AMENDED AND RESTATED JOINT DEVELOPMENT AND COMMERCIALIZATION AGREEMENT

Exhibit 10.11

Execution Copy

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separately with the Securities and Exchange Commission.

Asterisks denote such omissions.

AMENDED AND RESTATED JOINT DEVELOPMENT AND COMMERCIALIZATION

AGREEMENT

BY AND AMONG

GTC BIOTHERAPEUTICS, INC.

AND

LFB-BIOTECHNOLOGIES S.A.S.U.

AND

LFB/GTC LLC

AND

LFB BIOTECHNOLOGIES INC.

June 30, 2008

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with the Securities and Exchange Commission.

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TABLE OF CONTENTS

 

 

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AMENDED AND RESTATED JOINT DEVELOPMENT

AND COMMERCIALIZATION AGREEMENT

This Amended and Restated Joint Development and Commercialization Agreement (this “ Agreement ”) is entered into as of June 30, 2008 (the “ Restatement Date ”), by and among GTC Biotherapeutics, Inc., a Massachusetts corporation, having offices at 175 Crossing Boulevard, Framingham, Massachusetts 01702, USA (“ GTC ”); LFB Biotechnologies S.A.S.U., a société par actions simplifiée unipersonnelle, having offices at 3, avenue des Tropiques, Les Ulis, 91958 Courtaboeuf, France (“ LFB Biotech ”); LFB/GTC LLC, a New York limited liability corporation, having offices at 175 Crossing Boulevard, Framingham, Massachusetts 01702, USA (“ LFB/GTC LLC ”) and LFB Biotechnologies Inc., a Delaware corporation having a registered office at 2711 Centerville Road, Suite 400, Wilmington, Delaware (“ LFB-US ”). GTC, LFB Biotech, LFB-US and LFB/GTC LLC are sometimes referred to herein individually as a “ Party ” and collectively as the “ Parties .”

INTRODUCTION

A. LFB Biotech and its Affiliates possess certain intellectual property, know-how and skills with respect to processes and purification, expertise in clinical and regulatory affairs, manufacturing, molecular biology and biosecurity, extensive marketing and sales experience in therapeutic products, commercial infrastructure and financial resources.

B. GTC possesses certain intellectual property with respect to the production of transgenic proteins in milk, purification and promoters, know-how and skills in the areas of regulatory affairs, quality systems animal husbandry, milking, biosecurity, molecular biology, embryology, product recovery and purification.

C. GTC and LFB Biotech entered into a Joint Development and Commercialization Agreement effective as of September 29, 2006, as amended by an Amendment Agreement dated as of November 19, 2007 and by a Second Amendment Agreement dated as of May 14, 2008 (as so amended, the “ Original JDA ”) for the purpose of jointly developing and commercializing certain transgenic animal products based on, derived from or incorporating recombinant plasma proteins and monoclonal antibodies (the “ Collaboration ”).

D. LFB Biotech and GTC agreed that the first program to be undertaken pursuant to their Collaboration will be the development and commercialization of an rFVIIa product in respect of which LFB Biotech and its Affiliates have developed certain intellectual property, know how and skills.

E. LFB Biotech and GTC have added three more programs to their Collaboration since the date of the Original JDA, including programs for the development of an antibody to CD20 (the “ CD20 Antibody ”), a recombinant form of coagulation Factor IX (“ rFIX ”) and a recombinant form of the blood protein alpha-1 antitrypsin (“ rhAAT ”).

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F. As contemplated by Section 4.7 of the Original JDA, GTC and LFB Biotech (through its subsidiary LFB-US) have formed a separate legal entity in the form of LFB/GTC LLC to facilitate the continuing Collaboration.

G. LFB Biotech, GTC, LFB/GTC LLC and LFB-US wish to amend and restate the Original JDA to add LFB/GTC LLC and LFB-US as parties and to accurately reflect the reallocation of responsibilities of the Collaboration and the use of LFB/GTC LLC to facilitate the continuing Collaboration.

H. LFB Biotech is a wholly-owned subsidiary of Laboratoire Francais du Fractionnement et des Biotechnologies S.A., a French société anonyme (“ LFB SA ”). LFB-US is a wholly-owned subsidiary of LFB Biotech.

I. As a material inducement for GTC to enter into the Original JDA, GTC and LFB SA entered into a certain Keepwell Agreement concurrently with the execution of the Original JDA, pursuant to which, among other matters, LFB SA agreed to (i) cause LFB Biotech and the Affiliates of LFB Biotech to perform and comply with any relevant obligations under the Original JDA, (ii) be liable for any GTC damages caused by the failure of LFB Biotech or its Affiliates to perform and comply with such obligations, and (iii) indemnify and hold GTC harmless for any such failures.

NOW THEREFORE , in consideration of the foregoing and of the mutual covenants and agreements set forth herein, the Parties hereby agree as follows:

ARTICLE 1

DEFINITIONS

1.1 “ Accounting Standards ” shall mean (a) with respect to GTC and LFB/GTC LLC, United States Generally Accepted Accounting Principles, and (b) with respect to LFB Biotech and LFB-US, International Financial Reporting Standards.

1.2 “ Action ” means any claim, action, cause of action or suit (whether in contract or tort or otherwise), litigation (whether at law or in equity, whether civil or criminal), controversy, assessment, arbitration, investigation, hearing, charge, complaint, demand, notice or proceeding of, to, from, by or before any governmental authority.

1.3 “ Additional MAb Product ” means the Transgenic version of any therapeutic product based on, incorporating or derived from monoclonal antibodies, other than the CD20 Mab Product.

1.4 “ Additional Plasma Product ” means a Transgenic version of any therapeutic recombinant blood plasma product other than the Initial Product.

1.5 “ Affiliate ” means any Person who directly or indirectly controls or is controlled by or is under common control with a Party to this Agreement. For purposes of this Section 1.5, “control”, “controls”, or “controlled by” means ownership directly or through one or more Affiliates, of more than fifty percent (50%) or more of the shares of stock entitled to

 

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vote for the election of directors, in the case of a corporation, or more than fifty percent (50%) of the equity interest in the case of any other type of legal entity, status as a general partner in any partnership, or any other arrangement whereby a Party controls or has the right to control the Board of Directors or equivalent governing body of a corporation or other entity, or the ability to direct the management or policies of a corporation or other entity. The Parties acknowledge that in the case of certain entities organized under the laws of certain countries outside of the United States, the maximum percentage ownership permitted by law for a foreign investor may be less than fifty percent (50%), and that in such case such lower percentage shall be substituted in the preceding sentence, provided that such foreign investor has the power to direct the management and policies of such entity. For purposes of this Agreement, LFB/GTC LLC shall be deemed to be an Affiliate of each Operating Party.

1.6 “ Agreement ” shall have the meaning set forth in the preamble to this Agreement.

1.7 “ Alliance Affecting Core Business ” means, with respect to an Operating Party, a binding agreement between such Operating Party or its Affiliate and a Third Party for the development and/or commercialization of a product which (a) if developed or commercialized by the other Operating Party, would be within the Core Business of such other Operating Party, and (b) Competes with a Core Business Product of the other Operating Party as listed on Exhibit D .

1.8 “ Base Product Term ” shall have the meaning set forth in Section 14.1(b).

1.9 “ CD20 Antibody ” shall have the meaning set forth in the preamble to this Agreement.

1.10 “ CD20 Antibody Product ” means a Transgenic version of a therapeutic product incorporating, based on or derived from the CD20 Antibody.

1.11 “ Change of Control ” with respect to a Party means (a) a sale of all or substantially all of such Party’s assets or business to which this Agreement relates; (b) a merger, reorganization or consolidation involving such Party in which the stockholders of such Party immediately prior to such transaction cease to own collectively a majority of the voting equity securities of the successor entity; or (c) a Person or group of Persons acting in concert acquires more than fifty percent (50%) of the voting equity securities of such Party. For purposes of this Agreement, a Party shall be deemed to have undergone a Change of Control in the event that any of the transactions listed in (a), (b) or (c) above take place with respect to: (1) an Affiliate of such Party that Controls such Party, or (2) an Affiliate of such Party whose performance or assets are material to such Party’s performance of its obligations under this Agreement, including without limitation those obligations under any Development Plan or Commercialization Plan hereunder.

1.12 “ Co-Exclusive Territory ” means the rest of the world outside the European Territory and the North American Territory, except, in the case of the rFIX Product, the Co-Exclusive Territory shall be limited to Monaco, Andorra, Mexico and Japan.

 

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1.13 “ Collaboration Term ” means the term of this Agreement, as set forth in Section 14.1.

1.14 “ Combination Product ” shall have the meaning set forth in Section 1.84.

1.15 “ Commercial License ” shall mean a commercial license agreement, substantially upon the terms set forth in Exhibit C , that is executed by the Operating Parties in the circumstances described in Section 8.2(c)(ii).

1.16 “ Commercialization ” or “ Commercialize ” means the promotion, detailing, sale and distribution of a Product in the Territory, including, without limitation, all LFB Biotech Commercialization Activities and GTC Commercialization Activities.

1.17 “ Commercialization Activities ” means the LFB Biotech Commercialization Activities and/or the GTC Commercialization Activities, as the context suggests.

1.18 “ Commercialization Costs ” means, with respect to a Product, all direct external costs and direct internal costs properly incurred or paid by each Operating Party with respect to such Product plus, to the extent permitted under Appendix II to Exhibit B indirect costs properly allocated by such Operating Party as Commercialization Costs, in each case during the Commercialization Phase for such Product, excluding the specific costs required to achieve the second Major Regulatory Approval and other costs properly allocated as Development Costs hereunder. Commercialization Costs shall include, without limitation, those costs described on Appendix II to Exhibit B , and which are related to marketing and selling of the Product, and the cost of producing and distributing Product for sale, sample and other uses approved in the Commercialization Plan. For the avoidance of doubt, Commercialization Costs shall exclude any transfer pricing mark-up or other intercompany transactions, payable by a Party to one of its Affiliates in connection with such Affiliates’ performance of activities under a Commercialization Plan. Subject to Joint Steering Committee approval, costs incurred for phase IV studies, distribution, sales force, and any related promotional costs are to be considered Commercialization Costs. For the avoidance of doubt, (a) any Development Costs, including without limitation significant costs of expanding a Product’s labeled indication or approved territory or other costs included in the determination of Product Participation shall not be included as Commercialization Costs in the calculation of Net Profits, and (b) Commercialization Costs shall not be included in the determination of the Product Participation of each Operating Party, and shall be included in the determination of Net Profits as per Exhibit B .

1.19 “ Commercialization Phase ”, with respect to a Product, shall mean the period commencing upon the first Major Regulatory Approval of such Product and continuing throughout the remaining Product Term with respect to such Product; provided that, notwithstanding commencement of the Commercialization Phase, (a) Development Activities shall continue in other countries or regions of the Territory until Regulatory Approval has been obtained in all countries or regions set forth in the applicable Development Plan and (b) certain costs incurred by the Operating Parties during the Commercialization Phase shall be allocated as Development Costs as specified herein.

 

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1.20 “ Commercialization Plan ” shall have the meaning set forth in Section 6.1.

1.21 “ Commercially Reasonable Efforts ” means, with respect to each Operating Party, commercially reasonable efforts in accordance with such Operating Party’s business, legal, ethical, medical and scientific judgment, and in accordance with the efforts and resources such Operating Party would use for a product owned by it or to which it has rights, which is of similar market potential, at a similar stage in its product life, taking into account the competitiveness of the marketplace, the proprietary position of the product, the regulatory structure involved, the profitability of the product and other relevant factors.

1.22 “ Compete ”, “ Competes ” or “ Competing ” means, with respect to any two therapeutic products, whether or not one of such products is a Product, and whether or not one or both of such products is Transgenic, that (a) one such product which is a ************.

1.23 “ Competing Product ” means any Transgenic or non-Transgenic therapeutic product, other than a Product, that Competes with a Product, provided that the term “Competing Product” shall not include any products that ************.

1.24 “ Confidential Information ” of a Party means any scientific, technical, trade or business information possessed, obtained by, developed for or given to a Party which is treated by such Party as confidential or proprietary, including, without limitation Research Materials (defined below), formulations, techniques, methodology, assay systems, formulae, protocols, SOPs, procedures, tests, equipment, data, reports, know-how, sources of supply, patent positioning, relationships with consultants and employees, pricing, business plans and business developments, information concerning the existence, scope or activities of any research, development, manufacturing or other projects of such Party (e.g., plans, rationale, competitive strategy or other information related to developing or marketing products or technology covered by such Party’s patents, patent applications or published patent applications), and any other confidential information about or belonging to such Party’s suppliers, licensors, licensees, partners, Affiliates, customers, potential customers or others and which is disclosed by such Party to the other Party during the Collaboration Term. “Research Materials” include, without limitation, genes, DNA sequences, plasmids, vectors, expression systems, cells, cell lines, organisms, antibodies, biological substances, and any constituents, progeny, mutants, derivatives or replications thereof or therefrom, together with all reagents, chemical compounds or other materials. It is understood and agreed by the Parties that (a) the GTC Know-How shall be deemed to be the Confidential Information of GTC for all purposes hereunder, (b) the LFB Biotech Know-How shall be deemed to be the Confidential Information of LFB Biotech for all purposes hereunder and (c) the terms of this Agreement shall constitute Confidential Information of each Party.

1.25 “ Control ” means, with respect to any information or intellectual property right, possession by a Party or its Affiliates 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, and without the payment of additional consideration (other than royalty payments, milestone payments and other amounts otherwise payable under the relevant agreement) to, any Third Party as of the time such Party would first be required hereunder to grant the other Party such access, license, or sublicense.

 

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1.26 “ Core Business ” means (a) with respect to LFB Biotech and its Affiliates, the development and commercialization of (i) protein obtained from human plasma fractionation and their recombinant counterparts and (ii) recombinant monoclonal antibodies with applications in oncology, auto immune diseases, infectious diseases and graft rejection; and, (b) with respect to GTC and its Affiliates, the development and commercialization of (i) therapeutic Transgenic protein products and (ii) recombinant monoclonal antibodies with applications in oncology, auto immune diseases, infectious diseases and asthma. The applications for monoclonal antibodies may be extended as provided in the definition of “Core Business Product”.

1.27 “ Core Business Competitor ” means, with respect to an Operating Party at the relevant time, any Third Party that is developing or commercializing one or more products that (a) if developed or commercialized by such Operating Party would be within the Core Business of such Operating Party and its Affiliates and (b) Competes with a Core Business Product of such Operating Party and its Affiliates.

1.28 “ Core Business Competitor Equity Acquisition ” means with respect to an Operating Party (a) the acquisition by a Core Business Competitor of such Operating Party of more than ************ of the voting equity securities of the other Operating Party or (b) a Core Business Competitor of such Operating Party obtaining the right to ************. For purposes of this Agreement, a Core Business Competitor Equity Acquisition shall be deemed to have occurred with respect to an Operating Party in the event that any of the transactions listed in (a) or (b) above take place with respect to: (1) an Affiliate of the other Operating Party that Controls such other Operating Party, or (2) an Affiliate of such other Operating Party whose performance or assets are material to such other Operating Party’s performance of its obligations under this Agreement, including without limitation those obligations under any Development Plan or Commercialization Plan hereunder.

1.29 “ Core Business Product/Products ” means, with respect to an Operating Party and its Affiliates, a specific product within the Core Business of such Operating Party and its Affiliates as set forth on Exhibit D as the same shall be amended in accordance with the following. Each Operating Party shall notify the other Parties annually of any change in the Core Business Products of such Operating Party and its Affiliates, together with adequate supporting documentation, and, absent a dispute, Exhibit D shall be amended to reflect such change subject to the following conditions: (i) neither Operating Party shall be required to delete any product which is ************; (ii) any ************ product ************ may be added to or deleted from Exhibit D by either Operating Party without restriction provided that in the case of an addition such product is under development or being commercialized by such Operating Party or its Affiliates; (iii) an Operating Party may add a ************ product to Exhibit D only if such product meets any one of the following criteria: (A) For products in the stage of research or development, (1) such Operating Party and its Affiliates have spent in the preceding year at least ************ for research and/or development of such product, or (2) such Operating Party or its Affiliates have developed a

 

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scalable manufacturing asset for such product, either through Transgenic process or a cell line, or (3) such product is in a pre-clinical research program at a stage that is reasonably expected to be within ************ of initiation of human clinical trials or (4) such product has been licensed from an outside institution, including a university or a company or partnership, provided that if after ************ of the license term such licensed product does not also satisfy either criteria, (2) or (3) above or the criteria set forth in the following clause (B) or such Operating Party or its Affiliates have not spent at least ************ in total during such ************ period on research and/or development of such product (such amount not to include license fees payable to the relevant outside institution), then such product shall be deleted from Exhibit D ; and (B) for products in the stage of commercialization a product which, on an annual basis accounts for more than ************ of such Operating Party’s or its Affiliates’ revenues, whether from sales, product milestones, royalties or other product revenues; and (iv) an Operating Party shall delete a ************ product from Exhibit D if for the preceding year it has not met any of the criteria set forth in the foregoing clauses (iii)(A) or (B). If a recombinant monoclonal antibody product of an Operating Party or its Affiliates would be eligible for addition to Exhibit D but is for an application not covered in the definition of “Core Business” of such Operating Party and its Affiliates, then such product may be added to Exhibit D and for so long as such product remains on Exhibit D the definition of “Core Business” of such Operating Party and its Affiliates shall be deemed amended to include such application.

1.30 “ Damages ” shall have the meaning set forth in Section 13.1.

1.31 “ Development ” or “ Develop ” means all activities performed by GTC or LFB Biotech on behalf of LFB/GTC LLC pursuant to the Development Plan with respect to a Product during the Development Phase, including, without limitation, all activities related to preclinical testing, DNA construct discovery and development, animal development and maintenance, test method development and stability testing, toxicology, formulation, process development, manufacturing scale-up, qualification and validation, quality assurance/quality control, clinical studies (from Phase I Trials through Phase III Trials), regulatory affairs, statistical analysis and report writing, and all other pre-marketing activities, each to the extent performed pursuant to the Development Plan.

1.32 “ Development Activities ” means, collectively or individually, as the context suggests, the LFB Biotech Development Activities and the GTC Development Activities, as the context suggests.

1.33 “ Development Costs ”, for purposes of determining an Operating Party’s Product Participation with respect to any Product under Section 8.2(b), shall mean all direct external costs and direct internal costs properly paid or incurred by such Operating Party in connection with the Development of such Product, plus, to the extent permitted under Appendix I to Exhibit B , indirect costs properly allocated by such Operating Party to the Development of such Product, in each case during the Development Phase or thereafter as expressly provided herein. Development Costs shall include, without limitation, all Pre-Marketing Costs and the cost of producing and distributing Product for preclinical, clinical and other uses approved in the Development Plan in addition to those other costs set forth on Appendix I to Exhibit B , in each case that are incurred in the performance of Development activities under the Development Plan.

 

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1.34 “ Development Phase ” shall mean, with respect to a Product, the period commencing upon the Product Start Date for such Product and continuing until the first Major Regulatory Approval for such Product; provided that certain costs incurred after the Development Phase shall be treated as Development Costs if specified herein or agreed to in writing in advance by the Joint Steering Committee.

1.35 “ Development Plan ” shall have the meaning set forth in Section 5.1.

1.36 “ Disclosing Party ” shall have the meaning set forth in Section 12.1.

1.37 “ Dispute ” shall have the meaning set forth in Section 15.1.

1.38 “ ECB ” means the European Central Bank.

1.39 “ Effective Date ” shall mean the effective date of the Original JDA, June 29, 2006.

1.40 “ EMEA ” means the European Agency for the Evaluation of Medicinal Products, or any successor organization.

1.41 “ European Territory ” means the member states (as of the Effective Date) of the European Union, as well as Switzerland, Norway, Lichtenstein, Iceland, Bulgaria,, Romania, Croatia, Serbia, Montenegro, Slovenia, Bosnia, Macedonia, Albania, Turkey, Byelorussia, Ukraine and Moldavia and each of their respective territories and possessions, except, in the case of the rFIX Product, the European Territory shall exclude Turkey and Ukraine.

1.42 “ FDA ” means the United States Food and Drug Administration, or any successor organization.

1.43 “ First Commercial Sale ” means the first commercial sale of a Product by or on behalf of an Operating Party or its Affiliate in a country as part of a nationwide introduction after Regulatory Approval has been achieved for such Product in such country. Sales for test marketing, clinical trial purposes or compassionate or similar use shall not be considered to constitute a First Commercial Sale.

1.44 “ FTE ” shall have the meaning set forth in Section 5.2(b).

1.45 “ Fully Absorbed Cost of Goods ” means, with respect to a Product and the Operating Party responsible for manufacturing or supplying such Product, (a) the variable costs and fixed costs incurred by such Operating Party associated with the manufacture (inclusive of finishing processes including filling, packaging, labeling and/or other preparation), quality assurance, quality control and other testing, storage and shipping of batches of such Product or (b) if such Product is not manufactured by such Operating Party, the amounts paid to a Third Party manufacturer for the manufacture of such Product plus, to

 

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the extent not included in the amounts paid to such Third Party manufacturer, the actual costs associated with the acquisition of shipments of Product from such Third Party manufacturer. For purposes of this definition, “ variable costs ” means the cost of labor, raw materials, scrap (being product losses normally recorded in the process of manufacturing and to the exclusion of abnormal waste, spillage, processing, handling or idle facility costs), supplies and other resources directly consumed in the manufacture, quality assurance, quality control and other testing, storage and shipping of batches of the applicable Product, and “ fixed costs ” means the cost of facilities, utilities, insurance (including any product liability insurance or accrual for self-insurance), facility and equipment depreciation (unless the capital cost of such facility or equipment has been directly charged to the program), manufacturing overhead (cost accounting, personnel management, and information technology), and other fixed costs directly related to the manufacture, quality assurance, quality control and other testing, storage and shipping of batches of such Product, as well as amounts required to be paid to Third Parties in connection with the manufacture, use, sale, offer for sale or import of such Product to the extent not otherwise included as Development Costs or Commercialization Costs of such Operating Party. Fixed costs shall be allocated to such Product based upon the proportion of such costs directly attributable to support of the manufacturing, quality assurance, quality control and other testing, storage and shipping processes for such Product. If a facility is used to manufacture Products and has the capacity to manufacture products for other programs of such Operating Party, fixed costs shall be allocated in proportion to the actual use of such facility for the manufacture of Products and the capacity to manufacture products for such other programs. For the avoidance of doubt, no idle capacity of a manufacturing facility, or a proportionate use thereof, shall be included in Fully Absorbed Cost of Goods except, in the case of a facility dedicated solely to the manufacture of Products, it shall be included to the extent the JSC determines that such facility is appropriately sized. Fully Absorbed Cost of Goods shall exclude all costs otherwise covered under Development Costs or Commercialization Costs. Unless otherwise expressly provided in this Agreement, all cost determinations made in the calculation of Fully Absorbed Cost of Goods shall be in accordance with the Operating Parties’ respective Accounting Standards, consistently applied.

1.46 “ GMP ” means the current Good Manufacturing Practices of the FDA or any similar practice standards promulgated by applicable Regulatory Authorities with jurisdiction over the manufacture, use, or sale of Product, as then in effect.

1.47 “ Greater Funding Party ” means, with respect to a Product, an Operating Party that has funded more than ************ of the costs of Development of such Product hereunder as of or after the date the Product Participation percentages of the Operating Parties are first set pursuant to Section 8.2(b), and prior to full reimbursement to such Operating Party of any IPV Difference in accordance with Section 8.2(d).

1.48 “ GTC Assumed Liability ” shall have the meaning set forth in Section 13.2.

1.49 “ GTC Commercialization Activities ” means, with respect to a Product, the designated Commercialization activities undertaken by GTC on behalf of LFB/GTC LLC as specified in the Commercialization Plan for such Product.

 

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1.50 “ GTC Development Activities ” shall have the meaning set forth in Section 5.2(c).

1.51 “ GTC Indemnitee ” shall have the meaning set forth in Section 13.1.

1.52 “ GTC Know-How ” means all Know-How that is Controlled by GTC or its Affiliates as of the Effective Date or during the Collaboration Term that is necessary or reasonably useful for the Development and/or Commercialization of Products under this Agreement.

1.53 “ GTC Patent Rights ” means all Patent Rights Controlled by GTC or its Affiliates as of the Effective Date or during the Collaboration Term the practice of whose claims are necessary or useful to the Development and/or Commercialization of Products under this Agreement, excluding Joint Patent Rights.

1.54 “ GTC Technology ” means, collectively, GTC Know-How and GTC Patent Rights.

1.55 “ Indemnified Party ” shall have the meaning set forth in Section 13.3.

1.56 “ Indemnifying Party ” shall have the meaning set forth in Section 13.3.

1.57 “ Initial Collaboration Term ” shall have the meaning set forth in Section 14.1(a).

1.58 “ Initial Development Plan ” shall have the meaning set forth in Section 5.1.

1.59 “ Initial Product ” means a Transgenic version of a therapeutic product incorporating, based on or derived from rFVIIa.

1.60 “ Insolvency Event ” means, with respect to an Operating Party, (a) such Operating Party’s filing a petition in voluntary bankruptcy or making an assignment for the benefit of creditors or consenting to the appointment of a receiver of all or any substantial part of its property, or filing a petition to take advantage of any laws affecting debtors generally, in each of the foregoing cases only if it is directed to and will result in liquidation of such Operating Party, or (b) the commencement against such Operating Party of any case, proceeding or other action seeking the adjudication of such Operating Party as bankrupt by a court of competent jurisdiction or the appointment by such a court of a trustee or receiver or receivers of such Operating Party of all or any substantial part of the property of such Operating Party upon the application of any creditor in any insolvency or bankruptcy proceeding or other creditors suit, which case, proceeding or other action is not dismissed within sixty (60) days after its commencement, in each of the foregoing cases only if it is directed to and will result in liquidation of such Operating Party.

1.61 “ Invention ” means any invention or discovery, whether or not patentable, made as a result of the activities of a Party or the Parties pursuant to this Agreement, which invention or discovery relates to a Product in any manner, including, but not limited to, any invention or discovery relating to the making, using or selling of a Product.

 

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1.62 “ Investment Present Value ” or “ IPV ” means, with respect to a Product, the net present value of the Operating Parties’ Development Costs for such Product during the period commencing on the Product Start Date for such Product and ending on the date of the first Major Regulatory Approval for such Product, as calculated in accordance with the applicable Product Participation Model, and subject to adjustment pursuant to Section 8.2(b)(iv).

1.63 “ IPV Difference ” means, with respect to a Product, the difference between a Greater Funding Party’s IPV and the IPV if the Development Costs of such Product were shared ************, taking into consideration the weighting of Development Costs set forth in Section 8.2(b)(ii).

1.64 “ IPV Payment ” has the meaning set forth in Section 14.3(a)(iv).

1.65 “ Joint Inventions ” shall have the meaning set forth in Section 9.1(b).

1.66 “ Joint Patent Rights ” shall have the meaning set forth in Section 9.1(b).

1.67 “ Joint Steering Committee ” or “ JSC ” shall have the meaning set forth in Section 4.1.

1.68 “ Joint Technology ” means the Joint Patent Rights and any Joint Inventions.

1.69 “ Keepwell Agreement ” has the meaning set forth in the Preamble to this Agreement.

1.70 “ Know-How ” means any information or materials (whether or not proprietary or patentable and whether stored or transmitted in oral, documentary, electronic or other form), including, without limitation, ideas, concepts, formulas, methods, procedures, designs, compositions, plans, documents, data, inventions, discoveries, developments, works of authorship, biological materials, and any information relating to research and development plans, experiments, results, compounds, therapeutic leads, candidates and products, clinical and preclinical data, toxicological data, pharmacological data, formulations, trade secrets and manufacturing, marketing, financial, regulatory, personnel, customer sales and invoicing and other business information and plans, and any scientific, clinical, regulatory, marketing, financial and commercial information or data which relates to a Product in any manner.

1.71 “ LFB Biotech Assumed Liability ” shall have the meaning set forth in Section 13.1.

1.72 “ LFB Biotech Commercialization Activities ” means, with respect to a Product, the designated Commercialization activities undertaken by LFB Biotech on behalf of LFB/GTC LLC as specified in the Commercialization Plan for such Product.

1.73 “ LFB Biotech Development Activities ” shall have the meaning set forth in Section 5.2(b).

1.74 “ LFB Biotech Indemnitees ” shall have the meaning set forth in Section 13.2.

 

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1.75 “ LFB Biotech Know-How ” means all Know-How that is Controlled by LFB Biotech or its Affiliates as of the Effective Date or during the Collaboration Term that is necessary or reasonably useful for the Development and/or Commercialization of Products under this Agreement.

1.76 “ LFB Biotech Patent Rights ” means all Patent Rights Controlled by LFB Biotech or its Affiliates as of the Effective Date or during the Collaboration Term the practice of whose claims are necessary or useful to the Development and/or Commercialization of Products under this Agreement, excluding Joint Patent Rights.

1.77 “ LFB Biotech Technology ” means, collectively, LFB Biotech Know-How and LFB Biotech Patent Rights.

1.78 “ LFB Licensed Technology ” means, collectively, LFB Biotech Technology and LFB Biotech’s and LFB-US’s rights in any and all Joint Technology.

1.79 “ LLC Agreement ” means the agreement between GTC and LFB-US dated as of June 30, 2008 establishing and governing LFB/GTC LLC.

1.80 “ Major Market EU Countries ” means, individually and collectively, France, Germany, Italy, Spain and the United Kingdom.

1.81 “ Major Regulatory Approval ” means a Regulatory Approval from the FDA or the EMEA.

1.82 “ Major Regulatory Filing ” means a Regulatory Filing with the FDA or the EMEA.

1.83 “ Net Profits ” means, with respect to a Product for a particular reporting period, aggregate profits or losses resulting from the Commercialization of such Product worldwide and shall be equal to (a) worldwide Net Sales of and any other revenues relating to such Product for such period, including without limitation any royalties, sublicense income or other payments received from Third Parties, less (b) Commercialization Costs for such Product, before income taxes. For the avoidance of doubt, Net Profits will be determined by the Parties on a consolidated basis exclusive of any inter-company profits or mark-up between the Parties and/or their Affiliates and will be shared based on each Operating Party’s Product Participation as described in Section 8.2.

1.84 “ Net Sales ” means, with respect to a Product, the net sales on behalf of an Operating Party or any Affiliate, licensee or sublicensee of such Operating Party, for the Product sold to Third Parties (other than licensees or sublicensees) in bona fide, arm’s-length transactions, as determined in accordance with applicable IFRS Accounting Standards, as consistently applied, and which shall include the following customary deductions from the invoiced sale price, as generally and consistently applied by an Operating Party:

(a) ************.

 

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(b) ************.

(c) ************.

(d) ************.

(e) ************.

(f) ************.

(g) ************.

(h) ************.

(i) ************.

(j) ************.

(k) ************.

************.

************.

************.

1.85 “ North American Territory ” means the United States and Canada, and their respective territories and possessions.

1.86 “ Operating Party ” or “ Operating Parties ” means GTC or LFB Biotech, or both, as the context shall suggest, each of which is undertaking the Development and Commercialization efforts of the Collaboration on behalf of LFB/GTC LLC as set forth in this Agreement.

1.87 “ Originating Party ” means, with respect to a Product, the Operating Party responsible for introducing such Product to the Collaboration under this Agreement. The Parties acknowledge and agree that LFB Biotech is the Originating Party of the Initial Product and GTC is the Originating Party of any rhAAT Products.

1.88 “ Party ” and/or “ Parties ” shall have the respective meanings set forth in the preamble to this Agreement.

1.89 “ Patent Rights ” means any patent applications and any divisions, continuations, or continuations-in-part thereof, and any patents issuing thereon and all substitutions, reissues, reexaminations and extensions thereof and supplemental protection certificates relating thereto, and all counterparts of the foregoing in any country.

 

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1.90 “ Person ” means any natural person, corporation, firm, business trust, joint venture, association, organization, company, partnership, or other business entity, or any government, or any agency or political subdivision thereof.

1.91 “ Phase I Trial ” means a clinical trial as defined in 21 C.F.R 312.21(a), as may be amended from time to time, or any non-US equivalent thereto, in each case that is designed to determine the metabolism and pharmacologic actions of the applicable Product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

1.92 “ Phase II Trial ” means a clinical trial as defined in 21 C.F.R. 312.21(b), as may be amended from time to time, or any non-US equivalent thereto, in each case that is designed to assess the clinical efficacy of the applicable Product for a particular indication or indications and to determine the common side-effects and safety risks associated with the use of such Product.

1.93 “ Phase III Trial ” means a clinical trial as defined in 21 C.F.R. 312.21(c), as may be amended from time to time, or any non-US equivalent thereto, in each case that is designed to gather additional information about the efficacy, tolerability and safety of the applicable Product that is needed to evaluate the overall benefit-risk relationship of the Product and to provide an adequate basis for physician labeling.

1.94 “ Pivotal Trial ” means, with respect to a Product, a Phase III Trial or other clinical trial, the results of which are identified by the JSC as the essential data from which a Regulatory Authority will determine whether to grant Regulatory Approval for such Product.

1.95 “ Pivotal Trial Completion Date ” means, with respect to a Product, the date of the JSC’s decision that the results of the Pivotal Trial are adequate to support a Regulatory Filing for purposes of obtaining the first Major Regulatory Approval for such Product.

1.96 “ Pre-Marketing Costs ” means all costs related to market research and development, strategic market plans, strategic product positioning, pricing studies, inventory build and all other pre-approval activities, each to the extent performed pursuant to the Development Plan. As part of Development Costs, Pre-Marketing Costs should be approved by the Joint Steering Committee and reflected in the Development Plan. For the avoidance of doubt, Pre-Marketing Costs approved and incurred are included as Development Costs for the calculation of Product Participation.

1.97 “ Product ” or “ Products ” means one or more of the following, as the context suggests: (a) the Initial Product, (b) the rhAAT Product, (c) the rFIX Product, (d) the CD20 MAb Product and (e) (i) any Additional Plasma Products and (ii) any Additional MAb Products, and that are, with respect to (e)(i) and (ii), selected by the Parties for inclusion in the Collaboration hereunder pursuant to Section 2.1.

1.98 “ Product Participation ” shall have the meaning set forth in Section 8.2(a).

 

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1.99 “ Product Participation Model ” means, with respect to a Product, the model agreed upon by the Operating Parties, substantially in the form attached as Exhibit B hereto, for calculating the Operating Parties’ respective contributions to the Development of such Product and, based upon such contributions, determining the percentage of each Operating Party’s respective participation in the aggregate Net Profits that are derived from such Product, all as more fully described in Section 8.2.

1.100 “ Product Start Date ” means, (a) with respect to the Initial Product, the Effective Date, and (b) with respect to any other Products, the date the relevant Product becomes subject to this Agreement pursuant to Section 2.1.

1.101 “ Product Trademark ” shall have the meaning set forth in Section 10.1(a).

1.102 “ Product Term ” shall have the meaning set forth in Section 14.1(b)(iii).

1.103 “ Publishing Party ” shall have the meaning set forth in Section 12.5(a).

1.104 “ rFIX ” shall have the meaning set forth in the preamble to this Agreement.

1.105 “ rFIX Product ” means the Transgenic version of any therapeutic product incorporating, based on or derived from rFIX.

1.106 “ rFVIIa ” means recombinant human blood factor VIIa.

1.107 “ rFVIIa Goat ” means a transgenically modified goat that produces rFVIIa in its milk.

1.108 “ rFVIIa Rabbit ” means a transgenically modified rabbit that produces rFVIIa in its milk.

1.109 “ Recall ” means the removal or correction of a marketed Product that the FDA, EMEA or an equivalent Regulatory Authority considers to be in violation of law and against which a Regulatory Authority would otherwise initiate legal action (e.g., a seizure).

1.110 “ Receiving Party ” shall have the meaning set forth in Section 12.1.

1.111 “ Regulatory Approvals ” mean any approvals, licenses, registrations or authorizations (including pricing and reimbursement approvals) of any Regulatory Authority, whether or not conditional, that are necessary for the commercial sale of a Product in a regulatory jurisdiction in the Territory.

1.112 “ Regulatory Authority ” means any and all national, supra-national, regional, state, or local regulatory agency, department, bureau, commission, council, or other governmental entity, whose approval or authorization is necessary for, or to whom notice must be given prior to, the manufacture, distribution, use, or sale of a Product in the Territory, including, without limitation, the FDA and the EMEA.

 

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1.113 “ Regulatory Filings ” mean all applications, filings, dossiers and the like submitted to a Regulatory Authority in the Territory for the purpose of obtaining a Regulatory Approval from such Regulatory Authority in the Territory.

1.114 “ Restatement Date ” means the date set forth in the preamble of this Agreement.

1.115 “ rhAAT ” shall have the meaning set forth in the preamble to this Agreement.

1.116 “ rhAAT Product ” means the Transgenic version of any therapeutic product incorporating, based on or derived from rhAAT.

1.117 “ Senior Management ” means, for a Party, the Chief Executive Officer or a senior executive who is designated by the Chief Executive Officer of such Party.

1.118 “ Shared Liability Claims ” shall have the meaning set forth in Section 13.4(a).

1.119 “ Specifications ” shall have the meaning set forth in Section 7.3.

1.120 “ Stock and Note Purchase Agreement ” shall have the meaning set forth in Section 8.1.

1.121 “ Supply Agreement ” means, with respect to a Product, a definitive agreement executed between the Operating Parties to govern the terms and conditions of manufacture and supply of such Product hereunder.

1.122 “ Target Antigen ” means the ************.

1.123 “ Target Receptor ” means the ************.

1.124 “ Territory ” means, individually or collectively, as the context shall suggest, the European Territory, the North American Territory and the Co-Exclusive Territory.

1.125 “ Third Party ” means any person or entity (including, without limitation, any governmental authority) other than a Party or its Affiliates.

1.126 “ Third Party Claims ” shall have the meaning set forth in Section 13.1.

1.127 “ Trademark Owner ” shall mean the Operating Party owning a Product Trademark pursuant to Section 10.1.

1.128 “ Trademark User ” shall have the meaning set forth in Section 3.4.

 

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1.129 “ Transgenic ” means, with respect to any therapeutic product, including without limitation a Product, that such product was produced or derived from transgenically modified animals.

1.130 “United States”, “US” or “USA” shall mean the United States of America and its territories and possessions, including without limitation the Commonwealth of Puerto Rico and the U.S. Virgin Islands.

1.131 “ Unsettled Shared Damages ” shall have the meaning set forth in Section 13.4.

ARTICLE 2

SCOPE OF COLLABORATION; JOINT OBLIGATIONS; DILIGENCE

2.1 Scope of Collaboration .

(a) General . LFB Biotech, GTC, LFB/GTC LLC and LFB-US have established in this Agreement and the LLC Agreement and wish to continue a collaborative alliance to Develop and Commercialize Products in the Territory on behalf of LFB/GTC LLC and using LFB/GTC LLC as a vehicle for such Collaboration, all as more specifically described herein, the LLC Agreement and in the applicable Development Plan and Commercialization Plan. Without limiting the foregoing, the Parties agree to: (i) engage in Development of Products on behalf of LFB/GTC LLC, with the goal of obtaining Regulatory Approval for each Product as soon as reasonably practicable in each market where it makes commercial sense to do so given the size of the potential market and the safety and efficacy profile of the relevant Product; and (ii) engage in Commercialization of Products on behalf of LFB/GTC LLC, with the goal of optimizing the profit available to each Party. Each Party agrees to use Commercially Reasonable Efforts in performing its tasks and responsibilities and in conducting all activities ascribed or assigned to it from time to time under this Agreement, the then current Development Plan, and the then current Commercialization Plan with respect to each Product.

(b) Initial Product . The Parties shall continue to collaborate to Develop and Commercialize the Initial Product on behalf of LFB/GTC LLC, in accordance with the terms and conditions of this Agreement, the LLC Agreement, the Initial Development Plan and the Commercialization Plan for the Initial Product.

(c) Other Products in Development . As of the Restatement Date, the Operating Parties have begun to collaborate to Develop CD20 MAb, rhAAT and rFIX Products, and the Parties shall continue to collaborate to Develop and Commercialize the CD20 Product, the rhAAT Product and the rFIX Product on behalf of LFB/GTC LLC, in accordance with this Agreement, the LLC Agreement and the respective Development Plan and Commercialization Plan for each such Product.

 

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(d) Additional Plasma Products .

(i) Either Operating Party may, from time to time during the Term, but is not obligated to, propose to the non-Originating Party for inclusion in the Collaboration under this Agreement and the LLC Agreement any Additional Plasma Products that such Operating Party believes are reasonably likely to enhance the goals of the Collaboration.

(ii) The Originating Party may propose such Additional Plasma Product for inclusion in the Collaboration by providing the non-Originating Party with a written proposal for the Development of such Additional Plasma Product, and the non-Originating Party shall have ************ following the receipt of such proposal to inform the Originating Party whether or not it wishes to include such Additional Plasma Product as a Product under this Agreement and the LLC Agreement.

(iii) If the non-Originating Party notifies the Originating Party in writing within such ************ day period that it wishes to include such Additional Plasma Product under this Agreement and the LLC Agreement, the Operating Parties shall negotiate in good faith for a period not to exceed ************, or such longer time as the Parties may mutually agree, a preliminary Development Plan with respect to such Additional Plasma Product, which Development Plan shall include a preliminary Development budget. If the Operating Parties reach agreement on a Development Plan for such Additional Plasma Product within such time period or such longer time period as the Operating Parties may mutually agree, such Additional Plasma Product shall become subject to this Agreement and the LLC Agreement as a “Product” hereunder and thereunder.

(iv) If (a) the non-Originating Party (1) notifies the Originating Party that it does not wish to pursue the Development or Commercialization of such Additional Plasma Product hereunder, or (2) does not notify the Originating Party in writing within such ************ period of its intention whether or not to include such Additional Plasma Product hereunder, or (b) the non-Originating Party timely notifies the Originating Party that it wishes to pursue such Additional Plasma Product hereunder, but the Operating Parties are unable to agree in good faith upon a Development Plan for the proposed Additional Plasma Product within the time frame provided in subsection (iii) above, the Originating Party may pursue the development and commercialization of such Additional Plasma Product unilaterally or negotiate and enter into an agreement with any Third Party for the development and commercialization of such Additional Plasma Product with no further obligation to the non-Originating Party or LFB/GTC LLC with respect thereto, subject to the provisions of Section 3.10.

(e) Additional MAb Products .

(i) Either Operating Party may, from time to time during the Term, but is not obligated to, propose to the non-Originating Party for inclusion in the Collaboration under this Agreement and the LLC Agreement any Additional MAb Products that such Operating Party believes are reasonably likely to enhance the goals of the Collaboration.

 

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(ii) The Originating Party may propose an Additional MAb Product for inclusion in the Collaboration by providing the non-Operating Party with a written proposal for the Development of such MAb Product and the non-Originating Party shall have ************ following the receipt of such proposal to inform the Originating Party whether or not it wishes to include such MAb Product as a Product under this Agreement and the LLC Agreement.

(iii) If the non-Originating Party notifies the Originating Party in writing within such ************ period that it wishes to include such Additional MAb Product under this Agreement and the LLC Agreement, the Operating Parties shall negotiate in good faith for a period not to exceed ************, or such longer time as the Operating Parties may mutually agree, a preliminary Development Plan with respect to such Additional MAb Product, which Development Plan shall include a preliminary Development budget. If the Operating Parties reach agreement on a Development Plan for such MAb Product within such time period or such longer time period as the Operating Parties may mutually agree, such Additional MAb Product shall become subject to this Agreement and the LLC Agreement as a “Product” hereunder and thereunder.

(iv) If (a) the non-Originating Party (1) notifies the Originating Party that it does not wish to pursue the Development or Commercialization of such Additional MAb Product hereunder, or (2) does not notify the Originating Party in writing within such ************ period of its intention whether or not to include such Additional MAb Product hereunder, or (b) the non-Originating Party timely notifies the Originating Party that it wishes to pursue such Additional MAb Product hereunder, but the Operating Parties are unable to agree in good faith upon a Development Plan for the proposed Additional MAb Product within the time frame provided in subsection (iii) above, the Originating Party may pursue the development and commercialization of such Additional MAb Product unilaterally or negotiate and enter into an agreement with any Third Party for the development and commercialization of such Additional MAb Product with no further obligation to the non-Originating Party or LFB/GTC LLC with respect thereto, subject to the provisions of Section 3.10.

2.2 Conduct of Parties . Each Operating Party understands and agrees that it is to its mutual benefit and the benefit of LFB/GTC LLC to maximize the clinical and commercial potential of the Products. Each Operating Party shall conduct itself and its activities hereunder consistent with that understanding and with sound and ethical business and scientific practices, and in accordance with the applicable Development Plan and Commercialization Plan, provided that the foregoing shall not limit the activities of the Operating Parties with respect to any product that is not a Product or a Competing Product and is not otherwise subject to Section 3.10.

2.3 Assistance . Each Party agrees to provide to the other Parties all reasonable assistance and take all actions reasonably requested by the other Parties that are necessary to enable the requesting Party to comply with its obligations under this Agreement and the LLC Agreement or otherwise meet the mutual objectives of the Parties set forth in Section 2.2 above, or with any applicable law or regulation.

2.4 Product List . Exhibit A attached hereto sets forth the Products under Development pursuant to this Agreement as of the Restatement Date. As other Products become subject to this Agreement as provided above, Exhibit A shall be updated by including such other Products.

 

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ARTICLE 3

GRANT OF RIGHTS

Superseded Licenses; Restatement. All licenses granted under Article 3 of the Original JDA are hereby superseded by the following licenses and sublicenses granted pursuant to this Agreement.

3.1 LFB Biotech License to LFB-US. LFB Biotech shall grant LFB-US an exclusive license in and to the LFB Licensed Technology.

3.2 LFB-US Sublicense Grant to LFB/GTC LLC .

(a) Research and Development License . Subject to the terms and conditions of this Agreement and in consideration of the mutual covenants and the other good and valuable consideration contained herein and in the LLC Agreement , LFB-US hereby grants to LFB/GTC LLC an exclusive (even as to LFB-US) right and sublicense during the Term, with the right to grant additional sublicenses as described below, in the Territory, under the LFB Licensed Technology, to:

(i) with respect to the Initial Product, (A) create and breed one or more herds of rFVIIa Rabbits and/or rFVIIa Goats and use such rFVIIa Rabbits and/or rFVIIa Goats to produce rFVIIa for use in making the Initial Product and (B) Develop, make and have made the Initial Product, all in accordance with applicable laws and regulations and the Initial Development Plan; and

(ii) with respect to subsequent Product(s), (A) create and breed one or more herds of transgenic mammals, and use such transgenic mammals to produce material for use in making such Product(s) and (B) Develop, make and have made Product(s), all in accordance with applicable laws and regulations and the applicable Development Plan.

(b) Commercialization License . Subject to the terms and conditions of this Agreement and in consideration of the mutual covenants and the other good and valuable consideration contained herein and in the LLC Agreement, LFB-US hereby grants to LFB/GTC LLC an exclusive (even as to LFB-US) right and sublicense, with the right to grant additional sublicenses as described below, in the Territory, during the Term, commencing upon the Commercialization Phase with respect to the applicable Product, under the LFB Licensed Technology, to:

(i) with respect to the Initial Product, sell, offer for sale, and import the Initial Product, all in accordance with applicable laws and regulations and the applicable Commercialization Plan; provided, that, if a Regulatory Authority requires a second site for the production of the Initial Product, such license shall be extended to the use of rFVIIa Rabbits and rFVIIa Goats to manufacture commercial quantities of rFVIIa and to the making of the Initial Product for distribution and sale in the Territory; and

 

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(ii) with respect to subsequent Product(s), (A) use transgenic mammals created pursuant to the license under Section 3.2(a)(ii) to manufacture commercial quantities of material for use in the manufacture of Product(s) and (B) make, have made, sell, offer for sale, and import Product(s), all in accordance with applicable laws and regulations and the applicable Commercialization Plan.

3.3 GTC License Grant to LFB/GTC LLC .

(a) Research and Development License . Subject to the terms and conditions of this Agreement and in consideration of the mutual covenants and the other good and valuable consideration contained herein and in the LLC Agreement , GTC hereby grants to LFB/GTC LLC an exclusive (even as to GTC) right and license during the Term, with the right to grant sublicenses as described below, in the Territory, under the GTC Technology and GTC’s interest in any and all Joint Technology, to:

(i) with respect to the Initial Product, (A) create and breed one or more herds of rFVIIa Rabbits and/or rFVIIa Goats and use such rFVIIa Rabbits and/or rFVIIa Goats to produce rFVIIa for use in making the Initial Product and (B) Develop, make and have made the Initial Product, all in accordance with applicable laws and regulations and the Initial Development Plan; and

(ii) with respect to subsequent Product(s), (X) create and breed one or more herds of transgenic mammals, and use such transgenic mammals to produce material for use in making such Product(s) and (Y) Develop, make and have made Product(s), all in accordance with applicable laws and regulations and the applicable Development Plan.

(b) Commercialization License . Subject to the terms and conditions of this Agreement and in consideration of the mutual covenants and the other good and valuable consideration contained herein and in the LLC Agreement , GTC hereby grants to LFB/GTC LLC an exclusive (even as to GTC) right and license, with the right to grant sublicenses as described below, in the Territory, during the Term, commencing upon the Commercialization Phase with respect to the applicable Product, under the GTC Technology and GTC’s interest in any and all Joint Technology, to:

(i) with respect to the Initial Product, sell, offer for sale, and import the Initial Product all in accordance with applicable laws and regulations and the applicable Commercialization Plan; provided, that, if a Regulatory Authority requires a second site for the production of the Initial Product, such license shall be extended to the use of rFVIIa Rabbits and rFVIIa Goats to manufacture commercial quantities of rFVIIa and to the making of the Initial Product for distribution and sale in the Territory; and

 

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(ii) with respect to subsequent Product(s), (A) use transgenic mammals created pursuant to the license under Section 3.3(a)(ii) to manufacture commercial quantities of material for use in the manufacture of Product(s) and (B) make, have made, sell, offer for sale, and import Product(s), all in accordance with applicable laws and regulations and the applicable Commercialization Plan.

3.4 Sublicenses to GTC

(a) Research and Development Sublicense . Subject to the terms and conditions of this Agreement, LFB/GTC LLC hereby grants to GTC a co-exclusive (together with LFB Biotech) right and sublicense during the Term, in the Territory, under the LFB Licensed Technology, the GTC Technology and GTC’s interest in any and all Joint Technology, in each case, to the extent licensed to LFB/GTC LLC pursuant to Section 3.2 and/or 3.3, to:

(i) with respect to the Initial Product, (A) create and breed one or more herds of rFVIIa Rabbits and/or rFVIIa Goats and use such rFVIIa Rabbits and/or rFVIIa Goats to produce rFVIIa for use in making the Initial Product and (B) Develop, make and have made the Initial Product, all in accordance with applicable laws and regulations and the Initial Development Plan; and

(ii) with respect to subsequent Product(s), (X) create and breed one or more herds of transgenic mammals, and use such transgenic mammals to produce material for use in making such Product(s) and (Y) Develop, make and have made Product(s), all in accordance with applicable laws and regulations and the applicable Development Plan.

(b) Commercialization Sublicense . Subject to the terms and conditions of this Agreement, LFB/GTC LLC hereby grants to GTC an exclusive or co-exclusive (as described below) right and sublicense during the Term, commencing upon the Commercialization Phase with respect to the applicable Product, under the LFB Licensed Technology; the GTC Technology and GTC’s interest in any and all Joint Technology, in each case, to the extent licensed to LFB/GTC LLC pursuant to Section 3.2 and/or 3.3, to:

(i) with respect to the Initial Product, (A) use the rFVIIa Rabbits and/or rFVIIa Goats to manufacture commercial quantities of rFVIIa, (B) make, have made, sell, offer for sale, and import the Initial Product in the North American Territory, (C) subject to Section 3.6, in cooperation with LFB Biotech and LFB/GTC LLC, make, have made, sell, offer for sale, and import the Initial Product in the Co-Exclusive Territory, and (D) make, have made, and sell Initial Product to LFB-US and LFB Biotech for further distribution and sale by LFB-US and LFB Biotech in the European Territory, all in accordance with applicable laws and regulations and the applicable Commercialization Plan; and

(ii) with respect to subsequent Product(s), (A) use transgenic mammals created pursuant to the sublicense under Section 3.4(a)(ii) to manufacture commercial quantities of material for use in the manufacture of Product(s), (B) make, have made, sell, offer for sale, and import Product(s) in the North American Territory, (C) subject to Section 3.6, in cooperation with LFB Biotech and LFB/GTC LLC, make, have made, sell, offer for sale, and import Product(s) in the Co-Exclusive Territory, and (D) make, have made, and sell Product(s) to LFB-US and LFB Biotech for further distribution and sale by LFB-US and LFB Biotech in the European Territory, all in accordance with applicable laws and regulations and the applicable Commercialization Plan.

 

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For purposes of clarity, the foregoing sublicense shall be exclusive to GTC for the North American Territory under Sections 3.4(b)(i)(B) and 3.4(b)(ii)(B) above and co-exclusive (together with LFB Biotech) in the Co-Exclusive Territory under Sections 3.4(b)(i)(C) and 3.4(b)(ii)(C) above.

3.5 Sublicenses to LFB-US.

(a) Research and Development Sublicense . Subject to the terms and conditions of this Agreement, LFB/GTC LLC hereby grants to LFB-US a co-exclusive (together with GTC) right and sublicense during the Term, in the Territory, under the GTC Technology, GTC’s interest in any and all Joint Technology and the LFB Licensed Technology in each case, to the extent licensed to LFB/GTC LLC pursuant to Section 3.2 and/or 3.3, to:

(i) with respect to the Initial Product, (A) create and breed one or more herds of rFVIIa Rabbits and/or rFVIIa Goats and use such rFVIIa Rabbits and/or rFVIIa Goats to produce rFVIIa for use in making the Initial Product and (B) Develop, make and have made the Initial Product, all in accordance with applicable laws and regulations and the Initial Development Plan; and

(ii) with respect to subsequent Product(s), (X) create and breed one or more herds of transgenic mammals, and use such transgenic mammals to produce material for use in making such Product(s) and (Y) Develop, make and have made Product(s), all in accordance with applicable laws and regulations and the applicable Development Plan.

(b) Commercialization Sublicense . Subject to the terms and conditions of this Agreement, LFB/GTC LLC hereby grants to LFB-US an exclusive or co-exclusive (as described below) right and sublicense during the Term, commencing upon the Commercialization Phase with respect to the applicable Product, under the GTC Technology, GTC’s interest in any and all Joint Technology and the LFB Licensed Technology, in each case, to the extent licensed to LFB/GTC LLC pursuant to Section 3.2 and/or 3.3, to:

(i) with respect to the Initial Product, (A) sell, offer for sale, and import the Initial Product in the European Territory and (B) subject to Section 3.6, in cooperation with GTC and LFB/GTC LLC, sell, offer for sale, and import the Initial Product in the Co-Exclusive Territory, all in accordance with applicable laws and regulations and the applicable Commercialization Plan provided that if a Regulatory Authority requires a second site for the production of the Initial Product, such sublicense shall be extended to the use of rFVIIa Rabbits and rFVIIa Goats to manufacture commercial quantities of rFVIIa and to the making of the Initial Product for distribution and sale in the Territory; and

(ii) with respect to subsequent Product(s), (A) use transgenic mammals created pursuant to the sublicense under Section 3.5(a)(ii) to manufacture commercial quantities of material for use in the manufacture of Product(s), (B) make, have made, sell,

 

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offer for sale, and import Product(s) in the European Territory, (C) subject to Section 3.6, in cooperation with GTC and LFB/GTC LLC, make, have made, sell, offer for sale, and import Product(s) in the Co-Exclusive Territory and (D) make, have made, and sell Product(s) to GTC for further distribution and sale by GTC in the North American Territory, all in accordance with applicable laws and regulations and the applicable Commercialization Plan; provided, that, LFB-US may not exercise the license to make and have made Products granted pursuant to the foregoing unless and until the JSC determines to establish a second manufacturing site, or LFB Biotech notifies GTC of its decision to establish a second manufacturing site, in each case in accordance with the provisions of Section 7.4.

For the purposes of clarity, the foregoing sublicense shall be exclusive to LFB-US with respect to the European Territory under Sections 3.5(b)(i)(A) and 3.5(b)(ii)(B) above and co-exclusive (together with GTC) in the Co-Exclusive Territory under Sections 3.5(b)(i)(B) and 3.5(b)(ii)(C) above.

3.6 Exercise of Commercialization Rights in Co-Exclusive Territory . Each Operating Party acknowledges and agrees that the Commercialization rights sublicensed to an Operating Party under Sections 3.4(b)(i)(C), 3.4(b)(ii)(C), 3.5(b)(i)(B) and 3.5(b)(ii)(C) shall only be exercisable by such Operating Party with respect to each country or region of the Co-Exclusive Territory that the JSC has designated to such Operating Party as provided in Section 6.2(c), and neither Operating Party shall exercise such rights in a country or region of the Co-Exclusive Territory that the JSC has exclusively designated to the other Operating Party, its Affiliate or to a Third Party as provided in Section 6.2(c).

3.7 Trademark License . Subject to the terms and conditions of this Agreement, each Trademark Owner hereby grants to the other Operating Party (the “Trademark User”) during the Term (a) a fully paid up, royalty free, exclusive right and license to use the Product Trademarks of such Trademark Owner to Commercialize Products in the Territory which is exclusive to the Trademark User as provided in this Agreement, and (b) a fully paid up, royalty free, co-exclusive right and license (together with the Trademark Owner) to use the Product Trademarks to Commercialize Products in the Co-Exclusive Territory, all in accordance with applicable laws and regulations and the applicable Commercialization Plan, and subject to the following limitations:

(i) The Trademark User acknowledges that the Trademark Owner is and shall remain the owner of the Product Trademarks owned by such Trademark Owner and that all use of such Product Trademarks by the Trademark User shall inure to the benefit of the Trademark Owner.

(ii) The Trademark User agrees that it will use such Product Trademark in connection with the relevant Products manufactured by or for GTC or LFB Biotech, as the case may be, pursuant to, or as permitted by, this Agreement and for no other purpose, and shall agree to comply with such reasonable quality assurance provisions of the Trademark Owner as the Trademark Owner may reasonably specify in writing to ensure that the quality of any Product manufactured by or on behalf of GTC or LFB Biotech, as the case may be, remains, in all material respects, at least as high as that of Product manufactured by the Trademark Owner.

 

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(iii) The Trademark User agrees to use the Product Trademarks of the Trademark Owner only in the form and manner, and with appropriate proprietary markings, reasonably prescribed in writing from time to time by the Trademark Owner. The Trademark Owner will deliver such initial requirements with respect to the form and manner of Product Trademarks use to the Trademark user prior to launch of the applicable Product. The Trademark User agrees not to use any other trademark in combination with the relevant Product Trademark or in connection with the relevant Product without prior written approval of the Trademark Owner, which approval will not be unreasonably withheld.

(iv) The Trademark User agrees, during the term of this Agreement and thereafter, not to seek to register the Product Trademarks of the Trademark Owner or any confusingly similar trademark in any country or region.

The Trademark User may sublicense the rights granted under this Section 3.7 to a Third Party engaged by such Trademark User to Commercialize Products with the approval of the JSC in accordance with Section 3.6 solely for purposes of such Commercialization.

3.8 . Performance of Development and Commercialization Activities By Third Parties . Neither Operating Party may subcontract any significant element of its Development Activities and/or Commercialization Activities to one or more Third Parties without the prior approval of the JSC.

3.9 Reservation of Rights . Each Party expressly reserves and retains all intellectual property rights not expressly granted herein, and no right or license under any Patent Rights, trademarks, Know How or other proprietary rights of any Party is granted or shall be granted by implication.

3.10 Competing Products .

(a) During the Term, each Operating Party agrees not to, and shall cause its Affiliates not to, alone or together with a Third Party, (i) develop or commercialize any Competing Product in the Territory, or (ii) acquire, directly or indirectly, any rights or interest in or to a Competing Product which is being detailed, promoted, marketed or sold in the Territory. In addition to any other remedies that may be available for a breach of the foregoing restrictions, in the event an Affiliate of an Operating Party takes any of the actions described in subsections (i) or (ii) above, the other Operating Party shall have the right to immediately terminate this subsection 3.10(a) with respect to itself and its Affiliates upon written notice and in the event of such termination shall no longer be subject to the restrictions set forth in this Section 3.10(a).

(b) Each Operating Party further undertakes that (i) it shall not, and shall cause its Affiliates not to, enter into any undertaking with a Third Party which would prohibit such Operating Party from Developing and/or Commercializing any Product hereunder, and (ii) at the time a proposal is made for the inclusion of a Product for Development and Commercialization pursuant to this Agreement, each Operating Party will disclose to the other Operating Party ************.

 

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3.11 Third Party Patent Rights . In the event that a license under any Third Party patent or other intellectual property right is necessary for the use, Development, manufacture, sale, offer for sale or importation of a Product, the costs of obtaining and maintaining such license shall be ************.

3.12 Effect of Bankruptcy on License Grants . All rights and licenses granted under or pursuant to this Agreement by any Party are, and will otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that each Party, as a licensee of such rights under this Agreement, will retain and may fully exercise all of such Party’s rights and elections under the U.S. Bankruptcy Code.

ARTICLE 4

COLLABORATION GOVERNANCE

4.1 Team Leaders/Project Managers . Within ************ after the Effective Date, each Operating Party shall designate an individual (each, a “ Team Leader ”) to facilitate communication among the Parties and mutually manage the objectives and activities of the Parties, as specified by the JSC, with respect to the Development and Commercialization of Products under this Agreement and who will be the primary contact person within each Operating Party’s organization for matters pertaining to the Collaboration hereunder. Each Operating Party may change its designated Team Leader from time to time upon notice to the other Operating Party and to LFB/GTC LLC, it being acknowledged by both Operating Parties that they should endeavor to maintain continuity to the maximum extent practicable. In addition, with respect to each Product to be Developed within the Collaboration as decided by the JSC, the Originating Party shall designate an individual (each such individual a “ Project Leader ”) who will be responsible for the management of the Development of such Product and, if the JSC deems appropriate, for its Commercialization. The non-Originating Party will also designate an individual (a “ Project Liaison ”) to work closely with the Project Leader with respect to such Development and Commercialization and who will have overall responsibility within such other Operating Party for oversight of such Product. The same individuals may be Team Leaders and Project Leaders/Project Liaisons. Neither the Team Leaders nor the Project Leaders shall have authority to make decisions with respect to the Development or Commercialization of Products, which authority shall be within the sole power of the JSC.

4.2 Joint Steering Committee; Minutes . The Joint Steering Committee shall be responsible for the operational management of the Collaboration. The same individuals shall be members of the JSC and the Management Committee of LFB/GTC LLC under the LLC Agreement and the members of the JSC shall, to the extent practicable, schedule meetings of the JSC and the Management Committee of LFB/GTC LLC on the same day. The chairperson of the JSC shall be responsible for providing an agenda for each meeting of the JSC

 

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************ in advance of such meeting. Agenda items shall be added at the request of either Operating Party provided that the chairperson receives such request no later than ************ in advance of such meeting. The chairperson of the JSC (or the vice chairperson) shall prepare written draft minutes of all meetings in reasonable detail and distribute such draft minutes to all members of the JSC for comment and review within ************ after the relevant meeting. The members of the JSC shall have ************ to provide comments. The chairperson (or the vice chairperson) shall incorporate timely received comments and distribute finalized minutes to all members of the JSC within ************ following the relevant meeting.

4.3 Subcommittees . As provided in the LLC Agreement, the JSC shall have the right to establish subcommittees as determined by the JSC. GTC and LFB Biotech, through LFB-US, shall have the right to have ************ serve on each subcommittee.

4.4 Responsibilities of the JSC . In addition to its other responsibilities and activities expressly described in this Agreement and the LLC Agreement, the JSC shall have the responsibility and authority to: (a) monitor and oversee all aspects of the Development and Commercialization of Products under this Agreement; (b) agree upon, adopt and/or amend or modify the Development Plans, Commercialization Plans and Product Participation Models, and all updates or amendments thereto; (c) establish and approve budgets for the activities of the Operating Parties under this Agreement to be included in the Development Plans and Commercialization Plans; (d) establish subcommittees pursuant to Section 4.3, and address disputes or disagreements arising in any subcommittee so established; (e) serve as the initial forum for discussion of and attempts to resolve any disputes or disagreements between the Operating Parties relating to this Agreement; (e) approve the design of clinical trials for studies that form the basis of Regulatory Filings; (f) oversee the Regulatory Approval process for all Products and create mechanisms for interaction of the Operating Parties with respect to submission of Regulatory Filings; (g) coordinate efforts of the Operating Parties to assure proper reporting of all adverse events; (h) develop standard operating procedures for addressing customer inquiries and complaints; (i) make decisions in such other matters pertaining to the implementation of this Agreement as may be necessary; and (j) perform such other functions as the Parties may agree in writing.

4.5 Decisions . The JSC shall attempt to decide all matters by consensus, in accordance with the LLC Agreement. The members of the JSC shall act in good faith to cooperate with one another and to reach agreement with respect to issues to be decided by the JSC. In the event that the members of the JSC cannot achieve consensus within ************ with respect to any matter over which the JSC has authority and responsibility, the JSC shall refer the matter to Senior Management of GTC and LFB Biotech, who shall in good faith attempt to resolve such dispute. If Senior Management of GTC and LFB Biotech are unable to resolve such matter with ************ thereafter, then, at the request of either of the Operating Parties, the matter shall be submitted to non-binding mediation by a mutually agreed independent third party knowledgeable as to the matter(s) in dispute who shall render his/her decision within ************. If both Operating Parties do not accept the decision of such mediator within ************ after such decision having been rendered, or if the Operating Parties have not agreed on a mediator within ************ after a request for mediation, then, subject to the rights and obligations of the Operating Parties under this Agreement, and, except for those matters expressly excluded from arbitration hereunder, the matter shall be referred to arbitration as described in Section 15.2.

 

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ARTICLE 5

DEVELOPMENT PHASE

5.1 Development Plan.

(a) All Development with respect to any Product hereunder shall be conducted pursuant to a Development Plan prepared and approved by the JSC, which shall set forth the plan for the pre-clinical and clinical Development, and Regulatory Approval of such Product in each of the European Territory, the North American Territory and the Co-Exclusive Territories and the activities to be carried out related thereto by LFB Biotech and GTC on behalf of LFB/GTC LLC, together with a proposed budget for such activities (each, a “ Development Plan ”). The Development Plan for the Initial Product (the “ Initial Development Plan ”) has been agreed to by the Parties. Each Development Plan and updated Development Plan shall include a projection of (a) the plan of Development activities with respect to the relevant product and timelines for performing such activities, (b) the proposed budget for such Development activities, (c) expected Development funding by each Operating Party, and (d) a non-binding forecast of clinical supply of Product to be supplied as provided under Article 7. The Development Plan for a Product shall also specify the jurisdictions (other than the US and EU) where Regulatory Approval will be sought for such Product and prospective indication extension after the First Major Regulatory Approval. Such business case shall be reviewed and updated on a regular basis by the JSC.

(b) For so long as necessary to complete Development of any Product, the Operating Parties, through the JSC, shall update the Development Plan with respect to such Product on an annual basis prior to the commencement of the next calendar year, or more often as determined by the JSC.

(c) The JSC will review performance against the Development Plan for each Product on a quarterly basis, and will report any variations to the Operating Parties in writing. If, in any quarter, there is a variation of ************ or greater from the budget, the JSC will revise the Development Plan and budget for the applicable Product ************ prior to the commencement of the second quarter following the quarter in which the variation occurred. For example, if a ************ variation is reported in quarter one, a revised Development Plan and budget must be prepared at least ************ prior to the commencement of quarter three.

(d) Until such time as a Development Plan is updated in accordance with this Section 5.1, the preceding Development Plan (including, without limitation, all budget projections and minimum expenditures therein) shall remain in effect. The JSC shall not update any Development Plan in a manner that is inconsistent with or contradicts the terms of this Agreement.

 

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5.2 Development Activities.

(a) General . Each Operating Party shall be responsible for carrying out its designated activities relating to Development of the relevant Product on behalf of LFB/GTC LLC, as set forth in and in accordance with this Agreement, the LLC Agreement and the applicable Development Plan. Each Operating Party will commit those financial and human resources specified for such Operating Party in the Development Plan for each Product, it being acknowledged that (i) neither Operating Party is required to commit all its financial and human resources to the implementation of a Development Plan, and (ii) those capital and human resources utilized by an Operating Party to the Development of Products hereunder are not required to be exclusively dedicated to the Collaboration.

(b) LFB Biotech Development Activities . The designated Development activities undertaken by LFB Biotech on behalf of LFB/GTC LLC as specified in the applicable Development Plan shall be referred to as the “ LFB Biotech Development Activities ”. In its performance of the LFB Biotech Development Activities with respect to any Product, LFB Biotech shall devote no less than the minimum levels of effort (in terms of full-time equivalent personnel “ FTEs ”) and financial resources as set forth in the applicable Development Plan. Without limiting the foregoing, the LFB Biotech Development Activities with respect to the Initial Product shall include the following:

(i) Generate and supply to GTC reasonable quantities of rFVIIa produced by ************ for use by GTC in the performance of its activities under this Agreement and the Initial Development Plan, ************.

(ii) Provide Know-How and expertise in the areas of process development, purification and product characterization, design and management of clinical trials, regulatory affairs, sales and marketing, plasma proteins and monoclonal antibodies.

(iii) Under the direction and supervision of the JSC, and in accordance with the Initial Development Plan, assume primary responsibility for clinical trials in the Territory for the Initial Product pursuant to Section 5.7(b).

(c) GTC Development Activities . The designated Development activities undertaken by GTC on behalf of LFB/GTC LLC as specified in the applicable Development Plan shall be referred to as the “ GTC Development Activities ”. In its performance of the GTC Development Activities with respect to any Product, GTC shall devote no less than the minimum levels of effort (in terms of FTEs) and financial resources as set forth in the applicable Development Plan. Without limiting the foregoing, the GTC Development Activities with respect to the Initial Product shall include the following:

(i) Generate rFVIIa Goats using GTC’s ************ to be used for production of rFVIIa pursuant to this Agreement.

 

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(ii) Provide all necessary GTC Technology for purposes of herd development, including for transgenic production of proteins in milk, purification technology and promoters.

(iii) Provide Know-How and expertise in the areas of regulatory affairs, quality systems, molecular biology, embryology, animal husbandry and milking, process development and product recovery and purification.

(iv) Manufacture and supply rFVIIa material to LFB Biotech ************ in sufficient quantities for Phase II Trials and Phase III Trials during the Development Phase, and to the Operating Parties as specified below during the Commercialization Phase.

5.3 Diligence Requirements.

(a) Development Milestones . The Operating Parties shall agree on objective time-based Development milestones with respect to each Product for each of the European Territory, the North American Territory and the Co-Exclusive Territory, which shall be included in the Development Plan for each Product. Each Operating Party will be responsible for meeting the milestones in its respective exclusive Territory and in each country or region in the Co-Exclusive Territory designated to such Operating Party in the applicable Development Plan.

(b) Failure to Meet Development Milestones . The failure of an Operating Party to achieve any Development milestone for a Product shall ************.

5.4 Development Costs.

(a) Initial Product . Unless otherwise specified in the applicable Development Plan, this Agreement or the LLC Agreement, subject to Section 5.7(b)(ii), each Operating Party shall bear ************ costs and expenses incurred in connection with its respective Development Activities with respect to the Initial Product, as such costs are incurred. Notwithstanding the foregoing, LFB Biotech shall purchase from GTC quantities of the Initial Product for the conduct of the LFB Biotech Development Activities in the European Territory and the Co-Exclusive Territory pursuant to the applicable Development Plans, as set forth in Article 7.

(b) Other Products . Unless otherwise specified in the applicable Development Plan, this Agreement or the LLC Agreement, subject to Section 8.2(c), each Operating Party shall bear fifty percent (50%) of the costs and expenses incurred in connection with the Development of each Product other than the Initial Product.

5.5 Right of Reference to Data . Subject to this Section 5.5, the Operating Party conducting any clinical trial or other Development Activities under the relevant Development Plan shall own all data arising or resulting therefrom; provided that ownership of Regulatory Filings and Regulatory Approvals shall be determined in accordance with Sections 5.8 and

 

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5.9, respectively. Each Operating Party and LFB/GTC LLC agrees to provide the other Operating Party and LFB/GTC LLC, as the case may be, in a timely manner, with access to all clinical, safety and other data arising from its respective Development Activities. The other Operating Party and LFB/GTC LLC shall have the right to cross-reference all such data and information in any Regulatory Filing for any Product under this Agreement.

5.6 Transfer of Know-How . Within ************ of the preparation of the preliminary Development Plan with respect to any Product hereunder, each Operating Party shall disclose and transfer to the other Operating Party and LFB/GTC LLC all Know-How Controlled by such Operating Party and its Affiliates not previously disclosed hereunder that is necessary or useful to the other Operating Party in the performance of its obligations on behalf of LFB/GTC LLC under this Agreement with respect to such Product. Throughout the Product Term with respect to each Product, each Operating Party will disclose and supply to the other Operating Party and LFB/GTC LLC from time to time any material modifications or updates to the Know-How Controlled by such Operating Party or its Affiliates that are necessary or useful to the other Operating Party in the performance of its obligations under this Agreement with respect to such Product. The transfer of Know-How pursuant to this Section 5.6 may occur by means of written documentation, personal consulting or other communications between the Operating Parties and LFB/GTC LLC, or by demonstration (show-how). All Know-How transferred hereunder shall be used by the Operating Party receiving the same solely in accordance with this Agreement and the LLC Agreement and shall be the Confidential Information of the Operating Party providing the same.

5.7 Conduct of Clinical Trials .

(a) General . The clinical Development and Regulatory Approval program with respect to each Product, and the respective activities and responsibilities of each Operating Party with respect thereto, shall be included in the Development Plan for such Product. It is the intention of the Parties that all clinical studies for Products shall be conducted in a manner such that the results will be acceptable to Regulatory Authorities in the European Territory and the North American Territory, as well as the Co-Exclusive Territory to the extent reasonably possible. Unless otherwise specified in the applicable Development Plan, subject to Section 8.2(c), each Operating Party shall bear fifty percent (50%) of the costs and expenses incurred in connection with the clinical studies of each Product other than the Initial Product.

(b) Initial Product .

(i) Conduct of Phase II Trials and Phase III Trials by LFB Biotech . Under the direction and supervision of the JSC, LFB Biotech shall, on behalf of LFB/GTC LLC, have primary responsibility for the conduct of Phase II Trials and Phase III Trials for the Initial Product in the entire Territory in accordance with this Agreement and the applicable Development Plan. ************ data from such Phase II Trials and Phase III Trials shall be fully shared with GTC and LFB/GTC LLC, and such data may be used by both Operating Parties in applications for Regulatory Approval pursuant to Section 5.8.

 

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(ii) Funding of Clinical Development . LFB Biotech will bear all costs of clinical trials with respect to the Initial Product in the entire Territory, subject to GTC’s option to co-fund as provided below. GTC shall have the option, but not the obligation, to fund up to ************ of the costs of clinical trials with respect to the Initial Product in the Territory. GTC may exercise such option by providing LFB Biotech with written notice of its election to co-fund at any time prior to ************ with respect to the Initial Product together with payment of the amount of funding GTC is willing to contribute. If GTC elects not to participate, or not to fully participate, in the funding of clinical trials with respect to the Initial Product, the Product Participation with respect to the Initial Product shall be adjusted in accordance with the Product Participation Model on Exhibit B to reflect LFB Biotech’s greater participation in the funding of clinical trials, subject to readjustment pursuant to Section 8.2(b)(iv). Notwithstanding the foregoing, provided that GTC’s participation in the funding of the Development of the Initial Product is at least ************ of the total IPV, GTC’s Product Participation with respect to the Initial Product shall be no less than ************.

5.8 Regulatory Filings and Approvals .

(a) Preparation of Proposed Regulatory Filings . The Parties agree to seek Regulatory Approvals from the FDA, the EMEA, and the applicable Regulatory Authorities in each of the other countries listed in the applicable Development Plan, as may be amended by the Parties from time to time. LFB Biotech shall, subject to Section 5.9, prepare all Regulatory Filings for Products in the European Territory. GTC shall, subject to Section 5.9, prepare all Regulatory Filings for Products in the North American Territory. The JSC shall determine, on a country-by-country basis, which Operating Party shall be responsible for preparing Regulatory Filings and Regulatory Approvals in the Co-Exclusive Territory. All such Regulatory Filings shall be prepared in accordance with the applicable Development Plan and all applicable laws and regulations. Each Operating Party shall submit to the other Parties each proposed Regulatory Filing for the other Parties’ review and comment. The reviewing Parties shall notify the Operating Party responsible for such Regulatory Filing in writing of any proposed modifications to such Regulatory Filing as soon as reasonably practicable after receipt of such filing, and the Operating Party preparing such Regulatory Filing shall consider, in good faith, whether to implement such proposed modifications; provided that the Operating Party responsible for making such Regulatory Filing shall have the right to make the final determination, in its sole discretion, as to the form and substance of such Regulatory Filing.

(b) Submission to Regulatory Authorities . Each Operating Party agrees to use Commercially Reasonable Efforts to file promptly, in its own name, all Regulatory Filings finalized in accordance with Section 5.8(a) with the proper Regulatory Authority.

(c) Copies of Regulatory Filings . Each Operating Party shall provide to the other Parties copies of all Regulatory Filings for Products submitted to Regulatory Authorities in the Territory within a reasonable time following the filing thereof. In addition, the Parties shall share all correspondence and communications, other than Regulatory Filings, with Regulatory Authorities relating to a Product in the Territory.

 

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(d) Interactions with Regulatory Authorities . The Operating Party responsible for making a Regulatory Filing pursuant to this Section 5.8 shall also be responsible for and control all interactions with Regulatory Authorities with respect to such Regulatory Filing on behalf and for the benefit of LFB/GTC LLC. To the extent practicable, each Operating Party shall provide to the other Parties reasonable advance written notice of meetings and conference telephone calls with any Regulatory Authority related to the Product in the Territory, and shall use Commercially Reasonable Efforts to invite one senior executive or regulatory counsel of the other Parties to attend meetings with such Regulatory Authorities as a silent observer, if and to the extent permitted by the relevant Regulatory Authority.

5.9 Ownership of Regulatory Approvals . Subject to Section 5.5, LFB Biotech shall own and maintain all Regulatory Filings and all Regulatory Approvals that relate to the Product in the European Territory. LFB/GTC LLC shall own and maintain all Regulatory Filings and all Regulatory Approvals that relate to the Product in the United States and, unless otherwise decided by the JSC, the rest of the world.

ARTICLE 6

COMMERCIALIZATION PHASE

6.1 Commerci