred under 21 U.S.C.
Sec. 335(a) or (b) in the performance of any activities in connection with this Agreement. If a
Party becomes aware of the debarment or threatened debarment of any individual, corporation,
partnership or association providing services to such Party which directly or indirectly relate to
the activities under this Agreement (but not if such Party only has a financial interest in the
Agreement), then such Party shall notify the other Party immediately. Upon the receipt of such
notice or if the other Party otherwise becomes aware of such debarment or threatened debarment
(other than if such Party only has a financial interest in the Agreement), the other Party shall
have the right to terminate this Agreement immediately upon written notice to such Party.




          (d) Termination by a Party under this Section shall be deemed termination under Section
14.5(a) if the Debarred Party is Roche or Section 14.5(b) if the Debarred Party is Alnylam.




ARTICLE VIII




DILIGENCE



     Section 8.1 General. Each of Alnylam and Roche shall use Diligent Efforts (a) to
execute and to perform, or cause to be performed, the activities assigned to such Party under the
Joint Research Plan and, unless and until either Party exercises its Opt-Out Right, under the
Development Plan (as applicable), (b) with respect to technology Controlled by such Party, to
apply, in the conduct of Discovery and Development activities under the Joint Research Plan or the
Development Plan (as applicable), the technology that such Party believes to be the optimal
technology to yield the desired results and data under the Program, and (c) to cooperate with the
other in carrying out the Joint Research Plan and the Development Plan (as applicable), in each



 -25- 









 




case in good scientific manner and in compliance with applicable Law, Good Clinical Practice
and Good Laboratory Practice.




     Section 8.2 Development and Commercialization. Subject to the obligation to update
the JSC and JCT, and without limiting the generality of Section 8.1, unless and until either Party
exercises its Opt-Out Right with respect to a particular Licensed Product(s), Roche will be solely
responsible for, and with respect to the Major EU Countries shall use Diligent Efforts with respect
to, the Development and Commercialization of such Licensed Product(s) in the Field in the ROW
Territory. Without limiting the generality of the immediately foregoing sentence, the
Commercializing Party(-ies) shall use Diligent Efforts to seek and obtain Regulatory Approval for
the Licensed Product(s) in each Major Market Country, and to Commercialize the Licensed Product(s)
in those countries in the Territory in which such Commercializing Party has obtained Regulatory
Approval.



ARTICLE IX




FINANCIAL PROVISIONS



     Section 9.1 Event Payments.



          (a) Development Events.




               (i) Until such time as either Party exercises its Opt-Out Right, Roche shall pay Alnylam [**]
percent ([**]%) of the payments set forth in Column A below upon achievement of the corresponding
event set forth below by or on behalf of Roche or any of its Related Parties.



               (ii) If Alnylam unilaterally exercises its Opt-Out Right, Roche shall pay Alnylam an amount
equal to [**] percent ([**]%) of the amount set forth in Column B, Column C, Column D or Column E
in the chart below (as applicable) corresponding to the Opt-Out Point at which Alnylam exercised
its Opt-Out Right, upon achievement of the corresponding event set forth below by or on behalf of
Roche or any of its Related Parties from and after the effective date of Alnylam’s exercise of such
Opt-Out Right.



               (iii) If Roche unilaterally exercises its Opt-Out Right, Alnylam shall pay Roche the following
percentages of the amount set forth in Column B, Column C, Column D or Column E in the chart below
(as applicable) corresponding to the Opt-Out Point at which Roche exercised its Opt-Out Right, upon
achievement of the corresponding event set forth below by or on behalf of Alnylam or any of its
Related Parties from and after the effective date of Roche’s exercise of such Opt-Out Right:



                    (A) [**] percent ([**]%) if opt-out occurs at or before First Phase II Completion; and



                    (B) [**] percent ([**]%) if opt-out occurs after First Phase II Completion.



 -26- 









 





	 	 	 	 	 	 	 	 	 	 	 
	 	 	Payments
	 	 	(In US$[**])
	 	 	Column A	 	Column B	 	Column C	 	Column D	 	Column E
	Development Event	 	[**]	 	[**]	 	[**]	 	[**]	 	[**]
	(1) Initiation of
the first Phase I
Study for Licensed
Product

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(2) Initiation of
the first Phase II
Study for Licensed
Product

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(3) Initiation of
the first Phase III
Study for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(4) Initiation of
the first Phase III
Study for Licensed
Product for a
second (2nd)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(5) First filing
of an NDA in the
United States for
Licensed Product
for the first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(6) First filing
of an NDA in the EU
or with the EMEA
for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(7) First filing
of an NDA in Japan
for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(8) First filing
of an NDA in the
United States for
Licensed Product
for a second (2nd)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(9) Regulatory
Approval in the
U.S. for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]






 -27- 









 






	 	 	 	 	 	 	 	 	 	 	 
	 	 	Payments
	 	 	(In US$[**])
	 	 	Column A	 	Column B	 	Column C	 	Column D	 	Column E
	Development Event	 	[**]	 	[**]	 	[**]	 	[**]	 	[**]
	(10) Regulatory Approval
in the EU
or from the EMEA
for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(11) Regulatory
Approval in Japan
for Licensed
Product for the
first (1st)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	(12) Regulatory
Approval in the
U.S. for Licensed
Product for a
second (2nd)
Indication

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	 	 	 	 	 	 	 	 	 	 
	Total Development
Event Payments

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]





The event payments set forth in this Section 9.1(a) are payable once for each Licensed Product to
achieve the applicable event. If, upon achievement of a particular event for a Licensed Product,
any previous (i.e., higher in the above table) event payment has not been paid for such Licensed
Product, then each event payment payable upon achievement of any such previous event shall become
payable with the payment of the event payment for the subsequent event then achieved. For purposes
of clarity, if a Party opts-out, in no event shall the Continuing Party be responsible for payment
of any previous event payment that was payable, but not paid, by the Party opting-out.




          (b) Sales Events.




               (i) Until such time as either Party exercises its Opt-Out Right, Roche shall pay Alnylam [**]
percent ([**]%) of the amount set forth in Column A upon achievement of the corresponding event set
forth below by or on behalf of Roche or any of its Related Parties.



               (ii) If Alnylam unilaterally exercises its Opt-Out Right, Roche shall pay Alnylam [**] percent
([**]%) of the amount set forth in Column B, Column C, Column D or Column below (as applicable)
corresponding to the Opt-Out Point at which Alnylam exercised its Opt-Out Right, upon achievement
of the corresponding event set forth below by or on behalf of Roche or any of its Related Parties
from and after the effective date of Alnylam’s exercise of such Opt-Out Right.



               (iii) If Roche unilaterally exercises its Opt-Out Right, Alnylam shall pay Roche [**] percent
([**]%) of the amount set forth in Column B, Column C, Column D or



 -28- 









 




Column E below (as applicable) corresponding to the Opt-Out Point at which Alnylam exercised
its Opt-Out Right, upon achievement of the corresponding event set forth below by or on behalf of
Alnylam or any of its Related Parties from and after the effective date of Roche’s exercise of such
Opt-Out Right.




	 	 	 	 	 	 	 	 	 	 	 
	 	 	Payments
	 	 	(In US$[**])
	 	 	Column A	 	Column B	 	Column C	 	Column D	 	Column E
	Sales Event	 	[**]	 	[**]	 	[**]	[**]	[**]
	Aggregate Worldwide
Annual Net Sales of
all Licensed
Products in the
Territory equal to
or greater than
$[**]

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	Aggregate Worldwide
Annual Net Sales of
all Licensed
Products in the
Territory equal to
or greater than
$[**]

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	 	 	 	 	 	 	 	 	 	 
	Total Sales Event
Payments

	 	[**]
	 	[**]
	 	[**]
	 	[**]
	 	[**]






          (c) Achievement of Events. Where Roche is obligated to make a payment to Alnylam
under Sections 9.1(a) or 9.1(b), Roche shall notify Alnylam within [**] Business Days after
achievement or occurrence of an event under Section 9.1(a) or 9.1(b), and Alnylam shall deliver an
invoice reflecting such event and the payment amount to Roche. Where Alnylam is obligated to make
a payment to Roche under Sections 9.1(a) or 9.1(b), Alnylam shall notify Roche within [**] Business
Days after achievement or occurrence of an event under Section 9.1(a) or 9.1(b), and Roche shall
deliver to invoice reflecting such event and the payment amount to Alnylam. Each event payment
under Section 9.1(a) and 9.1(b) shall be deemed earned as of the achievement or occurrence of the
related event and, except as expressly provided otherwise pursuant to Section 9.1(a), shall be paid
within [**] days after such achievement or occurrence.




          (d) Event Payments Payable Only Once. Each event payment under this Section 9.1 shall
be payable only once, upon the first achievement of the applicable event or, in the case of Section
9.1(b), upon the first achievement of the applicable Net Sales threshold in a given Calendar Year.
If more than one of the sales events set forth in Section 9.1(b) first occurs based on sales of
Licensed Product in the same Calendar Year, all of such event payments shall be paid for such
Calendar Year.




     Section 9.2 Profit-sharing and sharing of Commercialization Costs.



          (a) Allocation of Profit and Commercialization Costs in the United States. If neither
Party has exercised its Opt-Out Right, the Parties shall [**] in Profit for as long as





 -29- 











 




Licensed Product(s) are sold in the United States during the Term, as well as [**] of the
Commercialization Costs for as long as Licensed Product(s) are sold in the United States during the
Term. Profit and Commercialization Costs shall be calculated in accordance with the Financial
Appendix (Exhibit E).




          (b) Effect of Opt-Out. For purposes of clarity, notwithstanding any of the foregoing
in this Section 9.2, if either Party exercises its Opt-Out Right, and the other Party elects to
continue Developing and Commercializing the Licensed Product(s), then (i) neither Party shall have
any further rights or obligations to share in Profit and Commercialization Costs as set forth in
clause (a) above, and (ii) the Party that is deemed the Commercializing Party with respect to such
Licensed Product(s) under this Agreement shall be obligated to pay the other Party (A) event
payments pursuant to Section 9.1 upon achievement by the Commercializing Party or its Related
Parties of the relevant events with respect to such Licensed Product(s), and (B) royalties pursuant
to Section 9.3 with respect to Net Sales of such Licensed Product(s) by such Commercializing Party
or its Related Parties.




     Section 9.3 Royalties.



          (a) Ex-US Royalties Payable by Roche if Neither Party Opts-Out. Subject to the
remainder of this Section 9.3, if neither Party has exercised its Opt-Out Right, Roche shall pay,
or cause to be paid, to Alnylam the following royalties on Annual Net Sales of each Licensed
Product in the ROW Territory during the Royalty Term:




	 	 	 	 	 
	 	 	Incremental Royalty
	 	 	Rate
	 	 	Applicable to Such
	Annual Net Sales of a Licensed Product in the ROW Territory during the applicable Calendar Year:	 	Annual Net Sales
	Less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**], but less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**], but less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**], but less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**], but less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**], but less than or equal to $[**]
	 	 	[**]	%
	Greater than $[**]
	 	 	[**]	%





By way of example, if Annual Net Sales of a Licensed Product are [**] dollars and no deductions
were to apply under the remainder of this Section 9.3, then the royalty payable by Roche to Alnylam
under this Section 9.3(a) would be as follows:




	 	 	 	 	 	 	 	 	 	 	 	 	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	 	 	 	 	 	 	 
	Total Royalty Due	 	 	=	 	 	 	[**]	 






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          (b) Worldwide Royalties Payable by Roche if Alnylam Opts-Out. Subject to the
remainder of this Section 9.3, if Alnylam exercises its Opt-Out Right and Roche elects to continue
Developing and Commercializing the Licensed Product(s), Roche shall pay, or cause to be paid, to
Alnylam royalties on Annual Net Sales of each Licensed Product in the Territory during the Royalty
Term, at the royalty rates set forth below corresponding to the Opt-Out Point at which Alnylam
exercised its Opt-Out Right:




	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	Incremental Royalty Rate Applicable to Such Portion of
	Annual Net Sales of a Licensed	 	Annual Net Sales
	Product in the Territory during	 	Column A	 	Column B	 	Column C	 	Column D
	the applicable Calendar Year:	 	[**]	 	[**]	 	[**]	 	[**]
	Less than or equal to $[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 





By way of example, if Alnylam opted-out at First Phase II Completion and Annual Net Sales of a
Licensed Product are [**] dollars and no deductions were to apply under the remainder of this
Section 9.3, then the royalty payable by Roche to Alnylam under this Section 9.3(b) would be as
follows:




	 	 	 	 	 	 	 	 	 	 	 	 	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	 	 	 	 	 	 	 
	Total Royalty Due	 	 	=	 	 	 	[**]	 






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          (c) Worldwide Royalties Payable by Alnylam if Roche Opts-Out. Subject to the
remainder of this Section 9.3, if Roche exercises its Opt-Out Right and Alnylam elects to continue
Developing and Commercializing the Licensed Product(s), then Alnylam shall pay, or cause to be
paid, to Roche royalties on Annual Net Sales of each such Licensed Product in the Territory during
the Royalty Term, at the following percentages of the royalty rates set forth below corresponding
to the Opt-Out Point at which Roche exercised its Opt-Out Right:




               (i) [**] percent ([**]%) if opt-out occurs at or before First Phase II Completion; and



               (ii) [**] percent ([**]%) if opt-out occurs after First Phase II Completion.



	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	 	 	Incremental Royalty Rate Applicable to Such Portion of
	 	 	Annual Net Sales
	 	 	Column A	 	Column B	 	Column C	 	Column D
	Annual Net Sales of a Licensed Product in the Territory during the applicable Calendar Year:	 	[**]	 	[**]	 	[**]	 	[**]
	Less than or equal to $[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**], but
less than or equal to
$[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	Greater than $[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 






     By way of example, if Roche opted-out at First Phase II Completion and Annual Net Sales of a
Licensed Product are [**] dollars and no deductions were to apply under the remainder of this
Section 9.3, then [**]% would be applied to the royalty rates set forth in Column B above and the
royalty payable by Alnylam to Roche under this Section 9.3(c) would be as follows:



-32-









 





	 	 	 	 	 	 	 	 	 	 	 	 	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	[**]
	 	 	[**]	 	 	 	[**]	 	 	 	[**]	 
	 	 	 	 	 	 	 
	Total Royalty Due	 	 	=	 	 	 	[**]	 






          (d) Royalties Payable Only Once. For the avoidance of doubt, the Commercializing
Party’s obligation to pay royalties under this Section 9.3 is imposed only once with respect to the
same unit of Licensed Product, including by reason of such Licensed Product being Covered by more
than one Valid Claim of Alnylam Platform Patent Rights, Alnylam Patent Rights, Roche Patent Rights,
Alnylam Collaboration Patent Rights, Roche Collaboration Patent Rights or Joint Collaboration
Patent Rights.




          (e) Expiration of Patent Coverage. If no Valid Claim of the Alnylam Platform Patent
Rights, Alnylam Patent Rights, Roche Patent Rights, Alnylam Collaboration Patent Rights, Roche
Collaboration Patent Rights or Joint Collaboration Patent Rights Covers a Licensed Product in a
given country, and the Manufacture of such Licensed Product is not Covered by a Valid Claim of any
such Patent Rights in the country of Manufacture, then the royalty rate applicable to such Licensed
Product in such country shall be reduced to [**] percent ([**]%) of the applicable royalty rate set
forth in Section 9.3(a), 9.3(b) or 9.3(c) (as applicable) for any remaining portion of the Royalty
Term which applies to such Licensed Product in such country.




          (f) Royalty Stacking. The Commercializing Party shall be entitled to deduct, from the
royalty payments payable by such Commercializing Party under Section 9.3(a), 9.3(b) or 9.3(c), as
applicable, for a reporting period, [**] percent ([**]%) of Required Third Party Payments paid by
such Commercializing Party with respect to Licensed Products during the applicable reporting
period; provided that in no event shall a deduction under this Section 9.3(f)
reduce any royalty payment payable by the Commercializing Party under Section 9.3(a), 9.3(b) or
9.3(c), as applicable, by more than [**] percent ([**]%).




          (g) Payments in Respect of Third Party In-Licenses.




               (i) In addition to any royalty set forth in Section 9.3(a), 9.3(b) or 9.3(c) which may be
payable by Roche as the Commercializing Party during the Royalty Term, Roche shall reimburse
Alnylam for [**] percent ([**]%) of all royalty payments payable (each such payment, a “Listed
Third Party Payment,” collectively, the “Listed Third Party Payments”) to Third Parties
pursuant to Listed Alnylam Third Party Agreements in respect of Net Sales of Licensed Products;
provided that in no event shall the royalty payments payable by Roche as the
Commercializing Party hereunder in respect of such Listed Third Party Payments in any reporting
period exceed in the aggregate [**] percent ([**]%) of Net Sales of Licensed Products for such
reporting period. The Parties shall cooperate to coordinate such reimbursements by Roche as the
Commercializing Party in a manner that ensures all amounts payable by Roche



-33-









 




hereunder pursuant to Listed Alnylam Third Party Agreements are paid in a timely manner and
otherwise in compliance with such Third Party agreements.




               (ii) Roche, if the Commercializing Party, shall have the right to have an independent public
accountant reasonably acceptable to Alnylam audit Alnylam’s books and records solely for purposes
of verifying such Listed Third Party Payments, which right shall be exercisable [**] per year
solely with respect to records covering up to the [**] Calendar Years prior to audit notification,
upon reasonable advance notice and during Alnylam’s business hours, subject to the confidentiality
provisions of Article IX hereof. Audit results and findings shall be shared by the Parties. If
the audit reveals an overpayment by Roche, as the Commercializing Party, under this Section 9.3(g),
the amount of such overpayment shall be credited towards any future reimbursement amounts payable
by Roche, as the Commercializing Party, under this Section 9.3(g), subject to Section 9.3(h). If
the audit reveals an underpayment by Roche, Roche shall make up such underpayment within [**] days.
The failure of Roche to request verification of any Listed Third Party Payments hereunder within
the [**] Calendar Year period set forth above shall be deemed acceptance of the calculation of such
Listed Third Party Payments.



          (h) Deductions. Notwithstanding anything in this Agreement to the contrary, in no
event shall total deductions under Sections 9.3(e) and 9.3(f) reduce any quarterly royalty payment
by Roche as the Commercializing Party in respect of Net Sales of a given Licensed Product to less
than [**] percent ([**]%) more than Alnylam owes with respect to royalty payments payable to Third
Parties pursuant to Listed Alnylam Third Party Agreements based solely on Net Sales of such given
Licensed Product. Alnylam (if Roche is the Commercializing Party) shall have the burden of
demonstrating the amount of royalty payments payable to Third Parties pursuant to Listed Alnylam
Third Party Agreements. Any deductions allowable under Sections 9.3(e) and 9.3(f) which cannot be
used against any quarterly royalty payment payable by Roche as the Commercializing Party hereunder
due to the foregoing limitation may be carried forward and used against future quarterly royalty
payments that are payable by Roche as the Commercializing Party hereunder, subject to the
limitation set forth above.




          (i) Loss of Listed Third Party Agreements. If Roche is the Commercializing Party and
Alnylam ceases to be a licensee of Alnylam Patent Rights under any Listed Alnylam Third Party
Agreement other than as a result of any action or omission by Roche, and Roche directly licenses
such terminated Patent Rights (“Terminated Patent Rights”) from that Third Party, then
Roche may deduct the full amount of any consideration paid to such Third Party for such license(s)
that is attributable to Licensed Products Covered by such Terminated Patent Rights from any
royalties otherwise payable to Alnylam hereunder; provided, that prior to Roche, as
the Commercializing Party, entering into any such license of such Terminated Patent Rights from
such Third Party, Roche shall notify Alnylam of its intent to do so and shall provide to Alnylam an
opportunity to explain its rationale for ceasing to license such Terminated Patent Rights and Roche
shall consider in good faith such rationale. If Roche does not agree with Alnylam’s rationale,
then, at Roche’s request, Alnylam shall use commercially reasonable efforts to reinstate the
license for such Terminated Patent Rights within a [**] day period; provided,
however, that Alnylam shall not be required to continue to undertake such efforts
if the Third Party requires payments which are incremental to what would otherwise be owed to such
Third Party had such Terminated Patent Rights not been terminated, or the imposition of additional
terms and conditions. If Alnylam is unable to reinstate the license, then Roche, as the





-34-











 




Commercializing Party, may obtain a direct license for such Terminated Patent Rights from such
Third Party; provided, that in no event shall total deductions under this Section
9.3(i) reduce any quarterly royalty payment by Roche in respect of Net Sales of a given Licensed
Product to less than the amount that Alnylam owes with respect to royalty payments payable to Third
Parties pursuant to then-current Listed Alnylam Third Party Agreements based solely on Net Sales of
such given Licensed Product.




          (j) Duration of Royalty Payments; First Commercial Sale. The royalties payable under
Section 9.3(a), 9.3(b) or 9.3(c), as applicable, shall be paid on a country-by-country basis on
each Licensed Product commencing upon the occurrence of the First Commercial Sale of such Licensed
Product until the expiration of the applicable Royalty Term for such Licensed Product. The
Commercializing Party shall notify the other Party of the occurrence of First Commercial Sale of
each Licensed Product within [**] days after its occurrence.



          (k) Payment of Royalty. The Commercializing Party shall calculate royalties on Net
Sales quarterly as of March 31, June 30, September 30 and December 31 (each being the last day of
an “Accounting Period”) and shall pay royalties on Net Sales within the [**] days after the
end of each Accounting Period in which such Net Sales occur. Royalties on Net Sales shall be paid
in U.S. Dollars.



          (l) Reporting. With each payment the Commercializing Party shall provide in writing
for the relevant Accounting Period the following information on a Licensed Product-by-Licensed
Product and country-by-country basis, including without limitation the United States, each of the
Major Market Countries, and each territory in the rest of world in which Licensed Product(s) are
sold: (a) Adjusted Gross Sales; (b) Net Sales; (c) the total royalties payable for the applicable
period; and (d) any other reasonable information necessary for Alnylam to comply with its reporting
and payment obligations to Third Parties under Alnylam Third Party Obligations (if the
Commercializing Party is Roche), subject to Alnylam’s obligations under Section 3.1(e).



          (m) Currency Computation. Whenever calculating royalties requires conversion from any
currency, the Commercializing Party shall make such conversion as follows:



               (i) If Roche is the Commercializing Party, when calculating the Adjusted Gross Sales for
countries other than the United States, Roche shall convert the amount of such sales in currencies
other than Swiss Francs into Swiss Francs using for internal foreign currency translation Roche’s
then current standard practices actually used on a consistent basis in preparing its audited
financial statements. Upon converting the amount of Adjusted Gross Sales into Swiss Francs, Roche
shall convert into US Dollars (or other currency), using the daily rate (Reuters) at the last
working day for the applicable period.



               (ii) If Alnylam is the Commercializing Party, when calculating the Adjusted Gross Sales for
countries other than the United States, Alnylam shall convert the amount of such sales directly
into US Dollars (or other currency), using the daily rate (Reuters) at the last working day for the
applicable period.



-35-









 





     Section 9.4 Withholding Taxes. Any tax required to be withheld by the Commercializing
Party under the laws of any country for the account of the other Party shall be promptly paid by
such Commercializing Party for and on behalf of the other Party to the appropriate governmental
authority, and such Commercializing Party shall furnish to the other Party with proof of payment of
such tax. Any such tax actually paid on a Party’s behalf shall be deducted from royalty payments
due to such Party hereunder. The Commercializing Party shall assist the other Party in minimizing
the withholding taxes applicable to any payment made by such Commercializing Party and in claiming
tax refunds at the other Party’s request.



     Section 9.5 Financial Records. Each Party shall keep, and shall require its
Affiliates and Licensee Partners to keep, for [**] years, full, true and accurate books of account
containing all particulars that may be necessary for the purpose of calculating all amounts payable
under this Agreement or to verify compliance with this Agreement, including Development Costs,
Commercialization Costs, Net Sales, FBMC, royalties, event payments, and other payments and the
elements required to calculate Profit share, Development Cost share, Commercialization Cost share
or royalty payments hereunder. Such books of accounts shall be kept at their principal places of
business.



     Section 9.6 Audits.



          (a) At the expense of Alnylam, Alnylam has the right to engage an independent public
accountant reasonably acceptable to Roche to perform, on behalf of Alnylam, an audit of such books
and records of Roche and its Affiliates and Licensee Partners, that are deemed necessary by
Alnylam’s independent public accountant to verify amounts paid or payable under this Agreement for
the period or periods requested by Alnylam and the correctness of any report or payments made under
this Agreement. Upon timely request and at least [**] Business Days’ prior written notice from
Alnylam, such audit shall be conducted in the countries specifically requested by Alnylam, during
regular business hours in such a manner as to not unnecessarily interfere with Roche’s (or its
Affiliates’ or Licensee Partners’, as the case may be) normal business activities, and shall be
limited to results in the [**] Calendar Years prior to audit notification. Such audit shall not be
performed more frequently than [**] per Calendar Year nor more frequently than [**] with respect to
records covering any specific period of time. All information, data documents and abstracts herein
referred to shall be used only for the purpose of verifying royalty statements and other amounts
payable under this Agreement, or compliance with this Agreement, shall be treated as Confidential
Information of Roche subject to the obligations of this Agreement and need neither be retained more
than [**] after completion of an audit hereof, if an audit has been requested; nor more than [**]
years from the end of the Calendar Year to which each shall pertain; nor more than [**] after the
date of termination of this Agreement. Audit results and findings shall be shared by the Parties.
If the audit reveals an overpayment, Alnylam shall reimburse Roche for the amount of the
overpayment within [**] days. If the audit reveals an underpayment, Roche shall make up such
underpayment within [**] days with interest as set forth in Section 9.7. In addition, if the
underpayment is equal to or greater than five percent (5%) of the amount that was otherwise due,
Roche shall pay all of the costs of such audit. The failure of Alnylam to request verification of
any royalty calculation within the period during which corresponding records must be maintained
shall be deemed acceptance of the royalty reporting.



-36-









 





          (b) At the expense of Roche, Roche has the right to engage an independent public accountant
reasonably acceptable to Alnylam to perform, on behalf of Roche, an audit of such books and records
of Alnylam and its Affiliates and Licensee Partners, that are deemed necessary by Roche’s
independent public accountant to verify amounts paid or payable under this Agreement for the period
or periods requested by Roche and the correctness of any report or payments made under this
Agreement. Upon timely request and at least [**] Business Days’ prior written notice from Roche,
such audit shall be conducted in the countries specifically requested by Roche, during regular
business hours in such a manner as to not unnecessarily interfere with Alnylam’s (or its
Affiliates’ or Licensee Partners’, as the case may be) normal business activities, and shall be
limited to results in the [**] Calendar Years prior to audit notification. Such audit shall not be
performed more frequently than once per Calendar Year nor more frequently than [**] with respect to
records covering any specific period of time. All information, data documents and abstracts herein
referred to shall be used only for the purpose of verifying royalty statements and other amounts
payable under this Agreement, or compliance with this Agreement, shall be treated as Confidential
Information of the audited Party subject to the obligations of this Agreement and need neither be
retained more than [**] after completion of an audit hereof, if an audit has been requested; nor
more than [**] years from the end of the Calendar Year to which each shall pertain; nor more than
[**] after the date of termination of this Agreement. Audit results and findings shall be shared
by the Parties. If the audit reveals an overpayment, Roche shall reimburse Alnylam for the amount
of the overpayment within [**] days. If the audit reveals an underpayment, Alnylam shall make up
such underpayment within [**] days with interest as set forth in Section 9.7. In addition, if the
underpayment is equal to or greater than five percent (5%) of the amount that was otherwise due,
Alnylam shall pay all of the costs of such audit. The failure of Roche to request verification of
any royalty calculation within the period during which corresponding records must be maintained
shall be deemed acceptance of the royalty reporting.



     Section 9.7 Late Payments. A Party shall pay the other Party interest on the
aggregate amount of any payments payable by such Party that are not paid on or before the date such
payments are due under this Agreement at a rate per annum equal to the lesser of the one month
London Interbank Offering Rate of interest plus one percent (1%), as reported by The Wall Street
Journal for the applicable period, or the highest rate permitted by applicable Law, calculated on
the number of days such payment is delinquent.



ARTICLE X




INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS



     Section 10.1 Inventorship. Inventorship for patentable inventions conceived or
reduced to practice during the course of the performance of activities pursuant to this Agreement
shall be determined in accordance with United States patent laws for determining inventorship.



     Section 10.2 Ownership of Collaboration IP.



          (a) Subject to the licenses and rights granted to Roche under this Agreement, Alnylam shall
own the entire right, title and interest in and to Alnylam Collaboration IP. Subject



-37-









 




to the licenses and rights granted to Alnylam under this Agreement, Roche shall own the entire
right, title and interest in and to Roche Collaboration IP.




          (b) The Parties shall jointly own any Joint Collaboration IP. Subject to (a) the rights
granted to each Party under this Agreement, including the licenses granted to a Party under Section
3.1(c) or Section 3.2(c) and patent prosecution, maintenance and enforcement rights and obligations
of each Party hereunder, (b) the restrictions on licensing set forth in Sections 3.1(d) and 3.2(d),
(c) the exclusivity obligations of the Parties set forth in Section 3.7, and (d) the payment
obligations set forth in Section 4.8 and Article VII, each Party shall have the right to use, sell,
keep, license, sublicense or assign its interest in Joint Collaboration IP (except for Product
Specific Know-How or Product Specific Patent Rights) and otherwise undertake all activities a sole
owner might undertake with respect to such Joint Collaboration IP (except for Product Specific
Know-How or Product Specific Patent Rights) without the consent of and without accounting to the
other Party.



     Section 10.3 Prosecution and Maintenance of Patent Rights.



          (a) Roche Technology (Other than Product Specific Patent Rights). Roche shall have
the sole right to, at Roche’s discretion, file, prosecute, and maintain (including the defense of
any interference or opposition proceedings) all Patent Rights comprising Roche Technology (other
than Roche Collaboration Patent Rights that constitute Product Specific Patent Rights) in Roche’s
name.



          (b) Alnylam Technology (Other than Product Specific Patent Rights). Alnylam shall
have the sole right to, at Alnylam’s discretion, file, prosecute, and maintain (including the
defense of any interference or opposition proceedings) all Patent Rights comprising Alnylam
Technology (other than Alnylam Collaboration Patent Rights that constitute Product Specific Patent
Rights) in Alnylam’s name.



          (c) Product Specific Patent Rights.



               (i) Roche shall have the first right, but not the obligation, to, at Roche’s discretion, file,
prosecute, and maintain (including the defense of any interference or opposition proceedings) Roche
Collaboration Patent Rights that constitute Product Specific Patent Rights. Roche shall provide to
Alnylam copies of all prosecution filings related to such Product Specific Patent Rights sent to or
received from patent offices in the Territory, unless otherwise directed by Alnylam, and, with
respect to patent applications containing such Product Specific Patent Rights having information
not previously filed that is intended to be submitted to patent offices in the Territory, shall use
reasonable efforts to provide Alnylam with a draft of each such filing reasonably in advance of
submission and shall consider in good faith any comments regarding such draft application that
Alnylam may timely provide. If Roche decides (A) not to file a patent application on Roche
Collaboration Know-How that would contain Product Specific Know-How, (B) to abandon prosecution of
any Roche Collaboration Patent Right that would constitute a Product Specific Patent Right, or (C)
not to otherwise maintain or extend any such Product Specific Patent Right, Roche shall give
Alnylam written notice sufficiently in advance of any loss of rights to allow Alnylam to file,
prosecute, maintain or extend, as the case may be, such Product Specific Patent Rights, in Roche’s
name.



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               (ii) Alnylam shall have the first right, but not the obligation, to, at Alnylam’s discretion,
file, prosecute, and maintain (including the defense of any interference or opposition proceedings)
Alnylam Collaboration Patent Rights that constitute Product Specific Patent Rights. Alnylam shall
provide to Roche copies of all prosecution filings related to such Product Specific Patent Rights
sent to or received from patent offices in the Territory, unless otherwise directed by Roche, and,
with respect to patent applications containing such Product Specific Patent Rights having
information not previously filed that is intended to be submitted to patent offices in the
Territory, shall use reasonable efforts to provide Roche with a draft of each such filing
reasonably in advance of submission and shall consider in good faith any comments regarding such
draft application that Roche may timely provide. If Alnylam decides (A) not to file a patent
application on Alnylam Collaboration Know-How that would contain Product Specific Know-How, (B) to
abandon prosecution of any Alnylam Collaboration Patent Right that would constitute a Product
Specific Patent Right, or (C) not to otherwise maintain or extend any such Product Specific Patent
Right, Alnylam shall give Roche written notice sufficiently in advance of any loss of rights to
allow Roche to file, prosecute, maintain or extend, as the case may be, such Product Specific
Patent Rights, in Alnylam’s name.



          (d) Joint Collaboration Patent Rights.



               (i) Alnylam shall have the first right, but not the obligation, to, at Alnylam’s discretion,
file, conduct prosecution, and maintain (including the defense of any interference or opposition
proceedings), all Joint Collaboration Patent Rights, in the names of both Alnylam and Roche. Roche
shall use Diligent Efforts to make available to Alnylam or its authorized attorneys, agents or
representatives, such of its employees as Alnylam in its reasonable judgment deems necessary in
order to assist it in obtaining patent protection for such Joint Collaboration Patent Rights. Each
Party shall sign, or use Diligent Efforts to have signed, all legal documents reasonably necessary
to file and prosecute patent applications or to obtain or maintain patents in respect of such Joint
Collaboration Patent Rights, at its own cost.



               (ii) If Alnylam elects not to seek or continue to seek or maintain patent protection on any
Joint Collaboration IP in the Territory, Roche shall have the right to, at Roche’s discretion, to
seek, prosecute and maintain in any country in the Territory patent protection on such Joint
Collaboration IP in the names of both Alnylam and Roche. Alnylam shall use Diligent Efforts to
make available to Roche its authorized attorneys, agents or representatives, such of Alnylam’s
employees as are reasonably necessary to assist Roche in obtaining and maintaining the patent
protection described under this Section 10.3(d)(ii). Alnylam shall sign or use Diligent Efforts to
have signed all legal documents reasonably necessary to file and prosecute such patent applications
or to obtain or maintain such patents.



               (iii) With respect to Joint Collaboration Patent Rights, the Party filing, prosecuting and
maintaining such Patent Rights shall provide the other Party, within [**] Business Days after
submitting or receiving such filings or correspondence, with copies of all filings and
correspondence submitted to and received from patent offices in the Territory and, with respect to
substantive filings and correspondence to be submitted to patent offices in the Territory, shall
use reasonable efforts to provide the other Party with drafts of such filings and correspondence
reasonably in advance of submission and shall consider in good faith any comments regarding such
filings and correspondence that the other Party may timely provide.



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          (e) Effects of Opt-Out. Notwithstanding any of the foregoing in this Section 10.3, if
either Party exercises its Opt-Out Right, then the Continuing Party shall have the first right, but
not the obligation, to, at such Continuing Party’s discretion, file, prosecute, and maintain
(including the defense of any interference or opposition proceedings) all Alnylam Collaboration
Patent Rights, Roche Collaboration Patent Rights and Joint Collaboration Patent Rights, in each
case solely to the extent that such Patent Rights constitute Product Specific Patent Rights. The
Party that is not the Continuing Party shall have the step-in rights described in Section 10.3(c)
or Section 10.3(d), as applicable.



          (f) Patent Term Extensions. The Parties shall cooperate, if necessary and
appropriate, with each other in gaining patent term extensions (including those extensions
available under U.S. Drug Price Competition and Patent Term Restoration Act of 1984, the
Supplementary Certificate of Protection of Member States of the EU and other similar measures in
any other country) wherever applicable to Patent Rights Controlled by either Party that Cover the
Licensed Product(s) in the Territory. The Parties shall, if necessary and appropriate, use
reasonable efforts to agree upon a joint strategy relating to patent term extensions, but, in the
absence of mutual agreement with respect to any extension issue, the patent or the claims of the
patent shall be selected on the basis of the scope, enforceability and remaining term of the patent
in the relevant country or region. All filings for such extensions shall be made by the Party
responsible for filing, prosecuting and maintaining such Patent Rights in accordance with this
Section 10.3.



          (g) Patent Expenses. The patent filing, prosecution and maintenance expenses incurred
after the Effective Date with respect to Patent Rights (“Patent Expenses”) relating to
Alnylam Technology and Roche Technology shall be borne by the Party responsible for filing,
prosecuting and maintaining such Patent Rights under this Section 10.3, and any Patent Expenses
related to Joint Collaboration Patent Rights shall be shared equally by the Parties.



     Section 10.4 Third Party Infringement.



          (a) Notices. Each Party shall promptly report in writing to the other Party any (i)
known or suspected infringement of any Alnylam Technology or Roche Technology being used in the
Collaboration, including any Joint Collaboration IP, or (ii) 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 only to the extent relevant to the Development, Manufacture or Commercialization of
the Licensed Product(s) and involving a Competitive Product (“Competitive Infringement”) in
the Territory, and shall provide the other Party with all available evidence supporting such
infringement, or unauthorized use or misappropriation.



          (b) Rights to Enforce.



               (i) First Right to Enforce. Subject to Sections 10.4(b)(ii) and 10.4(iii), the
Commercializing Party shall have the sole and exclusive right to initiate an infringement or other
appropriate suit anywhere in the world against any Third Party who at any time has infringed, or is
suspected of infringing, any Patent Rights, or of using without proper authorization any Know-How,
comprising the Commercializing Party’s Patent Rights, Know-How, or Collaboration IP.
Notwithstanding anything contained herein to the contrary, and



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subject to Sections 10.4(b)(ii) and 10.4(iii), outside the U.S., the Commercializing Party
shall have the first right to initiate an infringement or other appropriate suit against any Third
Party with respect to a Competitive Infringement in the Territory of any Product Specific Patent
Rights or Product Specific Know-How regardless of which Party Controls such Product Specific Patent
Rights or Product Specific Know-How. If both Parties are Commercializing Parties in the U.S., then
Roche shall have the sole and exclusive right to initiate an infringement or other appropriate
suit.




               (ii) Requests to Initiate Enforcement Action. If the Commercializing Party, or Roche
in the case of co-Commercialization in the U.S., elects not to initiate such suit with respect to
any such Product Specific Patent Rights or Product Specific Know-How Controlled by Alnylam, or
otherwise does not commence suit with respect to such Product Specific Patent Rights or Product
Specific Know-How within [**] days, reduced to [**] days in the case of a certification filed
pursuant to 21 U.S.C. §355(b)(2)(A)(iv) or 355(j)(2)(A)(vii)(IV), then the non-Commercializing
Party shall have the right to initiate such suit with respect to such Product Specific Patent
Rights or Product Specific Know-How and to join the Commercializing Party as a party if required.



               (iii) Effect of Opt-Out. Notwithstanding any of the foregoing in this Section 10.4,
if either Party exercises its Opt-Out Right, then the Continuing Party shall have the first right
to initiate an infringement or other appropriate suit anywhere in the world against any Third Party
who at any time has infringed, or is suspected of infringing, any Patent Rights, or of using
without proper authorization any Know-How, comprising Alnylam Collaboration IP, Roche Collaboration
IP or Joint Collaboration IP, as the case may be, that constitute Product Specific Patent Rights or
Product Specific Know-How. The Party that is not the Continuing Party shall have the right to
request that the Continuing Party initiate action as described above in clause (ii).



          (c) Procedures; Expenses and Recoveries.



               (i) The Party having the right to initiate any infringement suit under Section 10.4(b) shall
have the sole and exclusive right to select counsel for any such suit and shall pay all expenses of
the suit, including attorneys’ fees and court costs and reimbursement of the other Party’s
reasonable out-of-pocket expense in rendering assistance requested by the initiating Party;
provided that with respect to any such suit, the Parties may mutually agree to
jointly bear such costs and expenses, in which case the allocation of recoveries described below
may be adjusted as mutually agreed by the Parties. If required under applicable Law in order for
the initiating Party to initiate or maintain such suit, or if either Party is unable to initiate or
prosecute such suit 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 suit 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 suit at no charge to the initiating Party except for reimbursement by the initiating
Party of reasonable out-of-pocket expenses incurred in rendering such assistance. The
non-initiating Party shall have the right to participate and be represented in any such suit by its
own counsel at its own expense.



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               (ii) If the Parties obtain from a Third Party, in connection with such suit, any damages,
license fees, royalties or other compensation (including any amount received in settlement of such
litigation) in respect of a Competitive Infringement in the ROW Territory (if neither Party has
exercised its Opt-Out Right) or the entire Territory, such amounts shall be allocated, subject to
any adjustment to such allocation agreed by the Parties in connection with an agreement to jointly
bear the costs and expenses of the infringement action as described above, as follows:



                    (A) first, to reimburse each Party for all expenses of the suit incurred by such Party,
including attorneys’ fees and disbursements, court costs and other litigation expenses; and



                    (B) then, [**] percent ([**]%) of the remainder to be paid to the Party initiating the suit
and [**] percent ([**]%) of the remainder to be paid to the other Party.



               (iii) With respect to any such suit in the United States (if neither Party has exercised its
Opt-Out Right), any damages, license fees, royalties or other compensation (including any amount
received in settlement of such litigation) in respect of a Competitive Infringement in the United
States, shall be included in the calculation of Development Cost or Commercialization Cost, as
applicable.



     Section 10.5 Claimed Infringement; Third Party Challenges to Patent Rights.



          (a) If a Party (i) becomes aware of any claim that the Development, Manufacture or
Commercialization of the Licensed Product(s) in the Territory infringes the Patent Rights of any
Third Party or (ii) receives any notices regarding or becomes party to any action in which a Third
Party challenges or denies the validity or enforceability of any Patent Rights licensed to the
other Party hereunder, or any claim thereof (A) Controlled by such Party in the United States, (B)
Covering Licensed Product, (C) specific to Licensed Product and (D) not broadly applicable to RNAi
Products, such Party shall promptly notify the other Party.



          (b) With respect to any matter described in the foregoing clause (a)(i), in any such instance,
the Parties shall cooperate and shall mutually agree upon an appropriate course of action, which
may include settlement of such claim. Each Party shall have an equal right to participate in any
settlement discussions that are held with such Third Parties.



          (c) If there is a dispute between the Parties as to whether or not Third Party Patent Rights
at issue in such matter described in the foregoing clause (a)(i) Cover Licensed Product, the
Parties agree to select an independent patent counsel to decide whether or not the subject Third
Party Patent Rights Cover Licensed Product. The Parties agree that if such patent counsel
determines that such Third Party Patent Rights Cover Licensed Product, they will accept such
determination for purposes of calculating Commercialization Costs under Section 9.2 or royalties
under Section 9.3, as the case may be. If the decision is that such Third Party Patent Rights do
not Cover Licensed Product, either Party may still obtain a license, but shall be solely
responsible for any payment obligations to the Third Party.



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          (d) With respect to any matter described in the foregoing clause (a)(ii), the Parties shall
cooperate and shall mutually agree upon an appropriate course of action, and the Party responsible
for filing, prosecuting and maintaining such Patent Rights pursuant to Section 10.3 shall have
responsibility for defending the patentability, validity or enforceability of such Patent Rights in
such action. If neither Party has exercised its Opt-Out Right, the reasonable out-of-pocket costs
incurred by the defending Party or any of its Related Parties with respect to such action described
in the foregoing clause (a)(ii) shall be included in Commercialization Costs as set forth in
Section 5.2. For the avoidance of doubt, the costs incurred by a defending Party or any of its
Related Parties with respect to an action of the kind described in the foregoing clause (a)(ii),
but with respect to Patent Rights outside the United States, shall be borne solely by the Party
defending such action; provided that, if such matter arises in the context of an
action brought by a Party pursuant to Section 10.4, the costs of such action shall be borne as
provided in Section 10.4.



          (e) Each Party shall also provide to the other Party copies of any other notices it receives
or has received from Third Parties regarding any patent nullity actions, any declaratory judgment
actions and any alleged infringement or misappropriation of Third Party intellectual property
relating to the Development, Manufacture or Commercialization of Licensed Product in the Territory.
Such notices shall be provided promptly, but in no event after more than [**] days after receipt
thereof.



     Section 10.6 Third Party Technology.



          (a) If after the Effective Date, (i) Alnylam or any of its Affiliates acquires from a Third
Party Know-How or Patent Rights that would fall within the definition of Alnylam Patent Rights but
for payment obligations to such Third Party, or (ii) Roche or any of its Affiliates acquires from a
Third Party Know-How or Patent Rights that would fall within the definition of Roche Patent Rights
but for payment obligations to such Third Party (the foregoing clauses (i) and (ii), collectively,
“Third Party Technology”), then the Party acquiring the Third Party Technology shall
promptly so notify the other Party and provide such other Party with a copy of the agreement and a
written description of the payment obligations that would be allocated to the other Party
hereunder.



          (b) Roche may elect to include Third Party Technology acquired by Alnylam or any of its
Affiliates in the rights and licenses granted to Roche under Section 3.1 with respect to the
Discovery, Development, Manufacture or Commercialization of the Licensed Product(s) in the Field
in the Territory by providing written notice to Alnylam of such election, and, in such event, (i)
Roche shall be obligated to pay Alnylam the applicable amounts payable to such Third Party for such
Third Party Technology, if Roche is the Commercializing Party, in accordance with Section 9.3(g)
and subject to deduction from royalties payable to Alnylam pursuant to Section 9.3(f), (ii) such
Third Party Technology shall be deemed included within the definition of Alnylam Patent Rights and
Alnylam Know-How, as applicable, and (iii) the agreement with the Third Party under which such
Third Party Technology was acquired shall be included in the definition of Listed Alnylam Third
Party Agreements. Notwithstanding anything in this Agreement to the contrary, neither Alnylam nor
any of its Affiliates shall enter into any agreement with any Third Party or take any other action
that would prevent such Third Party



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Technology acquired by Alnylam or any of its Affiliates from becoming Alnylam Technology upon
Roche’s election in accordance with this Section 10.6(b).




          (c) Alnylam may elect to include Third Party Technology acquired by Roche or any of its
Affiliates in the rights and licenses granted to Alnylam pursuant to Section 3.2 with respect to
the Discovery, Development, Manufacture or Commercialization of the Licensed Product(s) in the
Field in the Territory by providing written notice to Roche of such election, and, in such event,
(i) Alnylam shall be obligated to pay Roche the applicable amounts payable to such Third Party for
such Third Party Technology, if Alnylam is the Commercializing Party, in accordance with Section
9.3(g) and subject to deduction from royalties payable to Roche pursuant to Section 9.3(f), and
(ii) such Third Party Technology shall be deemed included within the definition of Roche Patent
Rights and Roche Know-How, as applicable. Notwithstanding anything in this Agreement to the
contrary, neither Roche nor any of its Affiliates shall enter into any agreement with any Third
Party or take any other action that would prevent such Third Party Technology acquired by Roche or
any of its Affiliates from becoming Roche Technology upon Alnylam’s election in accordance with
this Section 10.6(c).



     Section 10.7 Patent Marking. Each Party agrees to comply with the patent marking
statutes in each country in which a Licensed Product is sold by such Party or its Related Parties.



     Section 10.8 Product Labeling.



          (a) Each Party and its Affiliates shall retain all right, title and interest in and to its and
their respective corporate names and logos.



          (b) To the extent permitted under applicable Laws:



               (i) the Licensed Product(s) offered for sale in the United States shall carry the
Commercializing Party’s name and logo; and



               (ii) provided neither Party exercises its Opt-Out Right all written promotional materials
associated with the Licensed Product(s) in the United States shall indicate that the Licensed
Product(s) was co-developed by the Parties.



          (c) Each Party shall have the right to monitor the quality of the Licensed Products on which
such Party’s name and logo appear in accordance with reasonable quality control procedures to be
agreed upon by the Parties.



ARTICLE XI




CONFIDENTIALITY



     Section 11.1 Confidential Information. All Confidential Information disclosed by a
Party to the other Party in connection with the activities contemplated by this Agreement shall not
be used by the receiving Party except in connection with the activities and licenses contemplated
by this Agreement, shall be maintained in confidence by the receiving Party, and shall not
otherwise be disclosed by the receiving Party to any other Person, without the prior



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written consent of the disclosing Party, except to the extent that the Confidential
Information (as determined by competent documentation):




          (a) was known or used by the receiving Party or its Affiliates prior to its date of disclosure
to the receiving Party; or



          (b) either before or after the date of the disclosure to the receiving Party or its
Affiliates, is lawfully disclosed to the receiving Party or its Affiliates by sources other than
the disclosing Party who are rightfully in possession of the Confidential Information and not
subject to an obligation of confidentiality or non-use owed to the disclosing Party; or



          (c) either before or after the date of the disclosure to the receiving Party or its
Affiliates, becomes published or generally known to the public other than through the wrongful act
or default of the receiving Party or its Affiliates or its or its Affiliates’ representatives; or



          (d) is independently developed by the receiving Party or its Affiliates without reference to
or reliance upon the Confidential Information.



     Notwithstanding anything set forth herein to the contrary, this Article IX shall not prohibit
the receiving Party from disclosing Confidential Information of the disclosing Party to defend or
prosecute litigation; provided that, to the extent practicable, the receiving Party
provides prior written notice of such disclosure to the disclosing Party and assists the disclosing
Party in its reasonable and lawful efforts to avoid or minimize the degree of such disclosure.
Notwithstanding the foregoing provisions of this Section 9.1, either Party may only disclose the
terms of this Agreement if such Party reasonably determines, based on advice from its counsel, that
it is required to make such disclosure by applicable Law, regulation or legal process, including
without limitation 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 NASDAQ, or pursuant to relevant accounting standards, such as IFRS or GAAP, in which
event such Party shall provide prior notice of such intended disclosure to the other Party
sufficiently in advance to enable the other Party to seek confidential treatment or other
protection for such information unless the disclosing Party is prevented by Law from providing such
advance notice and shall disclose only such terms of this Agreement as such disclosing Party
reasonably determines, based on advice from its counsel, are required by applicable Law or legal
process to be disclosed. Alnylam shall be permitted to disclose in confidence (pursuant to a
written agreement with confidentiality obligations no less restrictive than set forth herein) the
terms of this Agreement to the extent Alnylam is contractually obligated to do so pursuant to
Alnylam Third Party Obligations; provided, that Alnylam shall redact such portions
as Roche reasonably requests.



     Section 11.2 Employee and Advisor Obligations. Each Party agrees that it may provide
Confidential Information received from the other Party (including the terms of this Agreement) only
to its and its Affiliates’ (a) employees, consultants, advisors and contractors who have a need to
know such information in order for the receiving Party to exercise its rights or perform its
obligations under this Agreement, and (b) potential and existing investors, lenders and acquirors,
in each case who have an obligation to treat such information and materials as




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confidential under terms no less restrictive than those set
forth herein; provided, that such Party shall redact such portions as the other
Party reasonably requests.




     Section 11.3 Publicity. Upon execution of this Agreement, the Parties shall jointly
issue a press release announcing the execution of this Agreement in form and substance
substantially as set forth on Exhibit F hereto. Thereafter, neither Party shall issue any
press release or public announcement relating to this Agreement or the Collaboration or Licensed
Products without the prior written approval of the other Party, which approval shall not be
unreasonably withheld, conditioned or delayed, except that a Party may issue a press release or
public announcement if 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 NASDAQ or pursuant to relevant accounting standards, such as
IFRS or GAAP; provided that the other Party has received prior notice of such
intended press release or public announcement if practicable under the circumstances and the Party
subject to the requirement includes in such press release or public announcement only such
information relating to this Agreement as is necessary to comply with applicable Law. The rights
of approval and notice granted to a Party in accordance with the preceding sentence shall only
apply for the first time that specific information is to be disclosed, and shall not apply to the
subsequent disclosure of substantially similar information that has previously been made public
other than through a breach of this Agreement by the issuing Party or its Affiliates.



     Section 11.4 Publications. A Party (the “Publishing Party”) shall provide the
other Party with a copy of any proposed publication or presentation at least [**] days (or at least
[**] days in the case of abstracts or oral presentations) prior to submission for publication by
the Publishing Party or its Affiliates so as to provide such other Party with an opportunity to
recommend any changes it reasonably believes are necessary to continue to maintain the Confidential
Information disclosed by the other Party to the Publishing Party in accordance with the
requirements of this Agreement. The incorporation of such recommended changes shall not be
unreasonably refused; and if such other Party notifies the Publishing Party in writing, within [**]
days after receipt of the copy of the proposed publication or presentation (or at least [**] days
in the case of oral presentations), that such publication or presentation in its reasonable
judgment (a) contains an invention, solely or jointly conceived or reduced to practice by the other
Party, for which the other Party reasonably desires to obtain patent protection or (b) could be
expected to have a material adverse effect on the commercial value of any Confidential Information
disclosed by the other Party to the Publishing Party, the Publishing Party shall prevent such
publication or delay such publication for a mutually agreeable period of time. In the case of
inventions, a delay shall be for a period reasonably sufficient to permit the timely preparation
and filing of a patent application(s) on such invention, and in no event less than [**] days from
the date of notice from the non-Publishing Party. In the case of Confidential Information, any of
the non-Publishing Party’s Confidential Information shall be deleted as requested.



     Section 11.5 Clinical Trial Registry. Unless and until Roche exercises its Opt-Out
Right hereunder, (a) Roche, in accordance with its internal policies and procedures, shall have the
right to publish all Clinical Studies with respect to the Licensed Product(s) and results thereof
on the clinical trial registries which are maintained by or on behalf of Roche, and (b) Alnylam
shall have the right to access Roche’s clinical trial registry via a link from Alnylam’s clinical
trial registry, and, in accordance with applicable Law, to post Clinical Study information with
respect to the Licensed Product(s) on clinicaltrials.gov or any other mandated registry.



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ARTICLE XII




REPRESENTATIONS AND WARRANTIES



     Section 12.1 Mutual Representations and Warranties.



          (a) Representations of Authority. Each Party represents and warrants to the
other Party that, as of the Effective Date, it has full corporate right, power and authority to
enter into this Agreement and to perform its obligations under this Agreement.




          (b) Consents. Each Party represents and warrants to the other Party that
all necessary consents, approvals and authorizations of all government authorities and other
Persons required to be obtained by it as of the Effective Date in connection with the execution,
delivery and performance of this Agreement have been obtained.




          (c) No Conflict. Each Party represents and warrants to the other Party that
the execution and delivery of this Agreement and the performance of its obligations hereunder (i)
does not violate or conflict with the provisions of its certificate of incorporation or by-laws,
(ii) does not conflict with or violate any requirement of applicable Laws effective as of the
Effective Date, and (iii) does not and will not conflict with, violate, breach or constitute a
default under any contractual obligations of it or any of its Affiliates existing as of the
Effective Date.




          (d) Authorization and Binding Nature. Each Party represents and warrants to
the other Party that the execution, delivery and performance of this Agreement and the performance
of all obligations hereunder have been duly authorized by all requisite corporate action on the
part of such Party and this Agreement constitutes valid and legally binding obligations of such
Party, limited by applicable bankruptcy, insolvency, reorganization, moratorium and other laws of
general application affecting the enforcement of creditors’ rights generally and (ii) as may be
limited by laws relating to the availability of specific performance, injunctive relief or other
equitable remedies.




          (e) Employee Obligations. Each Party represents and warrants that all of
its employees, officers and consultants have executed agreements or have existing obligations under
Law requiring assignment to such Party of all intellectual property and proprietary rights made
during the course of and as the result of their association with such Party, and obligating such
individuals to maintain as confidential the Confidential Information of such Party and of a Third
Party which such Party may receive.




     Section 12.2 Representations and Warranties of Alnylam. Alnylam represents and
warrants to Roche that, as of the Effective Date:



          (a) Organization and Good Standing. Alnylam is a corporation duly
organized, validly existing and in good standing under the Laws of the State of Delaware.




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          (b) Authority. Alnylam and its Affiliates have the right and authority to
grant the licenses to Roche set forth in Sections 3.1(a), 3.1(b) and 3.1(c) of this Agreement as
contemplated under this Agreement.




          (c) Listed Alnylam Third Party Agreements. Exhibit B-2 identifies
all Listed Alnylam Third Party Agreements existing as of the Effective Date, excluding Listed Third
Party Agreements (as defined in the LCA). All such Listed Alnylam Third Party Agreements are in
full force and effect, and no dispute presently exists between Alnylam and Listed Alnylam
Counterparties under the agreements listed on Exhibit B-2 or Alnylam Pre-Existing Alliance
Parties under the agreements listed on Exhibit B-1 that would place in jeopardy any of the
licenses granted by Alnylam under this Agreement.




          (d) Alnylam Pre-Existing Alliance Agreements. Exhibit B-1
identifies all Alnylam Pre-Existing Alliance Agreements existing as of the Effective Date,
excluding the Pre-Existing Alliance Agreements (as defined in the LCA).




          (e) Protecting IP Rights. Alnylam and its Affiliates have taken reasonable
measures to protect the Alnylam Technology, consistent with prudent commercial practices in the
biotechnology industry.




     Section 12.3 Representations and Warranties of Roche. Roche represents and warrants
to Alnylam that, as of the Effective Date:



          (a) No Dispute With UBC. Roche is not engaged in a dispute with UBC.




          (b) Organization and Good Standing. Roche Basel is a corporation duly
organized, validly existing and in good standing under the Laws of Switzerland; Roche Nutley is a
corporation duly organized, validly existing and in good standing under the Laws of the State of
New Jersey.




          (c) Authority. Roche and its Affiliates have the right and authority to
grant the licenses to Alnylam set forth in Sections 3.2(a), 3.2(b) and 3.2(c) of this Agreement as
contemplated under this Agreement.




          (d) Protecting IP Rights. Roche and its Affiliates have taken reasonable
measures to protect the Roche Technology, consistent with prudent commercial practices in the
pharmaceutical industry.




     Section 12.4 No Warranties. EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS ARTICLE
X, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR
IMPLIED, TO THE OTHER PARTY, INCLUDING ANY WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A
PARTICULAR PURPOSE.



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ARTICLE XIII




INDEMNIFICATION; INSURANCE



     Section 13.1 Indemnification by Roche. Roche shall defend, indemnify and hold
harmless Alnylam, its Affiliates, and their respective directors, officers, employees and agents
(the “Alnylam Indemnitees”), at Roche’s cost and expense, from and against any liabilities,
losses, costs, damages, fees or expenses (including reasonable attorneys’ fees) (collectively,
“Losses”) arising out of any Third Party claim based on or resulting from: (a) any breach
by Roche of any of its representations, warranties, covenants or obligations pursuant to this
Agreement; (b) the negligence or willful misconduct of Roche or its Related Parties, or any of
their respective directors, officers, employees and agents, in the performance of obligations or
exercise of rights under this Agreement; (c) the Development, Manufacture, Commercialization, or
use of the Licensed Product(s) by Roche as the Commercializing Party hereunder, or by any of its
Related Parties, including any Product Liability Claim relating to such Licensed Product(s) (except
as provided in Section 13.3); (c) any Advertising Claims; or (d) the pricing and commercial terms
of Licensed Product(s) in the U.S., or any policy governing the handling of returns, recalls, order
processing, invoicing and collection, distribution, and inventory and receivables for, Licensed
Product(s) in the U.S., if Roche is responsible hereunder for booking sales of such Licensed
Product(s) in the U.S. Roche 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 this Agreement, or any breach or
violation of any covenant or obligation of Alnylam or its Related Parties in or pursuant to this
Agreement, or the negligence or willful misconduct by or of any of the Alnylam Indemnitees.



     Section 13.2 Indemnification by Alnylam. Alnylam shall defend, indemnify and hold
harmless Roche, its Affiliates and their respective directors, officers, employees and agents (the
“Roche Indemnitees”), at Alnylam’s cost and expense, from and against any Losses arising
out of any Third Party claim based on or resulting from: (a) any breach by Alnylam of any of its
representations, warranties, covenants or obligations pursuant to this Agreement; (b) the
negligence or willful misconduct of Alnylam or its Related Parties, or any of their respective
directors, officers, employees and agents, in the performance of obligations or exercise of rights
under this Agreement; (c) the Development, Manufacture, Commercialization, or use of the Licensed
Product(s) by Alnylam as the Commercializing Party hereunder, or by any of its Related Parties,
including any Product Liability Claim relating to such Licensed Product(s) (except as provided in
Section 13.3) and excluding Advertising Claims (except if and to the extent that Alnylam is the
Party responsible hereunder for booking sales of such Licensed Product(s) in the U.S.); or (d) the
pricing and commercial terms of Licensed Product(s) in the U.S., or any policy governing the
handling of returns, recalls, order processing, invoicing and collection, distribution, and
inventory and receivables for, Licensed Product(s) in the U.S., if Alnylam is responsible hereunder
for booking sales of such Licensed Product(s) in the U.S. Alnylam shall have no obligation to
indemnify the Roche 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 Roche in
this Agreement, or any breach or violation of any covenant or obligation of Roche or its Related
Parties in or pursuant to this Agreement, or the negligence or willful misconduct by or of any of
the Roche Indemnitees.



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     Section 13.3 Product Liability Claims. If neither Party has exercised its Opt-Out
Right, any Losses arising out of Product Liability Claims shall be treated as Commercialization
Costs, to the extent such Losses were incurred with respect to the Development, Manufacture or
Commercialization of the Licensed Product(s) in the United States, except to the extent such Losses
arise out of any Third Party claim based on (a) a Party’s breach of any of its representations,
warranties, covenants or obligations pursuant to this Agreement, or (b) the negligence or willful
misconduct of a Party or its Related Parties, or any of their respective directors, officers,
employees and agents, in the performance of obligations (including Manufacture and supply
obligations) or exercise of rights under this Agreement.



     Section 13.4 Claims for Indemnification with respect to Third Parties.



          (a) With regard to any Third Party claim for which indemnification may be sought
under this Article XI against a person entitled to indemnification under this Article XI (an
“Indemnified Party”), the Indemnified Party shall give prompt written notification to the
person from whom indemnification is sought (the “Indemnifying Party”) of the commencement
of any action, suit or proceeding relating to such Third Party claim or, if earlier, upon the
assertion of any such claim by a Third Party (it being understood and agreed, however, that the
failure by an Indemnified Party to give notice of a Third Party claim as provided in this Section
13.4(a) shall not relieve the Indemnifying Party of its indemnification obligation under this
Agreement except and only to the extent that such Indemnifying Party is actually prejudiced as a
result of such failure to give notice).




          (b) Within [**] days after delivery of such notification, the Indemnifying Party
may, upon written notice thereof to the Indemnified Party, assume control of the defense of such
action, suit, proceeding or claim with counsel reasonably satisfactory to the Indemnified Party.
If the Indemnifying Party does not assume control of such defense, the Indemnified Party shall
control such defense.




          (c) The Party not controlling such defense may participate therein at its own
expense; provided that if the Indemnifying Party assumes control of such defense
and the Indemnified Party reasonably concludes, based on advice from counsel, that the Indemnifying
Party and the Indemnified Party have conflicting interests with respect to such action, suit,
proceeding or claim, the Indemnifying Party shall be responsible for the reasonable fees and
expenses of counsel to the Indemnified Party solely in connection therewith; provided
further, however, that in no event shall the Indemnifying Party be responsible for the fees
and expenses of more than one counsel in any one jurisdiction for all Indemnified Parties.




          (d) The Party controlling such defense shall keep the other Party advised of the
status of such action, suit, proceeding or claim and the defense thereof and shall consider
recommendations made by the other Party with respect thereto.




          (e) The Indemnified Party shall not agree to any settlement of such action, suit,
proceeding or claim without the prior written consent of the Indemnifying Party, which shall not be
unreasonably withheld. The Indemnifying Party shall not, without the prior written consent of the
Indemnified Party, agree to any settlement of such claim or consent to any judgment in respect
thereof that does not include a complete and unconditional release of the




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Indemnified Party from all liability with respect thereto or that imposes any liability or obligation on the Indemnified
Party.




     Section 13.5 Insurance. Each Party shall maintain appropriate product liability
insurance (or self-insurance) with respect to its Discovery, Development, Manufacture and
Commercialization activities hereunder in such amount as such Party customarily maintains with
respect to its other products for similar patient populations and commercial markets. Each Party
shall maintain such insurance for so long as it continues to conduct such activities hereunder, and
for so long as such Party customarily maintains insurance with respect to sales of its other
products for similar patient populations and commercial markets.



ARTICLE XIV




TERM AND TERMINATION



     Section 14.1 Term. Unless terminated earlier, this Agreement shall remain in force
for the period commencing on the Effective Date and shall expire, on a Licensed Product-by-Licensed
Product and country-by-country basis, upon the later of: (a) expiration of the applicable Royalty
Term for such Licensed Product in such country, or (b) with respect to the United States, if
neither Party has exercised its Opt-Out Right, until no Licensed Products have been Commercialized
for a continuous period of six (6) months (the “Term”). Upon expiration of the Term, the
licenses granted to the Commercializing Party(-ies) under Article III shall convert to perpetual,
non-exclusive, fully paid-up, non-royalty-bearing licenses. Expiration or termination of this
Agreement shall have no impact on the LCA.



     Section 14.2 Termination for Cause.



          (a) Roche may terminate this Agreement upon sixty (60) calendar days’ prior written
notice to Alnylam upon the material breach by Alnylam of any of its representations, warranties or
obligations under this Agreement (except for any Diligence Breach by Alnylam); provided
that such termination shall become effective only if (i) Alnylam fails to remedy or cure
the breach within such sixty (60) day period, or (ii) if such breach cannot be remedied or cured
through the application of Diligent Efforts within such sixty (60) day period, and Alnylam has
(within such time period) submitted a plan for cure as promptly as is reasonably practicable (but
in no event beyond an additional sixty (60) day period) through the application of Diligent Efforts
with a remedy or cure period reasonably acceptable to Roche, then after the earlier of the remedy
or cure date accepted by Roche or the date Alnylam ceases to use Diligent Efforts to remedy or cure
such breach.




          (b) Alnylam may terminate this Agreement upon sixty (60) calendar days’ prior
written notice to Roche upon the material breach by Roche of any of its representations, warranties
or obligations under this Agreement (except for any Diligence Breach by Roche); provided
that such termination shall become effective only if (i) Roche fails to remedy or cure the
breach within such sixty (60) day period, or (ii) if such breach cannot be remedied or cured
through the application of Diligent Efforts within such sixty (60) day period, and Roche has
(within such time period) submitted a plan for cure as promptly as is reasonably practicable (but
in no event beyond an additional sixty (60) day period) through the application of Diligent




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Efforts with a remedy or cure period reasonably acceptable to Alnylam, then after the earlier of the remedy
or cure date accepted by Alnylam or the date Roche ceases to use Diligent Efforts to remedy or cure
such breach.




          (c) If one Party in good faith believes the other Party has committed a Diligence
Breach, then the non breaching Party may terminate this Agreement upon ninety (90) calendar days’
prior written notice to the breaching Party, specifying the Diligence Breach and, if applicable,
the Major Territory(ies) as to which the Diligence Breach allegedly occurred. Such termination
shall become effective only if the allegedly breaching Party fails to remedy or cure such Diligence
Breach within such ninety (90) day period (“Diligence Breach Cure Period”); provided, that,
the allegedly breaching Party shall have the option, in its sole discretion, of electing to
terminate this Agreement without cause as set forth in Section 14.4 during the Diligence Breach
Cure Period in lieu of undertaking efforts to remedy or cure such Diligence Breach. If the
allegedly breaching Party fails to cure such Diligence Breach within the Diligence Breach Cure
Period (either through actual cure or through electing to terminate at will pursuant to Section
14.4), but provides written notice to the non-breaching Party during the Diligence Breach Cure
Period that such Party disputes in good faith the existence of such Diligence Breach, then either
Party may submit such dispute to the Executive Officers of Alnylam and Roche for resolution. If,
despite the Executive Officers’ efforts to resolve such dispute, the Executive Officers cannot
reach an agreement regarding such dispute within [**] days after submission to them for resolution,
then such dispute may be submitted to a court of competent jurisdiction for resolution, in which
event this Agreement shall terminate only upon the rendering of a final decision by such court
upholding the basis for termination (or once the breaching Party is no longer disputing such basis
in good faith, if earlier).




     Section 14.3 Termination for Patent Challenge.



          (a) If Roche or any of its Related Parties initiates, maintains or supports any
action to (i) oppose the grant of a patent, or (ii) challenge the validity, patentability,
enforceability or scope of an issued patent, in each case under the Alnylam Patent Rights or
Alnylam Collaboration Patent Rights, then Alnylam shall have the right, upon thirty (30) days’
prior written notice to Roche, to terminate this Agreement; provided, however,
that if Roche or any of its Related Parties, as relevant, cease such opposition or
challenge within such thirty (30) day period, then Alnylam shall not have the right to terminate
this Agreement.




          (b) If Alnylam or any of its Related Parties initiates, maintains or supports any
action to (i) oppose the grant of a patent, or (ii) challenge the validity, patentability,
enforceability or scope of an issued patent, in each case under the Roche Patent Rights or Roche
Collaboration Patent Rights, then Roche shall have the right, upon thirty (30) days’ prior written
notice to Alnylam, to terminate this Agreement; provided, however, that if
Alnylam or any of its Related Parties, as relevant, cease such opposition or challenge within such
thirty (30) day period, then Roche shall not have the right to terminate this Agreement.




     Section 14.4 Termination At Will.



          (a) If neither Party has exercised its Opt-Out Right, Roche shall have the right to
terminate, without cause, the licenses granted to Roche under this Agreement and all related




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terms and conditions, solely with respect to any Major Territory(ies) outside of the United States, by
providing ninety (90) calendar days’ prior written notice to Alnylam.




          (b) The Continuing Party shall have the right to terminate, without cause, the
licenses granted to such Continuing Party under this Agreement and all related terms and
conditions, with respect to any Major Territory(ies) by providing ninety (90) calendar days’ prior
written notice to the other Party.




          (c) In the event of an alleged Diligence Breach under Section 14.2(c), the breaching
Party shall have the right to terminate, without cause, the licenses granted to such breaching
Party under this Agreement and all related terms and conditions, solely with respect to the Major
Territory(ies) as to which the Diligence Breach allegedly occurred by providing ninety (90) days’
prior written notice to the non-breaching Party during the Diligence Breach Cure Period.




          (d) The Party receiving the termination notice under Section 14.4(a), 14.4(b) or
14.4(c) above shall have the right to notify the terminating Party thereunder during such ninety
(90) day period if such Party is interested in pursuing the Development and Commercialization of
Licensed Product(s) in any of the Major Territory(ies) being terminated.




               (i) If such Party notifies the terminating Party that such Party is interested in pursuing the
Development and Commercialization of Licensed Product(s) in such terminated Major Territory(ies)
during such 90-day period, the Parties shall negotiate in good faith the terms of (A) a transition
agreement to cover the reasonable wind-down and transition of the Licensed Product(s) to such Party
in such terminated Major Territory(ies), which wind-down and transition activities shall be
performed for a period not to exceed [**], with the pursuing Party bearing reasonable costs
incurred by the terminating Party (at the terminating Party’s FBMC plus the applicable percentage
set forth in Article VI) in performing such wind-down and transition activities; and (B) the
development, regulatory and sales events, the achievement of which shall trigger payment of event
payment amounts, the event payment amounts themselves, and royalty rates payable by the pursuing
Party with respect to Licensed Product(s) in such terminated Major Territory(ies); it being
understood that the Parties intend that all other terms and conditions of this Agreement that
otherwise apply to Licensed Product(s) shall remain in effect, subject to any minor adjustments, if
necessary, to reflect the Major Territory(ies) being terminated (e.g., exclusive license grant as
if the terminating Party had opted-out, general payment terms, royalty deductions). If, despite
such good faith negotiations, the Parties are unable to finalize the events/event payment amounts
and royalty rates payable with respect to Licensed Product(s) in the terminated Major
Territory(ies) within an additional ninety (90) calendar days, then the Parties shall submit such
dispute for resolution by Baseball Arbitration pursuant to the terms of Exhibit G.



               (ii) For purposes of clarity, if the Party receiving the termination notice under Section
14.4(a), 14.4(b) or 14.4(c) does not notify the terminating Party during such ninety (90) day
period that such Party is interested in pursuing the Development and Commercialization of Licensed
Product(s) in any of the Major Territory(ies) being terminated, the termination of this Agreement
shall become effective at the end of such ninety (90) day period.



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     Section 14.5 Effects of Termination.



          (a) Termination by Alnylam for Roche Material Breach (Other Than a Diligence
Breach) or Roche Patent Challenge if Neither Party has Opted-Out. Without limiting any other
legal or equitable remedies that Alnylam may have, if Alnylam terminates this Agreement as a result
of Roche’s uncured material breach pursuant to Section 14.2(a), or as a result of Roche (or its
Related Parties) taking any of the prohibited actions pursuant to Section 14.3(a), and the Parties,
at the time of such termination, were in a Profit and cost-sharing arrangement pursuant to Section
4.8 and 9.2, then:




               (i) Roche’s exclusivity obligations under Section 3.7 shall remain in effect for a period of
[**] after the effective date of termination;



               (ii) if such termination occurs after the Research Term, Roche shall (A) continue to pay for
any Clinical Study(ies) conducted, or committed to be conducted, by Alnylam at the time of such
termination notice, through completion or earlier termination of such Clinical Study(ies), and (B)
for a period of six (6) months following the date of notice of termination (if neither Party had
exercised its Opt-Out Right prior to such date), continue to pay [**] percent ([**]%) of all other
Development Costs actually incurred by Alnylam in connection with the Development of Licensed
Products and in Field for the United States during such six (6) month period, in each case provided
that such costs are shown on and consistent with the Development Plan in place as of the date of
notice of termination;



               (iii) the licenses granted to Roche in Section 3.1 shall terminate and have no further force
or effect, and Roche shall be deemed to have exercised its Opt-Out Right (with the consequences set
forth in this Section 14.5(a));



               (iv) if requested by Alnylam, Roche shall as promptly as practicable transfer to Alnylam or
Alnylam’s designee (A) possession and ownership of all governmental or regulatory correspondence,
conversation logs, filings and approvals (including all Regulatory Approvals and pricing and
reimbursement approvals) relating to the Development, Manufacture or Commercialization of the
Licensed Product(s) and all Roche trademarks then being used in connection with the Licensed
Product(s) (other than Roche’s corporate trademarks); (B) copies of all data, reports, records and
materials, Commercialization Plans, marketing plans, promotional materials, and other sales and
marketing related information in Roche’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 Licensed Product(s), including all non-clinical and clinical data relating
to the Licensed Product(s), and customer lists and customer contact information and all Safety Data
and other adverse event data in Roche’s possession or Control; provided that (I) Roche shall not be
required by this provision to provide any Confidential Information to Alnylam and (II) Roche shall
use Diligent Efforts to obtain for Alnylam the right to access all such data, reports, records,
materials, and other sales and marketing related information; and (C) all records and materials in
Roche’s possession or Control containing Confidential Information of Alnylam;



               (v) if requested by Alnylam, appoint Alnylam as Roche’s or Roche’s Related Parties’ agent for
all Licensed Product-related matters involving Regulatory Authorities



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in the Territory until all Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee;




               (vi) if the effective date of termination (or opt-out, solely for purposes of Section
4.9(b)(iii)) occurs after the First Commercial Sale of a Licensed Product in any country in the
Territory and Roche was the Commercializing Party immediately prior to such termination (or
opt-out, solely for purposes of Section 4.9(b)(iii)), then, if requested by Alnylam, Roche shall
appoint Alnylam as its exclusive distributor of Licensed
Product in the Territory and grant Alnylam the right to appoint sub-distributors, until such
time as all Regulatory Approvals in the Territory have been transferred to Alnylam or its designee;



               (vii) if Roche or its Related Parties are Manufacturing API Bulk Drug Substance, Delivery
Compound, Formulated Bulk or Finished Product, at Alnylam’s option, supply the API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product, as applicable, to Alnylam in the
Territory on terms no less favorable than those on which Roche supplied the API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product, as applicable, prior to such
termination to its most favored distributor in the Territory, until such time as all Regulatory
Approvals in the Territory 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 API
Bulk Drug Substance, Delivery Compound, Formulated Bulk or Finished Product supply, as applicable,
provided, that such period of time shall not exceed [**] (unless otherwise agreed
by Roche);



               (viii) if Alnylam so requests, Roche shall transfer to Alnylam any Third Party agreements
solely relating to the Development, Manufacture or Commercialization of the Licensed Product(s) to
which Roche is a party, subject to any required consents of such Third Party, which Roche shall use
Diligent Efforts to obtain promptly;



               (ix) subject to then-existing Third Party obligations, Roche hereby grants to Alnylam an
exclusive right and license, with the right to grant sublicenses subject to Section 3.2(d)(i) and
Section 3.3, under such Roche Technology as has been incorporated into, or has been used in or (as
documented in the Joint Research Plan, the Development Plan or the Commercialization Plan, or any
approved JSC or JCT minutes, as applicable) has been intended for use in, the Development,
Manufacture or Commercialization of the Licensed Product(s) under this Agreement as of the
effective date of such termination, solely to Develop, Manufacture and Commercialize the Licensed
Product(s) in the Field in the Territory; provided, that, (A) Alnylam shall not be
bound by the diligence obligations set forth in Article VIII, and (B) such license shall be subject
to Alnylam’s compliance with its obligation to pay to Roche (1) (if Alnylam had been the
Commercializing Party immediately prior to such termination) royalties at the royalty rates and
event payment amounts within the same Column as would have been payable to Roche had Alnylam
remained the Commercializing Party, or (2) (if Roche had been the Commercializing Party immediately
prior to such termination) royalties at the royalty rates and event payment amounts within the
Column that would have applied had Roche exercised its Opt-Out Right; provided,
however, that Alnylam may withhold [**] percent ([**]%) of each royalty payment due
hereunder until the actual amount of damages owed by Roche to Alnylam with respect to the breach of
this Agreement resulting in such termination is determined,



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whereupon such withheld amount shall be credited against such damages and any amount remaining shall be paid to Roche within [**] days
after such determination; and




               (x) Roche shall execute all documents and take all such further actions, including, where
applicable, the prompt assignment of Regulatory Approvals and Third Party agreements, as may be
reasonably requested by Alnylam in order to give effect to the foregoing clauses (i) through (ix)
as soon as practicable and in order to enable Alnylam to continue to Develop, Manufacture and
Commercialize the Licensed Product(s) in the Territory in the same manner as was being conducted by
the Commercializing Party prior to any such termination.



          (b) Termination by Roche for Alnylam Material Breach (Other Than a Diligence
Breach) or Alnylam Patent Challenge if Neither Party has Opted-Out. Without limiting any other
legal or equitable remedies that Roche may have, if Roche terminates this Agreement as a result of
Alnylam’s material uncured breach pursuant to Section 14.2(a), or as a result of Alnylam (or its
Related Parties) taking any of the prohibited actions pursuant to Section 14.3(b), and the Parties,
at the time of such termination, were in a Profit and cost-sharing arrangement pursuant to Section
4.8 and 7.2, then:




               (i) Alnylam’s exclusivity obligations under Section 3.7 shall remain in effect for a period of
[**] after the effective date of termination;



               (ii) if such termination occurs after the Research Term, Alnylam shall (A) continue to pay for
any Clinical Study(ies) conducted, or committed to be conducted, by Roche at the time of such
termination notice, through completion or earlier termination of such Clinical Study(ies), and
(B) for a period of six (6) months following the date of notice of termination (if neither Party
had exercised its Opt-Out Right prior to such date), continue to pay [**] percent ([**]%) of all
other Development Costs actually incurred by Roche in connection with the Development of Licensed
Products in the Field in the United States during such six (6) month period, in each case provided
that such costs are shown on and consistent with the Development Plan in place as of the date of
notice of termination;



               (iii) the licenses granted to Alnylam in Section 3.2 shall terminate and have no further force
or effect, and Alnylam shall be deemed to have exercised its Opt-Out Right (with the consequences
set forth in this Section 14.5(b));



               (iv) if requested by Roche, Alnylam shall as promptly as practicable transfer to Roche or
Roche’s designee (A) possession and ownership of all governmental or regulatory correspondence,
conversation logs, filings and approvals (including all Regulatory Approvals and pricing and
reimbursement approvals) relating to the Development, Manufacture or Commercialization of the
Licensed Product(s) and all Alnylam trademarks then being used in connection with the Licensed
Product(s) (other than Alnylam’s corporate trademarks); (B) copies of all data, reports, records
and materials, Commercialization Plans, marketing plans, promotional materials, and other sales and
marketing related information in Alnylam’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 Licensed Product(s), including all non-clinical and clinical data relating
to the Licensed Product(s), and customer lists



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and customer contact information and all Safety Data and other adverse event data in Alnylam’s possession or Control; provided that (I) Alnylam shall
not be required by this provision to provide any Confidential Information to Roche and (II) Alnylam
shall use Diligent Efforts to obtain for Roche the right to access all such data, reports, records,
materials, and other sales and marketing related information; and (C) all records and materials in
Alnylam’s possession or Control containing Confidential Information of Roche;




               (v) if requested by Roche, appoint Roche as Alnylam’s or Alnylam’s Related Parties’ agent for
all Licensed Product-related matters involving Regulatory Authorities in the Territory until all
Regulatory Approvals and other regulatory filings have been transferred to Roche or its designee;



               (vi) if the effective date of termination (or opt-out, solely for purposes of Section
4.9(b)(iv)) is after First Commercial Sale in any country in the Territory and Alnylam was the
Commercializing Party immediately prior to such termination (or opt-out, solely for purposes of
Section 4.9(b)(iv)), then, if requested by Roche, Alnylam shall appoint Roche as its exclusive
distributor of Licensed Product in the Territory and grant Roche the right to appoint
sub-distributors, until such time as all Regulatory Approvals in the Territory have been
transferred to Roche or its designee;



               (vii) if Alnylam or its Related Parties are Manufacturing API Bulk Drug Substance, Delivery
Compound, Formulated Bulk or Finished Product, at Roche’s option, supply the API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product, as applicable, to Roche in the
Territory on terms no less favorable than those on which Alnylam supplied the API Bulk Drug
Substance, Delivery Compound, Formulated Bulk or Finished Product, as applicable, prior to such
termination to its most favored distributor in the Territory, until such time as all Regulatory
Approvals in the Territory have been transferred to Roche or its designee, Roche has obtained all
necessary manufacturing approvals and Roche has procured or developed its own source of API Bulk
Drug Substance, Delivery Compound, Formulated Bulk or Finished Product supply, as applicable,
provided, that such period of time shall not exceed [**] (unless otherwise agreed
by Alnylam);



               (viii) if Roche so requests, Alnylam shall transfer to Roche any Third Party agreements
relating to the Development, Manufacture or Commercialization of the Licensed Product(s) to which
Alnylam is a party, subject to any required consents of such Third Party, which Alnylam shall use
Diligent Efforts to obtain promptly;



               (ix) subject to Alnylam Third Party Obligations, Alnylam hereby grants to Roche an exclusive
right and license, with the right to grant sublicenses subject to Section 3.1(d)(i) and Section
3.3, under such Alnylam Technology as has been incorporated into, or has been used in or (as
documented in the Joint Research Plan, the Development Plan or the Commercialization Plan, or any
approved JSC or JCT minutes, as applicable) has been intended for use in, the Development, Manufacture or Commercialization of
the Licensed Product(s) under this Agreement as of the effective date of such termination, solely
to Develop, Manufacture and Commercialize the Licensed Product(s) in the Field in the Territory;
provided, that, (A) Roche shall not be bound by the diligence obligations set forth
in Article VIII, and (B) such license shall be subject to Roche’s compliance with its obligation to
pay to Alnylam (1) (if



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Roche had been the Commercializing Party immediately prior to such
termination) royalties at the royalty rates and event payment amounts within the same Column as
would have been payable to Alnylam had Roche remained the Commercializing Party, or (2) (if Alnylam
had been the Commercializing Party immediately prior to such termination) royalties at the royalty
rates and event payment amounts within the Column that would have applied had Alnylam exercised its
Opt-Out Right; provided, however, that Roche may withhold [**] percent
([**]%) of each event and royalty payment due hereunder until the actual amount of damages owed by
Alnylam to Roche with respect to the breach of this Agreement resulting in such termination is
determined, whereupon such withheld amount shall be credited against such damages and any amount
remaining shall be paid to Alnylam within [**] days after such determination; and




               (x) Alnylam shall execute all documents and take all such further actions, including, where
applicable, the prompt assignment of Regulatory Approvals and Third Party agreements, as may be
reasonably requested by Roche in order to give effect to the foregoing clauses (i) through (ix) as
soon as practicable and in order to enable Roche to continue to Develop, Manufacture and
Commercialize the Licensed Product(s) in the Territory in the same manner as was being conducted by
the Commercializing Party prior to any such termination.



          (c) Termination for Material Breach (Other Than a Diligence Breach) or Patent
Challenge if a Party has Opted-Out. Without limiting any other legal or equitable remedies
that such Party may have, if a Party terminates this Agreement as a result of the other Party’s
material uncured breach pursuant to Section 14.2(a) or Section 14.2(b), as applicable, or as a
result of the other Party (or such other Party’s Related Parties) taking any of the prohibited
actions pursuant to Section 14.3(a) or 14.3(b), as applicable, and either Party had exercised its
Opt-Out Right at the time of such termination notice, then:




               (i) if the Party that had exercised its Opt-Out Right is the Party being terminated above,
then all rights and obligations of the Parties in effect immediately prior to such termination
shall remain in effect immediately following such termination; provided, however,
that, the Continuing Party shall not be bound by any diligence obligations hereunder; and



               (ii) if the Continuing Party is the Party being terminated above, then Section 14.4 shall
apply as if the Continuing Party had elected to terminate this Agreement at will.



          (d) Termination for Diligence Breach. Without limiting any other legal or
equitable remedies that such Party may have with respect to a Diligence Breach, if a court of
competent jurisdiction renders a final decision upholding the basis of termination by the
non-breaching Party under Section 14.2(c) with respect to such Diligence Breach (or unless and
until the breaching Party is no longer disputing such basis, if earlier), then, unless otherwise
agreed by the Parties, at the non-breaching Party’s request, the termination shall have the same
effect as if the breaching Party terminated at will in accordance with Section 14.4.




          (e) Subsequent Termination of Licenses by the Continuing Party following a
Termination Under Section 14.2 or Section 14.3. For purposes of clarity, if, following a
termination of this Agreement under Section 14.2 or 14.3, the Continuing Party (if any) decides to
terminate the licenses granted to such Party under Section 14.5(a)(ix) or Section 14.5(b)(ix),





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as the case may be, Section 14.4 shall apply as if the Continuing Party had elected to terminate this
Agreement at will.




     Section 14.6 Effect of Expiration or Termination; Survival.



          (a) Upon expiration or termination of this Agreement, each Party will within [**]
days return, or have returned by its Related Parties, to the other Party all tangible Confidential
Information of the other Party, except that each Party may retain (i) one copy which may be
retained in a secure location solely for
evidentiary purposes in the event of a dispute and (ii) any of the other Party’s Confidential
Information to the extent necessary to exercise any rights of such Party which survive termination.




          (b) Except as set forth in Section 14.5 above or this Section 14.6, upon expiration
or termination of this Agreement, each Party’s rights, obligations and licenses under this
Agreement shall terminate, either in its entirety or with respect to particular Major
Territory(ies), as the case may be; provided, however, that expiration or
termination of this Agreement shall not relieve the Parties of any obligation, including payment
obligations, accruing prior to such expiration or termination.




          (c) The provisions of Sections 3.7 (solely as set forth in Section 14.5), 4.3(f),
9.1-9.3 (solely as set forth in Section 14.5), 9.4-9.7, 10.1-10.2, 10.7-10.8 (solely to the extent
that a Party’s rights to the Licensed Product(s) survive termination hereunder), 12.4, 14.1 (last
sentence only), 14.5, 14.6, Articles XI, XIII and XV (except Section 15.15), and (if applicable)
Section 14.4(d)(i) and Paragraph 4 of Exhibit G shall survive any expiration or termination of this
Agreement in accordance with their terms.




ARTICLE XV




MISCELLANEOUS



     Section 15.1 Choice of Law. This Agreement shall be governed by and interpreted under
the laws in effect in the State of Delaware, excluding its conflicts of laws principles.



     Section 15.2 Notices. Any notice or report required or permitted to be given or made
under this Agreement by one of the Parties to the other shall be in writing and shall be deemed to
have been delivered upon personal delivery or (a) in the case of notices provided between Parties
in the continental United States, four (4) days after deposit in the mail or the next Business Day
following deposit with a reputable overnight courier and (b) in the case of notices provided by
telecopy (which notice shall be followed immediately by an additional notice pursuant to clause (a)
above if the notice is of a default hereunder), upon completion of transmissions to the addressee’s
telecopier, as follows (or at such other addresses or facsimile numbers as may have been furnished
in writing by one of the Parties to the other as provided in this Section 15.2):



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If to Alnylam:



Alnylam Pharmaceuticals, Inc.

300 Third Street, 3rd Floor

Cambridge, Massachusetts 02142

Attention: Vice President — Legal

Fax: (617) 551-8101



With a copy (which shall not constitute notice) to:



WilmerHale LLP

60 State Street

Boston, MA 02109

Attention: Steven D. Singer, Esq.

Fax: (617) 526-5000



If to Roche:



F. Hoffmann-La Roche Ltd

Grenzacherstrasse 124

4070 Basel

Switzerland

Attention: Legal Department

Fax: 41 61 688 1396




And: Hoffmann-La Roche Inc.


340 Kingsland Street

Nutley, New Jersey 07110

USA

Attention: Corporate Secretary

Fax: (973) 235-3500



With a copy (which shall not constitute notice) to:



F. Hoffmann-La Roche Ltd

Grenzacherstrasse 124

4070 Basel

Switzerland

Attention: Pharma Partnering

Fax: 41 61 688 7990




     Section 15.3 Severability. If, under applicable Law any provision hereof is invalid
or unenforceable, or otherwise directly or indirectly affects the validity of any other material
provision(s) of this Agreement (“Severed Clause”), then, it is mutually agreed that this
Agreement shall endure except for the Severed Clause. The Parties shall consult and use their best
efforts to agree upon a valid and enforceable provision which shall be a reasonable substitute for
such Severed Clause in light of the intent of this Agreement.




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     Section 15.4 Interpretation. Whenever the context may require, any pronoun shall
include the corresponding masculine, feminine and neuter forms. The words “include”, “includes”
and “including” shall be deemed to be followed by the phrase “without limitation.” The word “will”
shall be construed to have the same meaning and effect as the word “shall.” The word “or” shall be
construed to have the same meaning and effect as “and/or.” Unless the context requires otherwise,
(a) 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
amended, supplemented or otherwise modified (subject to any restrictions on such amendments,
supplements or modifications set forth herein or therein), (b) any reference to any Laws herein
shall be construed as referring to such Laws as from time to time enacted, repealed or amended, (c)
any reference herein to any Person shall be construed to include the Person’s successors and
assigns, (d) the words “herein”, “hereof’ and “hereunder”, and words of similar import, shall be
construed to refer to this Agreement in its entirety and not to any particular provision hereof,
and (e) all references herein to Articles, Sections, Exhibits or Schedules shall be construed to
refer to Articles, Sections, Exhibits and Schedules of this Agreement. The titles and subtitles
used in this Agreement are used for convenience only and are not to be considered in construing or
interpreting this Agreement.



     Section 15.5 Integration. This Agreement is being entered into in accordance with
Article IV of the LCA and supplements the LCA, and the execution of this Agreement fulfills the
Parties’ obligations under Article IV of the LCA. From and after the Effective Date of this
Agreement, this Agreement constitutes the entire agreement between the Parties with respect to the
within subject matter and supersedes all previous agreements, whether written or oral, including
Article IV of the LCA which shall have no further force or effect. The Parties acknowledge that
the LCA shall not be superseded by this Agreement except as expressly stated in this Agreement.
This Agreement may be amended only in writing signed by properly authorized representatives of each
of the Parties.



     Section 15.6 Independent Contractors; No Agency. Neither Party shall have any
responsibility for the hiring, firing or compensation of the other Party’s employees or for any
employee benefits. No employee or representative of a Party shall have any authority to bind or
obligate the other Party to this Agreement for any sum or in any manner whatsoever, or to create or
impose any contractual or other liability on the other Party without said Party’s written approval.
For all purposes, and notwithstanding any other provision of this Agreement to the contrary, each
Party’s legal relationship under this Agreement to the other Party shall be that of independent
contractor. The Parties agree and acknowledge that neither owes any fiduciary duties to the other.



     Section 15.7 Assignment; Successors. Neither Alnylam nor Roche may assign this
Agreement in whole or in part without the prior written consent of the other Party and such
attempted assignment shall be deemed null and void; provided, however, that
either Party may assign this Agreement without the prior written consent of the other Party (a) to
an Affiliate of such Party, provided that the assigning Party shall remain
primarily liable hereunder for the performance of all obligations by the assignee, or (b) subject
to Section 15.15 to a Third Party in connection with a merger, sale or transfer of all or
substantially all of the assigning Party’s business (in the case of Roche, its pharmaceutical
business related to RNAi technology and in the case of an assignment from Alnylam to [**], treated
as a [**] under Section 2.7 of the LCA)



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to which this Agreement relates, provided that such assignee shall agree in
writing to be bound by the terms and conditions of this Agreement. This Agreement shall be binding
upon, and shall inure to the benefit of, all permitted successors and assigns.




     Section 15.8 Execution in Counterparts; Facsimile Signatures. This Agreement may be
executed in counterparts, each of which counterparts, when so executed and delivered, shall be
deemed to be an original, and all of which counterparts, taken together, shall constitute one and
the same instrument even if both Parties have not executed the same counterpart. Signatures
provided by facsimile transmission shall be deemed to be original signatures.



     Section 15.9 Waivers. No failure on the part of Roche or Alnylam to exercise and no
delay in exercising any right, power, remedy or privilege under this 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 this 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.



     Section 15.10 No Consequential or Punitive Damages. NEITHER PARTY HERETO WILL BE
LIABLE FOR INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, EXEMPLARY OR MULTIPLE DAMAGES ARISING OUT
OF THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, OR FOR LOST PROFITS ARISING FROM OR
RELATING TO ANY BREACH OF, OR OTHERWISE UNDER, THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF SUCH
DAMAGES. NOTHING IN THIS SECTION 15.10 IS INTENDED TO LIMIT OR RESTRICT (A) THE INDEMNIFICATION
RIGHTS OR OBLIGATIONS OF EITHER PARTY WITH RESPECT TO THIRD PARTY CLAIMS UNDER ARTICLE XI, OR (B)
REMEDIES AVAILABLE TO EITHER PARTY WITH RESPECT TO A BREACH OF ARTICLE IX (CONFIDENTIALITY) OR
SECTION 3.7 (EXCLUSIVITY).



     Section 15.11 Actions of Affiliates. Each Party shall be liable for any failure by
its Affiliates to comply with the restrictions, limitations and obligations set forth in this
Agreement. Each Party may perform its obligations hereunder personally or through one or more
Affiliates, although each Party shall nonetheless be solely responsible for the performance of its
Affiliates. Neither Party shall permit any of its Affiliates to commit any act (including any act
of omission) that such Party is prohibited hereunder from committing directly. To the extent that
the rights granted to a Party hereunder may be and are exercised by an Affiliate of such Party,
such Affiliate shall be bound by the corresponding obligations of such Party.



     Section 15.12 Expenses. Except as otherwise expressly set forth in this Agreement,
each Party shall be solely responsible for the expenses it incurs in connection with its
performance of the activities contemplated by this Agreement.



     Section 15.13 No Third Party Beneficiaries. Except as expressly set forth in this
Agreement, no Person other than the Parties and their respective Affiliates and permitted assignees
hereunder shall be deemed an intended third party beneficiary hereunder or have any right to
enforce any obligation of this Agreement. Notwithstanding the foregoing, the Parties



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agree that UBC shall be deemed a third party beneficiary of, and shall have the right to
enforce directly against Roche, its Affiliates or Licensee Partners, certain terms of this
Agreement as set forth in the UBC Sublicense Agreement.




     Section 15.14 Bankruptcy. All licenses (and to the extent applicable rights) granted
under or pursuant to this Agreement by a Party to the other Party are, and shall otherwise be
deemed to be, for purposes of Section 365(n) of Title 11, US Code (the “Bankruptcy Code”)
licenses of rights to “intellectual property” as defined under Section 101(60) of the Bankruptcy
Code. Unless a Party elects to terminate this Agreement, the Parties agree that such Party shall
retain and may fully exercise all of its rights and elections under the Bankruptcy Code, subject to
the continued performance of its obligations under this Agreement.



     Section 15.15 Change of Control.



          (a) If a Party undergoes a Change of Control (the “Acquired Party”), such Acquired
Party shall provide the other Party with prompt written notice describing such Change of Control in
reasonable detail (but in no event later than [**] following the earlier of the public announcement
or the consummation of such Change of Control). Notwithstanding anything in this Agreement to the
contrary, the other Party may, by written notice to the Acquired Party within [**] days following
the consummation of such Change of Control, elect to do any or all of the following:




               (i) If the Parties were in a Profit and cost-sharing arrangement under Sections 4.8 and 9.2
immediately prior to the consummation of such Change of Control, the non-Acquired Party may elect
to have the Acquired Party transition to such Party all of the Development, Manufacturing and
Commercialization operational responsibilities of the Acquired Party within [**] following such
notice pursuant to a transition plan to be mutually agreed by the Parties; provided,
however, that following the transition of such responsibilities to the non-Acquired
Party, (i) each Party’s Opt-Out Right shall remain in effect, and (ii) the Profit and cost-sharing
arrangement under Sections 4.8 and 9.2 shall remain in effect (unless and until either Party
exercises its Opt-Out Right), provided, that, for as long as the Parties remain in
a Profit and cost-sharing arrangement under this Agreement, the non-Acquired Party shall not incur
Development Costs or Commercialization Costs exceeding the then-approved budget under the
Development Plan or Commercialization Plan, respectively, for the remainder of the term of such
Development Plan or Commercialization Plan, and that budgets for any period beyond such term be
reasonable and appropriate; and



               (ii) The non-Acquired Party may elect to terminate the Acquired Party’s voting, participation
and decision-making rights on any or all of the committees or subcommittees in existence at such
time, provided, that the Acquired Party shall continue to have the right to receive
and have access to information from the other Party, and the other Party shall continue to provide
such information and access to the Acquired Party, including pursuant to Sections 2.1(d) (last
paragraph), 3.1(e), 4.10(a), 9.1(c), 9.3(l), 9.5, 9.6 and 14.5, to the extent necessary for the
Acquired Party (i) to comply with its obligations to any of its Third Party licensors, (ii) to
determine whether or not to exercise its Opt-Out Right or, if the other Party exercises its Opt-Out
Right, to determine whether or not to continue the unilateral Development



-63-









 




and Commercialization of Licensed Product(s), as applicable, and (iii) to determine and verify
amounts payable by the other Party (and its Related Parties) to the Acquired Party.




          (b) Notwithstanding anything in Section 3.7 to the contrary, if a Third Party becomes an
Affiliate of the Acquired Party as a result of the Change of Control and such Third Party conducts,
or plans to conduct, any activities with respect to a Competitive Product(s) which would otherwise
become subject to the exclusivity provisions pursuant to Section 3.7 following such Change of
Control, the Acquired Party shall, in its sole discretion and within [**] days following the
consummation of such Change of Control, provide written notice to the other Party of its decision
to either:




               (i) discontinue such prohibited activities, with any necessary wind-down to occur within a
reasonable period of time thereafter; or



               (ii) exercise any Opt-Out Right with respect to the applicable Licensed Product(s), in which
event the lower development and sales event payment and royalty payment obligations associated with
an opt-out at the Opt-Out Point immediately preceding the actual Opt-Out Point shall apply to the
Continuing Party from the effective date of the opt-out.



[Remainder of This Page Intentionally Left Blank]






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     IN WITNESS WHEREOF, Alnylam and Roche have caused this Collaboration Agreement to be duly
executed by their authorized representatives, as of the Effective Date.



	 	 	 	 	 
	 	F. HOFFMANN-LA ROCHE LTD

 	 
	 	By:  	/s/ Nigel Sheail
 	 
	 	 	Name:  	Nigel Sheail 	 
	 	 	Title:  	Head of Corporate Business Development 	 
	 
	 	 	 
	 	By:  	/s/ Stefan Arnold
 	 
	 	 	Name:  	Stefan Arnold 	 
	 	 	Title:  	Head Corporate Law Pharma 	 
	 
	 	HOFFMANN-LA ROCHE INC.

 	 
	 	By:  	/s/ Ivor Macleod
 	 
	 	 	Name:  	Ivor Macleod 	 
	 	 	Title:  	Vice President & CFO 	 
	 
	 	ALNYLAM PHARMACEUTICALS, INC.

 	 
	 	By:  	/s/ John Maraganore
 	 
	 	 	Name:  	John Maraganore 	 
	 	 	Title:  	Chief Executive Officer 	 



-65-









 






	 	 	 	 	 



EXHIBIT A




Definitions




	 	 	As used in this Agreement, the following terms shall have the meanings set forth below:
	 
	1.	 	“Accounting Period” has the meaning set forth in Section 9.3(k).
	 
	2.	 	“Advertising Claim” means, with respect to a Licensed Product(s), any Third Party
claim, suit, action, proceeding, liability or obligation involving any actual or alleged death
or bodily injury arising out of or resulting from the use of such Licensed Product(s) based
upon (i) any label or other written, printed or graphic mater upon (a) any container or
wrapper utilized with such Licensed Product(s) in the U.S. or (b) any written material
accompanying any container or wrapper utilized with such Licensed Product(s) in the U.S.
including package inserts, and (ii) any communication or program associated with the promotion
of such Licensed Product(s) in the U.S., including such communications and programs that (a)
specifically identify or describe such Licensed Product(s) or (b) otherwise support such
Licensed Product(s) or raise awareness of the Field.
	 
	3.	 	“Affiliate” means any Person who directly or indirectly controls or is controlled by
or is under common control with another Person. For purposes of this definition, “control” or
“controlled” shall mean ownership, directly or through one or more Affiliates, of fifty
percent (50%) or more of the shares of stock entitled to vote for the election of directors,
in the case of a corporation, or fifty percent (50%) or more of the equity interest in the
case of any other type of legal entity, status as a general partner in any partnership, or any
other arrangement whereby a Party controls or has the right to control the Board of Directors
or equivalent governing body of a corporation or other entity, or the ability to direct the
management or policies of a corporation or other entity. The Parties acknowledge that in the
case of certain entities organized under the laws of certain countries outside of the United
States, the maximum percentage ownership permitted by law for a foreign investor may be less
than fifty percent (50%), and that in such case such lower percentage shall be substituted in
the preceding sentence, provided that such foreign investor has the power to direct the
management and policies of such entity. For purposes of this Agreement, [**], shall not be
deemed an “Affiliate” of Roche; provided, however, that if Roche were to assume day-to-day
control of [**], then Roche shall have the right, at its sole option, to designate [**] to be
an Affiliate upon written notice to Alnylam. For purposes of Sections 11.1, 11.2, 15.7, 15.11
(the second sentence only), and 15.13, Alnylam’s Affiliates shall not include [**], any
Affiliates of [**] (other than Alnylam and Persons “controlled” by Alnylam on the Effective
Date) or any Person that becomes an Affiliate of Alnylam as a result of a [**].
	 
	4.	 	“Agreement” shall have the meaning set forth in the Preamble, and shall include, for
the avoidance of doubt, all Exhibits attached hereto.
	 
	5.	 	“Alliance Manager” shall have the meaning set forth in Section 2.3.
	 
	6.	 	“Alnylam” shall have the meaning set forth in the Preamble.




A – Page 1









 












	7.	 	“Alnylam Collaboration IP” means Alnylam Collaboration Know-How and Alnylam
Collaboration Patent Rights.
	 
	8.	 	“Alnylam Collaboration Know-How” means any Know-How Controlled by Alnylam, patentable
or otherwise, first identified, discovered or developed solely by employees of Alnylam or its
Affiliates or other persons not employed by Roche or any of its Affiliates acting on behalf of
Alnylam or any of its Affiliates in the conduct of the Collaboration. Alnylam Collaboration
Know-How excludes Alnylam’s interest in Joint Collaboration Know-How.
	 
	9.	 	“Alnylam Collaboration Patent Rights” means any Patent Rights that claim or cover
Alnylam Collaboration Know-How and are Controlled by Alnylam. Alnylam Collaboration Patent
Rights excludes Alnylam’s interest in Joint Collaboration Patent Rights.
	 
	10.	 	“Alnylam Indemnitees” shall have the meaning set forth in Section 13.1.
	 
	11.	 	“Alnylam Know-How” means Know-How Controlled by Alnylam as of the Effective Date or
as to which Alnylam obtains Control during the Term that is necessary or reasonably useful for
Roche and its Affiliates to perform their obligations or exploit their rights under this
Agreement with respect to the Licensed Product(s), including their rights to Discover,
Develop, Manufacture, or Commercialize Licensed Product (other than Alnylam’s rights in Joint
Collaboration Know-How and Alnylam Collaboration Know-How); but excluding (a) Alnylam Platform
Know-How and (b) Know-How to the extent specifically related to Blocked Targets.
	 
	12.	 	“Alnylam Patent Rights” means those Patent Rights that are Controlled by Alnylam as
of the Effective Date or as to which Alnylam obtains Control during the Term that are
necessary or reasonably useful for Roche and its Affiliates to perform their obligations or
exploit their rights under this Agreement with respect to the Licensed Product(s), including
their rights to Discover, Develop, Manufacture, or Commercialize the Licensed Product(s)
(other than Alnylam’s rights in Joint Collaboration Patent Rights and Alnylam Collaboration
Patent Rights); but excluding (a) Alnylam Platform Patent Rights and (b) Patent Rights to the
extent specifically related to Blocked Targets.
	 
	13.	 	“Alnylam Platform Know-How” means the Licensed Know-How (as defined in the LCA).
	 
	14.	 	“Alnylam Platform Patent Rights” means the Licensed Patent Rights (as defined in the
LCA).
	 
	15.	 	“Alnylam Pre-Existing Alliance Agreements” means the Pre-Existing Alliance Agreements
(as defined in the LCA) and the agreements set forth on Exhibit B-1.
	 
	16.	 	“Alnylam Pre-Existing Alliance Parties” means the Third Party counterparties to
Alnylam Pre-Existing Alliance Agreements and their respective successors in interest.




A – Page 2









 






	17.	 	“Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam Patent Rights,
Alnylam Collaboration IP and Alnylam’s interest in Joint Collaboration IP, and any Third Party
Technology that is included in the definition of Alnylam Technology after the Effective Date
in accordance with Section 10.6.






	18.	 	“Alnylam Third Party Obligations” means Alnylam’s obligations to, and the rights of,
Alnylam Pre-Existing Alliance Parties and Listed Alnylam Counterparties with respect to the
Alnylam Technology under Alnylam Pre-Existing Alliance Agreements and Listed Alnylam Third
Party Agreements or Manufacturing Agreements, as applicable.
	 
	19.	 	“Annual Net Sales” means, with respect to a Licensed Product, the Net Sales of such
Licensed Product during a Calendar Year.
	 
	20.	 	“API Bulk Drug Substance” means siRNA in bulk form manufactured for use as an active
pharmaceutical ingredient.
	 
	21.	 	“Asia” means Brunei, Cambodia, China (including Hong Kong and Macao, but excluding
Taiwan), Indonesia, Japan, Laos, Malaysia, Myanmar, North Korea, Philippines, Singapore, South
Korea, Taiwan, Thailand and Vietnam.
	 
	22.	 	“Bankruptcy Code” shall have the meaning set forth in Section 15.14.
	 
	23.	 	“Baseball Arbitration” shall have the meaning set forth in Exhibit G.
	 
	24.	 	“Blocked Target” means any Target that is subject to a contractual obligation of an
Alnylam Pre-Existing Alliance Agreement that would be breached by the inclusion of such Target
as a Program Target under this Agreement.
	 
	25.	 	“Business Day” means a day on which banking institutions in Boston, Massachusetts are
open for business.
	 
	26.	 	“Calendar Quarter” means the respective periods of three (3) consecutive calendar
months ending on March 31, June 30, September 30 and December 31; provided
that the first Calendar Quarter of the Term shall begin on the Effective Date and end
on September 30, 2009, and the last Calendar Quarter of the Term shall end on the last day of
the Term.
	 
	27.	 	“Calendar Year” means each successive period of twelve (12) months commencing on
January 1 and ending on December 31; provided that the first Calendar Year of
the Term shall begin on the Effective Date and end on December 31, 2009 and the last Calendar
Year of the Term shall end on the last day of the Term.
	 
	28.	 	“Candidate Selection Stage” means the earlier of (a) the Parties’ selection of a
development candidate pursuant to Section 4.4, or (b) the completion of all activities
pursuant to the Joint Research Plan.
	 
	29.	 	“[**]Agreement” shall have the meaning set forth in Section 3.1(f).




A – Page 3









 






	30.	 	“cGMP” means current Good Manufacturing Practices and equivalent Laws outside the
United States.
	 
	31.	 	“Change of Control” means, with respect to a Party (the “Acquired Party”),
the occurrence of the closing of (a) a merger, reorganization or consolidation involving the
Acquired Party in which its shareholders immediately prior to such transaction would hold less
than fifty percent (50%) of the securities or other ownership or voting interests representing
the equity of the surviving entity immediately after such merger, reorganization or
consolidation, or (b) a sale to a Third Party of all or substantially all of the Acquired
Party’s assets or business relating to this Agreement.
	 
	32.	 	“Clinical Regulatory Filings” means data, filings or materials relating to Licensed
Product submitted to the applicable Regulatory Authorities, including (a) data derived from
Clinical Studies, (b) data derived from non-clinical studies, and (c) data, filings or
materials relating to or contained in the CMC or a DMF.
	 
	33.	 	“Clinical Study” means a Phase I Study, Phase II Study, or Phase III Study, as
applicable, but excluding any Post-Approval Studies.
	 
	34.	 	“CMC” means the chemistry, manufacturing and controls section of an IND or NDA in the
United States, or the equivalent section of regulatory filings made outside the United States.
	 
	35.	 	“Collaboration” means the collaboration of the Parties in the activities governed by
this Agreement, including such activities relating to the Discovery, Development, Manufacture
and Commercialization of the Licensed Product(s).
	 
	36.	 	“Combination Product” means a Licensed Product combined with any other clinically
active therapeutic or prophylactic ingredient, mechanism or device.
	 
	37.	 	“Commercialization” or “Commercialize” means any and all activities directed
to marketing, promoting, detailing, distributing, importing, having imported, exporting,
having exported, selling or offering to sell, or seeking to obtain reimbursement for, a
product, whether before or after Regulatory Approval for such product has been obtained.
	 
	38.	 	“Commercialization Costs” shall have the meaning ascribed in Exhibit E.
	 
	39.	 	“Commercialization Plan” shall have the meaning set forth in Section 5.3(a).
	 
	40.	 	“Commercializing Party(ies)” means (a) Roche and Alnylam in the United States and
Roche in the ROW Territory, if neither Party exercises its Opt-Out Right (unless otherwise
mutually agreed by the Parties), or (b) the Continuing Party, if either Party exercises its
Opt-Out Right or both Parties exercise their respective Opt-Out Rights, as the case may be.
	 
	41.	 	“Competitive Infringement” shall have the meaning set forth in Section 10.4(a).
	 
	42.	 	“Competitive Product” means any [**].




A – Page 4









 






	43.	 	“Confidential Information” means the terms of this Agreement and all Know-How or
other information, including proprietary information and materials (whether or not patentable)
regarding a Party’s technology, products, business information or objectives, that is treated
as confidential by the disclosing Party in the regular course of business or is otherwise
designated as confidential by the disclosing Party. For the avoidance of doubt, the identity
of any Program Targets shall be deemed the Confidential Information of both Parties.
	 
	44.	 	“Continuing Party” means the Party that decides (or is decided by mutual agreement of
the Parties, as the case may be) to unilaterally pursue the Development, Manufacture and
Commercialization of Licensed Product(s) following (a) the other Party’s exercise of its
Opt-Out Right or (b) the termination of this Agreement by the other Party pursuant to Section
14.2 or 14.3 (other than for a Diligence Breach).
	 
	45.	 	“Control” or “Controlled” means, with respect to any intellectual property
right or other intangible property, the possession by a Party (whether by ownership or
license) (other than a license granted pursuant to this Agreement), or “control” (as defined
in the definition of “Affiliate” above) over an Affiliate having possession (by ownership or
license), of the ability to grant access to, or a license or sublicense of, such rights or
property as contemplated under this Agreement, subject to the provisions of Section 10.6.
	 
	46.	 	“Cover”, “Covered” or “Covering” means, with respect to a Patent
Right, that, in the absence of a license granted to a Person under a Valid Claim included in
such Patent Right, the practice by such Person of an invention claimed in such Patent Right
would infringe such Valid Claim (or, in the case of a Patent Right that is a patent
application, would infringe a Valid Claim in such patent application if it were to issue as a
patent).
	 
	47.	 	“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.
	 
	48.	 	“Debarred Party” shall have the meaning set forth in Section 7.5(a).
	 
	49.	 	“Delivery Compound” means the chemical compound or compounds contained in either
Alnylam’s proprietary lipid nanoparticle system (LNP) or Roche’s proprietary dynamic
polyconjugate (DPC) system.
	 
	50.	 	“Designated Target” shall have the meaning set forth in the LCA.
	 
	51.	 	“[**]” shall have the meaning set forth in the LCA.
	 
	52.	 	“Develop” or “Development” means any and all preclinical and clinical drug
development activities, including test method development and stability testing, toxicology,
animal efficacy studies, formulation, quality assurance/quality control development,
statistical analysis, clinical studies, clinical trials and testing, regulatory affairs,
product approval and registration, chemical development and Manufacturing




A – Page 5









 






	 	 	development, packaging development and Manufacturing and development documentation efforts
in support of development activities anywhere in the world.
	53.	 	“Development Costs” shall have the meaning ascribed in Exhibit E.
	 
	54.	 	“Development Plan” shall have the meaning set forth in Section 4.5(a).
	 
	55.	 	“Diligence Breach” means a breach of a Party’s diligence obligations under Section
8.1 or Section 8.2, as applicable.
	 
	56.	 	“Diligence Breach Cure Period” shall have the meaning set forth in Section 14.2(c).
	 
	57.	 	“Diligent Efforts” means, with respect to each Party’s obligations relating to the
Licensed Product(s), the carrying out of such obligations in a diligent and sustained manner
using efforts substantially similar to the efforts a biopharmaceutical company of comparable
size and resources would typically devote to a product of similar market potential, profit
potential, similar stage in development or commercialization, or strategic value resulting
from its own research efforts, based on conditions then prevailing, and taking into account
other relevant factors, including technical, medical, clinical efficacy, safety,
manufacturing, and delivery considerations, product labeling or anticipated labeling, the
patent and other proprietary position of the product, the regulatory environment and
competitive market conditions.
	 
	58.	 	“Discover” or “Discovery” means any and all research or discovery activities,
including all activities pursuant to the Joint Research Plan, conducted anywhere in the world.
	 
	59.	 	“DMF” means a Drug Master File filed with the FDA, or an equivalent filing with any
other Regulatory Authority.
	 
	60.	 	“Effective Date” shall have the meaning set forth in the Preamble.
	 
	61.	 	“EMEA” means the European Medicines Agency or any successor agency thereto.
	 
	62.	 	“European Union” or “EU” means the countries of the European Union, as it is
constituted as of the Effective Date and as it may be expanded from time to time.
	 
	63.	 	“Executive Officers” means the Chief Executive Officer of Alnylam (or a senior
executive officer of Alnylam designated by Alnylam’s Chief Executive Officer) and the Global
Head of Pharma Roche (or a senior executive officer of Roche designated by Roche’s Global Head
of Pharma).
	 
	64.	 	“FBMC” shall have the meaning ascribed in Exhibit E.
	 
	65.	 	“FDA” means the United States Food and Drug Administration or any successor agency
thereto.
	 
	66.	 	“Field” means the treatment or prophylaxis of diseases in humans.




A – Page 6









 






	67.	 	“Finished Product” means the finished product formulation of Licensed Product,
containing API Bulk Drug Substance, filled into unit packages for final labeling and
packaging, and as finally labeled and packaged in a form ready for administration.
	 
	68.	 	“First Commercial Sale” means the first sale of a Licensed Product to a Third Party
in a country following Regulatory Approval of such Licensed Product in that country or, if no
such Regulatory Approval or similar marketing approval is required, the date upon which such
Licensed Product is first commercially launched in such country.
	 
	69.	 	“First-in-Man Stage” means the earlier of (a) the issuance of a study report upon
completion of GLP Toxicology Studies sufficient to file an IND in the United States or any
Major Market Country, or (b) the first dosing of the first human patient in a Clinical Study.
	 
	70.	 	“First Phase II Completion” means the issuance of a study report upon completion of
the first Phase II Study for a Licensed Product under the Development Plan.
	 
	71.	 	“Formulated Bulk” means the API Bulk Drug Substance which has been combined or
conjugated with Delivery Compound, as the case may be, before being filled into unit packages.
	 
	72.	 	“FTE” means the number of full-time-equivalent person-years of Development (each
consisting of a total of [**] hours, unless otherwise mutually agreed by the Parties),
Manufacturing or Commercialization work by each Party’s personnel on or directly related to
the applicable activity conducted hereunder.
	 
	73.	 	“GAAP” means the Parties’ respective generally accepted accounting principles, for
Alnylam, the United States generally accepted accounting principles applied on a consistent
basis, or any successor accounting principles generally accepted for public companies in the
United States (such as IFRS), and for Roche, the IFRS, or any successor accounting principles.
Unless otherwise defined or stated, financial terms shall be calculated by the accrual method
under GAAP.
	 
	74.	 	“GLP Toxicology Study” means a toxicology study that is conducted in compliance with
GLP and is required to meet the requirements for filing an IND.
	 
	75.	 	“Good Clinical Practice” means the current good clinical practice applicable to the
clinical Development of Licensed Product under applicable Law, to the extent such standards
are not less stringent than the U.S. current good clinical practice, including the ICH
guidelines.
	 
	76.	 	“Good Laboratory Practice” or “GLP” means the current good laboratory
practice applicable to the Development of Licensed Product under applicable Law, to the extent
such standards are not less stringent than the U.S. current good laboratory practice,
including 21 C.F.R. Part 58.
	 
	77.	 	“Governmental Authority” means any United States federal, state or local or any
foreign government, or political subdivision thereof, or any multinational organization or




A – Page 7









 






	 	 	authority or any authority, agency or commission entitled to exercise any administrative,
executive, judicial, legislative, police, regulatory or taxing authority or power, any court
or tribunal (or any department, bureau or division thereof), or any governmental arbitrator
or arbitral body.
	 
	78.	 	“ICH” means the International Conference on Harmonization of Technical Requirements
for Registration of Pharmaceuticals for Human Use.
	 
	79.	 	“IFRS” means International Financial Reporting Standards.
	 
	80.	 	“IND” means an application submitted to a Regulatory Authority to initiate human
clinical trials, including (a) an Investigational New Drug application or any successor
application or procedure filed with the FDA, (b) any non-U.S. equivalent of the foregoing, and
(c) all supplements and amendments that may be filed with respect to any of the foregoing.
	 
	81.	 	“Indemnified Party” shall have the meaning set forth in Section 13.4(a).
	 
	82.	 	“Indemnifying Party” shall have the meaning set forth in Section 13.4(a).
	 
	83.	 	“IND-Enabling Studies” means pharmacokinetic and toxicology studies required to meet
the requirements for filing an IND, including any GLP Toxicology Study.
	 
	84.	 	“Indication” means any disease or condition, or sign or symptom of a disease or
condition.
	 
	85.	 	“JCT” shall have the meaning set forth in Section 2.2(a).
	 
	86.	 	“JFT” means the Joint Finance Team as set forth in Section 2.3.
	 
	87.	 	“Joint Collaboration IP” means Joint Collaboration Know-How and Joint Collaboration
Patent Rights.
	 
	88.	 	“Joint Collaboration Know-How” means any Know-How, patentable or otherwise, first
identified, discovered or developed jointly by the Parties or their Affiliates or others
acting on behalf of Roche and Alnylam or their Affiliates in the conduct of the Collaboration.
	 
	89.	 	“Joint Collaboration Patent Rights” means any Patent Rights which claim or cover
Joint Collaboration Know-How.
	 
	90.	 	“Joint Future Technology Committee” shall have the meaning set forth in the LCA.
	 
	91.	 	“Joint Research Plan” means the written workplan and timetable attached hereto as
Exhibit C, as updated or amended from time to time in accordance with this Agreement.
The initial Joint Research Plan is expected to commence on the Effective Date and shall expire
on or before August 9, 2012.




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	92.	 	“JPDT” means the Joint Project Development Team as set forth in Section 2.3.
	 
	93.	 	“JSC” shall have the meaning set forth in Section 2.1(a).
	 
	94.	 	“JSC Chairperson” shall have the meaning set forth in Section 2.1(b).
	 
	95.	 	“Know-How” means any information, inventions, trade secrets or technology, whether or
not proprietary or patentable and whether stored or transmitted in oral, documentary,
electronic or other form. Know-How shall include ideas, concepts, formulas, methods,
procedures, designs, compositions, plans, documents, data, discoveries, developments,
techniques, protocols, specifications, works of authorship, biological materials, and any
information relating to research and development plans, experiments, results, compounds,
therapeutic leads, candidates and products, clinical and preclinical data, clinical trial
results, and Manufacturing information and plans (but excluding any scientific, regulatory,
pre-clinical or clinical information or data regarding specific Indications and any marketing,
financial, commercial, personnel and other business information and plans).
	 
	96.	 	“Law” means any law, statute, rule, regulation, ordinance or other pronouncement or
requirement having the effect of law of any federal, national, multinational, state,
provincial, county, city or other political subdivision, domestic or foreign.
	 
	97.	 	“LCA” shall have the meaning set forth in the Recitals.
	 
	98.	 	“Lead Regulatory Party” shall have the meaning set forth in Section 7.1(a).
	 
	99.	 	“Licensed Product” means an RNAi Product directed to a Program Target (or, subject to
Section 4.3, to both Program Targets), in the form and formulation Developed (or to be
Developed, as applicable) under the Program during the Research Term. All references to
Licensed Product in this Agreement shall be deemed to include Combination Product, to the
extent applicable.
	 
	100.	 	“Licensee Partner” means, with respect to a Party, any Third Party to which a
sublicense is granted by such Party in accordance with the terms of this Agreement, including
without limitation a Third Party distributor whose obligations to such Party or such Party’s
Affiliates include responsibility for sales, marketing or distribution efforts in a country on
behalf of such Party or such Party’s Affiliates, excluding wholesale distributors who purchase
Licensed Products from such Party or such Party’s Affiliates in an arm’s length transaction
and who have no other obligation to such Party or such Party’s Affiliates.
	 
	101.	 	“Listed Alnylam Counterparties” means the Third Party counterparties to Listed
Alnylam Third Party Agreements or to Manufacturing Agreements, as applicable, and their
respective successors in interest.
	 
	102.	 	“Listed Alnylam Third Party Agreement” means (a) the Listed Third Party Agreements
(as defined in the LCA), (b) any agreement listed on Exhibit B-2, or (c) any other
agreement between Alnylam and a Third Party executed during the Term, pursuant to




A – Page 9









 






	 	 	which Alnylam has rights and obligations with respect to, or which otherwise Cover, a
Licensed Product and where (i) the intellectual property that is the subject of such
agreement is included within Alnylam Technology, and (ii) such Alnylam Technology is
necessary or reasonably useful to Discover, Develop, Commercialize or Manufacture the
Licensed Product(s).
	 
	103.	 	“Listed Third Party Payment” shall have the meaning set forth in Section 9.3(g).
	 
	104.	 	“Losses” shall have the meaning set forth in Section 13.1.
	 
	105.	 	“Major EU Country(ies)” means Germany, France, the United Kingdom, Italy and Spain.
	 
	106.	 	“Major Market Country” means any of the United States, Germany, France, United
Kingdom, Italy, Spain, and Japan.
	 
	107.	 	“Major Territory” means any of (a) the United States, (b) the EU, (c) Asia, and (d)
all other territories not included within the foregoing clauses (a), (b) and (c).
	 
	108.	 	“Manufacture” or “Manufacturing” means any and all activities and operations
involved in or relating to the manufacturing, quality control testing (including in-process,
release and stability testing), releasing or packaging, for pre-clinical, clinical or
commercial purposes.
	 
	109.	 	“Manufacturing Agreement” means any agreement listed on Exhibit B-3.
	 
	110.	 	“Manufacturing Technology” shall have the meaning set forth in Section 6.4(b).
	 
	111.	 	“NDA” means an application submitted to a Regulatory Authority for marketing approval
of a product, including (a) a New Drug Application, Product License Application or Biologics
License Application filed with FDA or any successor applications or procedures, (b) any
non-U.S. equivalent of the foregoing, and (c) all supplements and amendments that may be filed
with respect to the foregoing.
	 
	112.	 	“Necessary Third Party Patents” shall be as defined in the definition of “Required
Third Party Payments” below.
	 
	113.	 	“Net Sales” means the amount calculated by subtracting from the amount of Adjusted
Gross Sales (as defined below) the following:
	 
		 	(a) With respect to Net Sales in the United States, a lump sum deduction of [**] percent
([**]%) of Adjusted Gross Sales in lieu of those sales-related deductions which are not
accounted for by the Commercializing Party, its Affiliates and Licensee Partners on a
product-by-product basis (e.g. outward freights, postage charges, transportation insurance,
packaging materials for dispatch of goods, custom duties, bad debt expense, discounts
granted later than at the time of invoicing);
	 
		 	(b) With respect to Net Sales in the Major Market Countries (other than the U.S.) and
Canada, a lump sum deduction of [**] percent ([**]%) of Adjusted Gross Sales in lieu of




A – Page 10









 






	 	 	those sales-related deductions which are not accounted for by the Commercializing Party, its
Affiliates and Licensee Partners on a product-by-product basis (e.g. outward freights,
postage charges, transportation insurance, packaging materials for dispatch of goods, custom
duties, bad debt expense, discounts granted later than at the time of invoicing); and
	 
		 	(c) With respect to Net Sales in all territories other than those set forth in subsections
(a) and (b) above, a lump sum deduction of [**] percent ([**]%) of Adjusted Gross Sales in
lieu of those sales-related deductions which are not accounted for by the Commercializing
Party, its Affiliates and Licensee Partners on a product-by-product basis (e.g. outward
freights, postage charges, transportation insurance, packaging materials for dispatch of
goods, custom duties, bad debt expense, discounts granted later than at the time of
invoicing).
	 
	 	 	For purposes of this definition of “Net Sales”, “Adjusted Gross Sales” shall mean the amount
of gross sales of the Licensed Product invoiced by the Commercializing Party, its Affiliates
and its Licensee Partners to Third Parties less deductions of returns and return reserves
(including allowances actually given for spoiled, damaged, out-dated, rejected, returned
Licensed Product sold, withdrawals and recalls), rebates and rebate reserves (to the extent
consistently applied by the Commercializing Party to its products), price reductions,
rebates to managed care organizations or social and welfare systems, charge backs or
reserves for chargebacks, cash sales incentives (but only to the extent it is a sales
related deduction which is accounted for within the Commercializing Party on a
product-by-product basis), cash discounts, government mandated rebates and similar types of
rebates (e.g., Pharmaceutical Price Regulation Scheme, Medicaid, each as consistently
applied by Commercializing Party to its products), volume (quantity) discounts, taxes (value
added or sales taxes, government mandated exceptional taxes and other taxes directly linked
to the gross sales amount).
	 
	 	 	In the case where a Licensed Product is a Combination Product, the Parties shall meet
approximately [**] prior to commercial launch of such Combination Product to negotiate in
good faith and agree to an appropriate adjustment to Net Sales to reflect the relative
significance of the RNAi Compound and the other pharmaceutically active agent(s) contained
in the Combination Product. If the Parties are unable to agree upon such adjustment to Net
Sales, royalties with respect to a Combination Product in a country shall be equal to the
rates set forth in Section 9.3(a), 9.3(b) or 9.3(c), as applicable, multiplied by a fraction
whose numerator is the Commercializing Party’s published sales price in such country for an
equivalent dosage of RNAi Compound contained in a given Combination Product, and whose
denominator is the Commercializing Party’s published sale prices in such country for an
equivalent dosage of all active pharmaceutical ingredients contained therein. If the
numerator or denominator cannot be determined in the manner set forth above within ninety
(90) days following the meeting between the Parties described in the first sentence of this
paragraph, then such matter shall be determined by binding arbitration conducted by one (1)
arbitrator in accordance with the rules of Judicial Arbitration and Mediation Services, Inc.
(JAMS). The arbitration shall be held in the State of Delaware and shall not last for a
period longer than six (6) months.




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	 	 	In such arbitration, the arbitrator shall be an independent expert in worldwide marketing in
the pharmaceutical industry mutually acceptable to the Parties or, if the Parties are unable
to agree upon such arbitrator, shall be selected by the President of the JAMS office located
in the State of Delaware.
	 
	114.	 	“Novartis” means Novartis Institutes for BioMedical Research, Inc.
	 
	115.	 	“[**]” shall have the meaning set forth in the LCA.
	 
	116.	 	“Opt-Out Point” shall have the meaning set forth in Section 4.9(a).
	 
	117.	 	“Opt-Out Product” shall have the meaning set forth in Section 4.9(a).
	 
	118.	 	“Opt-Out Right” means a Party’s right to opt out of the Program pursuant to Section
4.9(a).
	 
	119.	 	“Parties” means Alnylam and Roche; “Party” means either Alnylam or Roche.
	 
	120.	 	“Patent Expenses” shall have the meaning set forth in Section 10.3(g).
	 
	121.	 	“Patent Rights” means all patents (including all reissues, extensions, substitutions,
confirmations, re-registrations, re-examinations, invalidations, supplementary protection
certificates and patents of addition) and patent applications (including all provisional
applications, continuations, continuations-in-part and divisionals), and foreign equivalents
of any of the foregoing.
	 
	122.	 	“Person” means any natural person, corporation, firm, business trust, joint venture,
association, organization, company, partnership or other business entity, or any government,
or any agency or political subdivisions thereof.
	 
	123.	 	“Pharmacovigilance Agreement” shall have the meaning set forth in Section 7.2(b).
	 
	124.	 	“Phase I Completion” means the issuance of a study report upon completion of all
Phase I Studies for a Licensed Product under the Development Plan.
	 
	125.	 	“Phase I Study” means a human clinical trial in any country that would satisfy the
requirements of 21 C.F.R. § 312.21(a), as amended from time to time.
	 
	126.	 	“Phase II Completion” means the issuance of a study report upon completion of all
Phase II Studies for a Licensed Product under the Development Plan.
	 
	127.	 	“Phase II Study” means a human clinical trial in any country, for which the primary
endpoints include a determination of dose ranges or a preliminary determination of efficacy in
patients being studied as described in 21 C.F.R. § 312.21(b), as amended from time to time.
	 
	128.	 	“Phase III Completion” means the issuance of a study report upon completion of all
Phase III Studies for a Licensed Product under the Development Plan.




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	129.	 	“Phase III Study” means a human clinical trial in any country that is prospectively
designed to demonstrate statistically whether a product is safe and effective for use in
humans in a manner sufficient to obtain regulatory approval to market such product in patients
having the disease or condition being studied as described in 21 C.F.R. § 312.21(c), as
amended from time to time.
	 
	130.	 	“Post-Approval Study” means a clinical study of Licensed Product that is initiated in
a country in the Territory after receipt of Regulatory Approval for such Licensed Product in
such country.
	 
	131.	 	“Product Liability Claim” means, with respect to a product, any Third Party claim,
suit, action, proceeding, liability or obligation involving any actual or alleged death or
bodily injury arising out of or resulting from the use of such product, other than an
Advertising Claim or any claim, suit, action, proceeding, liability or obligation resulting
from the price and commercial terms of Licensed Product in the U.S., or any policy governing
the handling of returns, recalls, order processing, invoicing and collection, distribution,
and inventory and receivables for, Licensed Product(s) in the U.S.
	 
	132.	 	“Product Liability Costs” means costs associated with Product Liability Claims
resulting from the Development, Manufacture, Commercialization, or use of the Licensed
Product(s) under this Agreement in the United States and product liability insurance premiums
for policies covering the Development, Manufacture, Commercialization, or use of the Licensed
Product(s) in the United States (other than Losses entitled to indemnification under Section
13.1 or Section 13.2).
	 
	133.	 	“Product Specific Know-How” means Know-How that is specific to a Licensed Product
(and not broadly applicable to RNAi Products) or to particular sequences of a Licensed
Product, including composition information and any preclinical and clinical test data related
to any of the foregoing.
	 
	134.	 	“Product Specific Patent Rights” means claim(s) contained in Patent Rights that Cover
any Product Specific Know-How.
	 
	135.	 	“Profit” means Net Sales of the Licensed Product(s) in the United States by the
Commercializing Party and its Related Parties, minus (a) FBMC in the United States (as defined
in Exhibit E).
	 
	136.	 	“Program” means the Collaboration activities performed or to be performed by the
Parties with respect to the Licensed Product(s) under this Agreement.
	 
	137.	 	“Program Target” means (a) [**] and (b) one (1) additional Target directed to the
[**] as may be mutually agreed by the Parties) as may be selected by mutual agreement of the
Parties in accordance with Section 4.3. For purposes of clarity, [**].
	 
	138.	 	“Publishing Party” shall have the meaning set forth in Section 11.4.




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	139.	 	“Regulatory Approval” means, with respect to a product in a country, the approval of
the applicable Regulatory Authority necessary for the marketing and sale of such product in
such country.
	 
	140.	 	“Regulatory Authority” means any federal, national, multinational, state, provincial
or local regulatory agency, department, bureau or other governmental entity with authority
over the marketing, pricing or sale of a pharmaceutical product in a country, including the
FDA.
	 
	141.	 	“Related Party” means (a) with respect to Roche, any of Roche’s Affiliates or
Licensee Partners, and, (b) with respect to Alnylam, any of Alnylam’s Affiliates or Licensee
Partners.
	 
	142.	 	“Required Third Party Payments” means royalty payments to a Third Party made by the
Commercializing Party under Third Party agreements (other than Listed Alnylam Third Party
Agreements and Alnylam Pre-Existing Alliance Agreements, if Alnylam is a Commercializing
Party) to license Patent Rights Covering such Third Party’s technology if, in the absence of
such license, the licensed use by the Commercializing Party of the Patent Rights licensed by
such Commercializing Party from the other Party under Section 3.1 (if the Commercializing
Party is Roche) or Section 3.2 (if the Commercializing Party is Alnylam) would infringe such
Third Party Patent Rights (such Third Party Patent Rights, “Necessary Third Party
Patents”); provided, however, that Required Third Party Payments
shall not include any royalties or other amounts payable to obtain access to (a) a specific
Target or Targets so that such Target or Targets can be the subject of research and
development efforts, or (b) Third Party delivery technologies (other than Delivery Patent
Rights (as defined in the LCA)) which may be necessary or useful for delivery of
double-stranded oligonucleotide molecules, or manufacturing techniques for such delivery
technologies.
	 
	143.	 	“Research Term” means the period commencing on the Effective Date and ending on
August 9, 2012 (as may be extended by mutual agreement of the Parties).
	 
	144.	 	“RNAi Compound” means any compound that, in vitro or otherwise, functions through the
mechanism of RNA interference and consists of or encodes double-stranded oligonucleotides, and
which double-stranded oligonucleotides optionally may be chemically modified to contain
modified nucleotide bases or non-RNA nucleotides, and optionally may be administered in
conjunction with a delivery vehicle or vector.
	 
	145.	 	“RNAi Product” means any product that contains one or more RNAi Compounds as an
active ingredient.
	 
	146.	 	“Roche” shall have the meaning set forth in the Preamble.
	 
	147.	 	“Roche Basel” shall have the meaning set forth in the Preamble.
	 
	148.	 	“Roche Nutley” shall have the meaning set forth in the Preamble.




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	149.	 	“Roche Collaboration IP” means Roche Collaboration Know-How and Roche Collaboration
Patent Rights.
	 
	150.	 	“Roche Collaboration Know-How” means any Know-How Controlled by Roche, patentable or
otherwise, first identified, discovered or developed solely by employees of Roche or its
Affiliates or other persons not employed by Alnylam or any of its Affiliates acting on behalf
of Roche or any of its Affiliates, in the conduct of the Collaboration. Roche Collaboration
Know-How excludes Roche’s interest in Joint Collaboration Know-How.
	 
	151.	 	“Roche Collaboration Patent Rights” means any Patent Rights which claim or cover
Roche Collaboration Know-How and are Controlled by Roche. Roche Collaboration Patent Rights
exclude Roche’s interest in Joint Collaboration Patent Rights.
	 
	152.	 	“Roche Indemnitees” shall have the meaning set forth in Section 13.2.
	 
	153.	 	“Roche Know-How” means Know-How Controlled by Roche as of the Effective Date or as to
which Roche obtains Control during the Term that is necessary or reasonably useful for Alnylam
and its Affiliates to perform their obligations or exploit their rights under this Agreement
with respect to the Licensed Product(s), including their rights to Discover, Develop,
Manufacture, or Commercialize Licensed Product (other than Roche’s rights in Joint
Collaboration Know-How and Roche Collaboration Know-How).
	 
	154.	 	“Roche Patent Rights” means those Patent Rights that are Controlled by Roche as of
the Effective Date or as to which Roche obtains Control during the Term that are necessary or
reasonably useful for Alnylam and its Affiliates to perform their obligations or exploit their
rights under this Agreement with respect to the Licensed Product(s), including their rights to
Discover, Develop, Manufacture, or Commercialize the Licensed Product(s) (other than Roche’s
rights in Joint Collaboration Patent Rights and Roche Collaboration Patent Rights).
	 
	155.	 	“Roche Technology” means, collectively, Roche Know-How and Roche Patent Rights, Roche
Collaboration IP and Roche’s interest in Joint Collaboration IP, and any Third Party
Technology that is included in the definition of Roche Technology after the Effective Date in
accordance with Section 10.6.
	 
	156.	 	“ROW Territory” means the entire Territory other than the United States.
	 
	157.	 	“Royalty Term” means, separately with respect to each Licensed Product in each
country, the period commencing on the First Commercial Sale of such Licensed Product in such
country (provided that either (x) such Licensed Product is Covered by a Valid
Claim of the Alnylam Platform Patent Rights, Alnylam Patent Rights, Roche Patent Rights,
Alnylam Collaboration Patent Rights, Roche Collaboration Patent Rights or Joint Collaboration
Patent Rights in such country at the time of such First Commercial Sale in such country, or
(y) the Manufacture of such Licensed Product is Covered by a Valid Claim of the Alnylam
Platform Patent Rights, Alnylam Patent Rights, Roche Patent Rights, Alnylam Collaboration
Patent Rights, Roche Collaboration Patent Rights or Joint Collaboration Patent Rights in the
country or countries in which such Licensed Product is




A – Page 15









 






	 	 	Manufactured) and concluding on the expiration of the later of (a) the last to expire
Alnylam Platform Patent Right, Alnylam Patent Right, Roche Patent Right, Alnylam
Collaboration Patent Right, Roche Collaboration Patent Right or Joint Collaboration Patent
Right containing a Valid Claim Covering the Development, Commercialization or Manufacture of
such Licensed Product in that country, (b) the last to expire Alnylam Platform Patent Right,
Alnylam Patent Right, Roche Patent Right, Alnylam Collaboration Patent Right, Roche
Collaboration Patent Right or Joint Collaboration Patent Right containing a Valid Claim
Covering the Manufacture of such Licensed Product in the country or countries in which such
Licensed Product was Manufactured, or (c) ten (10) years from the date of First Commercial
Sale of such Licensed Product in such country.
	 
	158.	 	“[**]” means [**].
	 
	159.	 	“Sales Representative” means an individual, who engages in or manages sales calls and
other promotional efforts with respect to Licensed Product and who is employed by a Party or
an Affiliate of a Party.
	 
	160.	 	“Severed Clause” shall have the meaning set forth in Section 15.3.
	 
	161.	 	“Supply Agreement” shall have the meaning set forth in Section 6.3.
	 
	162.	 	“Supply Agreement Term Sheet” shall have the meaning set forth in Section 6.2(c).
	 
	163.	 	“Target” means (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic
intervention by a therapeutic agent; or a nucleic acid which is required for expression of
such polypeptide; (b) variants of a polypeptide (including any splice variant thereof),
cellular entity or nucleic acid described in clause (a); or (c) a defined non-peptide entity,
including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a virus shall be regarded as a single Target.
	 
	164.	 	“Term” shall have the meaning set forth in Section 14.1.
	 
	165.	 	“Terminated Patent Right” shall have the meaning set forth in Section 9.3(i).
	 
	166.	 	“Territory” means the entire world.
	 
	167.	 	“Third Party” means any Person other than Alnylam or Roche and their respective
Affiliates.
	 
	168.	 	“Third Party Contractors” means Third Party contractors such as contract research
organizations, contract employees, consultants, contract manufacturers and the like.
	 
	169.	 	“Third Party Technology” shall have the meaning set forth in Section 10.6(a).
	 
	170.	 	“UBC” means the University of British Columbia.




A – Page 16









 






	171.	 	“UBC Sublicense Agreement” means the Sublicense Agreement between Tekmira
Pharmaceuticals Corporation (formerly INEX Pharmaceuticals Corporation) and Alnylam
Pharmaceuticals, Inc., dated January 8, 2007.
	 
	172.	 	“United States” or “U.S.” means the United States of America and its
territories and possessions.
	 
	173.	 	“Valid Claim” means a claim (a) of any issued, unexpired patent that has not been
revoked or held unenforceable or invalid by a decision of a court or governmental agency of
competent jurisdiction from which no appeal can be taken, or with respect to which an appeal
is not taken within the time allowed for appeal, and that has not been disclaimed or admitted
to be invalid or unenforceable through reissue, disclaimer or otherwise, or (b) of any patent
application that has not been cancelled, withdrawn or abandoned, or been pending for more than
[**] from the earliest priority date for such patent application.






A – Page 17











 





EXHIBIT B-1




Alnylam Pre-Existing Alliance Agreements


Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Roche as of the Effective Date:





	1.	 	Amended and Restated Strategic Collaboration and License Agreement between Isis
Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., dated April 28, 2009






	2.	 	Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam Pharmaceuticals,
Inc., dated August 14, 2007






	3.	 	Amended and Restated Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam
Pharmaceuticals, Inc., dated May 30, 2008






	4.	 	Amended and Restated License and Collaboration Agreement between Tekmira Pharmaceuticals
Corporation and Alnylam Pharmaceuticals, Inc., dated May 30, 2008






	5.	 	License and Collaboration Agreement between Takeda Pharmaceutical Company Limited and Alnylam
Pharmaceuticals, Inc., dated May 27, 2008, as supplemented by letter agreement dated May 27,
2008






	6.	 	Sponsored Research Agreement between the University of British Columbia, AlCana Technologies,
Inc., and Alnylam Pharmaceuticals, Inc., dated July 27, 2009, as supplemented by the
Supplemental Agreement between Tekmira Pharmaceuticals Corporation, Protiva Biotherapeutics
Inc., the University of British Columbia, AlCana Technologies, Inc., and Alnylam
Pharmaceuticals, Inc., dated July 27, 2009






	7.	 	Letter amendments dated July 11, 2008 and July 11, 2009 to the Research Collaboration and
License Agreement, effective as of October 12, 2005, by and between Alnylam and Novartis, as
amended by the Addendum Re: Influenza Program effective as of December 13, 2005, Amendment No.
1 to such Addendum effective as of March 14, 2006, and Amendment No. 2 to such Addendum
effective as of May 5, 2006






	8.	 	Letter agreement dated January 31, 2008 to the Strategic Collaboration & License Agreement
between Isis Pharmaceuticals, Inc., and Alnylam Pharmaceuticals, Inc., dated March 11, 2004,
as supplemented or amended by letter agreements dated March 9, 2004 (as amended by letter
agreement dated October 28, 2005), March 11, 2004, and June 10, 2005




B-1 – Page 1









 











EXHIBIT B-2




Listed Alnylam Third Party Agreements


Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Roche as of the Effective Date:





	1.	 	License Agreement between Celo GmbH and Alnylam Pharmaceuticals, Inc., dated July 27, 2009






	2.	 	Licensing Agreement between ETH Zurich and Alnylam Pharmaceuticals, Inc., dated April 30,
2009






	3.	 	Amended and Restated Strategic Collaboration and License Agreement between Isis
Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., dated April 28, 2009






	4.	 	Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam Pharmaceuticals,
Inc., dated August 14, 2007






	5.	 	Amended and Restated Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam
Pharmaceuticals, Inc., dated May 30, 2008






	6.	 	Amended and Restated License and Collaboration Agreement between Tekmira Pharmaceuticals
Corporation and Alnylam Pharmaceuticals, Inc., dated May 30, 2008






	7.	 	Exclusive License Agreement between The Regents of the University of California and Alnylam
Pharmaceuticals, Inc., dated April 3, 2009






	8.	 	Waiver Amendment dated August 9, 2007 to the Co-Exclusive License Agreement between Max
Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Pharmaceuticals, Inc.,
dated December 20, 2002, as amended by Amendment dated July 2, 2003, and the Requirements
Amendment effective June 15, 2005






	9.	 	Letter agreement dated January 31, 2008 to the Strategic Collaboration & License Agreement
between Isis Pharmaceuticals, Inc., and Alnylam Pharmaceuticals, Inc., dated March 11, 2004,
as supplemented or amended by letter agreements dated March 9, 2004 (as amended by letter
agreement dated October 28, 2005), March 11, 2004, and June 10, 2005






	10.	 	Amendments dated May 7, 2008 and May 20, 2008 to the Amended and Restated Exclusive Patent
License Agreement between Alnylam Pharmaceuticals, Inc., and Massachusetts Institute of
Technology, dated May 9, 2007




B-2 – Page 1









 












	11.	 	License Agreement between Medical College of Georgia Research Institute, Inc., and
Nucleonics, Inc., dated May 18, 2001, as amended on November 19, 2001, April 18, 2003,
December 16, 2003, and July 20, 2004, and assigned from Nucleonics, Inc., to Alnylam
Pharmaceuticals, Inc., on December 5, 2008






	12.	 	License Agreement between Wyeth and Nucleonics, Inc, dated June 30, 2003, as amended on
August 28, 2006, and assigned from Nucleonics, Inc., to Alnylam Pharmaceuticals, Inc., on
December 5, 2008






	13.	 	License Agreement between Wyeth and Nucleonics, Inc., dated August 28, 2006, and assigned
from Nucleonics, Inc., to Alnylam Pharmaceuticals, Inc., on December 5, 2008 [Wyeth as
Licensor]






	14.	 	License Agreement between Wyeth and Nucleonics, Inc., dated August 28, 2006, and assigned
from Nucleonics, Inc., to Alnylam Pharmaceuticals, Inc., on December 5, 2008 [Nucleonics as
Licensor]






	15.	 	Sublicense Agreement between Wyeth and Nucleonics, Inc., dated June 30, 2003, and assigned
from Nucleonics, Inc., to Alnylam Pharmaceuticals, Inc., on December 5, 2008






	16.	 	Assignment between Wyeth and Nucleonics, Inc., dated July 13, 2007, and assigned from
Nucleonics, Inc., to Alnylam Pharmaceuticals, Inc., on December 5, 2008




B-2 – Page 2









 











EXHIBIT B-3




Manufacturing Agreements


Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Roche as of the Effective Date:



[**]










B-3 – Page 1









 








EXHIBIT C




Joint Research Plan



Alnylam-Roche [**] Collaboration Workplan

September 9, 2009

FINAL


[**]






C – Page 1









 








Summary of Research Plan and Timeline:




               [**]


A total of two pages were omitted pursuant to a request for confidential treatment.











C – Page 2









 








EXHIBIT D




Supply Agreement Term Sheet


1. Alnylam and Roche shall use their respective Diligent Efforts to enter into a Supply Agreement
which will be consistent with the terms of this Supply Agreement Term Sheet. From the Candidate
Selection Stage until the effective date of the Supply Agreement, the terms of the Agreement and
this Supply Agreement Term Sheet shall govern the Manufacture and supply of API Bulk Drug
Substance, Delivery Compound, Formulated Bulk and Finished Product (as applicable) under the
Agreement, including pre-clinical and clinical supply in the quantities and on the delivery terms
set forth in the Development Plan (or as otherwise mutually agreed by the Parties);
provided, however, that in the event of conflict between this Supply Agreement Term
Sheet and the Agreement, the terms of the Agreement shall apply.



2. The Parties shall be responsible for establishing the specifications (the
“Specifications”) and approving the master batch record, including the necessary
documentation, certificates of analysis and test results, for the API Bulk Drug Substance, Delivery
Compound, Formulated Bulk and Finished Product (as applicable), to be supplied under the Supply
Agreement.



3. Unless agreed otherwise in writing by the Parties, [**] before the commencement of each Calendar
Quarter, each Party will give to the other Party (and to the JSC if the JSC remains in effect) a
rolling [**] Calendar Quarter forecast (“Forecast”) of the estimated quarterly requirements
of API Bulk Drug Substance, Delivery Compound, Formulated Bulk and Finished Product (as applicable)
for which such other Party Controls the Manufacturing technology. Such Forecast will include
quantity and unit requirements for API Bulk Drug Substance, Delivery Compound, Formulated Bulk and
Finished Product (as applicable) in the United States and the ROW Territory. [**] percent ([**]%)
of forecasted requirements during the first [**] Calendar Quarters of such Forecast shall be
considered binding on the Parties. The purchasing Party will provide the supplying Party with
binding purchase orders at least [**] in advance of the requested delivery. If the purchasing
Party requests any changes to the Forecast, the supplying Party shall (i) use its commercially
reasonable efforts to accommodate such requests and (ii) use its commercially reasonable efforts to
minimize any costs incurred as a result of such changes.



4. In the event of an anticipated shortage of supply of API Bulk Drug Substance, Delivery Compound,
Formulated Bulk or Finished Product (as applicable), which a Party is responsible for supplying to
the other Party hereunder, such supplying Party shall promptly notify the other Party and, unless
otherwise agreed by the Parties, available supply shall be allocated between the United States and
the ROW Territory on a pro-rata basis based on good faith forecasts of requirements. In addition,
the supplying Party will use commercially reasonable efforts to engage a secondary source of supply
and to resolve all anticipated failure to supply issues as promptly as possible in consultation
with the other Party.



5. If and to the extent that a Failure to Supply (as hereinafter defined) occurs, the purchasing
Party, if the purchasing Party is also the Commercializing Party, shall have the right to assume
control of the Manufacture of the Licensed Product(s) by requesting a transfer of Manufacturing
pursuant to Section 6.4. For purposes of this Supply Agreement Term Sheet, a “Failure to
Supply” will be deemed to have occurred only after the supplying Party and all secondary






D – Page 1









 







sources of supply made available to the purchasing Party have failed to deliver [**] percent
([**]%) of the aggregate requirements for API Bulk Drug Substance, Delivery Compound, Formulated
Bulk and Finished Product (as applicable) for a given Calendar Quarter as described in the
Forecast, in [**] out of any [**] consecutive Calendar Quarters.



6. Each Party agrees that all API Bulk Drug Substance, Delivery Compound, Formulated Bulk and
Finished Product (as applicable) supplied to the other Party hereunder will, at the time of
delivery to such other Party, have been Manufactured in accordance with the Specifications and the
master batch record, and except for batches not intended for human use, with cGMP. The supplying
Party will be solely responsible for all costs and expenses caused by failed batches, including
batches which fail to meet the requirements of the previous sentence, as a result of the negligence
or intentional misconduct of any employee of such supplying Party. The purchasing Party will be
responsible for all costs and expenses caused by failed batches other than as a result of the
negligence or intentional misconduct of any employee of the supplying Party.



7. In addition to more detailed terms regarding the matters specified above in this Supply
Agreement Term Sheet, the Supply Agreement shall contain other customary supply agreement
provisions, including indemnification provisions appropriate for a supply agreement. Furthermore,
Alnylam and Roche will enter into a Technical and Quality Agreement with respect to the Licensed
Product(s) governing, among other things, quality assurance requirements, documentation and
procedures, audit and inspection rights and similar matters.










D – Page 2









 








EXHIBIT E




FINANCIAL APPENDIX



     This Exhibit E sets forth the principles for capturing, reporting and consolidating
Development Costs, Commercialization Costs, and Profit sharing. Roche shall be responsible for all
other costs with respect to Licensed Product(s).



     For such purpose, this Exhibit E sets forth the principles for reporting actual
results and budgeted plans in the United States, the frequency of reporting, the use of a single
“Functional Currency” (as defined under the heading “Foreign Exchange” below) and the methods of
determining payments to the Parties, auditing of accounts and other matters.



     This Exhibit E also provides agreed upon definitions of financial terms applicable to
the Parties for any Licensed Product. Except for the term Licensed Product, all capitalized terms
used herein without definition shall have the meanings ascribed thereto in the Agreement and, where
applicable, the further definitions contained herein. The term “Product” in this Exhibit E
shall mean Licensed Product. References in this Exhibit E to a “Party” or “Parties” shall
be construed to mean Alnylam or Roche, as the case may be, and in every case shall be deemed to
include a Party’s Affiliates or Licensee Partners under the Agreement. Capitalized terms used
herein, but not otherwise defined, shall have the meanings given them in the Agreement.



     Notwithstanding anything in the Agreement to the contrary, no cost, expense, amount or sum
allocable or chargeable to the Parties’ activities under the Agreement shall be allocated or
charged more than once. Unless otherwise specifically authorized by the Parties or the Agreement,
all costs, expenses, amounts or sums to be charged or allocated by one Party to the other Party
under the Agreement shall not be so chargeable or allocable unless they are both directly related
to the Agreement and the activities to be performed under the Agreement and are reasonable and
customary with respect to the global biopharmaceutical industry considering the respective size and
activities of the two Parties as collaborators under the Agreement.



ARTICLE I




REPORTING AND CONSOLIDATION OF DEVELOPMENT COSTS AND

COMMERCIALIZATION COSTS



     Section 1.1 Preparation of Budgets. Preparation of annual budgets will be initiated
in each July during such period and a preliminary budget will be presented for review by the JFT
before [**] during such period. The completed Development Plan budget or Commercialization Plan
budget, as applicable, should be approved by the Parties by the end of each November during such
period. Reporting by each Party will be performed as follows (with copies provided to the JPDT or
JCT and to the other Party):



E – Page 1









 





	 	 	 	 	 	 	 
	Reporting Event (calendar basis)	 	Submission	 	Frequency	 	Deadline
	Q1-Q3

	 	Actuals
	 	End of Calendar Quarter
	 	[**]
	Q4

	 	Actuals
	 	End of Calendar Quarter
	 	[**]
	Preliminary annual budget

	 	 	 	Annually
	 	[**]
	Final annual budget

	 	 	 	Annually
	 	[**]
	Forecasts for sales (current Calendar Year) for the United States

	 	 	 	Quarterly, except Q4
	 	[**]
	Full profit and loss forecast for the United States (current Calendar Year)

	 	 	 	Quarterly, except Q4
	 	[**]





Responsibility for preparing the Development Plan budget and Commercialization Plan budget (other
than the initial budget, which shall be determined by the Parties) will rest with the JPDT and JCT,
respectively. Both JPDT and JCT budgets shall be reviewed and approved by the JFT and presented to
the JSC for review (which shall then present to the Parties for approval).




     Section 1.2 Reporting. Each Party shall report to the other Party and the JFT
actual, budget and forecast results of operations related to the following, as applicable:


[**]



The JFT shall be responsible for the preparation of consolidated reporting (actuals, budgets and
forecasts) for the Development Costs, Commercialization Costs and Profit based upon the
Commercialization Plan Reports, Development Plan Reports and Sales Reports provided by the Parties
as specified below, as well as determination of the cash settlement.



Within [**] days after the end of each Calendar Quarter (or for the last Calendar Quarter of each
Calendar Year, within [**] days after the end of such Calendar Quarter), each Party shall provide
the other Party and the JFT with such Party’s “Development Plan Report” for such Calendar Quarter.
Such report shall be in writing and shall summarize the Development Program activities undertaken
by such Party (or its relevant local Affiliates) during such Calendar Quarter in connection with
the Development Plan, together with a detailed project-level statement of those expenses incurred
by such Party during such Calendar Quarter that are specific to the Development Plan and satisfy
those additional criteria necessary to qualify as Development Costs. Such report shall also
address any necessary adjustments of Development Costs for previous Calendar Quarters.







E – Page 2









 







Within [**] days after the end of each Calendar Quarter (or for the last Calendar Quarter of each
Calendar Year, within [**] days after the end of such Calendar Quarter), each Party shall provide
the other Party and the JFT with such Party’s “Commercialization Plan Report” for such Calendar
Quarter. Such report shall be in writing and shall summarize the marketing and promotional
activities undertaken by such Party (or its relevant local Affiliates) during such Calendar Quarter
in connection with the applicable Commercialization Plan, together with a detailed project-level
statement of commercialization-related expenses incurred by such Party during such Calendar Quarter
that are specific to the United States and satisfy those additional criteria necessary to qualify
as Commercialization Costs. Such report shall also address any necessary adjustments of
Commercialization Costs for previous Calendar Quarters. Within [**] days after the end of each
Calendar Quarter (or for the last Calendar Quarter of each Calendar Year, within [**] days after
the end of such Calendar Quarter), Roche shall provide Alnylam and the JFT with Roche’s “Sales
Report” for such Calendar Quarter. Such report shall be in writing and shall summarize the Product
sales made by Roche in the United States in such Calendar Quarter and the calculation of Adjusted
Gross Sales, Net Sales and Profit with respect to such sales. Such report shall also address any
necessary adjustments of Adjusted Gross Sales, Net Sales and Profit for previous Calendar Quarters.



The JFT will be responsible for monitoring and agreeing upon appropriate controls to ensure
reasonable and consistent calculation of Commercialization Costs, Development Costs and Profit
under the Agreement, including in the Development Plan Reports, Commercialization Plan Reports and
Sales Reports. More specifically, the JFT shall review the budgeted and forecasted versus actual
FTEs and external expenses per quarter. In any event, the JFT shall review use of FTE resources on
a quarterly basis. The Parties shall also use commercially reasonable efforts to provide access to
available discounts and discount programs available from existing vendors for the benefit of the
Parties under the Agreement. The Parties’ actual results compared to budget and forecast will be
calculated by the JFT and set forth in the Reconciliation Statement described below.



The Parties will work together to keep actual spending within the approved budget and forecast;
provided, that, the Parties shall continue to share in Development Costs and Commercialization
Costs that exceed the budget by up to [**] percent ([**]%). The Parties shall discuss in good
faith the adoption of additional control measures to address deviations from the approved budget
and forecast on an annual basis above [**] percent ([**]%). If a Party contemplates that any
expenditure will increase the annual budget associated with the Commercialization Plan by more than
[**] percent ([**]%), the Parties shall review the expenditure with the JCT prior to commitment to
that expenditure. The JFT will meet as appropriate to review and approve the reporting events
(actuals, budgets and forecasts) and any deviations from the approved budget.



Each Party shall report Development Costs and Commercialization Costs based on its project cost
system (which shall in any event track FTEs by functional area and by month) or using such other
system as such Party applies with respect to its internal programs and which system has been
reviewed with the JFT. In general, these project cost systems shall report actual and/or allocable
time spent on specific projects, apply the FTE rates, determined in the manner specified in Section
1.6 below.







E – Page 3









 








     Section 1.3 Reconciliation Statements. The financial representatives from each Party
on the JFT shall be responsible for, within [**] calendar days following the end of a Calendar
Quarter (or, for the last Calendar Quarter in a Calendar Year, within [**] days after the end of
such Calendar Quarter), preparing and providing to the other Party (through the JFT) and to the
JPDT and JCT, a statement (“Reconciliation Statement”), in a format agreed to by the
Parties and based on the information contained in Development Plan Reports, Commercialization Plan
Reports and Sales Report provided by Parties for such Calendar Quarter and any additional
information obtained by the JFT from the Parties, that shows each Party’s results, the calculations
of Development Costs, Commercialization Costs, cost-sharing under the Agreement and any cash
settlement required for such Calendar Quarter. The JPDT and JCT shall each promptly decide whether
to approve those portions of the Reconciliation Statement that are under its jurisdiction. If
there is a dispute within the JPDT or JCT (or both) regarding approval of a Reconciliation
Statement, the JFT shall submit such dispute to the Executive Officers of each Party for
resolution. The Executive Officers shall undertake good faith efforts to resolve such dispute and
approve the Reconciliation Statement (or, if applicable, an amended Reconciliation Statement) no
later than [**] days after the end of the applicable Calendar Quarter (or, for the last Calendar
Quarter in a Calendar Year, within [**] days after the end of such Calendar Quarter).



     Section 1.4 Foreign Exchange. The “Functional Currency” for accounting for
Development Costs and Commercialization Costs will be U.S. dollars.



     Section 1.5 Payments Between the Parties. Based upon the Reconciliation Statement,
as prepared by the JFT and approved by the JPDT and JCT or the Executive Officers of each Party, as
applicable, there shall be a cash settlement between the Parties of the amounts due under the
Reconciliation Statement and each Party’s share of the Profit. The Party that is owed any amount
under the Reconciliation Statement will provide the other Party an invoice for such amount, and
such other Party shall pay such invoice within [**] days after approval of the applicable
Reconciliation Statement and receipt of the applicable invoice. In the event any payment is made
after the date specified in the preceding sentence and provided that such payment is not otherwise
subject to good faith dispute, the paying Party shall pay interest as set forth in Section 9.7 of
the Agreement. For clarity, the Parties shall separately identify, and make a separate payment for
each of, the share of Profit provided for in Section 9.2 of the Agreement and the other payment
(for Development Costs and Commercialization Costs) required pursuant to the Reconciliation
Statement; however, both payments will take place on the same day.



     Section 1.6 FTE Rates.



     (a) The Parties have agreed on the Development FTE-rate, as set forth in clause (b) below,
that will be charged for the resources allocated to the Development Plan activities from the
functions directly operating the activities on a fractional Development FTE-basis. The Parties
contemplate that this rate captures total actual personnel and fixed costs attributable to the
performance of the Development Plan under this Agreement.



     (b) All Development FTE expenditures shall be included in Development Costs based on a rate of
US$[**] per Development FTE. For each Calendar Year after 2010, the Development FTE rate will be
adjusted by the increase or decrease in CPI as published by the



E – Page 4









 




U.S. Bureau of Labor Statistics for the previous Calendar Year. All people within these functions
will record the percent of time each month spent on the activities under the programs. For
clarity, Development FTE time recording should be made on a fractional basis. Each Party will also
use its respective project cost system with the purpose of tracking and reporting costs on a
project/product indication/work package level.




     (c) FTE rates (i.e., Sales Force FTE Rate, G&A FTE Rate, Medical Affairs FTE Rate, Marketing
FTE Rate) for purposes of determining Commercialization Costs hereunder shall be determined as set
forth in Article II below.




E – Page 5











 





ARTICLE II



RELEVANT DEFINITIONS




     Section 2.1 “Development Costs” shall mean the expenses incurred by a Party or for
its account that are consistent with the Development Plan and specifically are attributable to the
Development of a Product for a particular indication for approval in the U.S., commencing from the
completion of activities under the Joint Research Plan onward until First Commercial Sale of the
Product for such indication. Development Costs shall include amounts paid by a Party to Third
Parties involved in the Development of Products, and all internal costs incurred by a Party in
connection with the Development of Products. Notwithstanding anything to the contrary herein,
Development Costs shall not include any expenses associated specifically for Development for a
country other than the U.S.; except to the extent such expenses relate to Development activities
specifically included in the Development Plan for the purpose of generating data or information to
obtain expand and/or maintain Regulatory Approval in the United States.



     Development Costs shall include the Fully Burdened Manufacturing Cost for clinical supplies
for the Development Plan, the cost of the development plans and programs for the Development Plan,
and the Required Third Party Payments payable prior to First Commercial Sale in the U.S., and the
cost of Development pursued under the Development Plan through receipt of Regulatory Approval for
such Product (including the cost of studies on the toxicological, pharmacokinetic, metabolic or
clinical aspects of such Product conducted internally or by individual investigators or consultants
necessary for the purpose of obtaining approval of such Product by a government organization in the
U.S), and costs for preparing, submitting, reviewing or developing data or information for the
purpose of a submission to a Regulatory Authority to obtain Regulatory Approval of the Product in a
country within the Development Plan. For clarity, the cost of a human clinical trial conducted to
support the filing of a Supplemental NDA, as defined in the FD&C Act and applicable regulations
promulgated thereunder by the FDA, or equivalent application in any other regulatory jurisdiction
within the Development Plan, or conducted to otherwise support a new Regulatory Approval of a
Product in the U.S., shall be included within Development Costs, notwithstanding the fact that such
trial is conducted after receipt of a Regulatory Approval for such Product. Development Costs
shall not include Legal Expenses, Pre-Launch Marketing Expenses or Post-Approval Studies.



     Section 2.2 “Fully Burdened Manufacturing Cost” or “FBMC” shall mean the
manufacturing cost for a Product, as defined by Roche’s or Alnylam’s, as the case may be, standard
cost accounting practices and policies, both in accordance with IFRS or GAAP, as applicable. In
the event of any transfer of Product among Roche, Alnylam, its Affiliates or Licensee Partners,
FBMC shall exclude any profit or other mark-up by any such parties.



     Such FBMC shall include direct labor, materials, product testing costs (including quality
control and quality assurance bulk testing and in-process testing e.g. adventitious virus and
mycoplasma testing), direct Third Party contracting cost, Period Costs, cost of failed batches, and
manufacturing overhead allocable to the Product (including information technology, human resources,
manufacturing planning, manufacturing finance and control, energies, waste maintenance, insurance,
custom & duties, shipment & logistic cost, warehousing and storage and



E –Page 6









 




distribution cost, to the extent that each is manufacturing and Product-specific), for
manufacturing or contracting for each stage of the manufacturing process of the Product shipped.
The Parties will discuss and agree annually between October and January the main drivers of FBMC
for the up-coming Calendar Year. On or before October 31st of each Calendar Year, the parties will
agree to an estimated FBMC to be charged for the subsequent Calendar Year, subject to annual
true-up process, which will be agreed upon by the JFT.




     Such FBMC shall not include any costs associated with process development, scale up costs,
qualification lots and any other costs if they are included in Development Costs. If qualification
lots are used for Product sale, then Alnylam’s share of those Development Costs will be credited
towards FBMC in the United States. This credit shall be a variance to FBMC based upon the unit
pull-through of the qualification lots into Product Net Sales. The Parties shall discuss and agree
upon cost-sharing principles for pre-launch investments, including but not limited to expanded
production facilities and commitments to Third Parties, in case of unforeseen delay in launch.



     Section 2.3 “Period Costs” shall be comprised of:



     (a) Write offs and disposal cost of expired goods (raw materials, intermediates and Products
valued at FBMC) (it being understood that the collaboration shall consider the Commercialization
Plan requirements when establishing the manufacturing supply);



     (b) Inventory valuation differences: The valuation difference for inventory in stock resulting
from any change of standard FBMC at that respective point in time. At least annually, Roche will
review and compare its standard FBMC for a Product when that particular material was produced to
its new standard FBMC and make a retroactive adjustment to the inventory value;



     (c) Start up costs to the extent not included in Development Costs;



     (d) Excess capacity and idle plant cost to the extent associated with the Product and provided
for in the Commercialization Plan with the consent of Alnylam. Except with the consent of Alnylam,
FBMC shall not include excess capacity or idle plant cost that was not provided for in the
Commercialization Plan in view of the anticipated needs and associated demand forecast of the
Licensed Product. Period Costs will be credited for the costs of any idle plant that was
ear-marked for a different Roche product but actually used by a Product; and



     (e) Normal yield losses and variances that could have reasonably been expected and/or
justified in this area of technology.



     Section 2.4 “Commercialization Costs” means those expenses incurred by a Party which
are generally consistent with the Commercialization Plan (and associated budget) and are
specifically attributable to Products in the United States, and shall consist of (i) Marketing
Expenses, (ii) Medical Affairs Expenses, (iii) Out-of-Pocket Costs, (iv) Legal Expenses, (v) Third
Party License Fees, (vi) General and Administrative Expenses, (vii) Post- Launch Product R&D
Expenses, (viii) Sales Force Expenses, and (ix) Restructuring Expenses. Commercialization Costs
shall exclude Development Costs. Notwithstanding the foregoing,



E – Page 7









 





Legal Expenses need not be consistent with the Commercialization Plan (and associated budget) as
long as they have been approved by the JCT. Each Party shall allocate its Commercialization Costs
and each of the expenses based on reasonable accounting methodologies consistently applied
throughout such Party’s organization. The foregoing shall not include any Out-of-Pocket Costs or
other costs which have been included in Development Costs. For clarity, it is the intent of the
Parties that costs and headcount included in the foregoing will not be unfairly allocated to the
Products (to the extent that any Commercialization Cost is attributable, in part, to products or
activities other than the Products).




     Section 2.5 “Marketing Expenses” means the costs incurred by a Party, excluding Sales
Force Expenses, which are generally consistent with the Commercialization Plan (and associated
budget) and are specifically attributable to the sale, promotion, and/or marketing of a Product in
the United States. Marketing Expenses shall be the sum of Marketing Management, Market and
Consumer Research, Pre-Launch Marketing Expenses, Advertising, Trade Promotion and Consumer
Promotion (each of which is specified below). To the extent that Marketing Expenses consist of
costs other than Third Party costs, it shall mean the product of (a) the number of FTEs directly
involved in performing Marketing Management, Market and Consumer Research, Advertising, Trade
Promotion, and Consumer Promotion and (b) the applicable Marketing FTE Rate. For purposes of
calculating the number of FTEs, an allocated portion of the marketing staff directly involved in
the management of and the performance of the marketing functions in the United States for such
Product shall be included.



     (a) “Marketing FTE Rate” shall mean, for the Calendar Year in which the First
Commercial Sale in the United States occurs, a rate agreed upon by the Parties at least twelve (12)
months prior to the anticipated date of Regulatory Approval in the United States, based on the
fully burdened field force cost of major pharmaceutical companies in the United States.



     (b) “Marketing Management” shall include product management and sales promotion
management compensation and departmental expenses. This shall include costs associated with
developing overall sales and marketing strategies and planning for Products. In addition, payments
to Third Parties in connection with Product-specific trademark selection, filing, prosecution and
enforcement shall be included in this category.



     (c) “Market and Consumer Research” shall include compensation and departmental
expenses for market and consumer research personnel and payments to Third Parties related to
conducting and monitoring professional and consumer appraisals of existing, new or proposed
Products such as market share services (e.g., IMS data), special research testing, and focus
groups.



     (d) “Advertising” shall include all media costs associated with Product advertising as
follows: production expense/artwork including set up; design and art work for an advertisement;
the cost of securing print space, air time, etc. in newspapers, magazines, trade journals,
television, radio, billboards, etc.



     (e) “Trade Promotion” shall include the allowances given to retailers, brokers,
distributors, hospital buying groups, etc. for purchasing, promoting, and distribution of Products.
This shall include purchasing, advertising, new distribution, and display allowances as well as



E – Page 8









 




free goods, wholesale allowances and the cost of goods for reasonable field sales samples of
Products and the cost of administering these programs. To the extent multiple products are
involved and some of such products are not Products, then such allowances shall be allocated on a
pro rata basis based upon net sales of each respective product by such operating unit during the
most recent quarter.




     (f) “Consumer Promotion” shall include the expenses associated with programs to
promote Products directly to the end user. This category shall include expenses associated with
promoting products directly to the professional community such as professional samples,
professional literature, promotional material costs, patient aids and detailing aids. To the
extent multiple products are involved and some of such products are not Products, then such
allowances shall be allocated on a pro rata basis based upon net sales of each respective product
by such operating unit during the most recent quarter.



     (g) “Pre-Launch Marketing Expenses” shall include those Marketing Management, Market
and Consumer Research, Advertising, Trade Promotion, and Consumer Promotion expenses incurred
between the filing of a complete NDA for a Product and the First Commercial Sale of such Product.



     Section 2.6 “Medical Affairs Expense” means (a) the product of (i) the number of
field-and office-based FTEs supporting the coordination of pre-market authorization preparation as
well as Post-Approval Studies in the United States related to a Product as agreed upon in the
approved Commercialization Plan and its budget and (ii) the applicable Medical Affairs FTE Rate;
(b) the cost of performing Post-Approval Studies in the United States; and (c) External Education
Expenses (including journal clubs, congresses, and conferences, etc.). For purposes of calculating
the number of FTEs, an allocated portion of the medical affairs staff directly involved in the
coordination of pre-market authorization preparation for a Product or Post-Approval Studies in the
United States for a Product shall be included. Each medical affairs staff member shall record the
percent of time allocated to the Product and to all other products, and time allocated to other
products shall be excluded in calculating the number of FTEs.



     (a) The applicable “Medical Affairs FTE Rate” shall be a rate agreed upon by the
Parties at the time the Commercialization Plan is agreed upon by the Parties based upon the fully
burdened cost of medical affairs professionals reasonably appropriate for the United States. It is
anticipated that the Medical Affairs FTE Rate will equal the Marketing FTE Rate agreed upon under
“Marketing Expenses” above.



     (b) “External Education Expenses” shall include expenses associated with professional
education with respect to Products or AD/MCI in general through any means not covered above,
including articles appearing in journals, newspapers, magazines or other media; seminars,
scientific exhibits, and conventions; and symposia, advisory boards and opinion leader development
activities.



     Section 2.7 “Out-of-Pocket Costs” shall mean costs and expenses not included in any
other category under Commercialization Costs that are paid to Third Parties (or payable to Third
Parties and accrued in accordance with GAAP or IFRS) by either Party and/or its Affiliates in



E – Page 9









 




accordance with the applicable Development Plan or Commercialization Plan, other than Third Party
License Fees.




     Section 2.8 “Legal Expenses” means (a) the fees and expenses of outside counsel and
payments to Third Parties incurred after the Effective Date in connection with the preparation,
filing, prosecution, maintenance, interference, re-examination and re-issue of Product-specific
trademarks in the United States, (b) Losses associated with Product Liability Claims in the United
States, as provided in Section 13.3 of the Agreement (provided, that no internal legal costs shall
be included in Legal Expenses), and (c) the fees and expenses, including without limitation
reasonable fees for outside counsel, for any litigation or other action undertaken by a Party by
mutual consent pursuant to Section 10.5(c)(iii) or 10.5(d) of the Agreement.



     Section 2.9 “Third Party License Fees” means all Required Third Party Payments
payable by either Party after First Commercial Sale.



     Section 2.10 “General and Administrative Expenses” shall mean the product of (a) the
number of FTEs allocated towards general and administrative functions as set forth in the approved
Commercialization Plan and (b) the applicable G&A FTE Rate. For purposes of calculating the number
of FTEs, an allocated portion of the general and administrative staffs directly involved in the
management of and the performance of the general and administrative functions in the United States
for such Product shall be included.



     Section 2.11 “G&A FTE Rate” shall mean, for the Calendar Year in which the First
Commercial Sale in the United States occurs, a rate agreed upon by the Parties at the time the
Commercialization Plan is agreed upon by the Parties, based on the fully burdened general and
administrative staff cost reasonably appropriate for the United States. For purposes of
clarification, the G&A FTE Rate shall not include any items previously captured in the calculation
of the Marketing FTE Rate, Medical Affairs FTE Rate or Sales Force FTE Rate.



     Section 2.12 “Post-Launch Product R&D Expenses” shall include certain Development
Costs incurred by a Party in relation to a Product after the First Commercial Sale in the United
States and required to maintain Regulatory Approval in the United States and shall exclude (a)
administrative expenses and costs that are included within Fully Burdened Manufacturing Costs and
(b) Post-Approval Studies that are included within Medical Affairs Expenses.



     Section 2.13 “Sales Force Expenses” shall mean the product of (a) the number of FTEs
detailing and co-promoting Products in the United States as set forth in the approved
Commercialization Plan and (b) the applicable fully burdened Sales Force FTE Rate. For purposes of
calculating the number of FTEs, an allocated portion of the field sales forces, field sales
offices, and home offices staffs directly involved in the management of and the performance of the
selling functions in the United States for such Product shall be included, and any portion of staff
time allocated to other products shall be excluded. If any members of the field sales force are
detailing a Product and one or more other products, the Parties shall agree upon the relative value
(on a percentage basis), based on the placement of and emphasis on each product in such detailing,
of the detailing of such Product relative to the other products, and each such member of the field
sales force shall record such percentage for those details that involve



E – Page 10









 




such Product, and the number of FTEs shall exclude that percent of total details that involve,
in whole or in part, other products.




     Section 2.14 “Sales Force FTE Rate” shall mean, for the Calendar Year in which the
First Commercial Sale in the United States occurs, a rate agreed upon by the Parties at the time
the Commercialization Plan is agreed upon by the Parties, based on the fully burdened field force
cost reasonably appropriate for the United States.



     Section 2.15 “Restructuring Expenses” shall mean any expenses related to
re-organization or downsizing due to changes in the market environment of a Licensed Product. Such
expenses shall be related to the organization and infrastructure that is promoting and selling
Licensed Products. Such expenses shall include, but not be limited to, severance payments to
dismissed employees, committed orders to third parties that can not be cancelled, termination costs
for post-launch clinical marketing, and clinical studies. The Parties shall use Commercially
Reasonable Efforts to minimize Restructuring Expenses, including, without limitation, by assigning
employees to other products or organizations to be reviewed and approved by the Parties.



E – Page 11









 





EXHIBIT F



Press Release




Contacts:




	
	Alnylam Pharmaceuticals, Inc.

	Cynthia Clayton (Investors)

	617-551-8207

	 

	Kathryn Morris (Media) 

Yates Public Relations 

845-635-9828







DRAFT — Not for Release




Alnylam and Roche Advance RNAi Therapeutic Collaboration

Phase of Landmark 2007 Alliance




— Partners to Co-Develop and Co-Commercialize Certain RNAi Therapeutic Products

in U.S. Market —



— Collaboration to Include Alnylam Lipid Nanoparticle and Roche Dynamic Polyconjugate Delivery

Technologies —


CAMBRIDGE, Mass., November XX, 2009 — Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, announced today that it has advanced to the RNAi therapeutic collaboration
stage of its landmark alliance with Roche formed in 2007. In this phase of the collaboration, the
partners will jointly collaborate on the discovery and development of specific RNAi therapeutic
products and each will contribute key delivery technologies in the new disease target-focused
effort. New delivery technologies include Alnylam lipid nanoparticles and Roche Madison dynamic
polyconjugate delivery technologies. Alnylam and Roche will co-develop and co-commercialize RNAi
therapeutic products in the U.S. market and Alnylam is eligible to receive additional milestone and
royalty payments for products developed in the rest of world.



“We are excited to advance to this phase of our 2007 agreement, as our joint efforts combine many
strengths of the Alnylam and Roche platforms on specific disease target programs,” said Barry
Greene, President and Chief Operating Officer of Alnylam. “Our partnership with Roche remains very
strong and we look forward to working together to bring our innovation to patients.”



“Since the formation of our alliance with Alnylam and the establishment of Roche Kulmbach and Roche
Madison as Centers of Excellence for RNA therapeutic research, we have made significant progress in
advancing this technology as a potential new class of innovative medicines,” said Louis Renzetti,
Ph.D., Vice President of RNA Therapeutics Research of Roche. “We continue to view RNAi as having
true potential as a whole new class of differentiated drugs to benefit patients.”






F – Page 1









 







In July 2007, Alnylam granted to Roche a non-exclusive license providing access to broad Alnylam
intellectual property (IP) and know-how, including fundamental, chemistry and delivery IP, in the
fields of oncology, respiratory disease, metabolic disease, and certain liver diseases. In
addition, Alnylam and Roche agreed to collaborate on RNAi therapeutics drug discovery for a defined
number of disease targets, subject to certain Alnylam third party obligations. As part of the
agreement, Roche also acquired Alnylam’s Kulmbach-based research & development (R&D) organization
which has now become Roche Kulmbach, a Roche Centre of Excellence for RNA therapeutics. In July
2008, Roche acquired Madison, WI-based Mirus Technologies, Inc., a pioneer in the discovery of a
novel RNAi delivery technology known as dynamic polyconjugates. Mirus has become Roche Madison, an
additional Roche Centre of Excellence for RNA therapeutics.




About RNA Interference (RNAi)



RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding
how genes are turned on and off in cells, and a completely new approach to drug discovery and
development. Its discovery has been heralded as “a major scientific breakthrough that happens once
every decade or so,” and represents one of the most promising and rapidly advancing frontiers in
biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine.
RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to
mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation
of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi
therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs),
thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential
to treat disease and help patients in a fundamentally new way.




About Alnylam Pharmaceuticals



Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or
RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical
needs, many of which cannot effectively be addressed with small molecules or antibodies, the
current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of
innovative medicines with peer-reviewed research efforts published in the world’s top scientific
journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities
to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human
clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered
with Cubist and Kyowa Hakko Kirin. In addition, the company is developing RNAi therapeutics for
the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia,
Huntington’s disease, and TTR amyloidosis. The company’s leadership position in fundamental
patents, technology, and know-how relating to RNAi has enabled it to form major alliances with
leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and
Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam
established “RNAi 2010” in January 2008 which includes the company’s plan to significantly expand
the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical
development, and to form four or more new major business collaborations, all by the end of 2010.
Alnylam and Isis are joint owners of






F – Page 2









 







Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization
of microRNA-based therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge,
Massachusetts. For more information, please visit www.alnylam.com.




Alnylam Forward-Looking Statement



Various statements in this release concerning Alnylam’s future expectations, plans and prospects,
constitute forward-looking statements for the purposes of the safe harbor provisions under The
Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those
indicated by these forward-looking statements as a result of various important factors, including
the company’s ability to successfully research, develop, and commercialize RNAi therapeutics, and
the company’s ability to successfully collaborate with Roche on these products, as well as those
risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on
Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking
statements represent Alnylam’s views only as of today and should not be relied upon as representing
its views as of any subsequent date. Alnylam does not assume any obligation to update any
forward-looking statements.










F – Page 3









 








EXHIBIT G



Baseball Arbitration Provisions



1. General. In the event that the Parties are unable to agree upon the event payment
amounts or royalty rates payable by the pursuing Party with respect to Licensed Product(s) in
terminated Major Territory(ies) pursuant to Section 14.4(d)(i) (the “Financial Terms”),
such Financial Terms shall be determined through binding arbitration in accordance with the
provisions set forth below (“Baseball Arbitration”).





	 	(a)	 	The Baseball Arbitration shall be held in a location mutually agreeable to the
Parties, or if no such location can be agreed, in New York City, according to the
then-current commercial arbitration rules of the American Arbitration Association
(“AAA”), except to the extent such rules are inconsistent with this Exhibit
G.
	 
	 	(b)	 	The Baseball Arbitration will be conducted by one (1) arbitrator who shall be
reasonably acceptable to the Parties and who shall be appointed in accordance with AAA
rules. If the Parties are unable to select an arbitrator within [**] days following
the end of the negotiation period set forth in Section 14.4(d)(i), then the arbitrator
shall be appointed in accordance with AAA rules. Any arbitrator chosen hereunder shall
have educational training and industry experience sufficient to demonstrate a
reasonable level of scientific, financial, medical and industry knowledge relevant to
the particular dispute.
	 
	 	(c)	 	The (i) attorneys’ fees of the Parties in the Baseball Arbitration, (ii) fees
of the arbitrator and (iii) costs and expenses of the Baseball Arbitration shall be
borne by the Parties as determined by the arbitrator.
	 
	 	(d)	 	The proceedings and decisions of the arbitrator shall be confidential.




2. Exchange of Proposed Agreements. Within [**] days after the designation of the
arbitrator pursuant to Paragraph 1(b) above, the Parties shall exchange their proposed Financial
Terms, substantially in the form of Appendix 1 attached hereto, together with a brief or other
written memorandum supporting the merits of their proposed Financial Terms. Upon receipt of the
proposed Financial Terms from each Party, the arbitrator shall provide copies of the same to the
other Party. Within [**] days after the arbitrator has delivered to each Party a copy of the
Financial Terms proposed by the other Party (if any), each Party shall submit a written rebuttal of
the other Party’s proposed Financial Terms and may also amend and re-submit its original proposed
Financial Terms. The Parties and the arbitrator shall meet within [**] days thereafter, at which
time each Party shall have one hour to argue in support of its final proposed Financial Terms. The
Parties shall not call any witnesses in support of their arguments.



3. Selection of Proposed Agreement. The arbitrator shall be directed by the Parties to
select, within [**] days following the final hearing set forth in Paragraph 2 above, one of the
final proposed Financial Terms so submitted by the Parties as the final Transition Agreement. In
making such selection and ruling, the arbitrator shall not modify the terms or conditions of either
Party’s final proposed Financial Terms nor shall the arbitrator combine provisions from both






G – Page 1









 







proposed Financial Terms. However, the arbitrator may take into account the severity of the
Diligence Breach and the behavior of the breaching Party in selecting such Financial Terms. If a
Party fails to submit to the arbitrator any proposal on Financial Terms in accordance with the
terms of Paragraph 2 above, the arbitrator shall select the Financial Terms proposed by the other
Party.



4. Effect of Decision. The Parties shall include, as part of the transition agreement to
be executed by the Parties pursuant to Section 14.4(d)(i), the final Financial Terms selected by
the arbitrator within [**] days following the arbitrator’s ruling; provided that
the non-prevailing Party may elect not to accept such Financial Terms. If the non-prevailing Party
elects to accept such Financial Terms within such [**]-day period, the non-prevailing Party shall
signify such election by executing a counterpart signature page to the Financial Terms selected by
the arbitrator and providing such executed signature page to the prevailing Party within such
[**]-day period. If the non-prevailing Party does not provide such an executed signature page to
the prevailing Party within such [**]-day period, then thereafter this Agreement shall be
terminated with respect to Licensed Product(s) in the Major Territory(ies) proposed to be
terminated by the terminating Party, with neither Party having the right to Develop or
Commercialize the Licensed Product(s) under a license from the other Party in any such terminated
Major Territory(ies).



5. No Limitation. Nothing in this Exhibit G will preclude either Party from
seeking equitable, interim or provisional relief from a court of competent jurisdiction, including
a temporary restraining order, preliminary injunction or other interim equitable relief, either
prior to or during any Baseball Arbitration if necessary to protect the interests of such Party or
to preserve the status quo pending the Baseball Arbitration proceeding.





G – Page 2











 





Appendix 1




Form of Financial Terms


1. Development Event Payments with respect to terminated Major Territory(ies) (separately for
each Terminated Territory):




	 	 	 	 	 
	 	 	Payments	 
	Development Event	 	(In US$ [**])	 
	(1) Initiation of the first Phase I Study for Licensed Product for the Terminated Territory
	 	$	 	 
	(2) Initiation of the first Phase II Study for Licensed Product for the Terminated Territory
	 	$	 	 
	(3) Initiation of the first Phase III Study for Licensed Product for the first (1st) Indication for the Terminated Territory
	 	$	 	 
	(4) Initiation of the first Phase III Study for Licensed Product for a second (2nd) Indication for the Terminated Territory
	 	$	 	 
	(5) First filing of an NDA in the Terminated Territory for Licensed Product for the first (1st) Indication
	 	$	 	 
	(6) First filing of an NDA in the Terminated Territory for Licensed Product for the second (2nd) Indication
	 	$	 	 
	(7) Regulatory Approval in the Terminated Territory for Licensed Product for the first (1st) Indication
	 	$	 	 
	(8) Regulatory Approval in the Terminated Territory for Licensed Product for the second (2nd) Indication
	 	$	 	 
	Total Development Event Payments
	 	$	 	 





2. Sales Event Payments with respect to terminated Major Territory(ies):




	 	 	 	 	 
	 	 	Payments	 
	Sales Event	 	(In US$ [**])	 
	Aggregate Worldwide Annual Net Sales of all Licensed
Products in the Terminated Territory(ies) equal to or
greater than $[**]
	 	$	 	 
	Aggregate Worldwide Annual Net Sales of all Licensed
Products in the Terminated Territory(ies) equal to or
greater than $[**]
	 	$	 	 
	Total Sales Event Payments
	 	$	 	 






G – Page 3









 





3. Royalties Payable with respect to terminated Major Territory(ies):




	 	 	 	 	 
	 	 	Incremental
	 	 	Royalty Rate
	 	 	Applicable to Such
	Annual Net Sales of a Licensed Product in the Terminated Territory(ies) during the applicable Calendar Year:	 	Annual Net Sales
	Less than or equal to $[**]
	 	 	%	 
	Greater than $[**], but less than or equal to $[**]
	 	 	%	 
	Greater than $[**], but less than or equal to $[**]
	 	 	%	 
	Greater than $[**], but less than or equal to $[**]
	 	 	%	 
	Greater than $[**], but less than or equal to $[**]
	 	 	%	 
	Greater than $[**], but less than or equal to $[**]
	 	 	%	 
	Greater than $[**]
	 	 	%	 





Acknowledged and agreed to by:




	 	 	 	 	 
	F. HOFFMANN-LA ROCHE LTD

 	 
	By:  	 	 
	 	Name:  	 	 
	 	Title:  	 	 
	 
	 	 
	By:  	 	 
	 	Name:  	 	 
	 	Title:  	 	 
	 
	HOFFMANN-LA ROCHE INC.

 	 
	By:  	 	 
	 	Name:  	 	 
	 	Title:  	 	 
	 
	ALNYLAM PHARMACEUTICALS, INC.

 	 
	By:  	 	 
	 	Name:  	 	 
	 	Title:  	 	 
	 




G – Page 4