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EXCLUSIVE LICENSE AND RESEARCH COLLABORATION AGREEMENT between IDENIX PHARMACEUTICALS, INC. and METABASIS THERAPEUTICS, INC

Research and Development Agreement

EXCLUSIVE LICENSE AND RESEARCH COLLABORATION AGREEMENT between IDENIX PHARMACEUTICALS, INC. and METABASIS THERAPEUTICS, INC | Document Parties: IDENIX PHARMACEUTICALS, INC | METABASIS THERAPEUTICS, INC You are currently viewing:
This Research and Development Agreement involves

IDENIX PHARMACEUTICALS, INC | METABASIS THERAPEUTICS, INC

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Title: EXCLUSIVE LICENSE AND RESEARCH COLLABORATION AGREEMENT between IDENIX PHARMACEUTICALS, INC. and METABASIS THERAPEUTICS, INC
Governing Law: New York     Date: 3/13/2007
Industry: Biotechnology and Drugs     Sector: Healthcare

EXCLUSIVE LICENSE AND RESEARCH COLLABORATION AGREEMENT between IDENIX PHARMACEUTICALS, INC. and METABASIS THERAPEUTICS, INC, Parties: idenix pharmaceuticals  inc , metabasis therapeutics  inc
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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

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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


 
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