Exhibit 10.32
Execution Copy
***Text Omitted and Filed
Separately
with the Securities and Exchange
Commission.
Confidential Treatment Requested
Under 17 C.F.R. Sections
200.80(b)(4)
and 240.24b-2.
EXCLUSIVE LICENSE AND RESEARCH
COLLABORATION AGREEMENT
between
IDENIX PHARMACEUTICALS,
INC.
and
METABASIS THERAPEUTICS,
INC.
EXCLUSIVE LICENSE AND RESEARCH
COLLABORATION AGREEMENT
THIS EXCLUSIVE LICENSE AND
RESEARCH COLLABORATION AGREEMENT (the “Agreement” ) is
entered into as of October 24, 2006 (the
“Effective Date” ) by and between
IDENIX PHARMACEUTICALS, INC. , a Delaware corporation (
“Idenix” ), having an address of
60 Hampshire Street, Cambridge, Massachusetts 02139, and
METABASIS THERAPEUTICS, INC. , a Delaware corporation (
“Metabasis” ), having an address of
11119 North Torrey Pines Road, La Jolla, California
92037. In this Agreement, Idenix and Metabasis are each
referred to individually as a “Party” and
collectively as the “Parties.”
RECITALS
WHEREAS , Metabasis has developed Metabasis Technology
(as hereinafter defined) for the discovery and optimization of
liver targeted compounds and Idenix owns Idenix Nucleosides (as
hereinafter defined);
WHEREAS , Idenix and Metabasis desire to enter into a
business relationship to identify and develop the Collaboration
Compounds (as hereinafter defined) and sell Products upon the terms
and conditions set forth herein; and
WHEREAS , Idenix desires to obtain licenses under
Metabasis Technology and Metabasis’ interest in Collaboration
Technology and Joint Technology (as each such term is hereinafter
defined) to develop and commercialize Products in the Field (as
hereinafter defined), and Metabasis desires to grant such licenses,
in each case upon the terms and conditions set forth
herein.
AGREEMENT
NOW, THEREFORE,
in consideration of the foregoing
premises and the mutual covenants herein contained, the Parties
hereby agree as follows:
1.
DEFINITIONS
Unless specifically set forth to the
contrary herein, the following terms, whether used in the singular
or plural, shall have the respective meanings set forth below.
References to “Articles”, “Sections” and
“subsections” in this Agreement shall be to Articles,
Sections and subsections respectively, of this Agreement unless
otherwise specifically provided:
1.1
[***] shall have the meaning
provided in Section 12.6(a).
1.2
“Affiliate” shall mean any company or entity controlled by,
controlling, or under common control with a Party. For the
purposes of this definition, the term “control”
(including, with correlative meanings, the terms “controlled
by” and “under common control with”) as used with
respect to a Party means (a) in the case of a corporate entity,
direct or indirect ownership of voting securities entitled to cast
more than fifty percent (50%) of the votes in the election of
directors or (ii) in the case of a non-corporate entity, direct or
indirect ownership of more than fifty percent (50%) of the voting
securities with the power to direct the management and policies of
such entity.
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1.3
“Collaboration Compound” shall mean a chemical entity that is synthesized
solely by a Party or jointly by the Parties (or on behalf of a
Party or the Parties) in the course of the Research Program during
the Research Term that [***].
1.4
“Collaboration Know-How” shall mean any Information or Invention, to the
extent directed to a Collaboration Compound or a method of
making or using a Collaboration Compound, generated or conceived
solely by a Party (or on its behalf) or jointly by the Parties (or
on their behalf) in the course of the Research Program during the
Research Term.
1.5
“Collaboration Patents” shall mean Patents first filed after the
Effective Date with claims or portions thereof, to the extent that
they describe or claim a Collaboration Compound or a method of
making or using a Collaboration Compound, where such Invention is
conceived solely by a Party (or on its behalf) or jointly by the
Parties (or on their behalf) in the course of the Research Program
during the Research Term; provided that any Patent with the same
disclosure as an Idenix Patent described in Section 1.22(a) or a
Metabasis Patent described in Section 1.38(a), such as a renewal,
division, continuation (in whole), or request for continued
examination (RCE), reissue, reexamination or the like, will be
included in Section 1.22(a) or Section 1.38(a), as applicable,
rather than this Section 1.5.
1.6
“Collaboration Technology” shall mean Collaboration Know-How and
Collaboration Patents.
1.7
“Combination Therapy” shall mean a fixed dose product containing more
than one (1) active pharmaceutical ingredient.
[***]
1.8
“Committee” shall mean the joint research committee
established to facilitate the Research Program as more fully
described in Section 2.1.
1.9
“Confidential Information” shall have the meaning given such term in
Section 7.1.
1.10
“Confidentiality Agreement” shall mean the confidentiality agreement, dated
March 29, 2006, by and between the Parties.
1.11
“Control” shall mean, with respect to any Information,
Patent or other intellectual property right, possession by a Party
of the ability (whether by ownership, license or otherwise) to
grant access, a license or a sublicense to such Information or
intellectual property right without violating the terms of any
agreement or other arrangement with any Third Party (before taking
into account the effect of any licenses granted by such Party to
the other Party under this Agreement but after taking into account
the effect of Section 9.1(a)). For the avoidance of
doubt, any Information, Patent or other intellectual property right
that a Party licenses under this Agreement to the other Party shall
not be deemed to be under the “Control” of such other
Party.
1.12
“Development Candidate” shall have the meaning provided in
Section 4.1.
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1.13
“Failed Development Candidate” shall have the meaning provided in
Section 5.4.
1.14
“Field” shall
mean the treatment of chronic hepatitis C viral infections in
humans.
1.15
“First Commercial Sale” shall mean, with respect to any Product, the
first sale in a country after the governing health regulatory
authority of such country has granted Regulatory Approval.
For purposes of clarification, the first sale for end use or
consumption of a Product in a country after conditional approval
has been granted will constitute a First Commercial Sale for
purposes of this Agreement.
1.16
“FTE” shall
mean the equivalent of a full-time scientist’s work time over
a [***] (including normal vacations, sick days and
holidays).
1.17
“HepDirect Technology” shall mean (a) (i) any and all [***] and/or (ii)
any method of making or using any of the foregoing (this clause
(a), “ HepDirect Base Technology ”); which (b)
[***].
1.18
“Idenix Core Patent” shall mean any Patent listed in Exhibit
A .
1.19
“Idenix Indemnitee” shall have the meaning provided in
Section 11.2.
1.20
“Idenix Know-How” shall mean any (a) Information or
Invention, to the extent directed to any Idenix Nucleoside or
Collaboration Compound or a method of making or using an Idenix
Nucleoside or Collaboration Compound, that is Controlled by Idenix
as of the Effective Date, (b) Information or Invention, to the
extent directed to any Idenix Nucleoside or a method of making or
using an Idenix Nucleoside, that first becomes Controlled by Idenix
during the Research Term, and (c) Information or Invention, to the
extent directed to a Collaboration Compound or a method of making
or using a Collaboration Compound, that first becomes Controlled by
Idenix after the Research Term but prior to the First Commercial
Sale of any Product that contains such Collaboration
Compound. Notwithstanding the foregoing, subsection (b)
does not include any Information or Invention to the extent
directed to a Collaboration Compound or a method of making or using
a Collaboration Compound. For purposes of clarity, Idenix
Know-How does not include Metabasis Know-How.
1.21
“Idenix Nucleoside” shall mean either of the [***] nucleosides, the
[***] is specifically identified on Schedule I
to the Research Plan as of the Effective Date and [***] shall be
specified by Idenix in writing to Metabasis within [***] after the
Effective Date, subject to written approval by Metabasis, not to be
unreasonably withheld or delayed, and Schedule I to
the Research Plan shall be automatically amended to include
[***].
1.22
“Idenix Patents” shall mean (a) Patents with claims or portions
thereof, to the extent directed to any Invention that is an Idenix
Nucleoside or Collaboration Compound or a
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method of making or using an Idenix
Nucleoside or Collaboration Compound, where such Patents are
Controlled by Idenix as of the Effective Date, (b) Patents with
claims or portions thereof, to the extent directed to any Invention
that is an Idenix Nucleoside or a method of making or using an
Idenix Nucleoside, where such Invention first becomes Controlled by
Idenix during the Research Term (provided that any such Patent with
the same disclosure as a Patent described in subsection (a),
such as a renewal, division, continuation (in whole), or request
for continued examination (RCE), reissue, reexamination or the
like, will be included in subsection (a) rather than
subsection (b)) and (c) Patents with claims or portions
thereof, to the extent directed to any Invention that is a
Collaboration Compound or a method of making or using a
Collaboration Compound, where such Invention first becomes
Controlled by Idenix after the Research Term but prior to the First
Commercial Sale of any Product that contains such Collaboration
Compound. Notwithstanding the foregoing, subsection (b),
does not include any claims of such Patents or portions thereof to
the extent directed to any such Invention that is a Collaboration
Compound or a method of making or using a Collaboration
Compound. For purposes of clarity, Idenix Patents do not
include Metabasis Patents. The Idenix Patents existing on the
Effective Date are listed on Exhibit C .
1.23
“Idenix Technology” shall mean the Idenix Know-How and Idenix
Patents.
1.24
“IND” shall
mean an Investigational New Drug application, Clinical Study
Application, Clinical Trial Exemption, or similar application or
submission for approval to conduct human clinical investigations
filed with or submitted to a Regulatory Authority in conformance
with the requirements of such Regulatory Authority.
1.25
“Information” shall mean all tangible and intangible (a)
techniques, technology, practices, trade secrets, inventions
(whether patentable or not), methods, processes of manufacture,
intermediates, dosing regimens, formulations, knowledge, know-how,
skill, experience, test data and results (including
pharmacological, toxicological and preclinical and clinical test
data and results), analytical and quality control data, results or
descriptions, software and algorithms and (b) compositions of
matter, cells, cell lines, assays, animal models and physical,
biological or chemical material.
1.26
“Invention” shall mean any invention, conception, actual
reduction to practice, constructive reduction to practice, process,
method, use, composition of matter, article of manufacture,
discovery or finding, whether or not patentable.
1.27
“Joint Invention” shall mean any Invention conceived jointly by
the Parties (or on their behalf) in the course of the Research
Program during the Research Term; but excluding, in each case,
Collaboration Technology, Idenix Technology and Metabasis
Technology.
1.28
“Joint Patents” shall mean Patents claiming any Joint
Invention.
1.29
“Joint Patent Counsel” shall have the meaning provided in
Section 9.2(d)(i).
1.30
“Joint Technology” shall mean Joint Inventions and Joint
Patents.
1.31
“Losses” shall have the meaning provided in
Section 11.1.
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1.32
“Major European Market ” shall mean: (a) any [***] of the
following countries: [***]; or (b) [***].
1.33
“Major Market” shall mean the [***].
1.34
“Materials” shall have the meaning provided in
Section 3.8.
1.35
“Metabasis Core Patents” shall mean any Patent listed in Exhibit
B .
1.36
“Metabasis Indemnitee” shall have the meaning provided in
Section 11.1.
1.37
“Metabasis Know-How” shall mean any (a) Information or
Invention, to the extent directed to HepDirect Technology or
Collaboration Compound or a method of making or using HepDirect
Technology or a Collaboration Compound, that is Controlled by
Metabasis as of the Effective Date and (b) Information or
Invention, to the extent directed to HepDirect Technology or a
method of making or using HepDirect Technology, that first becomes
Controlled by Metabasis during the Research Term.
Notwithstanding the foregoing, subsection (b) does not include
any Information or Invention to the extent directed to a
Collaboration Compound or a method of making or using a
Collaboration Compound. For purposes of clarity, Metabasis
Know-How does not include Idenix Know-How.
1.38
“Metabasis Patents” shall mean (a) Patents with claims or portions
thereof, to the extent directed to any Invention that is HepDirect
Technology or Collaboration Compound or a method of making or using
HepDirect Technology or a Collaboration Compound, where such
Patents are Controlled by Metabasis as of the Effective Date, and
(b) Patents with claims or portions thereof, to the extent directed
to any Invention that is HepDirect Technology or a method of making
or using HepDirect Technology, where such Invention first becomes
Controlled by Metabasis during the Research Term (provided that any
such Patent with the same disclosure as a Patent described in
subsection (a), such as a renewal, division, continuation (in
whole), or request for continued examination (RCE), reissue,
reexamination or the like, will be included in subsection (a)
rather than subsection (b)). Notwithstanding the
foregoing, subsection (b) does not include any claims of such
Patents or portions thereof to the extent directed to any such
Invention that is a Collaboration Compound or a method of making or
using a Collaboration Compound. For purposes of clarity,
Metabasis Patents do not include Idenix Patents. The
Metabasis Patents existing on the Effective Date are listed on
Exhibit D .
1.39
“Metabasis Technology” shall mean the Metabasis Know-How and Metabasis
Patents.
1.40
“NDA” shall
mean a New Drug Application (as more fully defined in 21 C.F.R.
314.5 et seq. ) and all amendments and supplements thereto
filed with the FDA, or the equivalent application filed with any
equivalent agency or governmental authority outside the United
States of America (including any supra-national agency such as in
the European Union), including all documents, data, and other
information concerning a pharmaceutical product which are necessary
for gaining Regulatory Approval to market and sell such
pharmaceutical product.
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1.41
“Net Sales” shall mean, with respect to any Product, the
gross invoiced sales price of such Product by Idenix and
Sublicensees to Third Parties which are not Sublicensees (provided
that, if any Sublicensee is the end user of such Product, the
amount included in Net Sales shall be deemed to be the amount that
would be billed to a Third Party end user in an arm’s length
transaction), less the following deductions to the extent included
in the gross invoiced sales price for such Product or otherwise
directly paid or incurred by Idenix or Sublicensees with respect to
the sale of such Product:
(a)
normal and customary trade and
quantity discounts, credits and allowances actually allowed and
properly taken directly with respect to sales of such
Product;
(b)
amounts repaid or credited by reason
of rejections, recalls, returns, rebates, government mandated
rebates, and allowances;
(c)
chargebacks and other amounts paid
on sale or dispensing of such Product;
(d)
retroactive price reductions that
are actually allowed or granted;
(e)
tariffs, duties, excise, sales,
value-added or other taxes (other than taxes based on
income);
(f)
cash discounts for timely
payment;
(g)
delayed ship order
credits;
(h)
discounts pursuant to patient
discount programs; and
(i)
freight, shipping and insurance
charges.
In the event a Product (for purposes
of this paragraph, the “relevant Product”) comprises a
Development Candidate and an additional active pharmaceutical
ingredient sold in a country in combination for use as a fixed-dose
Product as a Combination Therapy, and both a Product comprising the
Development Candidate as the sole active ingredient and a
pharmaceutical product containing such additional active
pharmaceutical ingredient as the sole active ingredient are sold
separately in such country, the Net Sales for the relevant Product
in such country shall be calculated by multiplying Net Sales in
such country (as would otherwise be determined in accordance with
this definition of “Net Sales” (i.e., without giving
effect to this paragraph or the immediately following paragraph))
by the fraction A/(A+B), where A is the gross invoiced sales price
in such country of the Product comprising the Development Candidate
as the sole active ingredient (when sold separately from the
Combination Therapy), and B is the gross invoiced sales price in
such country of the pharmaceutical product comprising the
additional active pharmaceutical ingredient as the sole active
ingredient (when sold separately from the Combination Therapy).
Notwithstanding the foregoing, the fractional adjustment set forth
in this paragraph shall not apply (and the fractional adjustment
and procedures in the immediately following paragraph shall apply
instead) in the event actual sales of the separate pharmaceutical
product comprising the additional active pharmaceutical ingredient
as the sole active ingredient are not more than incidental in such
country.
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In the event a Product (for purposes
of this paragraph, the “relevant Product”) comprises a
Development Candidate and an additional active pharmaceutical
ingredient sold in a country in combination for use as a fixed-dose
Product as a Combination Therapy, and either a Product comprising
the Development Candidate as the sole active ingredient or the
pharmaceutical product comprising the additional active
pharmaceutical ingredient as the sole active ingredient is not sold
separately in such country, the Net Sales for the relevant Product
in such country shall be calculated by multiplying Net Sales in
such country (as would otherwise be determined in accordance with
this definition of “Net Sales” (i.e., without giving
effect to this paragraph or the immediately preceding paragraph))
by the fraction A/(A+B), where A is the fair market value in such
country of the Product comprising the Development Candidate as the
sole active ingredient (when or if it were (as applicable) sold
separately from the Combination Therapy), and B is the fair market
value in such country of the pharmaceutical product comprising the
additional active pharmaceutical ingredient as the sole active
ingredient (when or if it were (as applicable) sold separately from
the Combination Therapy). For purposes of calculating the fraction
specified in the immediately preceding sentence, Idenix shall make
a written proposal to Metabasis, for its review and approval, of
the fair market value of each component of such fraction,
reasonably supported by written documentation. If the Parties are
unable to reach agreement on such matters, the provisions of
Section 12.6 shall apply.
For clarification purposes, there
shall be no fractional adjustment in the calculation of Net Sales
(i.e., no effect shall be given to the immediately preceding two
paragraphs) with respect to any Product comprising a Development
Candidate that is sold together or promoted as a combination with a
separate pharmaceutical product (including any interferon) for
co-administration.
1.42
“Notice Date” shall have the meaning provided in
Section 12.6(b).
1.43
“Patents” shall mean (a) all patents, certificates of
invention, applications for certificates of invention, priority
patent filings and patent applications, including without
limitation patent applications under the Patent Cooperation and the
European Patent Convention, together with (b) any renewal,
division, continuation (in whole or in part), or request for
continued examination (RCE) of any of such patents, certificates of
invention and patent applications, and any and all patents or
certificates of invention issuing thereon, and any and all
reissues, reexaminations, extensions, divisions, renewals,
substitutions, confirmations, registrations, revalidations,
revisions, and additions of or to any of the foregoing, and any
foreign counterparts of any of the foregoing and any other patents
and patent applications claiming priority back to any of the
foregoing.
1.44
“Phase 1 Clinical Trial” shall mean a human clinical trial in any
country that is carried out to obtain data that can be submitted to
the FDA in satisfaction of the requirements of 21 CFR
312.21(a).
1.45
“Phase 2 Clinical Trial” shall mean a human clinical trial in any
country that is carried out to: (i) determine efficacy and dose
range; and (ii) obtain data that can be submitted to the FDA in
satisfaction of the requirements of 21 CFR 312.21(b).
Notwithstanding the foregoing, Phase 2 Clinical Trial shall not
include a phase 1b/2a clinical trial that includes a treatment
period less than twelve (12) weeks in length.
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1.46
“Phase 3 Clinical Trial” shall mean a pivotal human clinical trial in
any country that is carried out to obtain data that can be
submitted to the FDA in satisfaction of the requirements of 21 CFR
312.21(c).
1.47
“Process Chemistry Know-How” shall mean any Information or Invention, to the
extent directed to a process chemistry improvement to HepDirect
Technology, that first becomes Controlled by Idenix following
receipt of the information with respect to a Development Candidate
pursuant to Section 3.4 but prior to the First Commercial Sale of
any Product that contains such Development Candidate.
1.48
“Process Chemistry Patents” shall mean Patents with claims or portions
thereof, to the extent directed to any Invention that is a process
chemistry improvement to HepDirect Technology, that first becomes
Controlled by Idenix following receipt of the information with
respect to a Development Candidate pursuant to Section 3.4 but
prior to the First Commercial Sale of any Product that contains
such Development Candidate.
1.49
“Process Chemistry Technology” shall mean Process Chemistry Know-How and
Process Chemistry Patents.
1.50
“Product” shall mean any preparation in final form
containing a Development Candidate for sale by prescription,
over-the-counter or any other method.
1.51
“Project Leader” shall have the meaning provided in
Section 2.5.
1.52
“Proof of Concept” shall have the meaning provided in
Schedule II to the Research Plan.
1.53
“Proposed Resolution Deadline” shall have the meaning provided in Section
12.6(c).
1.54
“Regulatory Approval” shall mean any and all approvals (including
price and reimbursement approvals, if required), licenses,
registrations, or authorizations of any Regulatory Authority in a
particular jurisdiction that are necessary for the manufacture,
use, storage, import, transport and/or sale of a Product in such
jurisdiction in accordance with applicable laws.
1.55
“Regulatory Authority” shall mean any national or supranational
governmental authority, including, without limitation, the FDA and
the EMEA, that has responsibility in any country or other
regulatory jurisdiction over the development and/or
commercialization of Products. For purposes of this
Agreement, “FDA” shall mean the U.S. Food and Drug
Administration or any successor agency, and “EMEA”
shall mean the European Medicines Agency or any successor
agency.
1.56
“Research Plan” means the plan (the initial form of which has
been agreed upon in writing by the Parties as set forth in the
letter agreement dated as of the Effective Date) that sets out the
research work to be performed by Metabasis and Idenix in conducting
the Research Program, as such plan may be amended or modified by
the Committee or by mutual written agreement of the Parties as
contemplated under this Agreement.
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1.57
“Research Program” shall mean the research activities undertaken by
either or both of the Parties as set forth in Article 3
and the Research Plan.
1.58
“Research Term” shall mean the duration of the Research Program,
and “Initial Research Term ” and
“Extended Research Term” shall have the
respective meanings given such terms in
Section 3.6(a).
1.59
“Royalty-Extending Patent” shall mean any Specific Claim if a license to
such Specific Claim granted pursuant to Section 4.2(a)(iii)
provides Idenix or its Sublicensee with market exclusivity for the
applicable Development Candidate or Product and such market
exclusivity is due solely to the license granted to such Specific
Claim.
1.60
“Royalty Term” shall mean, in the case of any Product in any
country, the period of time commencing on the First Commercial Sale
of such Product in such country and ending upon the later of (a)
[***] after the date of First Commercial Sale of such Product in
such country, and (b) the expiration of the last to expire of
(i) the Metabasis Patents, Idenix Patents, Collaboration Patents,
or Joint Patents containing a Valid Claim that would, absent
ownership of or a license to such Patent, be infringed by the use
or sale of such Product or the Development Candidate therein or by
the manufacture of such Product or the Development Candidate
therein (if ownership of or a license to such a Patent containing a
Valid Claim of method of manufacturing such Development Candidate
or Product would provide market exclusivity for the applicable
Product) or (ii) any Royalty-Extending Patents.
1.61
“Specific Claims” shall have the meaning provided in
Section 4.2(a)(iii).
1.62
“Sublicensee” shall mean an Affiliate or Third Party to which
Idenix has (a) sublicensed some or all of Metabasis Technology or
Collaboration Technology or any Royalty-Extending Patent, or (b)
licensed some or all of Idenix Technology or Joint Technology to
develop, make, have made, use, sell, have sold, offer for sale or
import Development Candidates and Products in the Field during the
Term.
1.63
“Term” shall
have the meaning provided in Section 10.1.
1.64
“Territory” shall mean worldwide.
1.65
“Third Party” shall mean an entity other than Idenix and its
Affiliates, and Metabasis and its Affiliates.
1.66
“Third Party Patent” shall have the meaning provided in
Section 5.5(b)(iii).
1.67
“Title 11” shall have the meaning provided in
Section 10.7.
1.68
“Valid Claim” shall mean a claim of (a) an issued and
unexpired patent or a supplementary protection certificate, which
claim has not been held invalid or unenforceable by a court or
other government agency of competent jurisdiction from which no
appeal can be or has been taken and has not been held or admitted
to be invalid or unenforceable through re-examination or
disclaimer, opposition procedure, nullity suit or otherwise, or (b)
a pending patent application; provided, however , that if a
claim of a pending patent application shall not
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have issued within [***] (or in
Japan, [***] after the earliest filing date from which such claim
takes priority, such claim shall not constitute a Valid Claim for
the purposes of this Agreement unless and until a patent issues
with such claim.
2.
RESEARCH PROGRAM
GOVERNANCE
2.1
Joint Research Committee. Promptly after the Effective Date, the
Parties will form a Joint Research Committee (the
“Committee” ) composed of an equal number
of representatives of each of Idenix and Metabasis. One
member of the Committee shall be selected to act as the chairperson
of the Committee, with each chairperson acting for a term of twelve
(12) months. The chairperson shall be selected
alternately by Metabasis and Idenix, and [***] shall designate the
first chairperson. The purpose of the Committee is to ensure
that the goals and purpose of this Agreement are being carried out
in a timely and effective manner.
2.2
Meetings. The
Committee shall meet at least [***] times per year during the
Research Term or at such greater frequency as the Committee
agrees. Such meetings may be conducted by videoconference,
teleconference or in person, as agreed by the Parties, and the
Parties shall agree upon the time of meetings. In-person
meetings shall alternate between the facilities of Idenix in
Cambridge, Massachusetts, and the facilities of Metabasis in La
Jolla, California. No Committee meeting may be conducted
unless at least one representative of each Party is
participating. Each Party shall bear its own expenses related
to the attendance of such meetings by its representatives. A
reasonable number of additional representatives of a Party may
attend meetings of the Committee in a non-voting
capacity.
2.3
Minutes. The
hosting Party shall have responsibility for preparing definitive
minutes of each Committee meeting, a draft of which shall be
circulated for comment to all members of the Committee within ten
(10) business days after the relevant meeting. Such
minutes shall provide a description, in reasonable detail, of the
Research Program progress to date, and of the discussions at the
meeting, a list of any actions or determination approved by the
Committee and any disagreements not resolved by the
Committee. The Project Leaders shall discuss any comments on
such minutes and finalize the minutes by no later than
30 business days after the meeting. Any disagreement on
the minutes shall be resolved in accordance with
Section 2.4.
2.4
Committee Decision-Making. All decisions of the Committee shall be
unanimous, with the representatives of each Party collectively
having one (1) vote. If the Committee is unable to decide or
resolve unanimously any matter properly presented to it for action,
then at the written request of either Party, the issue shall be
referred to Metabasis’ Executive Vice President of Research
and Development and Idenix’s Senior Vice President, Biology,
who shall attempt in good faith to resolve such issue as promptly
as practicable. If such officers are unable to resolve such
issue within [***], then at the written request of either Party,
the issue shall be referred to the Chief Executive Officer of
Metabasis and the Chief Executive Officer of Idenix for
resolution. Such officers of the Parties will meet promptly
thereafter in order to resolve such issue as promptly as
practicable.
2.5
Project Leaders .
Idenix and Metabasis each shall appoint a person (a
“Project Leader” ) from the Committee to
coordinate its part of the Research Program. The
Project
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Leaders shall be the primary contact
between the Parties with respect to the Research Program.
Each Party shall notify the other Party as soon as practicable upon
changing this appointment.
3.
RESEARCH PROGRAM
3.1
General. Metabasis
and Idenix shall engage in the Research Program upon the terms and
conditions set forth in this Agreement. The activities to be
undertaken in the course of Research Program are set forth in the
Research Plan which may be amended from time to time upon the
mutual written agreement of authorized representatives of the
Parties.
3.2
Conduct of Research. Subject to the terms and conditions of this
Agreement, each Party shall be responsible for managing and
controlling its respective research obligations under the Research
Plan. Each Party shall conduct the Research Program in good
scientific manner, and in compliance in all material respects with
all requirements of applicable laws, rules and regulations.
Each Party hereby certifies that it will not and has not employed
or otherwise used in any capacity the services of any person
debarred under Section 21 USC 335a in performing any services
hereunder. Each Party shall proceed diligently and in a
timely manner with the work set out in the Research Program by
using commercially reasonable efforts to carry out the activities
assigned to such Party under the Research Program with sufficient
skills and experience as are required to accomplish the Research
Program in accordance with the terms of this Agreement and Research
Plan.
3.3
Research Commitment; Metabasis FTEs. During the Research Term, each Party shall
use its commercially reasonable efforts to carry out the activities
assigned to such Party under the Research Program in accordance
with such plan and the terms and conditions of this
Agreement. Without limiting the generality of the foregoing,
Metabasis shall devote to the performance of its responsibilities
under the Research Plan [***] FTEs per year during the Research
Term, all of whom shall be funded by Idenix in accordance with
Section 5.2. For purposes of clarification, in no event
shall Metabasis be obligated to devote to the Research Program more
than the number of FTEs being funded by Idenix under this
Agreement.
3.4
Exchange of Information. Upon execution of this Agreement, and from time
to time as necessary during the Research Term, Metabasis shall
disclose to Idenix all Collaboration Know-How not previously
disclosed and such Metabasis Know-How as is reasonably necessary,
in Metabasis’ reasonable judgment, for the performance by
Idenix of its responsibilities under the Research Program.
Following designation of a Development Candidate pursuant to
Section 4.1, Metabasis shall disclose to Idenix all Collaboration
Know-How regarding such Development Candidate not previously
disclosed and such Metabasis Know-How as is reasonably necessary
for the manufacture, use (including use for development) or sale of
Development Candidates and Products in the Field. Upon
execution of this Agreement, and from time to time as necessary
during the Research Term, Idenix shall disclose to Metabasis all
Collaboration Know-How not previously disclosed and such Idenix
Know-How as is reasonably necessary for the performance by
Metabasis of its responsibilities under the Research Program.
Nothing herein shall require either Party to disclose information
that is subject to bona fide confidentiality obligations to
a Third Party.
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3.5
Records and Reports. Metabasis and Idenix shall each maintain
records, in sufficient detail and in good scientific manner
appropriate for patent and regulatory purposes, which shall fully
and properly reflect all work done and results achieved in the
performance of the Research Program by such Party. Within
[***] during the Research Term, each Party shall provide to the
other Party a written progress report which shall summarize (a)
with respect to reports provided by Metabasis, data and results
regarding the Collaboration Compound with respect to each Idenix
Nucleoside that Metabasis identifies as most likely to meet the
Proof of Concept or Development Candidate criteria and (b) with
respect to reports provided by Idenix, test data and results
regarding Collaboration Compounds tested by Idenix to determine
whether or not such Collaboration Compounds meet the Proof of
Concept or Development Candidate criteria. Without limiting
the generality of the foregoing, each such progress report will
disclose any Collaboration Technology that such Party works on
during such calendar quarter.
3.6
Research Term.
(a)
Research Term.
Except as otherwise provided in Article 10, the Research Term
shall commence on the Effective Date and continue for a period of
two (2) years (the “Initial Research
Term” ). Thereafter, the Parties may extend the
Research Term by mutual written agreement of the authorized
representative of the Parties, and shall, in such case, amend the
Research Plan as applicable. Any such extension of the
Research Term shall be referred to herein as an
“Extended Research Term.”
(b)
Early Termination.
Notwithstanding anything to the contrary in this Section 3.6,
Idenix may, with or without cause and in its sole discretion,
terminate the Research Term:
(i)
effective as of the first
anniversary of the Effective Date upon written notice to Metabasis
given no later than [***] prior to the first anniversary of the
Effective Date; or
(ii)
at any time after designation of the
first Development Candidate in accordance with Section 4.1 and
payment of the corresponding milestone payment specified in
Section 5.4, by providing Metabasis with [***] written notice
to such effect.
3.7
Use of Subcontractors. Each Party shall be entitled to utilize the
service of Third Parties to perform their respective Research
Program activities only upon the prior written consent of the other
Party (not to be unreasonably withheld) or as specifically set
forth in the Research Plan. Notwithstanding any such consent,
each Party shall remain at all times responsible for the
performance of its respective responsibilities under the Research
Program and shall obtain the written agreement of each such Third
Party, prior to the time such Third Party initiates work, to assign
ownership of Inventions made in the course of Research Program
activities to such Party, and such Party will make such further
assignment of such Inventions as provided under Article 9
hereof.
3.8
Materials. In order
to facilitate the Research Program, either Party may provide to the
other Party certain biological materials or chemical compounds
Controlled by the
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supplying Party, including, but not
limited to, Collaboration Compounds (collectively,
“Materials” ) for use by the other Party
in furtherance of the Research Program. Except as otherwise
provided under this Agreement, all such Materials delivered to the
other Party will remain the sole property of the supplying Party,
will be used only in furtherance of the conduct of the Research
Program and, if applicable, the development, manufacture or
commercialization of Products in accordance with this Agreement,
will not be used or delivered to or for the benefit of any Third
Party without the prior written consent of the supplying Party, and
will be used in compliance with all applicable laws, rules and
regulations. The Materials supplied under this Agreement must
be used with prudence and appropriate caution in any experimental
work because not all of their characteristics may be known.
Except as expressly set forth herein, THE MATERIALS ARE PROVIDED
“AS IS” AND WITHOUT ANY REPRESENTATION OR WARRANTY,
EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY IMPLIED
WARRANTY OF MERCHANTABILITY OR OF FITNESS FOR ANY PARTICULAR
PURPOSE OR ANY WARRANTY THAT THE USE OF THE MATERIALS WILL NOT
INFRINGE OR VIOLATE ANY PATENT OR OTHER PROPRIETARY RIGHTS OF ANY
THIRD PARTY.
4.
DESIGNATION OF DEVELOPMENT
CANDIDATES; LICENSE GRANTS; DEVELOPMENT AND
COMMERCIALIZATION
4.1
Designation of Development Candidate. At any time during the Research Term or
within [***] after its expiration, Idenix may, by written notice to
Metabasis, designate one (1) or more Collaboration Compounds that
possess the properties specified in Schedule III
to the Research Plan as “Development
Candidates” for purposes of this
Agreement.
4.2
License Grants.
(a)
By Metabasis.
(i)
Collaboration Technology and Joint Technology.
Subject to the terms and
conditions of this Agreement, Metabasis hereby grants to Idenix an
exclusive (even as to Metabasis), royalty-bearing license in the
Territory, with the right to sublicense through multiple tiers of
sublicense, under Metabasis’ interest in Collaboration
Technology and Joint Technology, solely (A) to perform
Idenix’s obligations under the Research Program during the
Research Term and (B) to develop, make, have made, use, sell,
have sold, offer for sale and import Development Candidates and
Products in the Field during the Term; provided, however,
that Metabasis retains such rights under Metabasis’ interest
in Collaboration Technology and Joint Technology solely as are
necessary to perform its obligations under the Research
Program.
(ii)
Metabasis Technology. Subject to the terms and conditions of
this Agreement, (A) Metabasis hereby grants to Idenix a
non-exclusive, royalty-bearing license in the Territory, without
the right to sublicense (except that Idenix may subcontract), under
Metabasis Technology Controlled by Metabasis solely to perform
Idenix’s obligations under the Research Program during the
Research Term, and (B) Metabasis hereby grants to Idenix a
non-exclusive, royalty-bearing license in the Territory, with the
right to sublicense as described below through multiple tiers of
sublicense, under Metabasis Technology Controlled by
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Metabasis solely to develop, make,
have made, use, sell, have sold, offer for sale and import
Development Candidates and Products in the Field during the
Term. Idenix shall have the right to sublicense its rights
under Section 4.2(a)(ii)(B) only in conjunction with a
sublicense of its rights under Section 4.2(a)(i), and each
such sublicense under Section 4.2(a)(ii)(B) shall have the
same scope as the sublicense granted to the same Sublicensee under
Section 4.2(a)(i) (provided, however, that, if the sublicense
granted to the same Sublicensee under Section 4.2(a)(i) were
to expire solely due to expiration of the Collaboration Technology
and Joint Technology with respect to the relevant Product and
relevant country prior to the expiration of the Metabasis
Technology with respect to such Product and country, the sublicense
under Section 4.2(a)(ii)(B) shall continue for the remainder of the
Royalty Term with respect to such Product and country).
(iii)
Limited License Grant. With respect to each Development
Candidate, in the event that the development, making, having made,
use or import of such Development Candidate or the development,
making, having made, use, offer for sale, sale, having sold or
import by Idenix or Sublicensees of such Development Candidate
would infringe during the Term a Valid Claim of any issued Patent
with claims or portions thereof to the extent directed to any
Invention that is HepDirect Base Technology, where such Invention
first becomes Controlled by Metabasis after the Research Term but
prior to the First Commercial Sale of such Development Candidate
(provided that any such Patent with the same disclosure as a Patent
included in Metabasis Patents, Collaboration Patents or Joint
Patents, such as a renewal, division, continuation (in whole), or
request for continued examination (RCE), reissue, reexamination or
the like, will be included in Metabasis Patents, Collaboration
Patents or Joint Patents, and not subject to this
Section 4.2(a)(iii)) (the “Specific
Claims” ), which Patent is not a Metabasis Patent,
Collaboration Patent or Joint Patent, then, subject to the
terms and conditions of this Agreement, Metabasis hereby grants to
Idenix, a non-exclusive, royalty-bearing (included within the
royalties as set forth in Section 5.5) license in the
Territory, including the right to sublicense as described below
through multiple tiers of sublicense, under such Specific Claims
solely to develop, make, have made, use, sell, offer for sale, have
sold or import such Development Candidate in the Field during the
Term. Idenix shall have the right to sublicense its rights
under this Section 4.2(a)(iii) only in conjunction with a
sublicense of its rights under Section 4.2(a)(i), and each
sublicense under this Section 4.2(a)(iii) shall have the same scope
as the sublicense granted to the same Sublicensee under Section
4.2(a)(i) (provided, however, that, if the sublicense granted to
the same Sublicensee under Section 4.2(a)(i) were to expire
solely due to expiration of the Collaboration Technology and Joint
Technology with respect to the relevant Development Candidate and
relevant country prior to the expiration of the Specific Claims
with respect to such Development Candidate and country, the
sublicense under this Section 4.2(a)(iii) shall continue for the
remainder of the Royalty Term with respect to such Development
Candidate and country). Following designation by Idenix of
each Development Candidate and continuing until First Commercial
Sale of such Development Candidate, Metabasis shall not grant to
any Affiliate or Third Party any right or license under any
applicable Specific Claim such that Metabasis would no longer
Control the Specific Claim.
(b)
By Idenix. Subject to the
terms and conditions of this Agreement, Idenix hereby grants to
Metabasis (i) a non-exclusive, royalty-free license in the
Territory, without the right to sublicense, under Idenix Technology
solely to perform Metabasis’ obligations under the Research
Program during the Research Term, and (ii) a non-exclusive,
royalty-free, perpetual license, with the right to sublicense
through multiple tiers of sublicense, under Process
14
Chemistry Technology to develop,
make, have made, use, sell, have sold, offer for sale and import
products other than Collaboration Compounds, Development Candidates
and Product.
4.3
Development and Commercialization. Subject to the terms and conditions of
this Agreement, Idenix shall control, and be solely responsible for
the costs associated with, the worldwide preclinical and clinical
development, registration and commercialization of Development
Candidates and Products. Without limiting the generality of
the foregoing, Idenix shall be responsible for the worldwide supply
of all Development Candidates and Products necessary for the
foregoing activities.
4.4
Diligence Obligations. Idenix agrees to use commercially reasonable
efforts (directly and/or through one or more Sublicensees) to
develop for sale in the Major Markets and commercialize in each of
the Major Markets at least [***] Development Candidate or Product
in the Field.
(a)
In the event that Idenix:
(i) is not developing for sale in the Major Markets or
commercializing in a particular Major Market at least [***]
Development Candidate or Product in the Field, or (ii) decides
that it will not develop for sale in the Major Markets or
commercialize in a particular Major Market at least [***]
Development Candidate or Product in the Field, then Idenix shall
provide Metabasis with prompt written notice thereof.
(b)
In addition, if Metabasis in good
faith believes that Idenix is not using its commercially reasonable
efforts to develop for sale in the Major Markets or commercialize
in a particular Major Market at least [***] Development Candidate
or Product in the Field, Metabasis may provide Idenix with written
notice thereof, in which event Idenix will have [***] after the
date of such notice in which to reasonably demonstrate to Metabasis
that Idenix is meeting such diligence obligation.
(c)
If Idenix provides notice to
Metabasis pursuant to Section 4.4(a) that it is not and will not
meet its diligence obligation with respect to one or more Major
Markets, or fails to reasonably demonstrate to Metabasis pursuant
to Section 4.4(b) that it is meeting its diligence obligation
with respect to [***] or more Major Markets within [***] after
notice from Metabasis of failure to meet such diligence obligation,
then (i) this Agreement shall terminate with respect to such Major
Market(s) in which Idenix is not using its commercially reasonable
efforts to develop or commercialize at least [***] Development
Candidate or Product in the Field, and (ii)
“Territory” shall be redefined to be
[***]. With respect to Section 4.4(a), Idenix shall not be in
breach of this Agreement under Section 10.2(b) unless it provides
notice to Metabasis pursuant to Section 4.4(a) that it is not and
will not conduct development and commercialization of at least
[***] Development Candidate or Product in the Field in at least one
Major Market. With respect to Section 4.4(b), Idenix shall
not be in breach of this Agreement under Section 10.2(b) unless
Metabasis in good faith believes that Idenix is not using its
commercially reasonable efforts to develop or commercialize at
least [***] Development Candidate or Product in the Field in at
least [***] Major Market, Metabasis provides Idenix with written
notice thereof, and Idenix fails to reasonably demonstrate to
Metabasis within [***] after the date of such notice that Idenix is
meeting such diligence obligation in at least [***] of the Major
Markets.
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4.5
Disclosure Regarding Idenix Efforts. Idenix will keep Metabasis appropriately
informed about Idenix’s research, development, clinical trial
progress and commercialization efforts with respect to Development
Candidates and Products. Without limiting the generality of
the foregoing, Idenix shall provide Metabasis with prompt written
notice of the following:
(a)
filing of any IND for a Development
Candidate or Product;
(b)
initiation of a Phase 1
Clinical Trial, Phase 2 Clinical Trial or Phase 3
Clinical Trial of a Development Candidate or Product;
(c)
filing of any application for
Regulatory Approval with respect to any Product;
(d)
receipt of Regulatory Approval for
any Product; and
(e)
any other significant development or
commercialization plans, activities or results with respect to
Development Candidates or Products.
In addition, Idenix shall provide
Metabasis with [***] written reports summarizing Idenix’s
development and commercialization efforts with respect to
Development Candidates and Products during the applicable [***]
period. The provisions of this Section 4.5 shall survive
expiration or termination of the Research Term for so long as any
license granted to Idenix under Section 4.2(a) remains in
effect.
4.6
Negative Covenants; No Implied Licenses.
(a)
Idenix hereby covenants that it will
not, directly or indirectly (including through any Sublicensee),
conduct clinical development or commercialization activities
pursuant to this Agreement with respect to any Collaboration
Compound that has not been designated or deemed a Development
Candidate pursuant to this Agreement during the Term and Idenix
further acknowledges and agrees that it has no right or license
under Metabasis Technology, Collaboration Technology or Joint
Technology to do any of the foregoing and will not practice any
Idenix Technology Controlled by Idenix, which is directed to any
Collaboration Compound, the method of manufacture of any
Collaboration Compound or method of use of any Collaboration
Compound, to do any of the foregoing. In addition, during the
Term Idenix shall not use or practice any Metabasis Technology or
Specific Claims except as expressly permitted under this
Article 4. In no event shall Idenix (i) create or
synthesize, or attempt to create or synthesize (either itself or
through an Affiliate or Third Party), outside of the Research
Program during the Research Term, any chemical entity that [***];
or (ii) create or synthesize, or attempt to create or synthesize
(either itself or through an Affiliate or Third Party), after
expiration or termination of the Research Term, any chemical entity
that [***]; provided, however, that the restrictions set
forth in Section 4.6(a)(i) and (ii) shall not apply to the
synthesis of Development Candidates or Products for so long as any
license granted to Idenix under Section 4.2(a) remains in
effect. If Idenix creates or synthesizes (either itself or
through an Affiliate or Third Party) any chemical entity
that
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[***] in breach of this
Section 4.6(a), such chemical entity shall automatically be
deemed to be a Collaboration Compound and Development Candidate
subject to the terms of this Agreement.
(b)
Metabasis and its Affiliates shall
not, and shall not grant to any Third Party any rights to, use or
practice Metabasis Technology or Metabasis’ interest in
Collaboration Technology or Joint Technology with respect to the
Idenix Nucleosides, the Collaboration Compounds, Development
Candidates or Products during the Term, other than solely as
necessary to fulfill Metabasis’ obligations under the
Research Plan during the Research Term. Notwithstanding any
other provision of this Agreement to the contrary, but subject to
the licenses granted by Metabasis to Idenix under Section 4.2(a),
Metabasis at all times reserves the exclusive and unrestricted
right to use or practice, and to grant its Affiliates and Third
Parties the right to use or practice, Metabasis Technology for any
purpose other than the development, manufacture or
commercialization of the Idenix Nucleosides, the Collaboration
Compounds, Development Candidates or Products. In addition,
during the Term Metabasis shall not use or practice any Idenix
Technology except as expressly permitted under this
Article 4. In no event shall Metabasis create or
synthesize, or attempt to create or synthesize (either itself or
through an Affiliate or Third Party), outside of the Research
Program during the Research Term, any chemical entity that [***];
or (ii) create or synthesize, or attempt to create or synthesize
(either itself or through an Affiliate or Third Party), after
expiration or termination of the Research Term, any chemical entity
that [***].
(c)
No right or license under any
Patents or Information of either Party is granted or shall be
granted by implication. All such rights or licenses are or
shall be granted only as expressly provided in the terms of this
Agreement.
5.
PAYMENTS
5.1
Upfront Fee.
Idenix shall make a one-time, non-refundable, non-creditable
payment to Metabasis of $2,000,000 within fifteen (15) days
after the Effective Date.
5.2
Research Program FTE Funding. In consideration for Metabasis’
performance of its obligations under the Research Program, upon the
terms and conditions contained herein, Idenix shall fund each FTE
provided by Metabasis pursuant to Section 3.3 at the rate of
[***], which shall be subject to adjustment on an annual basis as
of January 1 of each year, beginning in 2007, by a factor which
reflects any increase in the Consumer Price Index for San Diego
County, California as reported as of January 1 in each applicable
year thereafter when compared to the comparable statistic for
January 1 of the preceding year. During the Research Period,
the first payment under this Section 5.2 shall be made within [***]
after the receipt by Idenix of an invoice from Metabasis for
payment of FTE funding for the period from the Effective Date to
December 31, 2006, and each subsequent payment shall be made on a
quarterly basis within a period of [***] after the receipt by
Idenix of an invoice from Metabasis for payment of FTE funding for
that quarterly
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period. Each invoice shall set
forth information regarding FTEs used by Metabasis on the Research
Program during the applicable quarter.
5.3
Proof of Concept Milestone. Within [***] after written notice by Metabasis
to Idenix of the achievement of the first Proof of Concept, Idenix
shall pay to Metabasis a one-time milestone payment of [***].
This one-time milestone payment shall be paid only once regardless
of the number of times that Proof of Concept is achieved by one or
more Collaboration Compounds.
5.4
Milestone Payments. Idenix shall pay to Metabasis each of the
milestone payments set forth below (whether such milestone is
achieved by Idenix or a Sublicensee):
|
Milestone Event
|
|
Milestone
Payment
|
|
[***]
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
*
[***]
Each of the milestone payments
described in this Section 5.4 shall be payable only [***] for
each Idenix Nucleoside, [***] which are developed or the number of
indications for which Development Candidates or Products based on
such Idenix Nucleoside are developed or commercialized.
Additionally, to the extent that any milestone payment has been
made with respect to a Development Candidate or Product based on a
particular Idenix Nucleoside that is subsequently deemed a Failed
Development Candidate, [***] in connection with the
development