Document:

EX-10.1

 Exhibit 10.1 

Execution Version 

AMENDMENT NO. 1 TO MASTER COLLABORATION AGREEMENT 

This First Amendment (this “Amendment”), effective as of the date of the last signature set forth below (the
“Amendment Effective Date”), amends that certain Master Collaboration Agreement dated January 11, 2014 (the “Master Agreement”), and certain of the License Terms attached thereto, by and between Alnylam
Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“Alnylam”), and Genzyme Corporation, a corporation organized and existing under the laws of the Commonwealth of Massachusetts
(“Genzyme”). The Master Agreement, together with the License Terms attached thereto, are referred to collectively herein as the “Collaboration Agreement.” Alnylam and Genzyme are individually referred to herein as a
“Party” and collectively referred to as the “Parties”.  
 RECITALS 

WHEREAS, the Parties entered into the Master Agreement which, among other things, provides Genzyme with certain Options to obtain from Alnylam
exclusive licenses and other rights to certain of Alnylam’s siRNAs targeting human genes as potential treatments for Orphan Diseases (a) on a regional basis outside North America and western Europe, (b) with respect to certain siRNAs,
on a global basis, or (c) with respect to a certain other siRNAs on a regional basis outside North America and western Europe with the right to co-Commercialize such siRNA in North America and western Europe, in each case on terms and
conditions set forth in the Master Agreement and the License Terms attached to the Master Agreement as Appendix A (Regional License Terms), Appendix B (Global License Terms) and Appendix C (Co-Co License Terms); and 

WHEREAS, the Parties desire to amend the Collaboration Agreement to allow for an early decision regarding the exercise of the Option for
ALN-AT3 by Genzyme and certain other changes solely with respect to ALN-AT3 as further described herein. 
 NOW THEREFORE, for and in
consideration of the mutual covenants contained herein and in the Collaboration Agreement, the Parties hereby agree as follows: 
 1.
Relationship to Agreement. Any capitalized terms that are not defined in this Amendment shall have the meaning set forth in the Collaboration Agreement, and references below to provisions, sections, exhibits or appendices of the Collaboration
Agreement are references to such provisions, sections, exhibits or appendices of the Collaboration Agreement. 
  

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

 2. Early Exercise of the Option for ALN-AT3. Section 1.2.155 (Option Exercise Period)
of the Master Agreement is hereby amended, only with respect to exercise of the Option for ALN-AT3 under Section 1.2.155(a), to mean the period [***]. For all other purposes, Section 1.2.155 (Option Exercise Period) of the Master Agreement
shall remain unchanged and in full force and effect. 
 3. Delivery of Initial Option Notice for ALN-AT3. Section 3.3.1 (Initial
Option Data Package) of the Master Agreement is hereby amended so that Alnylam shall deliver to Genzyme the Initial Option Notice for ALN-AT3 (including the Initial Option Data Package for ALN-AT3) no later than [***]. The Initial Option Data
Package for ALN-AT3 included within such Initial Option Notice shall contain all items listed on Schedule 1.2.123 (Initial Option Data Package) of the Master Agreement, including, but not limited to, [***]; provided, however, Genzyme
acknowledges that the [***], as applicable. For purposes of clarity, the Parties acknowledge and agree that Alnylam shall only be required to provide [***] for ALN-AT3 as specified by this Amendment and shall not be obligated to provide [***] for
ALN-AT3, provided, however, that the terms of [***] shall continue to apply. For all other purposes, Section 3.3.1 (Initial Option Data Package) of the Master Agreement and Schedule 1.2.123 (Initial Option Data Package) of the Master Agreement
shall remain unchanged and in full force and effect. 
 4. Option Exercise. 

4.1 [***]. Section 3.3.2 (Initial Evaluation Period) of the Master Agreement is hereby amended so that Genzyme [***]. For
all other purposes, Section 3.3.2 (Initial Evaluation Period) of the Master Agreement shall remain unchanged and in full force and effect. 

5. Automatic Amendments to the License Terms. 

5.1 Regional Licensed Product. As set forth in Section 3.4.3 (Regional Options) of the Master Agreement, on the
Option Exercise Date for the exercise of a Regional Option for ALN-AT3, ALN-AT3 shall automatically be deemed to be a Regional Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme for ALN-AT3
shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Regional License Terms, including the payment obligations set forth therein, shall be the
binding obligations of the applicable Party in respect of ALN-AT3. As part of the effectiveness of such license, the Regional License Terms shall automatically, with no further action by any Party, be deemed to be amended to incorporate Antithrombin
as a Licensed Target and to incorporate as part of the Regional License Terms or Master Agreement the schedules, appendices and exhibits in respect of ALN-AT3 that were included in the Initial Option Data Package delivered by Alnylam for ALN-AT3.
For the avoidance of doubt, the provisions of this Section 5.1 of the Amendment are for clarity only and all provisions of Section 3.4.3 (Regional Options) of the Master Agreement remain unchanged and in full force and effect. 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 5.2 Co-Co Licensed Product. Section 3.4.4.1 (ALN-AT3) of the Master
Agreement is hereby amended such that, on the Option Exercise Date for the exercise of a Co-Co/Global Option for ALN-AT3, ALN-AT3 shall automatically be deemed to be a Co-Co Licensed Product for all purposes under the Collaboration Agreement and the
license from Alnylam to Genzyme for ALN-AT3 shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Co-Co License Terms, including the payment
obligations set forth therein, shall be the binding obligations of the applicable Party in respect of ALN-AT3. As part of the effectiveness of such license, the Co-Co License Terms shall automatically, with no further action by any Party, be deemed
to be amended to incorporate Antithrombin as a Licensed Target and to incorporate as part of the Co-Co License Terms or Master Agreement the schedules, appendices and exhibits in respect of ALN-AT3 that were included in the Initial Option Data
Package delivered by Alnylam for ALN-AT3. For the avoidance of doubt, the provisions of this Section 5.2 of the Amendment are for clarity only and all provisions of Section 3.4.4.1 (ALN-AT3) of the Master Agreement remain in full force and
effect. 
 6. Product Joint Steering Committee Formation for ALN-AT3. Promptly following the Option Exercise Date for ALN-AT3, the
Parties shall form the PJSC for ALN-AT3 as described in Section 5.1 (Product Joint Steering Committee) of the Regional License Terms or Co-Co License Terms, as applicable. 

7. Public Disclosure. Either Party may issue a press release announcing Genzyme’s decision to exercise the Option for ALN-AT3, if
applicable. The form and subject matter of such press release shall be mutually agreed upon by the Parties. Subject to the foregoing, the provisions of Section 7.3 (Press Release) of the Master Agreement remain unchanged and in full force and
effect. 
 8. Amendment to Global R&D Costs. 

8.1 Regional License Terms. Section 2.3.1.2(b) (Global R&D Costs) of Appendix A (Regional License Terms) to the
Master Agreement is hereby amended so that if Genzyme exercises the Regional Option for ALN-AT3 prior to [***], the Global R&D Cost Opt-In Date for ALN-AT3 will be [***]. The remaining provisions of Section 2.3.1.2(b) (Global R&D Costs)
of Appendix A (Regional License Terms) to the Master Agreement remain unchanged and in full force and effect. 
 8.2 Co-Co
License Terms. Section 2.3.1.2(b) (Global R&D Costs) of Appendix C (Co-Co License Terms) to the Master Agreement is hereby amended so that if Genzyme exercises the Co-Co/Global Option for ALN-AT3 prior to [***], the ALN-AT3 Global
R&D Cost Opt-In Date will be [***]. The remaining provisions of Section 2.3.1.2(b) (Global R&D Costs) of Appendix C (Co-Co License Terms) to the Master Agreement remain unchanged and in full force and effect. 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 9. Amendment to the Termination Rights. 

9.1 Termination of Regional License Terms. Section 10.2.1 (Termination of a Regional Licensed Product for
Convenience) of Appendix A (Regional License Terms) to the Master Agreement is hereby amended to add a new subsection (g): 
 “(g)
Solely with respect to ALN-AT3, at any time during the Initial Evaluation Period for ALN-AS1 or in connection with the delivery by Genzyme of an Option Preservation Notice for ALN-AS1, Genzyme shall have the right to terminate these Regional License
Terms with respect to ALN-AT3 effective immediately upon written notice to Alnylam. In the event of such termination Genzyme shall pay to Alnylam [***] percent [***] of the Global R&D Costs for ALN-AT3 incurred through the effective date of
termination (not to exceed [***]).” 
 9.2 Termination of Co-Co License Terms. Section 12.2.1 (Termination
for Convenience) of Appendix C (Co-Co License Terms) to the Master Agreement is hereby amended to add a new subsection (g): 
 “(g)
Solely with respect to ALN-AT3, at any time during the Initial Evaluation Period for ALN-AS1 or in connection with the delivery by Genzyme of an Option Preservation Notice for ALN-AS1, Genzyme shall have the right to terminate these Co-Co License
Terms with respect to ALN-AT3 effective immediately upon written notice to Alnylam. In the event of such termination Genzyme shall pay to Alnylam [***] percent [***] of the Global R&D Costs and Global Regulatory Costs for ALN-AT3 incurred
through the effective date of termination (not to exceed [***]).” 
 The remaining provisions of Section 10.2.1 (Termination of a
Regional Licensed Product for Convenience) of Appendix A (Regional License Terms) and Section 12.2.1 (Termination for Convenience) of Appendix C (Co-Co License Terms) to the Master Agreement remain unchanged and in full force and effect. 

10. No Other Amendments. This Amendment shall be deemed to be a part of and incorporated into the Collaboration Agreement. In the event
of a conflict between this Amendment and the Collaboration Agreement, this Amendment shall control. Except as expressly set forth in this Amendment, all of the terms and conditions of the Collaboration Agreement shall remain unchanged and are
ratified and confirmed in all respects and remain in full force and effect. 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 11. Counterparts. This Amendment 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 or electronic transmission shall be deemed to be original signatures. 
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 IN WITNESS WHEREOF, the Parties hereto have entered into this Amendment by their duly authorized
representatives as of the Amendment Effective Date. 
  

									
	GENZYME CORPORATION	 		 	ALNYLAM PHARMACEUTICALS, INC.
					
	BY:	 	/s/ David G. Meeker	 		 	BY:	 	/s/ John Maraganore
			
	NAME: David Meeker, M.D.	 		 	NAME: John M. Maraganore, Ph.D.
			
	TITLE: President and Chief Executive Officer	 		 	TITLE: Chief Executive Officer
					
	DATE:	 	    July 1, 2015	 		 	DATE:	 	    July 1, 2015EX-10.2

 Exhibit 10.2 

EXECUTION COPY 
 AMENDMENT
NUMBER ONE 
 TO THE 

SECOND AMENDED AND RESTATED 

STRATEGIC COLLABORATION AND LICENSE AGREEMENT 

THIS AMENDMENT NUMBER ONE (the “Amendment”) to the Second Amended and Restated Strategic Collaboration and License
Agreement is entered into as of the 13 day of July, 2015 (the “Amendment Effective Date”) by and among Alnylam Pharmaceuticals, Inc., a Delaware corporation, with its principal place of business at 300 Third Street, Cambridge,
Massachusetts 02142 (“Alnylam”), and Isis Pharmaceuticals, Inc., a Delaware corporation, with its principal place of business at 2855 Gazelle Court, Carlsbad, California 92010 (“Isis”). 

RECITALS 

WHEREAS, Isis and Alnylam granted to each other certain exclusive rights with respect to certain targets pursuant to that certain
Second Amended and Restated Strategic Collaboration and License Agreement dated January 8, 2015 (the “Second Restated Agreement”); 

WHEREAS, Isis and Alnylam now desire to amend the Second Restated Agreement to expand such cross-license of exclusive rights to include
additional targets as provided herein. 
 AGREEMENT 

NOW, THEREFORE, in consideration of the mutual covenants contained herein, and other good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, Isis and Alnylam each agrees as follows: 
  

	1.	DEFINITIONS 

 Capitalized terms used herein and not defined elsewhere herein have the
meanings set forth in the Second Restated Agreement. 
  

	2.	AMENDMENTS 

 2.1 Section 12 of Exhibit 1.1 of the Second Restated Agreement is
deleted and replaced in its entirety by the following: 
 “Alnylam Exclusive Target” means an RNA Target or protein product of
(a) the antithrombin gene (AT, also known as AT3), (b) the aminolevulinate synthase 1 gene (AS1), (c) the hydroxyacid oxidase 1 gene (GO1) or (d) the alpha-1 antitrypsin gene (AAT), which genes are further identified and
described on Exhibit B. 
 2.2 Section 58 of Exhibit 1.1 of the Second Restated Agreement is deleted and replaced in its entirety by
the following: 
 “Isis Exclusive Target” means an RNA Target or protein product of (a) the Factor XI gene (FXI), (b) the
Apo(a) gene (Apoa1), (c) the diglyceride acyltransferase gene 2 (DGAT2) or (d) the growth hormone receptor gene (GHR), which genes are further identified and described on Exhibit A. 

 
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OF 1934. 

 2.3 Section 100 of Exhibit 1.1 of the Second Restated Agreement is deleted and replaced in
its entirety by the following: 
 “RNA Target” means a ribonucleic acid transcript with a defined sequence and/or function,
including, for example, non-coding transcripts, pre-mRNA transcripts, and mRNA transcripts, including all splice variants and mutant forms of any such transcripts. RNA Targets may be identified by reference to a gene encoding such ribonucleic acid
transcripts or, for transcripts that encode a protein, by reference to a protein encoded by such transcripts. 
 2.4 Exhibit A (Isis
Exclusive Targets), Exhibit B (Alnylam Exclusive Targets), and Exhibit 5.3(d) (Isis Third Party Agreements) to the Second Restated Agreement are deleted and replaced with Exhibit A, Exhibit B and Exhibit 5.3(d) attached hereto, respectively.
Schedules 1-8 (Alnylam Current Chemistry Patents), 1-9 (Alnylam Current Motif and Mechanism Patents), 1-14 (Alnylam Exclusive Target Patents), 1-17 (Alnylam Extended Field Patents), 1-52 (Isis Current Chemistry Patents), 1-53 (Isis Current Motif and
Mechanism Patents), 1-60 (Isis Exclusive Target Patents) and 1-63 (Isis Extended Field Patents) to the Second Restated Agreement are deleted and replaced with Schedules 1-8, 1-9, 1-14, 1-17, 1-52, 1-53, 1-60 and 1-63 attached hereto, respectively.

 2.5 Notwithstanding the provisions of Section 5.3(d) of the Second Restated Agreement, licenses to Isis Exclusive Target Patents
that cover the manufacture, use or sale of an Alnylam Exclusive Target Product that hybridizes to and modulates the Alnylam Exclusive Target known as GO1 or the Alnylam Exclusive Target known as AAT (described in clause (c) and (d) of the
definition of “Alnylam Exclusive Target”, respectively) and that are subject to contractual obligations between Isis and Third Parties in effect as of the Amendment Effective Date are licensed subject to the restrictions and other terms
described in the Isis Third Party Agreements. Prior to the Amendment Effective Date, Isis has provided Alnylam with copies of the Isis Third Party Agreements, provided, that Isis may redact copies of out-licenses Isis has granted Third
Parties so long as the redacted terms do not limit Alnylam’s rights hereunder or create obligations for Alnylam. Alnylam hereby agrees to comply, and to cause its sublicensees to comply, with such restrictions and other terms. 

2.6 The license to Isis Exclusive Target Patents granted in Section 5.1(h) with respect to the Alnylam Exclusive Target known as [***].

 2.7 Notwithstanding the provisions of Section 6.5(c), licenses to Alnylam Exclusive Target Patents that cover the manufacture, use
or sale of an Isis Exclusive Target Product that hybridizes to and modulates an Isis Exclusive Target known as [***]. 
  

	3.	MISCELLANEOUS 

 3.1 Other Terms. All other terms and conditions of the Second
Restated Agreement shall remain in full force and effect. 
 3.2 Representations and Warranties of the Parties. Each Party represents
and warrants to the other Party that, as of the Amendment Effective Date: 
 (a) Such Party is duly organized and validly existing under the
laws of the state of its incorporation and has full corporate power and authority to enter into this Amendment and to carry out the provisions hereof; 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 (b) Such Party has taken all corporate action necessary to authorize the execution and delivery
of this Amendment and the performance of its obligations under this Amendment; 
 (c) This Amendment is a legal and valid obligation of such
Party, binding upon such Party and enforceable against such Party in accordance with the terms of this Amendment. The execution, delivery and performance of this Amendment by such Party does not conflict with any agreement, instrument or
understanding, oral or written, to which such Party is a Party or by which such Party may be bound, and does not violate any law or regulation of any court, governmental body or administrative or other agency having authority over such Party. All
consents, approvals and authorizations from all governmental authorities or other Third Parties required to be obtained by such Party in connection with this Amendment have been obtained; and 

(d) Such Party has sufficient right, power and authority to enter into this Amendment, to perform its obligations under this Amendment and to
grant the licenses granted hereunder. 
 3.3 Counterparts. This Agreement may be executed in any number of counterparts, each of
which will be deemed an original, and all of which together will constitute one and the same instrument. 
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 IN WITNESS WHEREOF, the Parties hereby execute this Amendment Number One to the Second
Amended and Restated Strategic Collaboration and License Agreement as of the date first written above. 
  

			
	ALNYLAM PHARMACEUTICALS, INC.
		
	By:	 	/s/ John Maraganore
	Name:	 	John Maraganore
	Title:	 	Chief Executive Officer

  

			
	ISIS PHARMACEUTICALS, INC.
		
	By:	 	/s/ B. Lynne Parshall
	Name:	 	B. Lynne Parshall
	Title:	 	Chief Operating Officer

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 Exhibit A 

Isis Exclusive Targets 
  

	1.	The human Factor XI gene (also known as coagulation factor XI, plasma thromboplastin antecedent, F11, FXI). As of the Second Restatement Date, an example of an identifier for the Factor XI gene is NCBI Gene ID 2160.

  

	2.	The human Apo(a) gene (also known as apolipoprotein(a); LPA; Lipoprotein, Lp(a); Lp(a); Apo A-I; Apoa1). As of the Second Restatement Date, an example of an identifier for the Apo(a) gene is NCBI Gene ID 4018.

  

	3.	The human diacylglycerol acyltransferase 2 gene (also known as DGAT2, Acyl-CoA and diacylglycerol O-acyltransferase 2). As of the Amendment Effective Date, an example of an identifier for the DGAT2 gene is NCBI Gene ID
84649. 

  

	4.	The human growth hormone receptor gene (also known as GHR, GHBP and GHIP). As of the Amendment Effective Date, an example of an identifier for the GHR gene is NCBI Gene ID 2690. 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 Exhibit B 

Alnylam Exclusive Targets 
  

	1.	The human antithrombin gene (also known asSERPINC1, antithrombin3, AT3 and ATIII). As of the Second Restatement Date, an example of an identifier for the antithrombin gene is NCBI Gene ID 462. 

 

	2.	The human aminolevulinate delta-synthase gene (also known as ALAS-1, ALAS, ALAS3, ALASH, aminolevulinate delta-synthase, Delta-ALA synthase, Delta-Aminolevulinate synthase 1, 5-aminolevulinic acid synthase 1, ALAS-H,
5-aminolevulinate synthase, MIG4, aminolevulinate synthase-1, AS1). As of the Second Restatement Date, an example of an identifier for the ALAS-1 gene is NCBI Gene ID 211. 

 

	3.	The human Alpha-1 antitrypsin gene (also known as AAT, SERPINA1, PI, A1A, PI1, A1AT, PRO2275, alpha1AT). As of the Amendment Effective Date, an example of an identifier for the AAT gene is NCBI Gene ID 5265.

  

	4.	The human hydroxyacid oxidase 1 gene (also known as HAO1, GO, GO1, GOX, GOX1 and HAOX1). As of the Amendment Effective Date an example of an identifier for the HAO1 gene is NCBI Gene ID 54363. 

  
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 Exhibit C 

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

[***] 

  
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UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934. 

  
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 EXHIBIT 5.3(D) 

ISIS THIRD PARTY AGREEMENTS 

The following schedule of Isis Third Party Agreements is provided by Isis to Alnylam, in connection with the Agreement. Capitalized terms used
but not otherwise defined herein have the meanings given to such terms in the Agreement. 
 This schedule and the information and
disclosures contained in this schedule are intended only to qualify and limit the licenses granted by Isis to Alnylam in the Agreement and do not expand in any way the scope or effect of any such licenses. 

AGREEMENTS PROVIDING RIGHTS TO THIRD PARTIES IN
CERTAIN ISIS PATENT RIGHTS 
 [***] 

AGREEMENTS GRANTING THIRD PARTIES RIGHTS TO
CONDUCT TARGET VALIDATION 
 [***] 

RESEARCH LICENSE AGREEMENTS 

[***] 
 AGREEMENTS
CONTAINING CROSS-LICENSES TO NEW TECHNOLOGY ARISING FROM PARTNER COLLABORATIONS

 [***] 

GOVERNMENT RIGHTS IN ISIS IP 

 

	 	1.	Government Rights – Inventions claimed in US Patent Applications: [***] were funded in part by a Small Business Innovation Research grant administered by the National Institutes of Health. Accordingly, the
U.S. Federal Government retains certain rights to those inventions. 

  
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 Schedule 1-8 

Alnylam Current Chemistry Patents 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 15 pages were omitted. 

[***] 

  
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 Schedule 1-9 

Alnylam Current Motif and Mechanism Patents 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 39 pages were omitted. 

[***] 

  
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 Schedule 1-14 

Alnylam Exclusive Target Patents 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 52 pages were omitted. 

[***] 

  
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 Schedule 1-17 

Alnylam Extended Field Patents 

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

[***] 

  
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 Schedule 1-52 

Isis Current Chemistry Patents 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 26 pages were omitted. 

[***] 

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

  
 13 

 Schedule 1-53 

Isis Current Motif and Mechanism Patents 

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

[***] 

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

  
 14 

 Schedule 1-60 

Isis Exclusive Target Patents 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 25 pages were omitted. 

[***] 

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

  
 15 

 Schedule 1-63 

Isis Extended Field Patents 
 Confidential
Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted. 
 [***] 

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

  
 16

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