DEVELOPMENT, LICENSE AND COMMERCIALIZATION AGREEMENT

EXHIBIT 10.219

EXECUTION COPY

September 25, 2008

CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTIONS OF THIS DOCUMENT HAVE BEEN REDACTED AND HAVE BEEN FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION

DEVELOPMENT, LICENSE AND COMMERCIALIZATION AGREEMENT

by and between

INDEVUS PHARMACEUTICALS, INC.

and

TEVA PHARMACEUTICAL INDUSTRIES LTD.

TABLE OF CONTENTS

 

THIS DEVELOPMENT, LICENSE AND COMMERCIALIZATION AGREEMENT (the “Agreement”) is made as of September 25, 2008 (“Agreement Date”), by and between INDEVUS PHARMACEUTICALS, INC. , a corporation organized and existing under the laws of the State of Delaware and having its principal office at 33 Hayden Avenue, Lexington, MA 02421, United States (“Indevus”) and TEVA PHARMACEUTICAL INDUSTRIES LTD. , a limited liability company existing under the laws of Israel and having its principal office at Petah Tiqva 49131, Israel (“Teva”).

B A C K G R O U N D:

Indevus owns or Controls the Indevus Intellectual Property relating to Compound for the treatment of stuttering;

Teva and its Affiliates have significant experience in the development, marketing, promotion and sale of pharmaceutical products, and Teva desires to obtain on the Effective Date the exclusive worldwide right and license in the Territory under the Indevus Intellectual Property to further develop and thereafter Commercialize the Product for all possible indications in the Field (including for stuttering) and Indevus desires to grant to Teva on the Effective Date such exclusive worldwide right and license, on and subject to the terms and conditions set forth herein; and

Indevus and Teva desire to conduct certain Development for the U.S. market, all on and subject to the terms and conditions set forth below.

NOW, THEREFORE, in consideration of the mutual representations, warranties and covenants herein contained, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:

ARTICLE 1

DEFINITIONS

Unless specifically set forth to the contrary herein, the following terms, where used in the singular or plural, shall have the respective meanings set forth below:

1.1 “ Act ” means the United States Food, Drug, and Cosmetic Act of 1938, as amended, and the rules and regulations promulgated thereunder, or any successor act, as the same shall be in effect from time to time.

 

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1.2 “ Affiliate ” means with respect to a Party (i) any corporation or business entity of which more than fifty percent (50%) of the securities or other ownership interests representing the equity, the voting stock or general partnership interest are owned, controlled or held, directly or indirectly, by such Party; (ii) any corporation or business entity which, directly or indirectly, owns, controls or holds more than fifty percent (50%) (or the maximum ownership interest permitted by law) of the securities or other ownership interests representing the equity, voting stock or general partnership interest of such Party; (iii) any corporation or business entity of which, directly or indirectly, an entity described in the immediately preceding subsection (ii) controls or holds more than fifty percent (50%) (or the maximum ownership interest permitted by law) of the securities or other ownership interests representing the equity, voting stock or general partnership interest of such corporation or entity; or (iv) any corporation or business entity of which such Party has the right to acquire, directly or indirectly, more than fifty percent (50%) of the securities or other ownership interests representing the equity, voting stock or general partnership interest thereof.

1.3 “ Agreement Date ” has the meaning set forth in the preamble hereof.

1.4 “ Agreement Term ” has the meaning set forth in Section 9.1(a).

1.5 “ Authorized Generic Product ” has the meaning set forth in Section 2.4.

1.6 “ Authorized Generic Royalty Term ” means, in each country in the Territory, the period commencing on the date of First Commercial Sale of an Authorized Generic Product in the applicable country and expiring on the date of First Commercial Sale of the [***] Generic Product in such country.

1.7 “ Bankruptcy Code ” has the meaning set forth in Section 9.3.

1.8 “ Breaching Party ” has the meaning set forth in Section 9.2(b)(i).

 

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1.9 “ Business Day ” means any calendar day, except that if an activity to be performed or an event to occur falls on a Friday, Saturday, Sunday or a day which is recognized as a national holiday in the place of performance of an applicable activity or occurrence of an applicable event, then the activity may be performed or the event may occur on the next day that is not a Friday, Saturday, Sunday or nationally recognized holiday.

1.10 “ Calendar Quarter ” means for each Calendar Year, each of the three month periods ending March 31, June 30, September 30 and December 31; provided , however , that (a) the last Calendar Quarter of the U.S. Collaboration Period shall commence on the first day of the Calendar Quarter in which the U.S. Collaboration Period terminated and expire on the effective date of termination of the U.S. Collaboration Period, (b) the first Calendar Quarter of the Royalty Term for the United States shall commence on the first day of the U.S. License Period and expire at the end of the Calendar Quarter in which the U.S License Period commenced, (c) the first Calendar Quarter of any other period specified under this Agreement shall extend from the commencement of such period to the end of the first complete Calendar Quarter thereafter; and (d) the last Calendar Quarter shall end upon the expiration or termination of this Agreement.

1.11 “ Calendar Year ” means, for the first Calendar Year, the period commencing on the Effective Date and ending on December 31, 2008, and for each year thereafter, each successive period beginning on January 1 and ending twelve (12) consecutive calendar months later on December 31.

1.12 “ C.F.R. ” means the United States Code of Federal Regulations, as amended from time to time.

1.13 “ Change of Control ” means with respect to a Party, the occurrence of any of the following:

(a) any Third Party that was not, on the Effective Date, the beneficial owner, directly or indirectly, of more than fifty percent (50%) of the voting equity of such Party becomes (after the Effective Date) the beneficial owner, directly or indirectly, of more than fifty percent (50%) of the voting equity of such Party whether as a result of issuances, redemptions, repurchases or transfers of voting equity or otherwise; or

 

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(b) such Party consolidates with, or merges with or into, a Third Party or sells, assigns, conveys, transfers, leases or otherwise disposes of all, or substantially all, of its assets to a Third Party, or a Third Party consolidates with, or merges with or into, such Party, in any such event pursuant to a transaction in which the outstanding voting equity of such Party is converted into or exchanged for cash, securities, equity interests or other property and immediately after such transaction the persons who were the beneficial owners of the outstanding voting equity of such Party immediately prior to the transaction are not the beneficial owners, directly or indirectly, of more than fifty percent (50%) of the total voting equity of the surviving or transferee entity.

For purposes of this Agreement, any such Third Party or surviving or transferee entity resulting from any of the foregoing is referred to as a “ Successor Entity ” of the applicable Party.

1.14 “ Claims ” has the meaning set forth in Section 10.2.

1.15 “ Clinical Data Review ” has the meaning set forth in Schedule 1.64(a) .

1.16 “ Clinical Studies ” means any clinical studies of Product conducted on humans.

1.17 “ Commercialization ” and “ Commercialize ” means those activities undertaken with respect to the commercialization of Product, including promotion, marketing, sale, supply, manufacturing, purchasing, procurement, warehousing, import, export, distribution, educational activities, post-approval Clinical Study activities and pre-launch activities.

1.18 “ Commercially Reasonable Efforts ” means exerting such efforts and employing such resources as would normally be exerted or employed by the applicable Party for its other drug candidates and pharmaceutical products of a comparable stage of development and commercial potential, taking into account the cost effectiveness of efforts or resources, the competitiveness of alternative compounds or products that are or are expected to be in the marketplace, the patent and other proprietary position of the compound or product, the profitability of the compound or product and alternative compounds or products and other relevant commercial factors.

 

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1.19 “ Competing Product ” means any pharmaceutical product that is approved by the applicable Regulatory Authority with a labeled indication for stuttering.

1.20 “ Compound ” means [***] or pagoclone, as diagrammed on Schedule 1.20 and any pharmaceutically acceptable salts, hydrates, solvates, metabolites, enantiomers, amides, prodrugs and esters of the foregoing, or mixtures thereof.

1.21 “ Control ” means possession of the ability to grant a license or sublicense as provided for herein without violating the terms of any agreement or arrangement with any Third Party.

1.22 “ CSC ” means the Central Steering Committee formed by the Parties in accordance with Article 3.

1.23 “ Data ” means any and all research data, pharmacology data, preclinical data, clinical data, Chemistry, Manufacturing and Control (“CMC”) data and/or all other similar documentation generated in connection with the Compound or Product.

1.24 “ Data Management Plan ” has the meaning set forth in Schedule 1.64(a) .

1.25 “ Database Lock ” means, with respect to the Next Trial, the stage in which the clinical trial database is ready for code opening and analysis of the trial results, as described in Schedule 1.64(a) .

1.26 “ Decision Point ” means any date on which the following events occur during the U.S. Collaboration Period:

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[***]

1.27 “ Development ” means those activities undertaken with respect to the Compound or Product which are devoted to the exploration of a potential pharmaceutical product, including Clinical Studies and any other activities directed toward quality issues, publication, or as part of the process of obtaining Regulatory Approval of such Compound or Product.

1.28 “ Disputed Claim ” has the meaning set forth in Section 10.4(b).

1.29 “ Dollar ” or “ $ ” means the lawful currency of the United States.

1.30 “ Drug Approval Application ” means an application for Regulatory Approval required before commercial sale or use of a Product as a pharmaceutical product in a regulatory jurisdiction.

1.31 “ Effective Date ” means the date on which the waiting period, if any, under the HSR Act with respect to the transactions contemplated hereunder has expired or has been terminated.

1.32 “ EMEA ” means the European Medicines Agency and any successor agency thereof having substantially the same functions or, if the mutual recognition procedure is used for the Product in the EU, any governmental authority having the authority to regulate the sale of medicinal or pharmaceutical products in any country in the EU.

1.33 “ End-of-Phase II Meeting ” means Teva’s meeting with the FDA consistent with 21 C.F.R. Section 312.47(b)(1).

1.34 “ EU ” means all countries that are member states of the European Union at any time during the Agreement Term.

1.35 “ EU Major Market ” means any one of the following countries: United Kingdom, France, Germany, Italy or Spain.

 

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1.36 “ FDA ” means the Food and Drug Administration of the United States Department of Health and Human Services and any successor agency having substantially the same functions.

1.37 “ FDA Approval ” means all authorizations by the FDA which are required for the marketing of a Product in the United States as defined in 21 C.F.R. Section 314.105.

1.38 “ Field ” means the prevention, diagnosis or treatment of any disease or medical condition in humans.

1.39 “ First Commercial Sale ” means the first sale to a Third Party for end use or consumption of an applicable product in a country after receipt of Regulatory Approval in such country or, where Regulatory Approval is not required, then the first sale for end use or consumption of a product to a Third Party in that country in connection with the nationwide introduction of such product.

1.40 “ First Period Plan and Budget ” means the plan setting forth (a) activities and estimated timelines relating to Development and Commercialization throughout the Territory, including a description of activities designed to generate clinical, manufacturing and regulatory information required for filing the first NDA in the United States, and (b) the budget setting forth costs estimated to be incurred in performing such activities (the “ First Period Budget Costs ”), both in the aggregate and by Calendar Year, for the period commencing on the date Teva issues the Go Decision and ending on the date that is forecasted therein for the submission of the first NDA for the initial indication of Product (the “ First Period Plan and Budget Period ”), submitted by Teva to Indevus pursuant to Section 4.4(c)(i), and all revisions, amendments or updates thereto submitted by Teva to Indevus pursuant to Section 4.4(c)(ii). First Period Budget Costs shall include the external out-of-pocket costs and expenses incurred by and on behalf of Teva and its Affiliates and the costs of such activities performed by Teva’s FTEs, valued at the then current Teva FTE reimbursement rate, and consistent with Schedule 1.40 , but shall exclude any costs and expenses incurred for (x) Development activities conducted solely for Regulatory Approval outside the United States, and (y) Commercialization activities conducted solely for markets outside the United States.

 

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1.41 “ GAAP ” means generally accepted accounting principles in the United States, consistently applied.

1.42 “ Generic Competition ” shall be deemed to exist in a particular country as of any date if, during the [***] immediately preceding Calendar Quarters, (a) Generic Products have a market share in the applicable country of at least [***] of the then combined unit volume of Product and Generic Products, or (b) after the introduction of a Generic Product, Net Sales of Product decrease by at least [***] , provided that each of (a) and (b) herein shall be measured as an average taken over such [***] Calendar Quarters. If such market share or such decrease in Net Sales of Product is greater than [***] during the [***] immediately preceding Calendar Quarters in any country, similarly measured as an average taken over such [***] Calendar Quarters, then “ Substantial Level Generic Competition ” shall be deemed to exist in such country as of such date.

1.43 “ Generic Product ” means any product containing the Compound as an active ingredient sold by a Third Party (excluding, for these purposes, sublicensees of Teva).

1.44 “ Go Decision ” has the meaning set forth in Section 4.4(b).

1.45 “ HSR Act ” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended from time to time.

1.46 “ HSR Filing ” has the meaning set forth in Section 11.6(a).

1.47 “ Improvements ” means all inventions and Know-How, patentable or otherwise, made, created, developed, conceived or reduced to practice by or on behalf of a Party and/or any of its Affiliates pursuant to activities relating to or contemplated by this Agreement during the Agreement Term, that have application or relate to Compound or Product for use in the Field including developments in the manufacture, formulation, ingredients, preparation, presentation, means of delivery or administration, dosage, indication, methods of use or packaging and/or sale of Product.

1.48 “ IND ” means an Investigational New Drug application, as described in 21 C.F.R. Section 312.23, obtained for purposes of conducting clinical trials in accordance with the

 

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requirements of the Act and the regulations promulgated thereunder, including all supplements and amendments thereto relating to the use of Compound or Product in the Field, including IND Number [***] .

1.49 “ IND Transfer Date ” has the meaning set forth in Section 4.3.

1.50 “ Indevus Indemnified Parties ” has the meaning set forth in Section 10.1.

1.51 “ Indevus Intellectual Property ” means the Indevus Patent Rights and the Indevus Know-How.

1.52 “ Indevus Know-How ” means all Know-How that are as of the Agreement Date or become as a result of the Next Trial owned or Controlled by Indevus.

1.53 “ Indevus Patent Rights ” means all Patent Rights (a) that are owned or Controlled by Indevus as of the Agreement Date, and/or (b) which arise from inventions made, conceived, discovered, reduced to practice or generated during Development activities conducted by Indevus prior to the Go Decision, in each case including (i) any and all Indevus Patent Rights that are not SA Patents (the “ Assignable Patents ”), including the Patent Rights listed in Schedule 1.53(A) ; and (ii) any and all Patent Rights that are licensed to Indevus pursuant to the SA Agreement (the “ SA Patents ”), including the Compound Patent Rights listed in Schedule 1.53(B) and the Patent Rights listed in Schedule 1.53(C) (as each of such terms is defined in the SA Agreement), which schedule shall be updated as necessary from time to time.

1.54 “ Indevus Transition Team ” has the meaning set forth in Section 4.2(b).

1.55 “ Insurance ” has the meaning set forth in Section 10.6(a).

1.56 “ Intellectual Property ” means Patent Rights and Know-How, collectively.

1.57 “ Know-How ” means all proprietary information and technology, including trade secret information, developments, discoveries, methods, techniques, formulations, data, and other information, whether or not patentable, that relate to the Compound, Product or any Improvement, including methods relating to their development, manufacture or use and which are not disclosed or covered in Patent Rights.

 

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1.58 “ Law(s) ” means all laws, statutes, rules, regulations, ordinances and other pronouncements having the binding effect of law of any governmental authority.

1.59 “ Losses ” means any and all damages, awards, deficiencies, settlement amounts, defaults, assessments, fines, dues, penalties (including penalties imposed by any governmental authority), costs, fees, liabilities, obligations, taxes, liens, losses, lost profits and expenses (including court costs, interest and reasonable fees of attorneys, accountants and other experts) awarded or otherwise paid or payable to Third Parties.

1.60 “ NDA ” means a new drug application submitted to the FDA to obtain approval for the marketing of the Product in the United States, together with all subsequent submissions, supplements and amendments thereto.

1.61 “ Net Sales ” means the gross sales amount of Products (or, in the case of Sections 5.3(a)(v), 5.4(d), 5.5(c), 5.5(d) and 5.6, of Authorized Generic Products) invoiced to Third Parties by Teva, its Affiliates and sublicensees, less the following deductions only if recorded by Teva, its Affiliates and sublicensees as a reduction from gross to net sales and calculated in accordance with GAAP, except with respect to item (g) below, or to the extent included in such gross invoiced amount:

(a) quantity and/or cash discounts allocated to the applicable Product;

(b) customs, duties, sales and similar taxes;

(c) amounts allowed or credited by reason of rejections, return of goods (including as a result of recalls, market withdrawals and other corrective actions), and retroactive price reductions or allowances specifically identifiable as related to the sale of the Product;

(d) allowances and credits related to inventory management or similar agreements with wholesalers allocated to the applicable Product;

(e) amounts incurred resulting from government (or any agency thereof) mandated rebate programs in the Territory specifically identifiable as related to the sale of Product;

 

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(f) Third Party rebates, patient discount programs, administrative fees and chargebacks or similar price concessions specifically identifiable as related to the sale of the Product;

(g) bad debt recognized by Teva for accounting purposes as not collectible, adjusted for changes to reserve for bad debts;

(h) freight, packing, shipping or insurance;

(i) usual and customary commissions paid to agents or distributors to secure tender offers or other purchases by local authorities, to the extent specifically identifiable as related to the sale of Product; and

(j) as agreed by the Parties, such agreement not to be unreasonably withheld, any other specifically identifiable amounts included in a Product’s gross sales amount that were or ultimately will be credited and that are substantially similar to those listed above.

To the extent that such discounts, allowances, credits, rebates and other deductions are not specifically identifiable as related to Product, they shall be fairly and equitably allocated to the applicable Product and, to the extent applicable, other products or services of Teva or its Affiliates such that the Products do not bear a disproportionate portion of such deductions. For the avoidance of doubt, Net Sales shall not include sales by Teva to its Affiliates or sublicensees for resale; provided that , if Teva sells the Product to an Affiliate or sublicensee for resale, then the Net Sales calculation shall include the amounts invoiced by such Affiliate or sublicensee to Third Parties on the resale of the Product. For purposes of this Agreement, “sale” shall not include transfers or other distributions or dispositions of the Product, at no charge, for regulatory purposes, clinical trials, samples, free products or in connection with patient assistance programs or other charitable purposes or to physicians or hospitals for promotional purposes. The Product shall be considered “sold” only when billed or invoiced.

No amount included in subsections (a)-(j) above shall be included in the costs used by Teva under Section 1.91 in the calculation of the U.S. Gross Margin.

 

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1.62 “ Next Trial ” means the Phase II Clinical Study relating to Product, the protocol for which shall be agreed upon by the Parties as promptly as practicable but not later than [***] before the commencement of the Next Trial, which protocol shall be consistent with the budget setting forth costs associated with the Next Trial (the “ Next Trial Costs ”), as described in detail in Schedule 4.4(b) (the “ Next Trial Budget ”), the synopsis attached hereto as Schedule 1.62 , and the draft of which has been delivered by Indevus to Teva for its review and final comments (the “ Next Trial Protocol ”).

1.63 “ Next Trial Completion ” means the date of the Database Lock.

1.64 “ Next Trial Report ” has the meaning set forth in Section 4.4(b).

1.65 “ No Go Decision ” has the meaning set forth in Section 9.2(a)(i).

1.66 “ Party ” means Indevus or Teva.

1.67 “ Parties’ Patent Rights ” has the meaning set forth in Section 7.3(a).

1.68 “ Patent Rights ” means any patents, patent applications, certificates of invention, or applications for certificates of invention and any supplemental protection certificates, together with any extensions, registrations, confirmations, reissues, substitutions, divisions, continuations or continuations-in-part, reexaminations or renewals thereof that relate to the Compound, Product or any Improvement, including methods of development, manufacture or use invented pursuant to this Agreement and relating solely to the Compound or Product.

1.69 “ Primary Endpoint ” [***]

1.70 “ Product ” means any pharmaceutical preparation in final form (or, where the context so indicates, the form under development) containing the Compound as a primary active therapeutic ingredient, which requires a prescription from a physician or other health care professional, for use in the Territory. For purposes of clarity, “Product” does not include “Authorized Generic Product”.

1.71 “ Product Label(ing) ” shall have the same meaning as defined in the Act and as interpreted by the FDA.

 

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1.72 “ Proprietary Information ” means any and all scientific, clinical, regulatory, marketing, financial and commercial information or data, whether communicated in writing, orally or by any other means, which is owned and under the protection of one Party and is provided by that Party to the other Party in connection with this Agreement, and shall include Indevus Know-How and Teva Know-How, as applicable.

1.73 “ Regulatory Approval ” means approval by the relevant Regulatory Authority of an NDA or other Drug Approval Application, notice of compliance and any other license or permit required to be approved for the manufacture, use, storage, import, export, transport and sale of Product in a regulatory jurisdiction.

1.74 “ Regulatory Authority ” means any governmental or other competent authority in a country, region or other regulatory jurisdiction, including the FDA and the EMEA, that regulates the manufacture, use, storage, import, export, transport and sale of any Product.

1.75 “ Regulatory Documents ” has the meaning set forth in Section 4.3.

1.76 “ Royalty Conversion Event ” has the meaning set forth in Section 5.3(b).

1.77 “ Royalty Term ” means the period (a) commencing (i) in the United States, on the first day of the U.S. License Period, and (ii) in each country in the Territory other than the United States [***] , on the date of First Commercial Sale of Product by Teva, its Affiliates or sublicensees in the applicable country; and (b) expiring on the later of either (i) the expiration or invalidation of the last Valid Claim in the applicable country in the Territory or (ii) twelve (12) years from the date of First Commercial Sale of Product by Teva, its Affiliates or sublicensees in such country, subject in either case to early termination in the event of Substantial Level Generic Competition in the applicable country in the Territory.

1.78 “ SA Agreement ” means the License Agreement dated as of February 18, 1994 by and between Indevus (f/k/a Interneuron Pharmaceuticals, Inc.) and Sanofi-Aventis, SA (as successor to Rhone-Poulenc Rorer S.A.) (“ SA ”), as amended on October 29, 2001 and on March 27, 2008, a true and correct copy of which has been delivered to Teva concurrently with the execution of this Agreement.

 

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1.79 “ SEC ” means the United States Securities and Exchange Commission and any successor agency having substantially the same functions.

1.80 “ Second Period Plan and Budget ” means the plan setting forth (a) activities and estimated timelines relating to Development and Commercialization, including a description of the planned launch, educational, marketing and promotional activities related to Product for the initial indication in the United States, and (b) the budget setting forth costs estimated to be incurred in performing such activities (the “ Second Period Budget Costs ”), both in the aggregate and by Calendar Year, for the period commencing on the date of the submission of the first NDA for the initial indication of the Product and ending on the date that is forecasted therein to be twelve (12) months after the First Commercial Sale of Product in the United States by Teva, its Affiliates or sublicensees (the “ Second Period Plan and Budget Period ”), submitted by Teva to Indevus pursuant to Section 4.7(d)(i), and all revisions, amendments or updates thereto submitted by Teva to Indevus pursuant to Section 4.7(d)(ii). Second Period Budget Costs shall include the external out-of-pocket costs and expenses incurred by and on behalf of Teva and its Affiliates and the costs of such activities performed by Teva’s FTEs, valued at the then current Teva FTE reimbursement rate, and consistent with Schedule 1.40 , but shall exclude any costs and expenses incurred for (x) Development activities conducted solely for Regulatory Approval outside the United States, and (y) Commercialization activities conducted solely for markets outside the United States.

1.81 “ Significant Plan Amendment ” means:

(a) as used in Section 4.4(c), any revision, amendment or update to the First Period Plan and Budget that:

(i) for the period beginning on the date of the Go Decision and ending on and including the date of completion of the End-of-Phase II Meeting, would have the effect of increasing the First Period Budget Costs during any Calendar Year within the First Period Plan and Budget Period or the total aggregate First Period Budget Costs by an amount greater than [***] ;

and

 

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(ii) for the period beginning on the date immediately following the date of completion of the End-of-Phase II Meeting, would have the effect of increasing First Period Budget Costs by either:

(A) during any Calendar Year within the First Period Plan and Budget Period, the lesser of

1. an amount greater than a [***] increase of the First Period Budget Costs projected for such Calendar Year,

or

2. [***] ;

or

(B) an amount greater than a [***] increase from the total aggregate First Period Budget Costs included in the initial First Period Plan and Budget delivered to the CSC under Section 4.4(c)(i);

provided , however , that following the delivery by Teva of a revised First Period Plan and Budget pursuant to Section 4.4(c)(ii)(A), if such revision does not constitute a Significant Plan Amendment under Section 1.81(a)(ii)(A) or 1.81(a)(ii)(B) or it does constitute such a Significant Plan Amendment but Indevus does not deem the Decision Point set forth in Section 1.26(c) a Royalty Conversion Event pursuant to Section 5.3(b), then the First Period Budget Costs set forth in such revised First Period Plan and Budget delivered pursuant to Section 4.4(c)(ii)(A) will become the baseline for the determination of a Significant Plan Amendment under Section 1.81(a)(ii)(A) and 1.81(a)(ii)(B) for the remainder of the First Period Plan and Budget Period; and

(b) as used in Section 4.7(d) any revision, amendment or update to the Second Period Plan and Budget that:

(i) for the period beginning on the date of the submission of the first NDA for the initial indication of Product and ending on and including the date of FDA Approval of

 

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such NDA, would have the effect of increasing either the Second Period Budget Costs during any Calendar Year within the Second Period Plan and Budget Period or the total aggregate Second Period Budget Costs by the lesser of

(A) an amount greater than a [***] increase of such budget costs,

or

(B) $ [***] ;

and

(ii) for the period beginning the day immediately following the date of FDA Approval of the first NDA for the initial indication of Product and ending on and including the date forecasted to be twelve (12) months after the First Commercial Sale of Product by Teva, its Affiliates or sublicensees in the United States, would have the effect of increasing Second Period Budget Costs by either:

(A) during any Calendar Year within the Second Period Plan and Budget Period by the lesser of

1. an amount greater than a [***] increase of the Second Period Budget Costs projected for such Calendar Year,

or

2. [***] ;

or

(B) an amount greater than a [***] increase from the total aggregate Second Period Budget Costs included in the initial Second Period Plan and Budget delivered to the CSC under Section 4.7(d)(i);

provided , however , that following the delivery by Teva of a revised Second Period Plan and Budget pursuant to Section 4.7(d)(ii)(A), if such revision does not constitute a

 

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Significant Plan Amendment under Section 1.81(b)(ii)(A) or 1.81(b)(ii)(B) or it does constitute such a Significant Plan Amendment but Indevus does not deem the Decision Point set forth in Section 1.26(c) a Royalty Conversion Event pursuant to Section 5.3(b), then the Second Period Budget Costs set forth in such revised Second Period Plan and Budget delivered pursuant to Section 4.7(d)(ii)(A) will become the baseline for determination of a Significant Plan Amendment under Section 1.81(b)(ii)(A) and 1.81(b)(ii)(B) for the remainder of the Second Period Plan and Budget Period.

1.82 “ Successor Entity ” has the meaning set forth in Section 1.13.

1.83 “ Territory ” means the entire world.

1.84 “ Teva Indemnified Parties ” has the meaning set forth in Section 10.1.

1.85 “ Teva Know-How ” means all Know-How that becomes during the Agreement Term and pursuant to the terms of this Agreement owned or Controlled by Teva.

1.86 “ Teva Patent Rights ” means any Patent Right that becomes during the Agreement Term and pursuant to the terms of this Agreement owned or Controlled by Teva, which Patent Right discloses or claims subject matter resulting or derived from Development from and after the Go Decision.

1.87 “ Third Party(ies) ” means a person or entity who or which is neither a Party nor an Affiliate of a Party.

1.88 “ Third Party Agreements ” has the meaning set forth in Section 6.2(d).

1.89 “ Transition Period ” has the meaning set forth in Section 4.2(b).

1.90 “ U.S. Collaboration Period ” means, with respect to the United States, the period commencing on the Effective Date and, unless terminated earlier upon the occurrence of a Royalty Conversion Event pursuant to Section 5.3(b), expiring on the later of either (a) the expiration or invalidation of the last Valid Claim in the United States or (b) twelve (12) years from the date of First Commercial Sale of Product by Teva, its Affiliates or sublicensees in the United States.

 

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1.91 “ U.S. Gross Margin ” means, for a particular Calendar Quarter during the U.S. Collaboration Period, an amount equal to (a) Net Sales of Product in the United States for such Calendar Quarter, minus (b) either (i) during the Second Period Plan and Budget Period, the actual costs associated with activities set forth in the Second Period Plan and Budget or (ii) after the Second Period Plan and Budget Period, the actual costs associated with Commercialization and Development incurred by Teva consistent with Schedule 1.40 , in either case for such Calendar Quarter. Notwithstanding the foregoing, costs that would constitute a Significant Plan Amendment (whether incurred prior to or after delivery to Indevus of the Significant Plan Amendment) shall not be deemed costs included in the calculation of the U.S. Gross Margin hereunder if, within [***] after receipt of the required Significant Plan Amendment, Indevus deems such Significant Plan Amendment a Royalty Conversion Event pursuant to Section 5.3(b), provided , however , that all other costs incurred from and after Indevus’ receipt of such Significant Plan Amendment up to and including the date of a Royalty Conversion Event, if any, shall be included in the calculation of the U.S. Gross Margin.

1.92 “ U.S. License Period ” means, if the U.S. Collaboration Period is terminated upon the occurrence of a Royalty Conversion Event pursuant to Section 5.3(b), the period commencing on the day immediately following the effective date of such termination and continuing in effect until expiration or earlier termination of the Royalty Term.

1.93 “ Valid Claim ” means any claim issued in an unexpired Indevus Patent Right or Teva Patent Right which has not been held unenforceable, unpatentable or invalid by a decision of a court or other governmental agency of competent jurisdiction following exhaustion of all possible appeal processes, and which has not been admitted to be invalid or unenforceable through reissue, reexamination or disclaimer and has not been terminated for failure to pay maintenance fees.

1.94 “ Warner Assignment and License ” means the Assignment and License Agreement by and between Indevus and Warner Lambert Company LLC dated as of February 9, 2004, a true and correct copy of which has been delivered to Teva concurrently with the execution of this Agreement.

 

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1.95 “ Warner Know-How ” means the Warner Know-How, as such term is defined in the Warner Assignment and License.

ARTICLE 2

GRANT OF RIGHTS

2.1 Grants by Indevus .

(a) Subject to the terms and conditions of this Agreement, beginning on the Effective Date and ending upon the termination of this Agreement, Indevus hereby grants to Teva an exclusive (even as to Indevus) right and license throughout the Territory (with the right to grant sublicenses, subject to the provisions of Section 2.5) to practice under the Indevus Intellectual Property, to develop, make, have made, use, sell, have sold, offer for sale, import, export, register, market, promote and otherwise Commercialize the Compound and Products in the Field for all indications; provided , however , that the license granted under this Section 2.1 is expressly subject to the retained rights of Indevus to practice under the Indevus Intellectual Property solely to the extent necessary to carry out its express obligations under this Agreement. During the period beginning on the Agreement Date and ending on the Effective Date, Indevus shall take no action that adversely impacts or is otherwise inconsistent with the rights being granted to Teva hereunder.

(b) Teva does not expect or anticipate receiving any additional Indevus Intellectual Property created subsequent to the Next Trial Completion and through the Agreement Term, as Indevus has represented to Teva that it believes that it is remote that after the Next Trial Completion Indevus will be performing any research or development activities which would generate any additional Indevus Intellectual Property related to the license granted hereunder.

2.2 Sublicenses of Third Party Rights . The license granted to Teva under Section 2.1 includes exclusive sublicenses by Indevus in the Field (a) of certain Indevus Patent Rights and Indevus Know-How under the [***] , and (b) of certain Indevus Know-How under the [***] . Teva acknowledges that it is a sublicensee under the [***] and the [***] to the extent stated in the foregoing sentence and agrees to be bound (and that any sublicensee hereunder shall be bound) by the

 

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respective terms of such agreements, to the same extent as Indevus is bound by such terms, to the extent applicable to the sublicense granted to Teva hereunder. Provided that Teva has not materially breached this Agreement and has failed to cure such material breach pursuant to Section 9.2(b)(i), Indevus shall pay all amounts which Indevus shall owe pursuant to the [***] by virtue of this Agreement and shall perform in all material respects its obligations under the [***] that are required to enable Teva to perform its obligations and exercise its rights under this Agreement. In the event that Indevus receives notice of a breach of the [***] , which breach gives rise to a right to terminate the [***] in a way that would terminate or materially adversely affect Teva’s ability to perform its obligations or exercise its rights under this Agreement, Indevus shall notify Teva of such situation as soon as practicable, and use commercially reasonable efforts to promptly cure such breach. However, if Indevus is unable to cure such breach, Indevus shall, to the fullest extent possible, permit Teva to cure such breach, provided that Indevus shall reimburse Teva for any costs associated with curing such breach, or Teva shall be permitted to set off such costs against any amounts owed by Teva to Indevus hereunder. Without limiting the foregoing obligation of Indevus, Indevus shall use Commercially Reasonable Efforts to obtain within [***] of the Effective Date an agreement from [***] that, provided that Teva has not breached its obligations under this Agreement, in the event that the [***] is terminated for any reason, [***] agrees to grant Teva substantially equivalent rights on substantially equivalent terms as those granted to Indevus pursuant to the [***] as are necessary for Teva to exercise its rights and perform its obligations under this Agreement.

2.3 Retained Rights; No Implied Licenses . All rights not specifically granted to Teva under this Agreement are reserved and retained by Indevus. Nothing in this Agreement shall be deemed to constitute the grant of any license or other right to either Party, to or in respect of any product, patent, trademark, Proprietary Information, trade secret or other data or any other intellectual property of the other Party, except as set forth under this Agreement.

2.4 Competition . During the Agreement Term, neither Party will directly or indirectly distribute, promote, market or sell any Competing Product in the Territory; provided , however , that if during the Agreement Term a Party believes in good faith that at any time a launch of a Generic Product is imminent in any country, Teva shall have the right (but not the

 

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obligation) to launch a Generic Product of its own (an “ Authorized Generic Product ”) in such country, subject to the provisions of Section 5.3(a)(v). Notwithstanding the foregoing to the contrary, subject to the provisions of Section 11.2, in the event that Teva acquires a Third Party, or is acquired or becomes controlled by a Third Party, which is distributing, promoting, marketing or selling a Competing Product in a country in the Territory, Teva shall continue to use Commercially Reasonable Efforts to Develop and/or Commercialize the Product. Notwithstanding the foregoing, in the event that a Third Party is commercializing a pharmaceutical product with the same or similar labeling as Product but that does not contain the Compound as an active ingredient, nothing in this Agreement shall prohibit Teva from manufacturing, distributing, promoting, marketing or selling a generic version of such product, provided that the provisions under this Agreement regarding the use of Proprietary Information shall apply to such Third Party.

2.5 Proposed Sublicense by Teva . In the event Teva proposes to sublicense any of the rights or licenses granted to it by Indevus hereunder, the provisions of this Section 2.5 shall be applicable. Teva shall advise Indevus in advance of any proposed sublicense and give due consideration to Indevus’ comments thereto; provided , however that if any such proposed sublicense of a Product is with respect to [***] , then such sublicense shall be subject to the [***] . Any sublicense shall be subject to the terms and conditions of this Agreement, and the grant of any sublicense by Teva shall not relieve Teva of any of its obligations under this Agreement.

2.6 Third Party Agreements . Within [***] after the Go Decision, Indevus shall assign to Teva and Teva shall assume the Third Party Agreements listed in Schedule 2.6(a), including all obligations thereunder (subject to the other provisions of this Agreement). Indevus shall use its Commercially Reasonable Efforts to modify such provisions of the Third Party Agreements listed in Schedule 2.6(a) as Teva shall reasonably request. Within [***] after the Next Trial Completion, Indevus shall provide to Teva a Schedule 2.6(b) setting forth therein all Third Party Agreements entered into subsequent to the Agreement Date in connection with the Next Trial and consistent with the Next Trial Budget. Indevus shall assign to Teva and Teva shall assume the Third Party Agreements listed in Schedule 2.6(b)

 

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which Teva shall specifically request, including all obligations thereunder (subject to the other provisions of this Agreement), or terminate such Third Party Agreements as Teva shall request. Indevus shall provide Teva with a reasonable opportunity to review and comment upon any such Third Party Agreements that Indevus believes in good faith would reasonably affect the Indevus Intellectual Property prior to execution by Indevus. Upon assignment to Teva, (a) all such Third Party Agreements shall be in full force and effect in accordance with their terms, (b) neither Indevus nor any other party thereto shall be in default or breach in any material respect of such Third Party Agreements, and (c) Indevus shall not have received any notice of any defaults, breaches or violation thereunder. Subject to the foregoing, Indevus shall have no further obligations under any Third Party Agreements assigned to Teva. Without Teva’s prior written consent, Indevus shall not modify, assign, amend or terminate any Third Party Agreement (as well as the SA Agreement and the Warner Assignment and License) and Indevus shall not enter into any other agreements regarding the Compound or the Products.

ARTICLE 3

GOVERNANCE

3.1 Central Steering Committee .

(a) Members . As of the Effective Date, the Parties shall establish a central steering committee (the “ CSC ”), which shall consist of four (4) members, two (2) of whom shall be designated by Teva, and two (2) of whom shall be designated by Indevus. The initial members of the CSC are set forth on Schedule 3.1 . Teva and Indevus may replace any or all of its representatives on the CSC at any time upon written notice to the other Party. A Party may designate a substitute to temporarily attend and perform the functions of such Party’s designee at any meeting of the CSC; provided , however , that such designee shall have appropriate expertise. The CSC shall be chaired by a representative of Teva.

(b) Responsibilities . The CSC shall have as its overall purpose the supervision of Development and Commercialization in the United States. From time to time during the U.S. Collaboration Period, the CSC shall (i) review Development and Commercialization, as well as the First Period Plan and Budget and Second Period Plan and Budget and all revisions, updates or amendments thereto, and (ii) establish any additional committees deemed necessary or

 

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desirable to address other issues associated with the implementation of this Agreement. Indevus shall have the right, but not the obligation, to review and provide its comments to the First Period Plan and Budget and Second Period Plan and Budget, and all revisions, updates or amendments thereto, submitted by Teva to the CSC. The CSC shall have subordinate to it and shall oversee and supervise any such other committees as are formed by it from time to time and shall be responsible for ensuring that there is an alignment between the objectives of all such subordinate committees. The activities of such subordinate committees shall be responsive to, consistent with the decisions and direction of, and implement the policies of, the CSC.

(c) Decision Making . The CSC may make decisions with respect to any subject matter that is subject to the CSC’s decision-making authority and responsibilities as set forth in Section 3.1(b). Regardless of the number of individuals attending any CSC meeting, Teva and Indevus shall have a single vote each. The CSC shall attempt in good faith to reach unanimity with respect to matters that come before it for decision and shall give consideration to the views, positions and recommendations of each Party on such matters. If the CSC is unable to reach unanimity upon any issue or matter that is brought before it for decision within [***] after consideration by the CSC then, and in each such event, Teva shall be entitled to make the final decision for the CSC with respect to such issue or matter, which decision shall be binding upon the Parties; provided , however , that in case of a dispute regarding [***] , if such a dispute has not been resolved within [***] after presentation to the CSC, then the dispute shall be referred to the Chief Executive Officer of Indevus and an Executive Vice President of Teva for resolution. If the Parties’ respective officers are unable to resolve such dispute within [***] after presentation of the dispute to them for resolution, the dispute shall be resolved pursuant to Section 11.8.

3.2 Meetings . The chairperson of the CSC shall call meetings as reasonably requested during the U.S. Collaboration Period by one of the Parties; provided , however , that the CSC shall meet at least on a semi-annual basis during the U.S. Collaboration Period unless otherwise required by this Agreement or agreed to between the Parties, and that the first meeting of the CSC shall be held as soon as practicable, but no later than [***] after the Effective Date [***] . The chairperson shall establish the timing and agenda of all CSC meetings

 

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and shall transmit notice of such meetings, including the agenda therefor, to all CSC members; provided , however , either Party may request that specific items be included on the applicable agenda and may request that additional meetings be scheduled as needed. Meetings may be held in person, by telephone, or by video conference call and, except as set forth above, the location of each meeting shall alternate between the Parties’ selected locations in Israel or Massachusetts or such other location as may be mutually agreed upon by the Parties. On advance written notice to the other Party, additional participants may be invited by any representative to attend meetings where appropriate. Each Party shall be responsible for all travel and related costs and expenses for its members and other representatives to participate in or attend committee meetings. Any Proprietary Information disclosed in any meeting of the CSC or its subcommittees shall remain Proprietary Information of such Party.

3.3 Minutes of CSC and Subcommittee Meetings . Minutes of each CSC and CSC subcommittee meeting shall be transcribed and issued by a representative of Indevus within thirty (30) days after each meeting (or in any event at least ten (10) Business Days prior to the date of the next scheduled meeting of such committee) and shall be approved within thirty (30) days after each such meeting. Such minutes shall include only key discussion points and decisions made and provide a list of any identified issues yet to be resolved, either within such committee or through the relevant resolution process, if any.

3.4 Disbanding of CSC . The Parties shall have the right to disband the CSC upon mutual agreement. Teva shall have the right, in its sole discretion, to disband the CSC upon a Change of Control of Indevus. Additionally, if the CSC is not disbanded pursuant to the preceding sentences, and absent a mutual written agreement by the Parties to continue the CSC, the CSC shall be automatically disbanded effective on the earliest of (a) the termination of the U.S. Collaboration Period, (b) the [***] anniversary of the Effective Date or (c) the date of the first FDA Approval.

3.5 No Amendment . The CSC shall have only the powers assigned to it in this Article 3. All activities conducted by and decisions taken by the CSC shall be consistent with and subject to the provisions of this Agreement, and the CSC shall not have any power to take any action that conflicts with the terms of this Agreement or to amend, modify or waive compliance with any of the terms of this Agreement.

 

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ARTICLE 4

TRANSITION; DEVELOPMENT AND COMMERCIALIZATION

4.1 Information . Within [***] of the Effective Date, Indevus shall disclose and deliver to Teva electronic, where reasonably available, and hard copies (or, upon Teva’s request, originals) of all Data, all existing Indevus Intellectual Property, and any other documents regarding the Compound that may be necessary or useful for regulatory submissions (other than the IND). Without limiting the generality of the foregoing, Indevus shall deliver to Teva those items that were disclosed to Teva during the due diligence meetings held at Indevus’ offices on May 12-15, 2008, including all Data generated by any Third Party (including by SA (as successor to Rhone-Poulenc Rorer S.A.) and Warner Lambert Company LLC).

4.2 Transfer of Materials and Technical Assistance .

(a) Transfer of Materials . Within [***] after the Go Decision, Indevus shall deliver to Teva any Compound, analytical standards or markers for the Compound, intermediates, Product and any related substances that it owns or Controls and which are necessary or useful for the continued Development, Commercialization and research regarding the Compound and Products.

(b) Technical Assistance . Beginning on the date Teva issues the Go Decision and continuing for [***] thereafter (the “ Transition Period ”), Indevus shall provide for an orderly transition to Teva of the development, testing and regulatory activities performed by or on behalf of Indevus with respect to Compound and/or Product, subject to and in accordance with this Section 4.2. During the Transition Period, Indevus shall make available to Teva at Indevus’ facility in the United States, no fewer than [***] knowledgeable Indevus personnel familiar with the Indevus Know-How and clinical, regulatory, biostatistical, and chemistry, manufacturing and control (CMC) issues relating to Compound and/or Product (the “ Indevus Transition Team ”), to provide reasonable training and assistance to Teva with respect to the Indevus Know-How and such related issues, upon Teva’s reasonable request and at such times and places during normal

 

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business hours as may be mutually agreed to. After the expiration of the Transition Period, for a period not to exceed [***] , if Teva requests additional training or assistance, Teva shall pay Indevus, at Indevus’ then current FTE reimbursement rate, and bear all Indevus’ reasonable out of pocket expenses, in connection with such assistance, provided that Indevus shall not be required to provide in excess of [***] during such [***] period for such services.

4.3 Regulatory Filings, Approvals and Applications . As soon as reasonably practicable, but in any event within [***] after the Go Decision, Indevus shall submit to the FDA a letter authorizing the transfer of ownership from Indevus to Teva, and shall otherwise take action within its control to transfer to Teva, all regulatory filings, approvals and applications relating to the Compound or the Products, including all INDs and all Regulatory Approvals, Drug Approval Applications and all related documentation and information (the “ Regulatory Documents ”). Teva shall execute and submit to the FDA a letter, accompanied by the transfer letter referred to in the preceding sentence, acknowledging Teva’s assumption of ownership of and responsibility for the Regulatory Documents. The effective date of the transfer of ownership of the Regulatory Documents to Teva is referred to as the “ IND Transfer Date .”

4.4 Development .

(a) General . Except as specifically set forth in Section 4.4(b) with respect to the Next Trial, Development shall be conducted by Teva from and after the Go Decision with review by the CSC during the U.S. Collaboration Period, and Teva shall exercise Commercially Reasonable Efforts in doing so. Not less than [***] per Calendar Year, Teva shall provide to the CSC or, if the CSC has been disbanded, Teva shall provide to Indevus (i) a copy of the annual report that it submits to the FDA in connection with the periodic reporting requirement for the IND, and (ii) a written report summarizing the progress, status, and results of all Development and regulatory activities of Teva, its Affiliates and sublicensees relating to the Compound or Product, consistent with written reports issued by Teva in the ordinary course of its business. In addition, no more than [***] per Calendar Year, in addition to any meetings of the CSC, Indevus may request a meeting with Teva to discuss such written report at dates and locations to which the Parties mutually agree.

 

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(b) Next Trial . Commencing on the Effective Date, Indevus shall use Commercially Reasonable Efforts to conduct the Next Trial in accordance with the Next Trial Protocol and Next Trial Budget. No later than [***] following the Next Trial Completion, Indevus shall provide to Teva, in electronic format, the clinical trial database at Database Lock and all other information set forth on Schedule 1.64(a) . Next Trial Costs shall be funded in the manner set forth in Sections 5.2(a) and 5.4(a). Any revisions to the Next Trial Protocol and Next Trial Budget that would, individually or in the aggregate, have the effect of increasing by more than [***] the costs set forth in the original Next Trial Budget shall be subject to mutual agreement by the Parties and, if so agreed, shall be set forth in an amendment to Schedule 4.4(b ). Not later than [***] after the Next Trial Completion, Indevus shall deliver to Teva a report which shall be substantially similar in form to Schedule 1.64(b) (the “ Next Trial Report ”). Not later than [***] after the Next Trial Completion, Teva shall notify Indevus in writing of its decision in its sole discretion, either (i) to proceed with a Phase III clinical trial of the Compound for any indication, including stuttering (a “ Go Decision ”) or (ii) to terminate this Agreement pursuant to Section 9.2(a)(i).

(c) First Period Plan and Budget .

(i) First Period Plan and Budget . Not later than [***] after the Next Trial Completion, but in any event at least [***] prior to commencing any further Development under this Agreement, Teva shall prepare and deliver to the CSC the First Period Plan and Budget, which plan shall be consistent with plans employed by Teva in connection with pharmaceutical product projects of a comparable stage of development and similar market potential. Within [***] of receipt of the First Period Plan and Budget in accordance with this Section 4.4(c)(i), Indevus shall notify Teva of its decision, pursuant to the Decision Point set forth in Section 1.26(a), whether to continue the U.S. Collaboration Period or to deem such Decision Point a Royalty Conversion Event pursuant to Section 5.3(b).

(ii) Revisions, Amendments and Updates .

Teva shall:

(A) prepare and deliver to the CSC a revised First Period Plan and Budget within [***] following the date of completion of the End-of-Phase II Meeting; and

 

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(B) prepare and deliver to the CSC an update of its then outstanding First Period Plan and Budget on or before [***] during the U.S. Collaboration Period.

(iii) In addition to any other reporting obligations hereunder, Teva shall deliver to the CSC not later than [***] prior to any implementation thereof by Teva any Significant Plan Amendment to the First Period Plan and Budget. Within [***] of receipt of such Significant Plan Amendment, Indevus shall notify Teva of its decision, pursuant to the Decision Point set forth in Section 1.26(c), whether to continue the U.S. Collaboration Period or to deem such Decision Point a Royalty Conversion Event pursuant to Section 5.3(b).

(d) Additional Development . Either Party may at any time submit to the CSC a written proposal for additional development, including development of additional indications or Improvements. Such proposal shall contain, at a minimum, commercially reasonable information supporting the rationale for such development from a scientific, regulatory and commercial standpoint, as well as an estimated developmental critical path and an estimate of the time, cost and economic or other benefit of such efforts. In considering whether to recommend to the CSC approval of such proposal for additional development, the CSC shall evaluate whether the proposed program has scientific and technical merit and is likely to result in the approval of a new indication or dosage amount of Product, or is advisable to address safety or efficacy issues and/or whether the commercial return from sales of Product that may result from such development can reasonably be expected to offset the cost of development within a reasonable period of time. If any such additional development is approved by the CSC pursuant to Section 3.1, Teva shall promptly determine a development plan and budget for such development including the estimated cost and scope of work necessary for obtaining desired Regulatory Approval. If such budget for additional development contains costs that constitute a Significant Plan Amendment, then within [***] of receipt of such Significant Plan Amendment,

 

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Indevus shall notify Teva of its decision, pursuant to the Decision Point set forth in Section 1.26(c), whether to continue the U.S. Collaboration Period or to deem such Decision Point a Royalty Conversion Event pursuant to Section 5.3(b).

(e) Records . Any Party conducting Development activities under this Agreement shall maintain records, in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes and in accordance with good industry practice, which shall be complete and accurate in all material respects and shall fully and properly reflect all work done and results achieved, including all Know-How and including individual case report forms, in the performance of the Next Trial or Development activities, as applicable, in the form required under applicable Laws.

4.5 Regulatory Matters .

(a) Responsibility Before IND Transfer Date .

Prior to the IND Transfer Date:

(i) Indevus shall own and control all Regulatory Documents relating to a Product in the Field in the Territory and shall have sole authority and responsibility for the timely preparation, filing, prosecution and maintenance of all Regulatory Documents relating to a Product in the Territory, including any reports or amendments to such Regulatory Documents.

(ii) Indevus shall remain the primary contact with the FDA and shall be solely responsible for all communications with the FDA that relate to any Regulatory Document.

(iii) Teva shall have the right, but not the obligation, to assist and consult with Indevus with respect to all Regulatory Documents prior to Indevus’ making any submissions thereof. Notwithstanding anything contained in the foregoing to the contrary, Indevus shall provide Teva with copies of all such Regulatory Documents no less than [***] (except if a shorter period is required for such submission by the FDA or applicable laws) prior to filing or submission of the foregoing and shall consider in good faith any comments of Teva with respect to the same.

 

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(iv) Indevus shall provide advance notice to Teva of any planned meetings, discussions or other communications with the FDA relating to Products. Teva shall have the right, but not the obligation, to participate with respect to such meetings, discussions, or other communications; provided that , in providing any such assistance, Teva shall not contact the FDA without the prior approval of Indevus, which approval shall not be unreasonably withheld or delayed, and, if contacted by the FDA with respect to Product, shall refer such contact to Indevus.

(v) If contacted by the FDA with respect to a Product, Indevus shall notify Teva within [***] of such contact, and provide Teva with any related official correspondence received from the FDA, including as applicable minutes of any meetings or telephone conferences and/or discussions between Indevus and the FDA. Teva shall have a right to participate in and provide comments with respect to any subsequent meetings, discussions or other communications with respect to such contact.

(vi) To the extent Teva reasonably believes that a filing or submission relating to Products in the Territory is required by Law, Teva shall notify Indevus. If Indevus decides not to prepare such filing or submission, Indevus shall promptly notify Teva, but in no event later than [***] after Teva’s notification of Indevus, unless notified by Teva that a shorter period of review is mandated by the FDA or Law, and Teva shall be entitled to prepare such filing or submission, to be filed or submitted by Indevus; provided that , Teva shall use good faith efforts to include any comments of Indevus in such filing or submission.

(vii) Indevus shall promptly provide Teva with copies of all filings and submissions made by Indevus with any Regulatory Authorities with respect to Product.

(b) Responsibility After IND Transfer Date .

From and after the IND Transfer Date:

(i) Teva shall have sole authority and responsibility for the timely preparation, filing and prosecution of all filings, submissions, authorizations or approvals with Regulatory Authorities, and shall own and control all such filings, submissions, authorizations and approvals, including any IND, NDA or other Drug Approval Application.

 

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(ii) Teva shall be the primary contact with each Regulatory Authority and shall be solely responsible for all communications with each Regulatory