Confidential Materials omitted and
filed separately with the
Securities and Exchange Commission. Asterisks denote
omissions.
LICENSE AND COLLABORATION
AGREEMENT
This LICENSE AND
COLLABORATION AGREEMENT (this “ Agreement ”), is
entered into as of July 8, 2007 (the “ Execution
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, “ Licensee ”), 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 ”), and, solely for the
purposes set forth in Section 9.15 of this Agreement, Alnylam
Europe AG, a German stock corporation, with a registered office in
Kulmbach, Germany (“ Alnylam Europe AG
”).
1. Licensee
is engaged in the business of Discovering, Developing,
Commercializing and Manufacturing therapeutic products (each as
defined below).
2. Alnylam
has developed, acquired and licensed technology useful for the
Discovery, Development, Manufacture, characterization and use of
therapeutic products that function through the mechanism of RNA
interference (“ RNAi ”).
3. Alnylam
desires to grant licenses to such technology to Licensee, and the
Parties desire to collaborate on certain research and development
activities, in each case upon the terms and conditions set forth in
this Agreement.
NOW, THEREFORE, in
consideration of the respective representations, warranties,
covenants and agreements contained herein, and for other valuable
consideration, the receipt and adequacy of which are hereby
acknowledged, Alnylam and Licensee agree as follows:
1.1
Definitions. For the purpose of this Agreement, the following
terms, whether used in singular or plural form, shall have the
respective meanings set forth below:
“
Accounting Period ” shall have the meaning set forth
in Section 5.8.
“
Additional Field ” shall mean the treatment or
prophylaxis of all Indications in any Supplemental Therapeutic
Area, where such treatment or prophylaxis comprises an RNAi
Compound complementary to, and functional in mediating the RNAi of,
a Target known or believed to be primarily implicated in such
Supplemental Therapeutic Area.
“
Affiliate ” shall mean 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, [**], each shall not
be deemed an “Affiliate” of Licensee; provided ,
however , that if Licensee were to assume day-to-day
control of either [**], then Licensee shall have the right, at its
sole option, to designate [**], as applicable, to be an Affiliate.
For purposes of Sections 6.1, 6.2, 9.8, 9.12 (the second
sentence only), and 9.14, Alnylam’s Affiliates shall not
include [**], any Affiliates of [**] (other than Alnylam and
Persons “controlled” by Alnylam on the Execution Date)
or any Person that becomes an Affiliate of Alnylam as a result of a
[**].
“
Agreement ” shall have the meaning set forth in the
Preamble, and shall include, for the avoidance of doubt, all
Exhibits and Schedules attached hereto.
“ Alnylam
Change of Control ” shall be deemed to occur upon the
closing of (a) a merger, reorganization or consolidation
involving Alnylam 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 Alnylam’s assets or
business relating to this Agreement.
“ Alnylam
Third Party Obligations ” shall mean
(a) Alnylam’s obligations to, and the rights of,
Pre-Existing Alliance Parties and Listed Counterparties with
respect to the Licensed Intellectual Property under Pre-Existing
Alliance Agreements and Listed Alnylam Third Party Agreements,
respectively, and (b) Alnylam Europe AG’s obligations
to, and the rights of, Max Planck with respect to certain
Architecture and Chemistry Patent Rights under the Max Planck
European License Agreement; including without limitation Listed
Alnylam Third Party Payment obligations.
“ Annual
Net Sales ” shall mean, with respect to a Licensed
Product, the Net Sales of such Licensed Product during a calendar
year.
“
Architecture and Chemistry Intellectual Property ”
shall mean Architecture and Chemistry Know-How and Architecture and
Chemistry Patent Rights.
“
Architecture and Chemistry Know-How ” shall mean
Know-How Controlled by Alnylam as of the Effective Date that
relates to (a) the general structure, architecture, or design
of double-stranded oligonucleotide molecules which engage RNAi
mechanisms in a cell; (b) chemical modifications of
double-stranded oligonucleotides (including any modification to the
base, sugar or internucleoside linkage, nucleotide mimetics, and
any end
2
modifications)
which do not abolish the RNAi activity of the double-stranded
oligonucleotides in (a); (c) manufacturing techniques for the
double-stranded oligonucleotide molecules or chemical modifications
of (a) and (b); or (d) all uses or applications of
double-stranded oligonucleotide molecules or chemical modifications
in (a) or (b); but excluding (i) Know-How
to the extent specifically related to Blocked Targets, and
(ii) Delivery Know-How.
“
Architecture and Chemistry Patent Rights ” shall mean
the Patent Rights listed on Schedule C Controlled by
Alnylam or, solely in the case of Patent Rights licensed under the
Max Planck European License Agreement, by Alnylam Europe AG, each
as of the Effective Date, together with any future Patent Rights
that claim priority to or common priority with any of the
aforementioned Patent Rights, that Cover (a) the general
structure, architecture, or design of double-stranded
oligonucleotide molecules which engage RNAi mechanisms in a cell;
(b) chemical modifications of double-stranded oligonucleotides
(including any modification to the base, sugar or internucleoside
linkage, nucleotide mimetics, and any end modifications) which do
not abolish the RNAi activity of the double-stranded
oligonucleotides in (a); (c) manufacturing techniques for the
double-stranded oligonucleotide molecules or chemical modifications
of (a) and (b); or (d) all uses or applications of
double-stranded oligonucleotide molecules or chemical modifications
in (a) or (b); but excluding (i) Patent
Rights which specifically relate to Blocked Targets, and
(ii) Delivery Patent Rights. Notwithstanding anything in this
Agreement to the contrary, should it be reasonably determined after
the Effective Date that (x) any omitted Patent Rights which
Alnylam Controlled as of the Effective Date disclose any Valid
Claims that Cover any of clause (a) through (d) above,
but excluding any Patent Rights which specifically relate to
Blocked Targets and Patent Rights licensed under the [**] Agreement
(except as set forth in Section 2.3(b)(ii)), or (y) in the
course of prosecution of any Valid Claims under any of the Patent
Rights listed on Schedule C , any such Valid Claim
either no longer Covers any of clause (a) through (d) above or
specifically relates to Blocked Targets, Schedule C
shall be amended to reflect the inclusion or deletion, as the case
may be, of such Patent Right, to the extent that it does not
conflict with the terms of any Listed Alnylam Third Party Agreement
or Pre-Existing Alliance Agreement to do so. For the avoidance of
doubt, any Patent Rights which are subsequently included on
Schedule C pursuant to clause (x) above shall be
deemed “Architecture and Chemistry Patent Rights” for
all purposes hereunder.
“ Blocked
Target ” shall mean any Target that is subject to a
contractual obligation of a Pre-Existing Alliance Agreement that
would be breached by the inclusion of such Target as a Designated
Target under this Agreement.
“ Blocked
Target List ” shall mean a list of Blocked Targets
maintained by the Gatekeeper, as such list may be updated from time
to time.
“
Business Day ” shall mean a day on which banking
institutions in Boston, Massachusetts are open for
business.
“[**]
Agreement ” shall have the meaning set forth in
Section 2.3(b)(ii).
“
Collaboration Target ” shall have the meaning set
forth in Section 4.1.
3
“
Combination Product ” shall mean a Licensed Product
combined with any other clinically active therapeutic or
prophylactic ingredient, mechanism or device.
“
Commercialization ” or “ Commercialize
” shall mean 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.
“ Common
Stock Purchase Agreement ” shall mean the Common Stock
Purchase Agreement entered into by Licensee and Alnylam on the
Execution Date.
“
Confidential Information ” shall mean 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 Designated Targets,
Submitted Targets and Blocked Targets shall be deemed the
Confidential Information of both Parties.
“
Control ” or “ Controlled ” shall
mean, 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.
“
Cover ”, “ Covered ” or “
Covering ” shall mean, 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).
“
Delivery Intellectual Property ” shall mean Delivery
Know-How and Delivery Patent Rights.
“
Delivery Know-How ” shall mean Know-How Controlled by
Alnylam as of the Effective Date that relates to (a) delivery
technologies which may be necessary or useful for delivery of
double-stranded oligonucleotide molecules; or
(b) manufacturing techniques for the delivery technologies of
(a); but excluding Know-How to the extent
specifically related to Blocked Targets.
“
Delivery Patent Rights ” shall mean Patent Rights
listed on Schedule C Controlled by Alnylam as of the
Effective Date (or, solely with respect to the Patent Rights
covered by any option under Section 2.3(b)(ii) below, as of
the effective date of Licensee’s exercise of such option),
together with any future Patent Rights that claim priority to or
common priority with any of the aforementioned Patent Rights, that
Cover (a) delivery technologies necessary or useful for
delivery of double-stranded oligonucleotide molecules; or
(b) manufacturing techniques for the delivery technologies of
(a); but excluding Patent
4
Rights which
relate specifically to Blocked Targets. Notwithstanding anything in
this Agreement to the contrary, should it be reasonably determined
after the Effective Date that (x) any omitted Patent Rights
which Alnylam Controlled as of the Effective Date disclose any
Valid Claims that Cover any of clause (a) through
(b) above, but excluding any Patent Rights which specifically
relate to Blocked Targets and Patent Rights licensed under the [**]
Agreement (except as set forth in Section 2.3(b)(ii)), or
(y) in the course of prosecution of any Valid Claims under any
of the Patent Rights listed on Schedule C , any such
Valid Claim either no longer Covers any of clause (a) through
(b) above or specifically relates to Blocked Targets,
Schedule C shall be amended to reflect the inclusion or
deletion, as the case may be, of such Patent Right, to the extent
that it does not conflict with the terms of any Listed Alnylam
Third Party Agreement or Pre-Existing Alliance Agreement to do so.
For the avoidance of doubt, any Patent Rights which are
subsequently included on Schedule C pursuant to clause
(x) above shall be deemed “Delivery Patent Rights”
for all purposes hereunder.
“
Designated Target ” shall mean (a) at any time
during the Novartis Exclusivity Term, any Target which is
(i) selected by Licensee pursuant to Section 2.4(a) of
this Agreement which is not a Blocked Target, (ii) submitted
to Novartis pursuant to Licensee’s exercise of the Designated
Target Option pursuant to Section 2.6 of this Agreement, and
(iii) rejected or waived by Novartis, as evidenced by
Alnylam’s written notice to Licensee pursuant to
Section 2.6 of this Agreement; and (b) at any time
following the end of the Novartis Exclusivity Term, any Target
selected by Licensee pursuant to Section 2.4(a) of this
Agreement which is not a Blocked Target. For the avoidance of
doubt, (x) if Licensee selects any Target prior to the end of
the Novartis Exclusivity Term for submission to Novartis, but such
Target is not submitted to Novartis until after the end of the
Novartis Exclusivity Term, or (y) if Licensee selects any
Target prior to the end of the Novartis Exclusivity Term for
submission to Novartis and such Target is submitted to Novartis
prior to the end of the Novartis Exclusivity Term, but the time
period during which Novartis is obligated to reply does not end
until after the end of the Novartis Exclusivity Term, then such
Target shall not be deemed a “Designated Target”
hereunder until such Target has been rejected or waived by Novartis
pursuant to the terms of the Novartis Agreement.
“
Designated Target Option ” shall have the meaning set
forth in Section 2.6.
“[**]”
shall have the meaning set forth in Section 5.5.
“
Develop ” or “ Development ” shall
mean 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 development, packaging development and Manufacturing
and development documentation efforts in support of development
activities anywhere in the world.
“
Discover ” or “ Discovery ” shall
mean any and all research or discovery activities.
5
“
Discovery Collaboration ” shall mean collaboration
between the Parties regarding the Discovery and/or Development of
potential RNAi Compounds directed to a Designated Target [**],
pursuant to the terms of Article IV.
“
Discovery Collaboration Opportunity ” shall have the
meaning set forth in Section 4.1.
“
Effective Date ” shall mean the latest of (a) HSR
Clearance Date, (b) if no filing is to be made pursuant to the
HSR Act, the Execution Date, and (c) the Closing Date as
defined in the Share Purchase Agreement (such date being referred
to as the “ Scheduled Date ”), it being
understood that the Closing Date of the Share Purchase Agreement
and the Effective Date of this Agreement shall occur
simultaneously; provided , however , that if
between the Execution Date and the Scheduled Date there occurs an
event or series of events that result in a material adverse impact
upon the Licensed Patent Rights, taken as a whole, (including, for
example, the termination of any of the Listed Alnylam Third Party
Agreements, or Alnylam’s receipt of written notice of
termination from a party to a Listed Alnylam Third Party Agreement
(i) that has not been cured prior to the Scheduled Date, or
(ii) cannot be cured within the applicable cure period under
the Listed Alnylam Third Party Agreement), then Licensee shall have
the unilateral right to cause this Agreement not to become
effective resulting in no Effective Date; provided ,
further , that , notwithstanding anything in the
parenthetical above to the contrary, if between the Execution Date
and the Scheduled Date, Alnylam receives a written notice of
termination from a party to a Listed Alnylam Third Party Agreement
that results in a material adverse impact upon the Licensed Patent
Rights, taken as a whole, and such notice of termination can be
cured within the applicable cure period under such Listed Alnylam
Third Party Agreement, but such cure period ends after the
Scheduled Date, then Licensee shall have the unilateral right
(x) to delay the effectiveness of this Agreement until Alnylam
has effected the cure, at which time the Effective Date shall be
deemed to have occurred, or (y) if the applicable cure period
has lapsed without a cure having been effected, to cause this
Agreement not to become effective following the end of such cure
period, resulting in no Effective Date.
“
Execution Date ” shall have the meaning set forth in
the preamble to this Agreement.
“ FDA
” shall mean the United States Food and Drug Administration
or any successor agency thereto.
“
Field ” shall mean the Primary Field and, subject to
the exercise by Licensee of a Field Option with respect to any
Additional Field(s) pursuant to Section 2.5, any such
Additional Field(s).
“ Field
Definition Panel ” shall have the meaning set forth in
Section 2.5(a)(iv).
“ Field
Extension Opportunity ” shall have the meaning set forth
in Section 2.5(b)(i).
“ Field
Option ” shall have the meaning set forth in
Section 2.5(b)(ii).
6
“ Field
Option Fee ” shall have the meaning set forth in
Section 5.6.
“ First
Commercial Sale ” shall mean the first sale of a Licensed
Product by or on behalf of Licensee or any of its Affiliates or
Licensee Partners 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.
“ Future
Technology Patent Rights ” shall mean Patent Rights
Controlled by a Party after the Effective Date that Cover
(a) delivery technologies which may be necessary or useful for
delivery of double-stranded oligonucleotide molecules; or
(b) manufacturing techniques for the delivery technologies of
(a); but excluding (i) Patent Rights which
specifically relate to Blocked Targets, and (ii) Licensed
Patent Rights.
“
Gatekeeper ” shall have the meaning set forth in
Section 2.4(b).
“ GLP
Toxicology Study ” shall mean a toxicology study that is
conducted in compliance with GLP and is required to meet the
requirements for filing an IND.
“ HSR
Act ” shall mean the Hart-Scott-Rodino Antitrust
Improvements Act of 1976, as amended (15 U.S.C. Sec. 18a), and the
rules and regulations promulgated thereunder.
“ HSR
Clearance Date ” shall mean the earlier of (a) the
second Business Day after the date on which the United States
Federal Trade Commission shall notify Licensee and Alnylam of early
termination of the applicable waiting period under the HSR Act, or
(b) the second Business Day after the date on which the
applicable waiting period under the HSR Act expires.
“ IND
” shall mean 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, or any foreign equivalent thereof,
and (b) all supplements and amendments that may be filed with
respect to the foregoing.
“
IND-Enabling Studies ” shall mean pharmacokinetic and
toxicology studies required to meet the requirements for filing an
IND, including without limitation any GLP Toxicology
Study.
“
Indication ” shall mean any disease or condition, or
sign or symptom of a disease or condition.
“ Initial
Discovery Collaboration Opportunity Period ” shall have
the meaning set forth in Section 4.1.
“ Joint
Future Technology Committee ” shall have the meaning set
forth in Section 3.2.
“
Know-How ” shall mean any information, inventions,
trade secrets or technology, whether or not proprietary or
patentable and whether stored or transmitted in oral,
7
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).
“
Kulmbach Facility ” shall have the meaning set forth
in Section 3.1(a).
“ Law
” shall mean any law, statute, rule, regulation, ordinance or
other pronouncement having the effect of law of any federal,
national, multinational, state, provincial, county, city or other
political subdivision, domestic or foreign.
“
Licensed Collaboration Product ” shall mean any
Licensed Product directed to a Designated Target for which the
Parties have entered into a Discovery Collaboration pursuant to
Article IV.
“
Licensed Intellectual Property ” shall mean the
Licensed Know-How and Licensed Patent Rights.
“
Licensed Know-How ” shall mean (a) the
Architecture and Chemistry Know-How, and (b) the Delivery
Know-How.
“
Licensed Patent Rights ” shall mean (a) the
Architecture and Chemistry Patent Rights, and (b) the Delivery
Patent Rights.
“
Licensed Product ” shall mean any RNAi Product
(a) whose manufacture, use or sale would, but for the licenses
granted pursuant to this Agreement, infringe one or more Valid
Claims of the Licensed Patent Rights, or (b) which embodies
Licensed Know-How. All references to Licensed Product in this
Agreement shall be deemed to include Combination Product, to the
extent applicable.
“
Licensee Partner ” shall mean any Third Party to which
a sublicense is granted by Licensee in accordance with
Section 2.1(b), including without limitation Third Party
distributor whose obligations to Licensee or its Affiliates include
responsibility for sales, marketing and/or distribution efforts in
a country on behalf of Licensee or its Affiliates, excluding
wholesale distributors who purchase Licensed Products from Licensee
or its Affiliates in an arm’s length transaction and who have
no other obligation to Licensee or its Affiliates.
“ Listed
Alnylam Third Party Agreement ” shall mean an agreement
listed on Schedule D-1 .
“ Listed
Alnylam Third Party Payment ” shall have the meaning set
forth in Section 5.4(d).
8
“ Listed
Counterparties ” shall mean the Third Party
counterparties to Listed Alnylam Third Party Agreements and their
respective successors in interest.
“ Major
Market Countries ” shall have the meaning set forth in
Section 2.1(b).
“
Manufacture ” or “ Manufacturing ”
shall mean 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.
“ Max
Planck ” shall mean Max Planck Innovation GmbH (formerly
Garching Innovation GmbH).
“ Max
Planck European License Agreement ” shall mean
Co-Exclusive License Agreement between Max Planck and Alnylam
Europe AG (formerly Ribopharma AG), dated July 30, 2003, as
amended by the Requirement Amendment effective June 15,
2005.
“ NDA
” shall mean 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, or any foreign equivalent thereof, and (b) all
supplements and amendments that may be filed with respect to the
foregoing.
“ Net
Sales ” shall mean 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 Licensee,
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 those sales-related deductions
which are not accounted for by Licensee, 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 Licensee,
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).
9
For purposes of
this definition of “Net Sales”, “ Adjusted
Gross Sales ” shall mean the amount of gross sales of the
Licensed Product invoiced by Licensee, 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 Licensee 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 Licensee 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
Licensee 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 5.4(a), multiplied by a fraction whose numerator
is Licensee’s published sales price in such country for an
equivalent dosage of RNAi Compound contained in a given Combination
Product, and whose denominator is Licensee’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. 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.
“
Novartis ” shall mean Novartis Institutes for
BioMedical Research, Inc.
“
Novartis Agreement ” shall mean 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, and as the same may
be amended from time to time after the Execution Date in accordance
with Section 2.7(c).
“
Novartis Exclusivity Term ” shall mean the
“Exclusivity Term” as defined in the Novartis
Agreement.
“[**]”
shall have the meaning set forth in Section 2.7(b).
10
“[**]”
shall have the meaning set forth in
Section 2.7(b)(ii).
“ Option
Term ” shall mean the period commencing on the Effective
Date and ending on the fifth (5th) anniversary thereof.
“ Other
Transaction Documents ” shall mean (a) the Common
Stock Purchase Agreement, and (b) the Share Purchase
Agreement.
“
Party ” shall mean Alnylam or Licensee, as the case
may be; “ Parties ” shall mean both Alnylam and
Licensee.
“ Patent
Rights ” shall mean 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.
“
Person ” shall mean any corporation, limited or
general partnership, limited liability company, joint venture,
trust, unincorporated association, governmental body, authority,
bureau or agency, any other entity or body, or an
individual.
“ Phase I
Study ” shall mean 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, and the foreign equivalent
thereof.
“ Phase
II Study ” shall mean a human clinical trial, for which
the primary endpoints include a determination of dose ranges and/or
a preliminary determination of efficacy in patients being studied
as described in 21 C.F.R. § 312.21(b), or similar clinical
study in a country other than the United States.
“ Phase
III Study ” shall mean a human clinical trial 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), or a similar clinical study in a
country other than the United States.
“
Pre-Existing Alliance Agreements ” shall mean the
agreements set forth on Schedule E .
“
Pre-Existing Alliance Parties ” shall mean the Third
Party counterparties to Pre-Existing Alliance Agreements and their
respective successors in interest.
“ Primary
Field ” shall mean the treatment or prophylaxis of all
Indications in the Primary Therapeutic Areas, where such treatment
or prophylaxis comprises an RNAi Compound complementary to, and
functional in mediating the RNAi of, a Target known or believed to
be primarily implicated in one or more Primary Therapeutic
Areas.
11
“ Primary
Therapeutic Area ” shall mean each of the disease area
fields set forth on Schedule A to this
Agreement.
“ Product
Liability Claim ” shall mean, 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.
“
Regulatory Approval ” shall mean, 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.
“
Regulatory Authority ” shall mean 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.
“
Required Third Party Payments ” shall mean royalty
payments to a Third Party made by Licensee under Third Party
agreements (other than Listed Alnylam Third Party Agreements or
Pre-Existing Alliance Agreements) to license Patent Rights Covering
such Third Party’s technology if, in the absence of such
license, the licensed use by Licensee of the Licensed Patent Rights
licensed by Alnylam under Section 2.1(a) would infringe such
Patent Rights; 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) which may
be necessary or useful for delivery of double-stranded
oligonucleotide molecules, or manufacturing techniques for such
delivery technologies.
“ RNAi
Compound ” shall mean any compound that, in vitro or
otherwise, functions through the mechanism of RNAi and consists of
or encodes double-stranded oligonucleotides, and which
double-stranded oligonucelotides 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.
“ RNAi
Product ” shall mean any product that contains one or
more RNAi Compounds as an active ingredient.
“ Royalty
Term ” shall mean, 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 a Licensed Patent Right 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
a Licensed Patent Right in the country or countries in which such
Licensed Product is Manufactured) and concluding on the expiration
of the later of (a) the last to expire Licensed Patent Right
containing a Valid Claim Covering the Development,
Commercialization or Manufacture of such Licensed Product in that
country, (b) the last to expire Licensed Patent Right
containing a Valid Claim Covering the Manufacture of such Licensed
Product in the
12
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. For the avoidance of
doubt, if (x) a Licensed Product is not Covered by a Valid
Claim of a Licensed Patent Right in a country at the time of such
First Commercial Sale in such country, and (y) the Manufacture
of such Licensed Product is not Covered by a Valid Claim of a
Licensed Patent Right in the country or countries in which such
Licensed Product is Manufactured at the time of First Commercial
Sale, but at any time following First Commercial Sale, the Licensed
Product, or the Manufacture thereof, is Covered by a Valid Claim of
any patent under the Licensed Patent Rights that issues following
the time of such First Commercial Sale, then the Royalty Term shall
commence with respect to such Licensed Product at the time of such
issuance.
“ Share
Purchase Agreement ” shall mean the Share Purchase
Agreement entered into by and among Licensee, Licensee’s
Affiliate, Alnylam and Alnylam Europe AG on the Execution
Date.
“
Submitted Target ” shall have the meaning set forth in
Section 2.6.
“
Supplemental Therapeutic Area ” shall mean each of the
disease area fields set forth on Schedule B to this
Agreement.
“
Target ” shall mean (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.
“
Technology Transfer Period ” shall have the meaning
set forth in Section 3.1(a).
“
Technology Transfer Plan ” shall have the meaning set
forth in Section 3.1(a).
“
Terminated Patent Rights ” shall have the meaning set
forth in Section 5.4(f).
“ Third
Party ” shall mean any Person other than Alnylam or
Licensee and their respective Affiliates.
“ Third
Party Infringement Claim ” shall have the meaning set
forth in Section 2.8(a)(i).
“ UBC
” shall mean the University of British Columbia.
“ UBC
Sublicense Agreement ” shall mean the Sublicense
Agreement between Tekmira Pharmaceuticals Corporation (formerly
INEX Pharmaceuticals Corporation) and Alnylam Pharmaceuticals,
Inc., dated January 8, 2007.
13
“ Valid
Claim ” shall mean 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.
INTELLECTUAL PROPERTY
MATTERS
(a)
License Grants to Licensee .
(i) Alnylam
hereby grants to Licensee and its Affiliates a non-exclusive,
worldwide, perpetual, irrevocable, royalty-bearing right and
license, subject to the terms and conditions of this Agreement and
to Alnylam Third Party Obligations, under the Licensed Intellectual
Property to engage in any and all Discovery, Development,
Commercialization and Manufacturing activities in the Field (and,
to the extent expressly permitted in Section 2.5(a), any
Additional Field), including to make, have made, use, offer for
sale, sell and import Licensed Products in the Field (and, to the
extent expressly permitted in Section 2.5(a), any Additional
Field).
(ii) Alnylam
Europe AG hereby grants to Licensee and its Affiliates a
non-exclusive, worldwide, perpetual, irrevocable, royalty-bearing
right and license, subject to the terms and conditions of this
Agreement and to Alnylam Third Party Obligations, under Alnylam
Europe AG’s rights to the Architecture and Chemistry Patent
Rights licensed to Alnylam Europe AG pursuant to the terms of the
Max Planck European License Agreement, to engage in any and all
Discovery, Development, Commercialization and Manufacturing
activities in the Field (and, to the extent expressly permitted in
Section 2.5(a), any Additional Field), including to make, have
made, use, offer for sale, sell and import Licensed Products in the
Field (and, to the extent expressly permitted in
Section 2.5(a), any Additional Field).
(b)
Sublicense Rights . Subject to Alnylam Third Party
Obligations, Licensee shall have the right to grant sublicenses
within the scope of the licenses granted to it in Section 2.1(a),
on a Licensed Product-by-Licensed Product basis, to a Third Party
in the Field (and, to the extent expressly permitted in
Section 2.5(a), any Additional Field) solely for purposes of
Developing and/or Commercializing a Licensed Product which has
achieved the appropriate stage of Development (as determined by
Licensee using its reasonable business judgment in the management
of such Licensed Product within its portfolio of products, but in
no event [**] other than to Third Party contractors, including
contract research organizations, contract employees, consultants,
contract manufacturers and the like in connection with the licensed
activities); provided , however , that in no
event shall Licensee grant any sublicense of
14
any right
granted to Licensee under Section 2.1(a) for the Development
and/or Commercialization of any Third Party product unless such
product is licensed by Licensee from such Third Party and Licensee
and such Third Party are collaborating on the Development and/or
Commercialization of such Third Party product. Each such sublicense
agreement shall be consistent with the terms and conditions of this
Agreement. Licensee shall remain liable to Alnylam and Alnylam
Europe AG for each of its sublicensees’ failure to comply
with all applicable restrictions, limitations and obligations under
the sublicense agreement and this Agreement. No sublicense granted
by Licensee hereunder may be assigned, transferred or further
sublicensed to any Third Party without the prior written consent of
Alnylam or Alnylam Europe AG, as the case may be. Licensee shall
provide a redacted copy of such sublicense agreement to Alnylam
(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),
(x) if such sublicense impacts upon one or more of the
following countries: USA, Germany, France, United Kingdom, Italy,
Spain, and Japan (“ Major Market Countries ”),
and (y) upon request by Alnylam, in any country other than
those listed under clause (x) above.
2.2 No Other
Rights. Only the licenses granted to Licensee under
Section 2.1(a) hereof shall be of legal force and effect and
are limited to the scope expressly granted. Accordingly, except for
the rights expressly granted under Section 2.1(a) hereof, no
license, right, title or interest of any nature whatsoever is
granted hereunder by implication, estoppel, reliance or otherwise,
by Alnylam or Alnylam Europe AG to Licensee, and any of
Alnylam’s or Alnylam Europe AG’s rights to Licensed
Intellectual Property not specifically licensed to Licensee under
Section 2.1(a) hereof shall be retained by Alnylam or Alnylam
Europe AG, as the case may be. For purposes of clarity, nothing
contained in this Agreement shall prevent or restrict Alnylam or
Alnylam Europe AG from (a) granting to any Third Party any
non-exclusive licenses under Alnylam’s or Alnylam Europe
AG’s rights, as the case may be, in any Licensed Intellectual
Property, or (b) subject to the provisions of
Section 2.5(b)(i), granting to any Third Party any exclusive
licenses under Alnylam’s or Alnylam Europe AG’s rights
in any Licensed Intellectual Property outside of the then-current
Field.
2.3 Certain
License Limitations.
(a)
Pre-Existing Alliance Agreements .
(i) The
grants by Alnylam and Alnylam Europe AG under Licensed Intellectual
Property set forth in Section 2.1(a) are subject to, and are
limited to the extent of, the rights that Alnylam has previously
granted and is required to grant under Licensed Intellectual
Property to Pre-Existing Alliance Parties under the terms of the
Pre-Existing Alliance Agreements. As and to the extent that such
rights previously granted to Pre-Existing Alliance Parties under
Licensed Intellectual Property (whether such rights are previously
or subsequently exercised) lapse, terminate or otherwise revert to
Alnylam, they shall be automatically included in the non-exclusive
rights under Licensed Intellectual Property granted to Licensee in
the Field under Section 2.1(a).
(ii) Licensee
acknowledges that a Pre-Existing Alliance Party may from time to
time request rights under Licensed Intellectual Property with
respect to a
15
particular
Target that Alnylam is required, pursuant to the terms of a
Pre-Existing Alliance Agreement, to grant such rights to such
Pre-Existing Alliance Party with respect to such Target.
(b)
Contractual Obligations under Listed Alnylam Third Party
Agreements .
(i) For
the avoidance of doubt, the grants by Alnylam under Licensed
Intellectual Property set forth in Section 2.1(a) include,
subject to Section 2.3(b)(ii), the sublicense of Licensed
Intellectual Property that is not owned by Alnylam or Alnylam
Europe AG. Licensee’s rights and licenses under such Licensed
Intellectual Property are limited to the rights granted by Listed
Counterparties to Alnylam under the Listed Alnylam Third Party
Agreements and by Max Planck to Alnylam Europe AG under the Max
Planck European License Agreement, and Licensee shall comply, and
cause its Affiliates and Licensee Partners to comply, with those
restrictions and other terms applicable to sublicensees under such
agreements, certain of which restrictions and terms are summarized
on Schedule D-2 . Without limiting the generality of
the foregoing, Licensee acknowledges that certain obligations are
imposed on sublicensees of certain of the sublicensed Licensed
Intellectual Property, and agrees to comply (to the extent access
to obligations and requirements have been made available to
Licensee in unredacted form), and to require its Affiliates and
Licensee Partners to comply, with such obligations and
requirements. Notwithstanding the above, at the request of
Licensee, 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 Third
Party Agreements with the accounting and royalty reporting
provisions set forth in this Agreement.
(ii) Notwithstanding
anything to the contrary herein, the licenses to Licensed Patent
Rights hereunder initially shall not include licenses to Patent
Rights licensed by Alnylam or its Affiliates under the
Non-Exclusive License Agreement between [**] and Alnylam, dated
[**] (the “[**] Agreement ”), which Patent
Rights Licensee shall have the option, exercisable upon written
notice to Alnylam hereunder, to license, on a Licensed
Collaboration Product-by-Licensed Collaboration Product basis, upon
commencement of a Discovery Collaboration hereunder. Upon such
election, (x) the license granted to Licensee under
Alnylam’s rights to Delivery Patent Rights pursuant to
Section 2.1(a) shall include such Patent Rights with respect
to the designated Licensed Collaboration Product(s), (y)
Schedule C shall be amended to include such Patent
Rights, and (z) the [**] Agreement shall be deemed a Listed
Alnylam Third Party Agreement and Schedule D-1 and
Schedule D-2 shall be amended accordingly.
2.4 Blocked
Targets; Gatekeeper.
(i) From
time to time during the term of this Agreement but no more
frequently than [**] (except as set forth in clause (ii) of
this Section 2.4(a)), following an affirmative decision by
Licensee to initiate a program directed to the Discovery,
Development or Commercialization of RNAi Compounds directed to a
particular Target,
16
Licensee may
inquire of the Gatekeeper in writing whether or not such Target is
on the Blocked Target List by virtue of being subject to a
then-current exclusive or co-exclusive grant, option, right of
first refusal or similar right under a Pre-Existing Alliance
Agreement. The Gatekeeper shall, within [**] days following the
Gatekeeper’s receipt of such complete written request from
Licensee, notify Licensee in writing whether or not such Target is
on the Blocked Target List; provided , however , that
in no event will the Gatekeeper directly or indirectly notify or
communicate to any other Alnylam employee or consultant or any
Alnylam Affiliate or Third Party the contents or the existence of
Licensee’s inquiry hereunder without Licensee’s prior
written consent, which may be withheld at Licensee’s sole
discretion.
(ii) If
Alnylam becomes aware of the removal of any Target from the Blocked
Target List, Alnylam shall notify Licensee of such removal (but not
the identity of the Target which was removed) and Licensee shall
have the right to inquire of the Gatekeeper pursuant to, and in
compliance with, clause (i) above whether or not a Target is
on the Blocked Target List; provided , however ,
that the [**] limit set forth in clause (i) above on
the frequency of inquiries which may be made of the Gatekeeper
shall not apply with respect to an inquiry made under this
Section 2.4(a)(ii), nor shall an inquiry made under this
Section 2.4(a)(ii) be counted towards such [**]
limit.
(iii) Notwithstanding
the foregoing, the Parties acknowledge that a Pre-Existing Alliance
Party may subsequently request exclusive or co-exclusive rights
from Alnylam with respect to a particular Target as described in
Section 2.3(a)(ii) and the provisions of
Section 2.3(a)(ii) shall control.
(b)
Gatekeeper . Subject to the provisions of
Section 2.7(b), the inquiries and responses made by one Party
to the other in connection with Section 2.4(a) shall be made
in writing to the attention of a designated employee of Alnylam
mutually agreeable to both Parties (the “ Gatekeeper
”) who will be bound by confidentiality obligations to both
Parties. Each Party agrees to provide the Gatekeeper with full and
complete copies of all records and information (including
un-redacted copies of the relevant Third Party agreements) that are
necessary for the Gatekeeper to render his or her
determination.
2.5 Additional
Fields; Field Option.
(i) Licensee
shall initially conduct Discovery, Development, Commercialization
and Manufacturing activities directed to Targets only with respect
to Indications in the Field. After Licensee’s completion of a
Phase II Study with respect to any Licensed Product directed to a
specific Target in the Field, Licensee may engage in Discovery,
Development, and/or Manufacturing activities directed to such
Target for any Indication (each, an “ Additional
Indication ”) in any Additional Field (if such Additional
Field has not been the subject of Licensee’s exercise of a
Field Option) without having to pay a Field Option Fee;
provided , however , that (A) Licensee
shall notify Alnylam of its extension of Discovery, Development
and/or Manufacturing activities directed to such Target for such
Additional Indication in such Additional Field, and
(B) Licensee shall pay Alnylam the
17
following
amounts (which shall be in addition to any event payments which may
be owed under Section 5.3 below and except as provided in
clause (ii) below) upon achievement of the following events by
Licensee, its Affiliates or Licensee Partners with respect to each
such Additional Indication:
|
|
|
|
|
|
|
|
|
Payment for
|
|
|
|
Licensed Products
|
|
Development
Event:
|
|
(in [**]):
|
Initiation of Phase III for each Additional
Indication
|
|
$
|
[**]
|
|
Filing of an NDA for each Additional
Indication
|
|
$
|
[**]
|
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Regulatory Approval for each Additional
Indication
|
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$
|
[**]
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(ii) Notwithstanding
the foregoing provisions of clause (i) above, Licensee shall
pay Alnylam the following amounts (which shall be in addition to
any event payments which may be owed under Section 5.3 below
and in lieu of any amounts which may otherwise be owed under clause
(i) above) upon achievement of the following events by
Licensee, its Affiliates or Licensee Partners solely with respect
to a Licensed Product with respect to which Licensee extends its
activities for the first time to an Additional Indication in a
given Additional Field:
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Payment for
|
|
|
|
Licensed Products
|
|
Development
Event:
|
|
(in [**]):
|
Initiation of Phase III for a Licensed Product
for the first Additional Indication in a given Additional
Field
|
|
$
|
[**]
|
|
Filing of an NDA for a Licensed Product for the
first Additional Indication in a given Additional Field
|
|
$
|
[**]
|
|
Regulatory Approval for a Licensed Product for
the first Additional Indication in a given Additional
Field
|
|
$
|
[**]
|
|
(iii) The
amounts paid under subsections (i) and (ii) of this
Section 2.5(a) for Additional Indications within a given
Additional Field shall be fully creditable against Field Option
Fees which may be paid by Licensee pursuant to Section 5.6 for
such Additional Field. In no event shall the total event payments
made under this provision exceed $50 million for a given Additional
Field.
(iv) For
the avoidance of doubt, in no event shall Licensee conduct
Discovery, Development, Commercialization and Manufacturing
activities directed to any Target in any Additional Field other
than as permitted in this Section 2.5. In the event that
the
18
Parties are
unable to agree on whether or not Licensee’s activities fall
within or outside the Primary Field or any Additional Field in a
manner prohibited by this Agreement, the Parties shall submit such
dispute to a panel (the “ Field Definition Panel
”) consisting of three (3) independent experts in
clinical development, with each Party having the right to select a
single expert and the two (2) selected experts selecting the
third expert by mutual agreement. Such third expert shall serve as
the chairperson of the Field Definition Panel. The selection of the
experts for the Field Definition Panel shall occur within thirty
(30) days following the Parties’ decision to submit such
dispute to such a panel, and the Parties shall consult with such
Field Definition Panel for a period not to exceed thirty
(30) days from the selection of such experts. The Field
Definition Panel shall render a decision with respect to such
dispute, based on a majority vote, with each expert having one
(1) vote, within ten (10) days following the end of such
consultation period, which decision shall be binding on the
Parties. In the event that the Field Definition Panel determines
that Licensee’s Discovery, Development, Commercialization or
Manufacturing activities are being conducted in any Additional
Field in a manner which is prohibited hereunder, Licensee shall,
within ten (10) Business Days after such determination by the
Field Definition Panel, cease such proscribed activity.
(i) During
the Option Term, if Alnylam intends to grant to any Third Party
(other than Listed Counterparties or Pre-Existing Alliance Parties,
subject to the terms of the applicable Listed Alnylam Third Party
Agreements or Pre-Existing Alliance Agreements, as the case may be)
an exclusive license to any Additional Field(s) which is not
included in the then-current Field, Alnylam shall notify Licensee
thereof (“ Field Extension Opportunity ”).
Licensee shall have the right to extend the licenses granted under
Section 2.1(a) to include the Additional Field(s) covered by
such Field Extension Opportunity by notifying Alnylam in writing of
such intent within sixty (60) days after Alnylam’s
notice and paying the Field Option Fee for each such Additional
Field pursuant to Section 5.6. For the avoidance of doubt,
Alnylam and Alnylam Europe AG shall have the right to grant to any
Third Party any exclusive licenses under Alnylam’s or Alnylam
Europe AG’s rights, as the case may be, in any Licensed
Intellectual Property in any Additional Field to which Licensee has
not extended its licenses granted under Section 2.1(a)
pursuant to Licensee’s exercise of the Field Option under
this Section 2.5(b).
(ii) From
time to time during the Option Term, Licensee shall have the right,
upon written notice to Alnylam, to request the extension of the
license granted under Section 2.1(a) to include one or more
Additional Field(s) (“ Field Option ”) in which
Licensee has a good faith intention to seek to Discover, Develop,
Commercialize and Manufacture RNAi Compounds or RNAi Products,
which right shall be subject to any agreement which Alnylam may
have entered into with a Third Party with respect to such
Additional Field(s) following Licensee’s rejection of, or
failure to pay the Field Option Fee for, any Field Extension
Opportunity pursuant to clause (i) above. Upon
Licensee’s payment of the Field Option Fee for each such
Additional Field pursuant to Section 5.6, the licenses granted to
Licensee under Section 2.1(a) shall include such Additional
Field(s).
2.6 Designated
Target Option. From time to time during the Novartis
Exclusivity Term, Licensee shall have the right, upon written
notice to Alnylam, to select any
19
Target in the
Field which is not a Blocked Target for submission by Alnylam to
Novartis pursuant to the terms of the Novartis Agreement (a “
Submitted Target ”). Alnylam shall promptly provide
notice to Novartis of the Submitted Target(s) in accordance with
the provisions of the Novartis Agreement, and Licensee shall
cooperate with Alnylam in providing any information reasonably
requested by Novartis (but not the identity of Licensee or any of
Licensee’s RNAi Compounds) in order for Novartis to determine
whether or not to pursue Discovery, Development and/or
Commercialization activities directed to such Submitted Target. If
Novartis notifies Alnylam that it wishes (as such term is used in
the Novartis Agreement) to pursue Discovery, Development and/or
Commercialization activities directed to such Submitted Target,
then Alnylam shall so notify Licensee promptly upon Alnylam’s
receipt of such notification, and such Target shall be deemed a
Blocked Target for purposes of this Agreement. If Alnylam receives
notice from Novartis that Novartis has no interest in pursuing
Discovery, Development and/or Commercialization activities directed
to such Submitted Target, or if Novartis otherwise waives its right
to such Submitted Target under the terms of the Novartis Agreement,
then Alnylam shall notify Licensee promptly upon Alnylam’s
receipt of such notification or waiver. In such event, such
rejected or waived Submitted Target shall be deemed a
“Designated Target” for all purposes under this
Agreement, Licensee shall be deemed to have exercised its option
with respect to such Submitted Target (each, a “Designated
Target Option”), and Licensee shall be free, upon [**]
pursuant to Section 5.5, to Discover, Develop, Commercialize
or Manufacture RNAi Compounds and RNAi Products directed to such
Designated Target in accordance with the terms hereof without
further risk of such Target becoming a Blocked Target.
2.7 Special
Provisions Relating to Novartis.
(a)
Compliance with Novartis Agreement . It is the intent of the
Parties that this Agreement be construed in a manner which is
consistent with and in compliance with the terms of the Novartis
Agreement in all respects.
(b)
Alnylam Change of Control . In the event that, at any time
during the [**], an Alnylam Change of Control occurs in which [**]
(other than [**] or any controlled [**]) is the acquiring entity (a
“[**]”), it shall be a condition precedent to such [**]
that:
(i) Section 2.4(b)
of this Agreement shall be amended to provide that the
“Gatekeeper” shall not be a designated employee of
Alnylam but instead (A) shall be a Third Party who shall have
no material relationship (other than as Gatekeeper) with Alnylam,
[**], (B) shall be mutually agreeable to both Parties and
(C) shall be bound by confidentiality obligations to both
Parties, and to the extent that the consent of [**] shall be
required for such amendment, such consent shall have been obtained;
and
(ii)
[**], to the extent required, shall have agreed [**] that the[**]
contained therein ( i.e. , [**] thereof) shall terminate
upon such [**] and that [**] as a result of any obligations under
the [**] or as a result of any other actions [**] in connection
with [**] hereunder after the date of the agreement providing for
such [**] or, if there is no [**], after the date of such
[**].
20
Alnylam agrees
that the [**] shall include the consent of [**], as applicable,
required by clause (i) above and the agreement of [**], as
applicable, to the amendment required by clause (ii) above.
If, notwithstanding the foregoing, the [**] shall occur without the
amendment and consent contemplated by clause (i) above or
without the agreement and amendment contemplated by clause (ii)
above, then (A) [**] and (B) Alnylam shall pay to Licensee an
amount equal to [**]. Each Party agrees that if the [**] shall
occur without the amendment and consent contemplated by clause (i)
above or without the agreement and amendment contemplated by clause
(ii) above, the damages that Licensee and its Affiliates would
suffer would be irreparable and difficult to calculate with
certainty but in such event the amounts payable by Alnylam pursuant
to the immediately preceding sentence shall constitute fair and
reasonable amounts and not penalties.
(c) No
Adverse Amendments . Alnylam agrees not to enter into any
amendment or modification to the [**] which would have an adverse
impact on Licensee’s rights under this Agreement, without the
prior written consent of Licensee. Without limiting the foregoing,
the Parties acknowledge and agree that the following
amendments/modifications would have an adverse impact on
Licensee’s rights under this Agreement: [**]; (iv) any
amendment that would require Alnylam to provide to [**] any
Confidential Information of Licensee; and (v) any provision
that is inconsistent with the obligations of Alnylam to Licensee
hereunder.
(d)
Specific Performance . The Parties hereto agree that
irreparable damage would occur if any provision of this
Section 2.7 were not performed in accordance with the terms
hereof and that Licensee shall be entitled to an injunction or
injunctions to prevent breaches of this Agreement or to enforce
specifically the performance of the terms and provisions hereof in
any federal court located in the State of Delaware or any Delaware
state court, in addition to any other remedy to which they are
entitled at law or in equity.
2.8 Certain
Intellectual Property Matters
(a)
Claimed Infringement .
(i) In
the event that a Third Party at any time asserts a claim, or brings
an action, suit or proceeding against a Party or any of its
Affiliates or, with respect to Licensee, Licensee Partners,
claiming infringement of such Third Party’s Patent Rights or
unauthorized use or misappropriation of such Third Party’s
Know-How, based upon an assertion or claim arising out of any of
the activities taken in respect of the Discovery, Development,
Commercialization or Manufacture of Licensed Products, where such
claim, action, suit or proceeding and/or the defense thereof
involves, or is likely to involve, the validity, scope and/or
enforceability of the Licensed Intellectual Property (“
Third Party Infringement Claim ”), such Party shall
promptly notify the other Party in writing of the claim or the
commencement of such action, suit or proceeding, enclosing a copy
of the claim and all papers served.
(ii) Within
thirty (30) days after delivery of the notification required
to be delivered under clause (i) above, as between Alnylam and
Licensee and subject to Alnylam Third Party Obligations, Alnylam
shall, upon written notice thereof to Licensee,
21
assume control
of the defense of those aspects of any such Third Party
Infringement Claim which involve the validity, scope and/or
enforceability of Licensed Intellectual Property (either alone or
in combination with any other Patent Rights or Know-How), and
Licensee shall, upon written notice thereof to Alnylam, assume
control of the defense of any other Third Party Infringement Claim
or aspect thereof, as the case may be. Licensee and Alnylam,
subject to Alnylam Third Party Obligations, 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.
(iii) The
Party controlling the action, suit, proceeding, claim or defense
under Section 2.8(a) shall not agree to any settlement of such
action, suit, proceeding, claim or defense without the prior
written consent of the other Party, which shall not be unreasonably
withheld, conditioned or delayed; provided , that
Alnylam may settle or compromise any action, suit, proceeding,
claim or defense relating to Licensed Intellectual Property without
the prior written consent of Licensee.
(b)
Trademarks . Each Party and its Affiliates shall retain all
right, title and interest in and to its and their respective
corporate names and logos. Licensee shall not acquire any rights
under this Agreement in any trademark, service mark or Internet
domain name including the word “Alnylam” or any other
trademarks or trade dress of Alnylam or its Affiliates, and Alnylam
shall not acquire any rights under this Agreement in any trademark,
service mark or Internet domain name including the word
“Roche” or any other trademarks or trade dress of
Licensee or its Affiliates.
(c)
Enforcement of Licensed Intellectual Property . Alnylam
shall take reasonable measures to protect and, to the extent
Alnylam has such a right, to enforce the Licensed Intellectual
Property in the Field, consistent with prudent commercial practices
in the biotechnology industry.
(d)
Notice of Changes . Within sixty (60) days after each
anniversary of the Effective Date, Alnylam shall provide to
Licensee an updated Schedule C that reflects any
changes to the list of Licensed Patent Rights set forth on
Schedule C which have occurred during the prior
year.
2.9 Obligation
to Maintain Listed Alnylam Third Party Agreements. Alnylam
shall use commercially reasonable efforts to maintain the Listed
Alnylam Third Party Agreements in full force and effect as they
relate to the Licensed Patent Rights. If a Listed Alnylam Third
Party Agreement provides Alnylam with the opportunity to assume
prosecution of any Licensed Patent Right or risk that such right
will be abandoned, then Alnylam shall take reasonable measures to
prosecute such Licensed Patent Right in the Field, consistent with
prudent commercial practices in the biotechnology
industry.
22
JOINT FUTURE TECHNOLOGY
COMMITTEE
(a)
Initial Technology Transfer .
(i) Within
a period of [**] months following the Effective Date (“
Technology Transfer Period ”), Alnylam shall complete
the activities assigned to Alnylam as set forth on the technology
transfer plan attached hereto as Schedule F (as it may
be amended from time to time by mutual agreement of the Parties,
the “ Technology Transfer Plan ”), at no
additional cost to Licensee (subject to subsection 3.1(d) below),
to effect the transfer to Licensee (or its designated Affiliate(s))
of Licensed Intellectual Property that is reasonably necessary for
the exercise of Licensee’s rights under the licenses granted
pursuant to Section 2.1(a) and for the operation of the
facility in Kulmbach, Germany which is being transferred to
Licensee pursuant to the terms of the Share Purchase Agreement
(“ Kulmbach Facility ”). Alnylam shall make
available to Licensee such number of technical personnel as may be
set forth in the Technology Transfer Plan to answer any questions
or provide instruction as reasonably requested by Licensee
concerning the items delivered pursuant to this
Section 3.1(a), in connection with Licensee’s Discovery,
Development, Commercialization and Manufacture of Licensed Products
hereunder and the operation of the Kulmbach Facility.
(ii) During
the Technology Transfer Period, Licensee shall conduct, and shall
cause Licensee’s applicable Affiliate(s) to conduct, the
activities assigned to Licensee (and/or its Affiliates) as set
forth on the Technology Transfer Plan, at no additional cost to
Alnylam, to effect the transfer to Alnylam (or its designated
Affiliate(s)) of Know-How which is reasonably necessary to enable
Alnylam (or its Affiliate(s)) to transfer the performance of the
activities conducted at the Kulmbach Facility prior to the
Effective Date to an alternate facility in Cambridge, MA, U.S.A,
designated by Alnylam.
(b)
Technology Transfer to Alnylam After Technology Transfer
Period . Without limiting Licensee’s obligations under
Section 3.1(a), following the end of the Technology Transfer
Period, Licensee shall conduct, and shall cause Licensee’s
applicable Affiliates to conduct, the activities assigned to
Licensee and/or its Affiliates as set forth in the Technology
Transfer Plan, at no additional cost to Alnylam, to effect the
transfer to Alnylam (or its designated Affiliate(s)) of Know-How
associated with, or arising from, the Discovery, Development,
Commercialization and/or Manufacturing activities performed by
Licensee (and/or its Affiliate(s)) and its or its Affiliates’
employees and subcontractors at the Kulmbach Facility on behalf of
Alnylam and/or its Affiliates before and/or during the Transition
Period (as defined in the Share Purchase Agreement). Licensee shall
make available to Alnylam such number of technical personnel as may
be set forth in the Technology Transfer Plan to answer any
questions or provide instruction as reasonably requested by Alnylam
concerning the items delivered pursuant to this
Section 3.1(b).
23
(c)
Management of Transition Activities . Each Party shall
designate personnel to the Joint Transition Team (as defined in the
Share Purchase Agreement) who shall be responsible for coordinating
the technology transfer activities under the Technology Transfer
Plan. Each Party shall cooperate with the other Party in such other
Party’s conduct of technology transfer activities under the
Technology Transfer Plan.
(d)
Additional Services . If Licensee desires that Alnylam
continue to provide technology transfer services with respect to
Licensed Intellectual Property (i) beyond the scope of the
Technology Transfer Plan, or (ii) following the end of the
Technology Transfer Period, Alnylam shall, at its discretion and
upon mutual agreement of the Parties on the terms of such services
(including, as necessary, an amended Technology Transfer Plan),
continue to provide such services on terms to be agreed upon by the
Parties.
3.2 Joint
Future Technology Committee. Within thirty (30) days after
the Effective Date, the Parties shall establish a “ Joint
Future Technology Committee ”, comprised of at least one
(1) representative from each of Licensee and Alnylam, to
exchange information and facilitate discussions concerning any
Future Technology Patent Rights which may arise during the Option
Term. Unless otherwise agreed by the Parties, the Joint Future
Technology Committee shall remain in effect during the Option Term
and shall meet on a bi-annual basis, in a manner and at a location
mutually agreed by the Parties (including via telephone). During
the Option Term, either Party may notify the other Party of its
interest in obtaining a license under such other Party’s
rights to any Future Technology Patent Rights. Upon such
notification and subject to any rights of Third Parties to such
Future Technology Patent Rights, the Parties shall negotiate in
good faith for a period not to exceed one hundred twenty
(120) days the terms of any license to such Future Technology
Patent Rights, provided that neither Party shall be
obligated to grant any licenses to the other Party. For the
avoidance of doubt, the Joint Future Technology Committee shall
have no decision-making authority with respect to the acquisition
or grant of any licenses under any Future Technology Patent
Rights.
4.1 Discovery
Collaboration. Within [**] months following the Effective Date
during the Option Term (“ Initial Discovery Collaboration
Opportunity Period ”), Licensee shall propose to Alnylam
at least [**] Targets which are not Blocked Targets with respect to
which Licensee has an interest in entering into a Discovery
Collaboration with Alnylam (“ Discovery Collaboration
Opportunity ”), and shall provide to Alnylam any
available information concerning such Targets which Licensee
reasonably believes may be material to Alnylam in its evaluation of
such Discovery Collaboration Opportunity and the rationale for
pursuing an RNAi Compound directed to such Target. If Alnylam has
an interest in pursuing any such Discovery Collaboration
Opportunity with Licensee with respect to one or more of the
proposed Targets (each, a “ Collaboration Target
”), then Alnylam shall so respond within thirty
(30) days of Licensee’s notice. If any such
Collaboration Target is not already a Designated Target at the time
of Licensee’s proposal of the Discovery Collaboration
Opportunity directed to such Collaboration Target, then Licensee
shall submit such
24
Collaboration
Target(s) to Novartis during the Novartis Exclusivity Term in
accordance with Section 2.6 hereof. In the event that Novartis
rejects or waives such Collaboration Target and such Collaboration
Target becomes a Designated Target hereunder, [**], and the Parties
shall negotiate in good faith, for a period not to exceed six
(6) months, the terms of a Discovery Collaboration Opportunity
directed to such Designated Target in accordance with
Section 4.2. If the Parties are unable to negotiate the terms
of a Discovery Collaboration Opportunity within such six
(6) month period, the Parties shall refer the matter(s) under
negotiation to the Chief Executive Officer of Alnylam and the
Global Head of Pharma Research of Licensee, for discussion and
resolution within a thirty (30) day period. Licensee shall
have no obligation to pursue more than [**]; provided, that, the
Parties shall enter into at least [**] directed to at least [**]
within the Option Term.
4.2 Minimum
Terms. The terms of any Discovery Collaboration negotiated
between the Parties pursuant to Section 4.1 shall include, at
a minimum, the following: (a) each Party shall be responsible
for the costs of its own employees who perform work under the
Discovery Collaboration, (b) Licensee shall pay to Alnylam
event payments and royalties with respect to Licensed Collaboration
Product(s) which shall be in addition to those which would have
been payable by Licensee with respect to such Licensed
Collaboration Product(s) had Licensee independently Discovered,
Developed, Commercialized and/or Manufactured such Licensed
Collaboration Product(s) as Licensed Product(s) outside of any
Discovery Collaboration, which shall be commensurate with
Alnylam’s contributions to the Discovery Collaboration
(taking into account, at a minimum, the Patent Rights referred to
in subsection (c) below which shall be licensed to Licensee in
connection with such Discovery Collaboration in addition to the
Licensed Patent Rights); (c) the grant of licenses under each
Party’s rights to Patent Rights and Know-How developed by
such Party, its Affiliates and/sublicensees, either individually or
jointly with each other, during and in the performance of the
Discovery Collaboration; (d) the rights and obligations of
each Party with respect to prosecution, maintenance and enforcement
of the intellectual property rights set forth in the immediately
preceding clause (c); and (e) termination rights. Upon
finalization of the terms of any Discovery Collaboration pursuant
to this Section 4.2, the Parties shall (x) develop a
research plan in accordance with which each Party shall perform
activities specified under such Discovery Collaboration, and
(y) establish a joint steering committee made up of an equal
number of representatives from each Party to oversee, review and
coordinate the activities of the Parties under such Discovery
Collaboration. Notwithstanding the foregoing, if there is an
Alnylam Change of Control, then Licensee shall have the right not
to (i) begin, or continue, to propose Discovery Collaboration
Opportunities pursuant to Section 4.1, (ii) begin, or
continue to engage in, any negotiations with Alnylam with respect
to any such Discovery Collaboration Opportunity, or (iii) continue
with any ongoing Discovery Collaboration.
5.1 Equity
Investment. As of the Execution Date, the Parties have entered
into the Common Stock Purchase Agreement pursuant to which Licensee
has agreed to purchase shares of Alnylam’s Common Stock (as
defined in the Common Stock Purchase
25
Agreement) for
a total consideration of Forty-Two Million Four Hundred Sixty-Two
Thousand Five Hundred dollars ($42,462,500).
5.2 License
Grant Consideration. In consideration of the rights granted to
Licensee under this Agreement as of the Effective Date, Licensee
shall pay, or cause to be paid, to Alnylam Two Hundred
Seventy-Three Million Five Hundred Five Thousand Five Hundred
dollars ($273,505,500) within ten (10) Business Days following
the Effective Date.
(a)
Development Events . In connection with the Discovery and
Development of Licensed Products that are Covered by a Valid Claim
of Licensed Patent Rights, or the Manufacture of which Licensed
Products is Covered by a Valid Claim of a Licensed Patent Right,
and directed against a given Target hereunder, Licensee shall pay,
or cause to be paid, to Alnylam the following payments upon the
achievement of the events set forth below:
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Payment for
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|
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Licensed Products
|
|
Development
Event:
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(in [**]):
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Initiation of GLP Toxicology Studies
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$
|
[**]
|
|
Initiation of the first Phase I Study
|
|
$
|
[**]
|
|
Initiation of the first Phase II
Study
|
|
$
|
[**]
|
|
Initiation of the first Phase III Study for the
first Indication
|
|
$
|
[**]
|
|
Initiation of first Phase III Study for a second
Indication
|
|
$
|
[**]
|
|
First filing of an NDA in the U.S. for the first
Indication
|
|
$
|
[**]
|
|
First filing of an NDA in the EU for the first
Indication
|
|
$
|
[**]
|
|
First filing of an NDA in Japan for the first
Indication
|
|
$
|
[**]
|
|
First filing of an NDA in the U.S. or EU for a
second Indication
|
|
$
|
[**]
|
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Regulatory Approval in the U.S. for the first
Indication
|
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$
|
[**]
|
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Regulatory Approval in the EU for the first
Indication
|
|
$
|
[**]
|
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Regulatory Approval in Japan for the first
Indication
|
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$
|
[**]
|
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Regulatory Approval in the U.S. or EU for a
second Indication
|
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$
|
[**]
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26
(b) Sales
Events . With respect to each Target, Licensee shall pay, or
cause to be paid, to Alnylam the following payments based on Net
Sales of Licensed Products that are Covered by a Valid Claim of
Licensed Patent Rights, or the Manufacture of which Licensed
Products is Covered by a Valid Claim of a Licensed Patent Right,
upon the achievement of the events set forth below:
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Payment for
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Licensed Products
|
|
Sales
Event:
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(in [**]):
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Aggregate worldwide Annual Net Sales of all
Licensed Product(s) directed to such Target reach or exceed $[**]
(≥$[**])
|
|
$[**]
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Aggregate worldwide Annual Net Sales of all
Licensed Product(s) directed to such Target reach or exceed $[**]
(≥$[**])
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$[**]
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(c)
Achievement of Events . Licensee shall notify Alnylam within
thirty (30) days following achievement or occurrence of an
event under Section 2.5(a) and this Section 5.3, and
Alnylam shall deliver to Licensee an invoice for such event. Each
event payment under Section 2.5(a) and this Section 5.3 shall
be deemed earned as of the achievement or occurrence of the related
event and shall be paid by Licensee within sixty (60) days
following such achievement or occurrence.
(d) Event
Payments Payable Only Once . Each event payment under this
Section 5.3 shall be payable only once in relation to each
Target. By way of example, in the event that Licensee elects not to
proceed with the Development or Commercialization of a Licensed
Product directed to a Target for which one or more of the foregoing
event payments have been paid, Licensee shall not be required to
make any event payments previously paid under this Section 5.3
with respect to any back-up Licensed Product(s) directed at such
Target. In addition, if, with respect to the Development of a
Licensed Product, Licensee satisfies an event under this
Section 5.3, Licensee shall pay to Alnylam all earlier event
payments under this Section 5.3 that have not otherwise been
paid with respect to such Target (regardless of whether such
earlier events have been satisfied).
(a)
Royalty Rate . Subject to subsections (b)-(g) of this
Section 5.4, during each relevant Royalty Term, Licensee shall
pay, or cause to be paid, to Alnylam the following royalties on
Annual Net Sales of each Licensed Product:
27
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Royalty Rate
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Annual Net Sales
of a Licensed Product (on a
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Applicable to Such
|
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Target-by-Target
basis) during the applicable
|
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Annual Net Sales
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calendar
year:
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of Such Licensed Product:
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Less than or equal to $[**]:
|
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[**]
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%
|
Greater than $[**], but less than or equal to
$[**]:
|
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|
[**]
|
%
|
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
$[**]
|
|
|
[**]
|
%
|
|
|
|
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[**]
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%
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By way of
example, if Annual Net Sales of a Licensed Product are [**] dollars
and no deductions were to apply under Sections 5.4(b)-(g),
then the royalty payable by Licensee to Alnylam would be as
follows:
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= $[**] million
|
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|
= $[**] million
|
|
|
|
= $[**] million
|
|
|
|
= $[**] million
|
|
|
|
= $[**] million
|
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= $[**] million
|
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|
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= $[**] million
|
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= $[**] million
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For the
avoidance of doubt, Licensee’s obligation to pay royalties
under this Section 5.4 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
Licensed Patent Rights.
(b)
Expiration of Patent Coverage . If no Valid Claim of
Licensed 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 Licensed 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 rate set forth in Section 5.4(a) above for any
28
remaining
portion of the Royalty Term which applies to such Licensed Product
in such country.
(c)
Royalty Stacking . Licensee shall be entitled to deduct,
from the royalty payments payable by Licensee under
Section 5.4(a) for a reporting period, [**] percent ([**]%) of
Required Third Party Payments paid by Licensee with respect to
Licensed Products during the applicable reporting period;
provided that in no event shall a deduction under
this subsection (c) reduce any royalty payment payable by
Licensee under Section 5.4(a) by more than [**] percent
([**]%).
(d)
Payments in Respect of Alnylam In-Licenses . In addition to
any royalty set forth in Section 5.4(a) during the Royalty
Term, Licensee shall reimburse Alnylam for [**] percent ([**]%) of
all royalty payments payable (each such payment, a “
Listed Alnylam Third Party Payment ,” collectively,
the “ Listed Alnylam 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
Licensee hereunder in respect of such Listed Alnylam 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 Licensee in a manner that ensures all amounts
payable by Licensee hereunder pursuant to Listed Alnylam Third
Party Agreements are paid in a timely manner and otherwise in
compliance with such Listed Alnylam Third Party Agreements.
Licensee 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
Alnylam 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 VI hereof. Audit results
and findings shall be shared by Licensee and Alnylam. If the audit
reveals an overpayment by Licensee under this Section 5.4(d),
the amount of such overpayment shall be credited towards any future
reimbursement amounts payable by Licensee under this
Section 5.4(d), subject to Section 5.4(e). If the audit
reveals an underpayment by Licensee, Licensee shall make up such
underpayment within thirty (30) days. The failure of Licensee
to request verification of any Listed Alnylam Third Party Payments
hereunder within the [**] calendar year period set forth above
shall be deemed acceptance of the calculation of such Listed
Alnylam Third Party Payments.
(e)
Deductions . Notwithstanding anything in this Agreement to
the contrary, in no event shall total deductions under
Sections 5.4(b) and 5.4(c) reduce any quarterly royalty
payment by Licensee in respect of Net Sales of a given Licensed
Product to less than [**]. Alnylam 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 5.4(b) and 5.4(c) which
cannot be used against any quarterly royalty payment due to the
foregoing limitation may be carried forward and used against future
quarterly royalty payments, subject to the limitation set forth
above.
(f) Loss
of Listed Alnylam Third Party Agreements . If Alnylam ceases to
be a licensee of Licensed Patent Rights (as such, “
Terminated Patent Rights ”) under any
29
Listed Alnylam
Third Party Agreement (other than as a result of any action or
omission by Licensee) and Licensee directly licenses such
Terminated Patent Rights from that Third Party, then Licensee may
deduct the full amount of any [**] 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 Licensee
entering into any such license of such Terminated Patent Rights
from such Third Party, Licensee 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
Licensee shall consider in good faith such rationale. If Licensee
does not agree with Alnylam’s rationale, then, at
Licensee’s request, Alnylam shall use commercially reasonable
efforts to reinstate the license for such Terminated Patent Rights
within a sixty (60) 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 Licensee 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 5.4(f)
reduce any quarterly royalty payment by Licensee in respect of Net
Sales of a given Licensed Product to less than [**].
(g)
Duration of Royalty Payments; First Commercial Sale . The
royalties payable under Section 5.4(a) 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. Licensee shall notify Alnylam of the
occurrence of First Commercial Sale of each Licensed Product within
fifteen (15) days of its occurrence.
5.5 [**].
If Licensee exercises the [**] with respect to a Target pursuant to
Section 2.6, and such Target is deemed a [**] hereunder, then
Licensee shall pay Alnylam a fee (the [**]) of (a) [**] Dollars
($[**]) for each of the first [**] Targets to be [**] pursuant to
Licensee’s exercise of the [**] in any calendar year,
(b) following the [**] of the [**] Target as a [**] hereunder
in any calendar year, [**] Dollars ($[**]) for each of the next
[**] Targets [**] pursuant to Licensee’s exercise of the [**]
hereunder; (c) following the [**] of the [**] Target as a [**]
hereunder in any calendar year, [**] Dollars ($[**]) for each of
the next [**] Targets [**] pursuant to Licensee’s exercise of
the [**] hereunder; and (d) following the [**] of the [**]
Target as a [**] hereunder in any calendar year, [**] Dollars
($[**]) for each Target [**] pursuant to Licensee’s exercise
of the [**] hereunder. Licensee shall pay such [**] within thirty
(30) days following receipt of Alnylam’s invoice with
respect to the [**] hereunder.
5.6 Field
Option Fee. If Licensee exercises the Field Option with respect
to any Additional Field pursuant to Section 2.5, Licensee
shall pay Alnylam a fee (the “ Field Option Fee
”) of Fifty Million Dollars ($50,000,000) for each such
Additional Field. Licensee shall pay such Field Option Fee within
thirty (30) days following receipt of Alnylam’s invoice
therefor.
5.7 Most
Favored Licensee. During the Option Term, in the event that
Alnylam grants to a Third Party (other than Listed Counterparties
or Pre-Existing Alliance
30
Parties) rights
including a non-exclusive, worldwide license under the Licensed
Intellectual Property to Discover, Develop, Manufacture and
Commercialize Licensed Products, at a royalty rate (taking into
account any obligations to make payments to Third Parties) that is
more favorable to such Third Party than the royalty rate (taking
into account any obligations to make payments to Third Parties) set
forth in Section 5.4 of this Agreement with respect to such
license grant, then the royalty rate (taking into account any
obligations to make payments to Third Parties) under this Agreement
shall be reduced or adjusted to such more favorable Third Party
royalty rate on a prospective basis from the effective date of
Alnylam’s agreement with such Third Party with respect to
such rights. Notwithstanding the foregoing, if (a) the Third
Party has paid cash or other consideration, or there are other
elements of the overall transaction with such Third Party, that
justifies a royalty rate below the rate set forth in
Section 5.4 of this Agreement, or (b) the license has
been granted as part of a joint venture or similar collaborative
agreement, then such royalty rate reduction shall not apply. For
the avoidance of doubt, such more favorable royalty rate shall have
no retroactive effect and shall not apply to any royalties which
have been paid by Licensee or which have otherwise accrued under
this Agreement prior to the date of such reduction or
adjustment.
5.8 Payment of
Royalty. Licensee 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 sixty (60) days after the end of each
Accounting Period in which such Net Sales occur. Royalties on Net
Sales shall be paid by Licensee in U.S. Dollars.
5.9 Currency
Computation. Whenever calculating royalties requires conversion
from any currency, Licensee shall make such conversion as follows:
When calculating the Adjusted Gross Sales for countries other than
the United States of America, Licensee shall convert the amount of
such sales in currencies other than Swiss Francs into Swiss Francs
using for internal foreign currency translation Licensee’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, Licensee shall
convert into US Dollars (or other currency), using the daily rate
(Reuters) at the last working day for the applicable
period.
5.10
Reporting. With each payment Licensee shall provide in writing
for the relevant Accounting Period the following information split
by U.S., each of the Major Market Countries, and rest of world
(a) Adjusted Gross Sales; (b) Net Sales; (c) the
total royalties payable for the applicable period; and (d) any
other information necessary for Alnylam to comply with its
reporting and payment obligations to Third Parties under Alnylam
Third Party Obligations, subject to Alnylam’s obligations
under Section 2.3(b)(i).
5.11
Withholding Taxes. Any tax required to be withheld by Licensee
under the laws of any country for the account of Alnylam shall be
promptly paid by Licensee for and on behalf of Alnylam to the
appropriate governmental authority, and Licensee shall furnish
Alnylam with proof of payment of such tax. Any such tax actually
paid on Alnylam’s behalf shall be deducted from royalty
payments due to Alnylam hereunder. Licensee shall assist Alnylam in
minimizing the withholding taxes applicable to any payment made by
Licensee and in claiming tax refunds at Alnylam’s
request.
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5.12 Financial
Records. Licensee 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. Such
books of accounts shall be kept at their principal place of
business.
5.13 Audits by
Alnylam. At the expense of Alnylam, Alnylam has the right to
engage an independent public accountant reasonably acceptable to
Licensee to perform, on behalf of Alnylam, an audit of such books
and records of Licensee 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 thirty (30) 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 Licensee’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
Licensee subject to the obligations of this Agreement and need
neither be retained more than [**] year 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 [**] year after the date of termination of
this Agreement. Audit results and findings shall be shared by
Licensee and Alnylam. If the audit reveals an overpayment, Alnylam
shall reimburse Licensee for the amount of the overpayment within
thirty (30) days. If the audit reveals an underpayment,
Licensee shall make up such underpayment within thirty
(30) days with interest as set forth in Section 5.14
below. In addition, if the underpayment is equal to or greater than
five percent (5%) of the amount that was otherwise due, Licensee
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.
5.14 Late
Payments. Licensee shall pay interest to Alnylam on the
aggregate amount of any payments 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.
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6.1
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 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 VI
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 6.1, 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
33
to the extent
Alnylam is contractually obligated to do so pursuant to Alnylam
Third Party Obligations and to potential and existing investors,
lenders and acquirors; provided , that Alnylam shall
redact such portions as Licensee reasonably requests.
6.2 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 confidential under terms no less
restrictive than those set forth herein.
6.3
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
Schedule G hereto. Thereafter, neither Party shall
issue any press release or public announcement relating to this
Agreement or any Discovery Collaboration 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. Alnylam shall not issue any press
release or public announcement relating to Licensed Products
without the prior written approval of Licensee. 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.
REPRESENTATIONS AND
WARRANTIES
7.1 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.
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(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.
7.2
Representations and Warranties of Alnylam. Alnylam represents
and warrants to Licensee 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.
(b)
Non-Infringement . To Alnylam’s knowledge, (i) no
Third Party is currently infringing or misappropriating any
Licensed Intellectual Property, it being understood that there may
be Third Parties that are conducting research or clinical
development under the “safe harbor” exemption from
patent infringement under 35 USC 271(e)(1) or similar exemptions in
other jurisdictions, and (ii) the practice of the Licensed
Intellectual Property as contemplated under this Agreement does not
violate the intellectual property rights of any Third
Party.
(c)
Validity . All Licensed Intellectual Property that is owned
by Alnylam, and, to the best of Alnylam’s knowledge, all
Licensed Intellectual Property that is licensed by Alnylam pursuant
to Listed Alnylam Third Party Agreements, is in full force and
effect and all necessary registration, maintenance, and renewal
fees for such Licensed Intellectual Property have been paid on
time. Except for those oppositions or challenges which are publicly
disclosed in Alnylam’s filings with the U.S. Securities and
Exchange Commission, no Third Party has initiated a suit or other
proceedings to challenge the validity of the Licensed Patent
Rights. Alnylam has no reason to believe that the Licensed Patent
Rights are other than valid and enforceable.
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(d)
Litigation . Alnylam and its Affiliates are not aware of any
pending or threatened claim or litigation (nor has Alnylam received
notice of a potential claim or litigation) (i) which alleges
that any issued patents of a Third Party would be infringed by the
Development and Commercialization of any Licensed Product hereunder
or (ii) that questions the validity of this Agreement or the
right of Alnylam to enter into this Agreement, or to consummate the
transactions contemplated hereby. To Alnylam’s knowledge,
there are no legal actions or investigations pending or threatened
involving the employment by or with Alnylam of any of
Alnylam’s current or former officers, their use in connection
with Alnylam’s business or any information or techniques
allegedly proprietary to any of their former emplo
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