Amended and Restated Cross-License Agreement

Exhibit 10.39

***Text Omitted and Filed Separately
Confidential Treatment Requested
Under 17 C.F.R. §§ 200.80(b)(4) and 240.24b-2

Amended and Restated Cross-License Agreement

     This Amended and Restated Cross-License Agreement (the “ Agreement ”) is entered into as of June 28, 2004 (the “ Amendment Date ”) and is hereby made effective as of April 9, 2002 (the “ Effective Date ”), by and between Micromet AG , having its principal offices at Staffelseestrasse 2, 81477 Munich, Germany (“ Micromet ”), and Enzon Pharmaceuticals, Inc. , having its principal offices at 685 Route 202/206, Bridgewater, New Jersey 08807, USA (“ Enzon ”). Micromet and Enzon each may be referred to herein individually as a “ Party ,” or collectively as the “ Parties .”

      Whereas , the Parties have entered into that certain Cross-License Agreement, dated as of April 9, 2002 (the “ Original License Agreement ”), pursuant to which the Parties granted each other certain nonexclusive licenses with respect to certain patents owned by the Parties;

      Whereas , the Parties desire to amend and restate the Original License Agreement to reflect certain amendments agreed upon in connection with the amendment and restatement of that certain Amended and Restated Collaboration Agreement between Micromet and Enzon dated as of the Effective Date (the “ Collaboration Agreement ”);

      Now, therefore , in consideration of the foregoing premises and the mutual promises and covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, do hereby agree as follows:

1. Definitions

     When used in this Agreement, capitalized terms will have the meanings as defined below and throughout the Agreement. Unless the context indicates otherwise, the singular will include the plural and the plural will include the singular.

      1.1 “ Affiliate ” means a legal entity that, directly or indirectly, through one or more intermediaries, controls, is controlled by, or is under common control with a Party. For purposes of this definition only, “control” and, with correlative meanings, the terms “controlled by” and “under common control with” means (a) the possession, directly or indirectly, of the power to direct the management or policies of a legal entity, whether through the ownership of voting securities or by contract relating to voting rights or corporate governance, or (b) the ownership, directly or indirectly, of more than 50% of the voting securities or other ownership interest of a legal entity; provided that, if local law restricts foreign ownership, control will be established by direct or indirect ownership of the maximum ownership percentage that may, under such local law, be owned by foreign interests

      1.2 “ Antigen ” means any structure with binding affinity to antibody variable domains.

      1.3 “ BiTE Product ” means any composition or formulation consisting of, containing or comprising a bi-specific Single Chain Antibody expressed as a single polypeptide chain, binding to T-cells for the diagnosis, prophylaxis or treatment of human or non-human diseases or conditions, but excluding any BiTE Research Product.

      1.4 “ BiTE Research Product ” means any composition or formulation consisting of, containing or comprising a bi-specific Single Chain Antibody expressed as a single polypeptide chain binding to T-cells used for research purposes and not for the diagnosis, prophylaxis or treatment of human or non-human diseases or conditions.

      1.5 “ BLA ” means a Biologics License Application, as defined in the U.S. Federal Food, Drug, and Cosmetics Act, as amended, and the regulations promulgated thereunder, or a foreign equivalent to such application.

      1.6 “ Commencement ” with respect to a clinical trial means the administration of the first dose to a patient in the clinical trial.

      1.7 “ Commercialization Rights ” means the right or option (whether or not ultimately exercised) to market, co-market, promote, co-promote or sell a product.

      1.8 “ Consolidated Patent Portfolio ” means the combined intellectual property portfolio consisting of the Enzon Licensed Patents and the Micromet Licensed Patents.

      1.9 “ Control ” or “ Controlled ” means, with respect to any know-how, Patent, or other intellectual property right, possession of the right, whether directly or indirectly, and whether by ownership, license or otherwise, to assign, or grant a license, sublicense or other right to or under, such know-how, Patent or right as provided for herein without violating the terms of any agreement or other arrangements with any Third Party.

      1.10 “ Curis Cross-License Agreements ” means those certain cross-license agreements dated as of November 23, 1993, between Enzon and Creative BioMolecules, Inc., with respect to which Curis, Inc. was the assignee of Creative BioMolecules, Inc., and with respect to which Micromet was the assignee of Curis, Inc.

      1.11 “ Diagnostic SCA Product ” means an SCA Product that is under development, approved or used for the diagnosis of human diseases or conditions.

      1.12 “ Enzon License ” has the meaning assigned to it in section 2.2.1.

      1.13 “ Enzon Licensed Patents ” means those Patents now owned by or licensed to Enzon which were the subject of a nonexclusive license to Micromet, as ultimate assignee of Creative BioMolecules, Inc., pursuant to the Curis Cross-License Agreements, including without limitation those Patents identified in Appendix A hereto, but excluding any Collaboration Patents (as defined in the Collaboration Agreement).

      1.14 “ Enzon Pipeline Product ” means any Licensed Product, other than a BiTE Product or BiTE Research Product, as to which (a) Enzon obtains or retains Commercialization

Rights (whether exclusive or co-exclusive) in one or more Major Market Countries, or (b) Enzon or any of its Affiliates has filed or will file an IND in its own name.

      1.15 “ Exploit ” or “ Exploitation ” means to make, have made, import, use, sell, offer for sale, or otherwise dispose of a product, including all discovery, research, development, registration, modification, enhancement, improvement, manufacture, storage, formulation, exportation, transportation, distribution, promotion and marketing activities related thereto.

      1.16 “ First Phase III Trial ” means the first controlled, randomized human clinical trial the results of which could be or are used to establish the safety and efficacy of a pharmaceutical product as a basis for a BLA, or that would otherwise satisfy the requirements of 21 CFR 312.21(c).

      1.17 “ IL-2 Agreement ” means that certain IL-2 License Agreement between the Parties, dated as of the Amendment Date, relating to the transfer of certain rights and obligations with respect to products binding to IL-2.

      1.18 “ IND ” means an investigational new drug application filed with the United States Food and Drug Administration or its foreign equivalent, in each case for authorization to commence human clinical trials.

      1.19 “ Industrial SCA Product ” means any composition or formulation consisting of, containing or comprising one or more Single Chain Antibodies intended for any use other than for research or the diagnosis, prophylaxis, or treatment of disease or conditions in humans and other animals.

      1.20 “ Licensed Product ” means any SCA Product, Non-Human SCA Product, Research Product, Industrial SCA Product, BiTE Product, or BiTE Research Product, the composition, manufacture, use of which is claimed by one or more Valid Claims of the Consolidated Patent Portfolio.

      1.21 “ Micromet License ” has the meaning assigned to it in section 2.1.1.

      1.22 “ Major Market Country ” means the [***].

      1.23 “ Micromet Licensed Patents ” means those Patents now owned by or licensed to Micromet which were the subject of a nonexclusive sublicense to Enzon pursuant to the Curis Cross-License Agreements, including without limitation those Patents identified in Appendix B hereto, but excluding any Collaboration Patents (as defined in the Collaboration Agreement).

      1.24 “ Micromet Pipeline Product ” means any Licensed Product as to which (a) Micromet obtains or retains Commercialization Rights (whether exclusive or co-exclusive) in one or more Major Market Countries, or (b) Micromet or its Affiliates has filed or will file an IND in its own name.

      1.25 “ Net Sales ” means all consideration received by a Party, an Affiliate, or a sublicensee for the sale or other transfer or disposition of Licensed Products, less returns and customary trade discounts actually taken, outbound freight, value added, sales or use taxes, tariffs, and custom duties. For the avoidance of doubt, the above definition of Net Sales includes sales made by a sublicensee as if such sales were made directly by a Party. In the case of transfers of products to an Affiliate or sublicensee by a Party for sale or other disposition of such products to Third Parties by such Affiliate or sublicensee, Net Sales will be the greater of the total fees and other consideration charged by the Affiliate or sublicensee to Third Parties or the total fees and consideration charged by the Party to the Affiliate or sublicensee, but not both amounts, and no unit of any product will be subject to more than one sale or disposition that qualifies as a Net Sale, regardless of the number or form of sales or dispositions of such unit.

      1.26 “ Non-Human SCA Product ” means any composition or formulation consisting of, containing or comprising one or more Single Chain Antibodies under development, approved or used for the diagnosis, prophylaxis or treatment of non-human diseases or conditions, but excluding any BiTE Products.

      1.27 “ Patents ” means (a) all patents and patent applications in any country or supranational jurisdiction, and (b) any substitutions, divisions, continuations, continuations-in-part, reissues, renewals, registrations, confirmations, re-examinations, extensions, supplementary protection certificates and the like, and any provisional applications, of any such patents or patent applications.

      1.28 “ Pegylated TNF-alpha Agreement ” means that certain PEG TNF-alpha License Agreement between the Parties, dated as of the Amendment Date, relating to the transfer of certain rights and obligations with respect to a Pegylated Single Chain Antibody binding to TNF-alpha developed under the Collaboration Agreement.

      1.29 “ Research Product ” means a product consisting of, containing or comprising one or more Single Chain Antibodies used for research purposes and not intended, under development or used for the diagnosis, prophylaxis or treatment of human or non-human diseases or conditions, but excluding any BiTE Research Product.

      1.30 “ SCA Product ” means any composition or formulation consisting of, containing or comprising one or more Single Chain Antibodies that is under development, approved or used for the diagnosis, prophylaxis or treatment of human diseases or conditions, but excluding any BiTE Product.

      1.31 “ Single Chain Antibody ” means a single chain polypeptide having binding affinity for an antigen and a defined amino acid sequence whereby such polypeptide comprises (i) a first polypeptide segment having a light chain variable region, (ii) a second polypeptide having a heavy chain variable region, and (iii) at least one peptide linker linking the first and second polypeptides into a single chain polypeptide.

      1.32 “ Term ” has the meaning assigned to it in section 7.1.

      1.33 “ Therapeutic SCA Product ” means an SCA Product under development or approved for the treatment or prophylaxis of human diseases or conditions.

      1.34 “ Third Party ” means any party other than Micromet, Enzon or their respective Affiliates.

      1.35 “ Third Party Collaboration Agreement ” means any agreement executed during the Term between a Party and a Third Party under which (a) such Party grants to such Third Party a license to intellectual property or other rights Controlled by such Party (other than or in addition to any Patent within the Collaboration Patents or the Consolidated Patent Portfolio) which intellectual property or other rights are required for the performance of the research and development activities to be performed under the agreement or for the Exploitation of products resulting from such activities; and (b) each party to such agreement performs substantial research or development activities pursuant to such agreement.

     By way of example but not limitation, such an agreement will qualify as a “Third Party Collaboration Agreement” if the terms include (1) dedicated research funding paid by the Third Party to the Party, or from the Party to the Third Party, of at least US$[***] over a period of [***] following the execution of such agreement for the conduct of research pursuant to such agreement, or (2) the performance of a project plan over a period of not less than [***] with aggregate project costs for research activities of not less than US$[***] of which not less than US$[***] are incurred by the Party (regardless of whether or not such costs are reimbursed by the Third Party), or (3) governance provisions that provide [***] regarding the research activities to be performed by the parties prior to the filing of an IND. For the avoidance of doubt, “Third Party Collaboration Agreement” does not include any fee-for-service arrangement, or arrangement wherein the extent of a Party’s collaboration is so limited that the grant of rights is in effect a naked license grant.

      1.36 “ Third Party Collaboration Product ” means a product that is developed under and pursuant to a Third Party Collaboration Agreement.

      1.37 “ Valid Claim ” means (a) any claim of an issued and unexpired patent within the Enzon Licensed Patents or the Micromet Licensed Patents which has not been held unenforceable or invalid by a court or other governmental agency of competent jurisdiction in an unappealed or unappealable decision, and which has not been disclaimed or admitted to be invalid or unenforceable through reissue or otherwise, or (b) a pending claim in a pending patent application within the Enzon Licensed Patents or the Micromet Licensed Patents. Notwithstanding clause (b) above, in the event that a pending claim in a pending patent application does not issue as a valid and enforceable claim in an issued patent within [***] years after the earliest date from which such patent application claims priority, such a pending claim will not be a Valid Claim, unless and until such pending claim subsequently issues as a valid and enforceable claim in an issued patent, in which case such claim will be reinstated and be deemed to be a Valid Claim as of the date of issuance of such patent.

2. Grant Of License

      2.1 License Grant By Micromet.

           2.1.1 Micromet hereby grants to Enzon a non-exclusive, worldwide, royalty-bearing (as provided in section 3) license under the Micromet Licensed Patents to Exploit Licensed Products other than BiTE Products (the “ Micromet License ”), provided , however , that the Exploitation of BiTE Research Products will be limited to research activities that do not include administration to humans of a BiTE Research Product. Under no circumstances will Enzon engage in any commercial exploitation of BiTE Research Products (including, without limitation, any sale of such products and any development activities aimed at creating BiTE Research Products for commercial sale). The Micromet License shall be subject to the field limitations set forth on Appendix C .

           2.1.2 Enzon may grant and authorize the grant of sublicenses under the Micromet License and may grant licenses under the Enzon Licensed Patents only for Enzon Pipeline Products and Third Party Collaboration Products.

      2.2 License Grant By Enzon.

           2.2.1 Enzon hereby grants to Micromet a non-exclusive, worldwide, royalty-bearing (as provided in section 3) license, under the Enzon Licensed Patents to Exploit Licensed Products other than BiTE Products and BiTE Research Products (the “ Enzon License ”). The Enzon License shall be subject to the field limitations set forth on Appendix C .

           2.2.2 Except as otherwise permitted in that certain Exclusive IP Marketing Agreement between Micromet and Enzon dated as of the Effective Date (the “ Marketing Agreement ”), Micromet may grant and authorize the grant of sublicenses under the Enzon License only for Micromet Pipeline Products and Third Party Collaboration Products.

           2.2.3 Enzon hereby grants to Micromet an exclusive (even as to Enzon), worldwide, fully-paid, royalty-free, perpetual, irrevocable, non-terminable, license, with the right to grant and authorize the grant of sublicenses, under the Enzon Licensed Patents to Exploit any BiTE Products and BiTE Research Products (subject to Enzon’s right to Exploit BiTE Research Products in connection with research activities that do not include administration to humans of a BiTE Research Product); provided , that under no circumstances will Enzon engage in any commercial exploitation of BiTE Research Products (including, without limitation, any sale of such products and any development activities aimed at creating BiTE Research Products for commercial sale).

      2.3 Amending Field Limitations. The field limitations listed in Appendix C set forth the understanding of the Parties as of the Effective Date regarding the scope of such limitations arising from license agreements under which licenses to Patents within the Consolidated Patent Portfolio were granted to Third Parties prior to the Effective Date. Upon request of a Party, the Parties will amend Appendix C as necessary to include additional or different limitations of which the requesting Party in good faith was unaware as of the Effective Date. Furthermore, upon expiration or termination of a license agreement that was the basis of a

limitation listed in Appendix C , such limitation will be deemed stricken from Appendix C as of the date of such expiration or termination.

3. Milestones and Royalties

      3.1 Milestone Payments and Royalty Rates.

           3.1.1 Milestones.

                (a)  Each Party will pay to the other Party the following milestone payments for each Therapeutic SCA Product that is a Licensed Product Exploited by it, an Affiliate, or sublicensee:

      Milestones:

Upon acceptance of the first IND		US$[***]
Upon Commencement of First Phase III Trial*		US$[***]
Upon the first BLA approval in the United States		US$[***]

                (b)  Each Party will pay to the other Party the following milestone payments for (i) each Diagnostic SCA Product that is a Licensed Product, and (ii) each Non-Human SCA Product that is a Licensed Product, in each case that is Exploited by it, an Affiliate, or sublicense:

Milestones:

Upon the first commercial sale		US$[***]
Upon cumulative sales reaching US$[***]		US$[***]

           3.1.2 Royalties. Except as provided below and in section 3.1.3, each Party will pay to the other Party the following royalties on Net Sales of each Licensed Product Exploited by it, an Affiliate, or sublicensee:

      Royalties on annual worldwide Net Sales at the following incremental levels:

On Net Sales of each Licensed Product below US$[***]:			[***]	%
On Net Sales of each Licensed Product between US$[***]and US$[***]:			[***]	%
On Net Sales of each Licensed Product over US$[***]:			[***]	%

     The royalty payment obligations of Micromet and Enzon under this section 3.1.2: (a) arise without regard to the identity of the applicable Patents within the Consolidated Patent Portfolio ( i.e. , Enzon will pay royalties to Micromet even if the only applicable Patents are Enzon Licensed Patents, and Micromet will pay royalties to Enzon even if the only applicable Patents are Micromet Licensed Patents), and (b) will expire on a product-by-product and country-by-country basis upon the expiration of the last to expire Valid Claim embracing such product (or the manufacture or use thereof) in a particular country. For the avoidance of doubt, the royalty payment obligations of Micromet and Enzon under this section 3.1.2 arise only for Licensed Products that are made, used, or sold in countries wherein such activities are embraced by one or more Valid Claims within the Consolidated Patent Portfolio (each such country a “ Royalty Country ”), and the determination of the Net Sales level and the applicable royalty rate with respect to a particular Licensed Product are made based on the total Net Sales of such Licensed Product generated in all Royalty Countries in a particular calendar year.

           3.1.3 Notwithstanding anything in this Agreement to the contrary, Micromet has no obligation to pay any royalties to Enzon with respect to BiTE Products Exploited by Micromet, its Affiliates or sublicensees under this Agreement, and neither Party has an obligation to pay any royalties to the other Party with respect to BiTE Research Products Exploited by it, its Affiliates or sublicensees under this Agreement.

           3.1.4 No milestone or royalty payments will be due under this Agreement for Licensed Products jointly Exploited by both Parties under the terms of the Collaboration Agreement or any Product Development and Commercialization Agreement (as defined in the Collaboration Agreement) executed thereunder and the financial terms of such other agreements will govern with respect to products Exploited under such other agreements. In addition no royalties or milestone payments will be due under this Agreement with respect to the Exploitation of Licensed Products by Micromet under the terms of the IL-2 Agreement or by Enzon under the terms of the Pegylated TNF-alpha Agreement.

           3.1.5 If Micromet grants a Consolidated Patent License (as defined in the Marketing Agreement) for Third Party SCA Products (as defined in the Marketing Agreement) Exploited for the treatment or prophylaxis of human diseases or conditions that does not provide for at least either (a) an upfront license fee of at least US$[***] in cash or cash equivalents payable upon execution of same, or (b) license fees and milestone payments totaling at least US$[***]in cash or cash equivalents and a royalty equal to at least [***]% of the [***], then the milestones and royalties that Enzon is obligated to pay to Micromet under sections 3.1.1(a) and 3.1.2 above will be reduced (effective as of the grant of such Consolidated Patent License) at Enzon’s option to the extent necessary to equal those of such Consolidated Patent License.

      3.2 Payment.

           3.2.1 Payment of Milestones. The Party achieving a development milestone that triggers a milestone payment obligation pursuant to section 3.1 will give notice to the other

Party within [***] of achieving each milestone, and will make the corresponding milestone payment within [***] of the achievement of the corresponding milestone event.

           3.2.2 Payment of Royalties. A Party who is obligated to make royalty payments pursuant to section 3.1 will provide to the other Party within [***] after the end of each calendar quarter a written report with such Party’s good faith estimate of Net Sales accrued in the preceding calendar quarter and the royalties payable thereon. Such Party will make royalty payments to the other Party for products sold during a calendar quarter within [***] of the last day of that calendar quarter. Each royalty payment will be accompanied by a written report for that calendar quarter showing the cumulative Net Sales of the applicable product sold by such Party, its Affiliates and its sublicensees on a country-by-country basis worldwide during the quarterly reporting period and the corresponding royalties payable under this Agreement.

           3.2.3 Payment Method. All amounts due hereunder will be paid in US Dollars by wire transfer in immediately available funds to an account designated by the receiving Party. Any payments or portions thereof due hereunder which are not paid on the date such payments are due will bear interest from the due date until the date of payment at the rate which is the lower of (i) [***]% over the overnight London Interbank Offering Rate in effect on the due date or (ii) the highest rate permitted by applicable law, calculated on the number of days such payment is delinquent, compounded monthly.

           3.2.4 Currency Conversion for Milestone Payments and Calculation of Net Sales. For any currency conversion required in connection with any payment hereunder, or in determining the amount of royalties due, such conversion will be made at the prevailing commercial rate of exchange for purchasing the currency into which an amount is to be converted as publicly announced by Citibank N.A. (or its successor) in New York on the last business day of the calendar quarter to which such payments relate. The Net Sales used for computing the royalties will be computed in US Dollars. For purposes of determining the amount of royalties due, the amount of Net Sales in any foreign currency will be computed by converting such amount into US Dollars as provided in this section above.

           3.2.5 Records Retention. Each Party will maintain complete and accurate books, records and accounts in sufficient detail to confirm the accuracy of any payments required hereunder, which books, records and accounts will be retained by such Party until [***] years after the end of the period to which such books, records and accounts pertain.

           3.2.6 Audit. Each Party will have the right to have an independent certified public accounting firm of internationally recognized standing, reasonably acceptable to the audited Party, to have access during normal business hours, and upon reasonable prior written notice, to such of the records of the other Party as may be reasonably necessary to verify the accuracy of information needed to calculate payments required hereunder (“ Payment Information ”) for any calendar quarter ending not more than [***] months prior to the date of such request; provided , however , that the auditing Party will not have the right to conduct more than [***]. The accounting firm will disclose to both Parties whether such Payment Information

is correct or incorrect and the specific details concerning any discrepancies. The auditing Party will bear all costs of such audit, unless the audit reveals an underpayment of more than [***]% from the amount paid, in which case the other Party will bear the cost of the audit.

           3.2.7 Payment of Additional Amounts. If, based on the results of any audit, additional payments are owed by a Party under this Agreement, such Party will make such additional payments promptly after the accounting firm’s written report is delivered to both Parties. If, based on the results of any audit, payments made pursuant to section 3.1 exceeded payments indicated by the audit as being due thereunder, such excess will be credited against future amounts owed by the applicable Party under section 3.1.

           3.2.8 Confidentiality. Each Party will treat all information subject to review under this section 3.2 in accordance with the confidentiality provisions of section 6 and will cause its accounting firm to enter into a reasonably acceptable confidentiality agreement with the audited Party obligating such firm to maintain all such financial information in confidence pursuant to such confidentiality agreement.

4. Filing, Prosecution and Maintenance of Patent Rights

      4.1 Each Party will be solely responsible and bear all costs for the preparation, filing, prosecution and maintenance of its licensed Patents in its sole and absolute discretion.

      4.2 If either Party elects not to continue prosecution or maintenance of any of its licensed Patents, such Party will so notify the other Party at least [***] days prior to the final due date of a response to any official action or on which a maintenance fee is due or other action is required to maintain such Patent in force or continue prosecution of such Patent (in the case of a patent application). The other Party (the “ Continuing Party ”) may elect to continue prosecution or maintenance of such Patent, at its sole expense, in which event the non-Continuing Party will assign such Patent to the Continuing Party and such Patent will be deemed a licensed Patent of the Continuing Party, i.e. , one of the Enzon Licensed Patents if Enzon is the Continuing Party and one of the Micromet Licensed Patents if Micromet is the Continuing Party.

      4.3 Each Party will be solely responsible and bear all costs for (and enjoy all recovery from) any inter partes actions concerning its licensed Patents, including but not limited to reexaminations, oppositions, interferences, and infringement actions, all in its sole and absolute discretion.

      4.4 Each Party will (i) promptly notify the other of any actions that may arise pursuant to section 4.3 and (ii) provide the other on an annual basis a report on the status of its activities described in section 4.1.

5. Representation and Warranties

      5.1 Reciprocal Representations and Warranties. Each Party represents and warrants to the other Party that: (i) it has the right to grant the license