BMP-7 License and Development Agreement between Curis Inc. and Ortho Biotech Products, L.P.

Summary

Curis Inc. and Ortho Biotech Products, L.P. entered into an agreement on November 27, 2002, granting Ortho Biotech an exclusive license to develop and commercialize BMP-7, a compound with potential for treating renal and nervous system disorders. Curis retains certain rights for orthopedic and dental uses. Ortho Biotech is responsible for further development, regulatory approval, and commercialization of BMP-7 for all other indications. The agreement outlines the rights, obligations, and financial arrangements between the parties, including definitions, scope, and limitations of the licensed technology.

EX-10.1 3 dex101.txt AGREEMENT BETWEEN CURIS AND ORTHOBIOTECH Exhibit 10.1 Confidential Materials omitted and filed separately with the Securities and Exchange Commission. Asterisks denote omissions. AGREEMENT This Agreement is made effective as of the 27/th/ day of November, 2002 by and between CURIS INC., a Delaware corporation, having a place of business at 61 Moulton St., Cambridge, Massachusetts 02138 ("CURIS"), and Ortho Biotech Products, L.P., a New Jersey limited partnership, having a place of business at Route 22 East, P.O. Box 6914, Bridgewater, New Jersey, 08807-0914 ("OBI"). CURIS and OBI are each referred to by name or as a "Party" or, collectively, as "Parties". References to "CURIS" and "OBI" shall include their respective Affiliates (hereinafter defined), where appropriate under the terms of this Agreement. RECITALS 1. CURIS has on-going research and certain product development and clinical development capabilities and has identified a lead compound, BMP-7 with the potential to be further developed for the treatment of renal disease and related disorders or disorders of the nervous system, from acute or chronic insults. 2. OBI possesses research, development and commercialization capabilities, as well as proprietary technology in a broad range of therapeutic fields. 3. CURIS desire to license BMP-7 to OBI so that OBI may develop and commercialize BMP-7 for all indications, except certain orthopedic and dental indications. NOW, THEREFORE, in consideration of the premises and mutual covenants herein contained, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereto agree as follows: ARTICLE I - DEFINITIONS When used in this Agreement, each of the following terms, when capitalized, shall have the meaning set forth below. The term shall have the same meaning whether the singular or plural form is used. "BMP-7" means BMP-7 protein and nucleic acid and all variants, derivatives, fragments, antibodies, and agonists thereto and vectors and hosts containing the foregoing. "Bone Disease Field" means the prevention or treatment of Osteoporosis, Osteomalacia, and Paget's Disease other than (i) by the local application of 5 Licensed Products in an insoluble formulation directly on bone or joint tissue for local, as opposed to general or systemic, effect and (ii) the treatment of fractures regardless of whether they result from Osteoporosis, Osteomalacia and Paget's Disease. "Cell Line" means the cells and related biological materials that are useful in the production of BMP-7. "Combination Product" means a product sold by OBI which contains one or more Additional Components in addition to a Licensed Product. "Contract Year" means a year of 365 days (or 366 days in a leap year) beginning on the Effective Date and ending one (1) year thereafter and so on year-by-year. "Control" or "Controlled" means possession of the ability to grant a license or sublicense as provided for herein without violating the terms of any agreement or other arrangements with any Third Party. "CURIS Know-How" means Information which is within the Control of CURIS. Notwithstanding anything herein to the contrary, CURIS Know-How excludes published CURIS Patents. "CURIS Patent Rights" means the rights granted by any governmental authority under a Patent relating to a Licensed Product, which Patent is owned, co-owned or Controlled by CURIS during the term of this Agreement. CURIS Patents include but are not limited to Primary Third Party Patent Rights and Secondary Third Party Patent Rights. Patents that relate to CURIS Patent Rights are listed in Schedules A, B, C, D and E. "Date of First Sale" means the date on which OBI (or an Affiliate) first sells a Licensed Product to an unaffiliated Third Party in an arms length commercial transaction. "Dollars" or "$" means lawful money of the United States in immediately available funds. "Drug Approval Application" means an application for Regulatory Approval required before commercial sale or use of a Licensed Product as a drug in a regulatory jurisdiction. "Effective Date" means the date first written above. "EMEA" means the European Medicines Evaluation Agency or any successor agency. 6 "FDA" means the United States Food and Drug Administration or any successor agency. "Field" means the development, use, manufacture, distribution, marketing and sale of Licensed Products for all uses and applications of BMP-7 excluding (i) treatment, repair or replacement of bone and joint tissue, including without limitation, meniscus and articular cartilage and ligaments and tendons, but excluding the Bone Disease Field, and (ii) treatment, repair or replacement of the tooth, dentin, alveolar bone, cementum, enamel, gingiva (to the extent, but only to the extent, the gingiva functions as part of the apparatus holding the tooth to the jaw) and /or periodontal ligament, but excluding the treatment of Oral Ulcerations or any other disease or disorder of the tissues of the mouth not involving the tooth, dentin, bone (including alveolar bone), cementum, enamel, gingiva (to the extent but only to the extent the gingiva functions as part of the apparatus holding the tooth to the jaw), ligament (including the periodontal ligament), tendon and/or cartilage. "First Proof of Principle Clinical Study or First POP" means the first OBI proof of principle program in which BMP-7 is evaluated for a Renal Indication and is selected by OBI for further clinical development, produced in quantity under GMP conditions, preclinical toxicology studies are performed, and the first administration to human subjects is performed. "Generic Equivalent" means a compound that is being sold in a country without infringing a CURIS Patent covering a composition of matter of the Licensed Product being sold hereunder by OBI, which would have infringed such CURIS Patent or Program Patent if such CURIS Patent or Program Patent containing a Valid Patent Claim were in force in that country. "IND" means an investigational new drug application filed with the FDA as more fully defined in 21 C.F.R. (S)312.3 or its equivalent in any country. "Information" means information, generally not known to the public, relating to the Field and including (i) techniques and data, including, but not limited to, screens, models, inventions, practices, methods, knowledge, know-how, skill, experience, test data including pharmacological, toxicological and clinical test data, analytical and quality control data, marketing, pricing, distribution, costs, sales, manufacturing data, and patent and legal data or descriptions (to the extent that disclosure thereof would not result in loss or waiver of privilege or similar protection) and (ii) compounds, compositions of matter, assays and biological materials. "Licensed Product" means any form or dosage of BMP-7 for pharmaceutical use in humans or other animals or for any other use. 7 "Ludwig Agreement" is the Agreement among Creative Biomolecules, Inc., The Ludwig Institute for Cancer Research and the Japanese Research Foundation for Cancer Research dated June 1, 1997. "Ludwig Patent Rights" means those Patents co-owned by CURIS and Ludwig Institute listed in Schedule C "Major European Country" means Great Britain, France, Germany, Italy, or Spain. "NDA" means a New Drug Application and all supplements filed pursuant to the requirements of the FDA, including all documents, data and other information concerning a Licensed Product which are necessary for or included in, FDA approval to market a Licensed Product as more fully defined in 21 C.F.R. (S)314.50 et. seq. "Net Sales" means consistent with generally accepted accounting principles and OBI worldwide practices and procedures, consistently applied with respect to a Licensed Product, which contain as its active ingredients only BMP-7, the amount invoiced by OBI for sales of Licensed Products to a Third Party in the Territory, less estimates which will be adjusted to actual on a periodic basis (no less frequently than annually) of: (i), discounts, including cash discounts, discounts to managed care or similar organizations or government organizations, rebates paid, credit, accrued or actually taken, including government rebates such as Medicaid charge backs or rebates, and retroactive price reductions or allowances actually allowed or granted from the billed amount, and commercially reasonable and customary fees paid to distributors (other than to a distributor that is an Affiliate of OBI), but not any fees or discounts paid to Copromotion Partners, (ii) credits or allowances actually granted upon claims, rejections or returns of such sales of Licensed Products, including recalls, regardless of OBI requesting such recalls, (iii) taxes, duties or other governmental charges levied on or measured by the billing amount when included in billing, as adjusted for rebates, charge-backs, and refunds, and (iv) freight, postage, shipping and insurance charges paid for delivery of such Licensed Products, to the extent billed, and (v) provisions for uncollectable accounts determined in accordance with U.S. generally accepted accounting practices consistently applied to all products of OBI, provided, however, that if collected at a later date such amounts will be added to Net Sales in the quarter in which it is received; and with respect to Licensed Products that OBI has elected to sublicense to a Third Party, the amounts received by OBI in the form of royalties from such Third Parties, except for in the instance of further sublicense by OBI of rights granted to Curis by Stryker Corporation. In such instance, Net Sales must be computed by reference to Net Sales of OBI's sublicensee, not by reference to royalties paid OBI. With respect to Combination Products, Net Sales for such Combination Product sold by OBI will be calculated by determining the relative value provided by the 8 Licensed Product to the Combination Product. The general process and guidance to be followed in each market/country where a Combination Product is to be launched will be to determine weighted average net price per unit across all dosage forms of the combination product in that market in the 12 months preceding introduction of the combination product as well as the weighted average net price per unit across all dosage forms of additional components deemed to be key ingredients that are sold in that particular market in the 12 months preceding launch of the Combination Product. Further guidance for determining Net Sales of Licensed Product would be to multiply actual Net Sales for such Combination Product by the fraction A/(A+B) where A is the Price of the Collaboration Compound if the Licensed Product is sold separately, and B is the total Price of any Additional Components in the Combination Product if sold separately. If, on a country-by-country basis, either the Licensed Product or the Additional Components in the Combination Product are not sold separately in said country, Net Sales for the purpose of determining royalties of the Combination Product shall be calculated by multiplying actual Net Sales of such Combination Product by the fraction A/C where A is the Price of the Licensed Product, if sold separately, and C is the Price of the Combination Product. In all cases the computation of Net Sales for the purpose of determining royalties shall be determined by the parties to this Agreement in good faith based on the relative value of the Collaboration Compound and the Additional Components that are part of the Combination Product. This also includes the potential if, for any particular country, neither the Licensed Product nor the Additional Components of the Combination Product are sold separately in said country. Notwithstanding anything herein to the contrary, there will be no deductions from Net Sales of any fees paid or discounts granted to a Copromotion Partner for co-promoting a Licensed Product such as, for example, marketing fees. "Neural Indication" means central or peripheral nervous system disorder caused by acute injury including stroke and/or other trauma or a chronic condition including those conditions that are a consequence of a neuronal degeneration. "Oral Ulcerations" means the formation of lesions on the surface of skin lining the oral cavity caused by loss of tissue but does not include Periodontal Disease (as defined below) or any other disease or disorder involving the tooth, dentin, bone (including alveolar bone), cementum, enamel, gingiva (to the extent, but only to the extent, the gingiva functions as part of the apparatus holding the tooth to the jaw), ligament (including the periodontal ligament), tendon and/or cartilage. "Patent" means (i) valid and enforceable Letters Patent, including any extension, registration, confirmation, reissue, continuation, divisional, continuation-in-part, re-examination or renewal thereof and (ii) pending applications for Letters 9 Patents. "Patent Costs" means the reasonable fees and expenses paid to outside legal counsel and other Third Parties, and filing and maintenance expenses, incurred in connection with the establishment and maintenance of rights under Patents. "Periodontal Disease" means degeneration of the apparatus holding the tooth to the jaw involving damage to any or all of the gingiva (to the extent, but only to the extent, the gingiva functions as part of the apparatus holding the tooth to the jaw), alveolar bone, cementum, enamel and periodontal ligament. "Phase I" shall mean the portion of the clinical development program which provides for the first introduction into humans of a Licensed Product, including small scale clinical studies conducted in normal volunteers or patients to get information of Licensed Product safety, tolerability, pharmacological activity or pharmacokinetics, as more fully defined in 21 C.F.R. 312.21 (a). Such studies may include well controlled clinical studies in patients or volunteers lasting up to six (6) weeks per study. "Phase II" shall mean that portion of the clinical development program beyond Phase I, which provides for the definitive, well controlled clinical trials of a Licensed Product in patients, including clinical studies conducted in patients and designated to indicate clinical efficacy safety, as well as to obtain an indication of the dosage regimen required as more fully defined in 21 C.F. R. 312.21(b). "Phase III" shall mean that portion of the clinical development program beyond Phase II, which provides for large scale clinical studies conducted in a sufficient number of patients to establish the clinical efficacy of a Licensed Product for one or more indications and its safety, as more fully defined in 21 C.F.R. 312.21 (c). "Primary Third Party Patent Rights" means the rights granted to CURIS under Stryker Corporation Patents recited in Schedule B, Genetics Institute Patents listed in Schedule E and those co-owned Patents recited in Schedules C and D. "R&D Agreements" means the research and development agreements that consist of Material Transfer Agreements and Collaboration Agreements as listed in Schedule F. "Regulatory Approval" shall mean all official approvals by government, pricing or health authorities in a country (or super-national organizations, such as the EMEA) which are required for first use or sale, including, importation, manufacture (where manufacture is required), and if required, approvals for pricing or reimbursement of a pharmaceutical product in such country. 10 "Renal Indication" means a treatment directed to acute or chronic renal disorders and related disorders including, but not limited to, renal osteodystrophy and vascular calcification. "Replacement Compound" shall have the meaning described in Section 5.2. "Research" means all work performed by the Parties or on their behalf directed towards or in connection with the discovery, identification and synthesis of Licensed Product during the term of the Agreement. "Royalty Reporting Period" means the three month period ending on or about the exact dates of March 31, June 30, September 30 or December 31 of any year, with the beginning determined by Johnson & Johnson's calendar quarters. "Secondary Third Party Patent Rights" means the rights granted to CURIS, under Third Party Patents owned or Controlled by such Third Party, by virtue of an R&D Agreement between CURIS and a Third Party to make, use or sell BMP-7. "Sublicensee" shall mean, with respect to a particular Licensed Product, a Third Party to whom OBI or CURIS has granted a license or sublicense under any OBI Patents or CURIS Patents to make, use and sell such Licensed Product. As used in this Agreement, "Sublicensee" shall also include a Third Party to whom OBI has granted the right to distribute a Licensed Product, provided that such Third Party is responsible for marketing and promotion of such Licensed Product within its distribution territory."Territory" means all the countries of the world. "Third Party" means any entity other than CURIS, OBI or any Affiliates of CURIS or OBI. "Third Party Agreements" mean those Agreements listed in Schedule G. "Valid Patent Claim" means a claim in any unexpired CURIS Patent, which has matured into an issued patent which has not been held invalid by a non-appealed or unappealable decision by a court or other appropriate body of competent jurisdiction and claims BMP-7 or its use. The scope of a Valid Patent Claim shall be limited to its terms as set forth in the Patent itself and as further defined by any court, body or law of competent jurisdiction. For the purpose of royalty determination and payment, any claim being prosecuted in a pending patent application shall be deemed to be the equivalent of a Valid Patent Claim of an issued, unexpired patent, provided it is not pending for greater than six (6) years from the filing date of the patent application in which case it shall cease being a Valid Patent Claim until the patent issues. ARTICLE II - PRODUCT DEVELOPMENT 11 2.1 OBI's Development Responsibilities. OBI shall have the sole right to develop Licensed Product in the Field through First POP, Phases I, II and III, including but not limited to, preparing, filing and exclusively owning all Drug Approval Applications and obtaining and exclusively owning all Regulatory Approvals in the Territory. In this regard, OBI agrees to carry out development of Licensed Product consistent with its normal business practices regarding a compound of similar commercial potential. 2.2 CURIS' Responsibilities. Promptly after the Effective Date, CURIS shall transfer all Information relating to Licensed Product to OBI. ARTICLE III - COMMERCIALIZATION 3.1 OBI's Marketing Obligations For Licensed Products. All business decisions, including, but not limited to, the design, sale, price and promotion of Licensed Products under this Agreement and the decisions whether to market or not market any particular Licensed Product shall be within the sole discretion of OBI. Any marketing of a Licensed Product in one market or country shall not obligate OBI to market said Licensed Product in any other market or country. Furthermore, OBI makes no representation or warranty that the marketing of a Licensed Product shall be the exclusive means by which OBI will participate in any therapeutic field. In marketing any Licensed Product, OBI will use efforts that are consistent with the efforts it uses in commercializing its own pharmaceutical products (that are similar with regard to, for example, market potential, price per treatment, patient population and competitive position). 3.2 Trademarks. OBI shall select its own trademarks under which it will market Licensed Product and shall solely own such trademarks. ARTICLE IV - LICENSE GRANTS 4.1 Patent Licenses for BMP-7 and Licensed Products. As of the Effective Date and to the extent CURIS possesses exclusive rights itself and the right to sublicense CURIS hereby grants to OBI and its Affiliates an exclusive royalty bearing, worldwide license under CURIS Patent Rights with a right to grant sublicenses, to the extent that CURIS is able to grant such right to sublicense, to make, have made, use, import, offer for sale, sell, distribute and have sold Licensed Product in the Field. In the event CURIS does not possess exclusive rights to such CURIS Patent Rights, CURIS grants OBI the foregoing license on a non-exclusive basis but, in either case, exclusive as to CURIS. 4.2 CURIS agrees for the term of this Agreement not to make, use or sell in the Field or to grant a license to a Third Party to make, use or sell in the Field a product which is or includes a protein sharing at least 50% amino acid sequence identity with the Carboxy-terminal 7-cysteine domain sequence of the BMP-7 (a 12 "50% Homolog") or any truncated or species variant form of such 50% Homolog or homodimeric, heterodimeric or chimeric form of the 50% Homolog or any polyclonal or monoclonal antibodies to the 50% Homolog or DNA or RNA encoding the 50% Homolog. ARTICLE V - PAYMENTS In consideration of the assignments, rights and licenses granted under this Agreement, OBI agrees to pay CURIS as follows: 5.1 Upfront Payment. OBI agrees to pay to CURIS a non-refundable upfront payment of $3,500,000 by same day wire transfer within fifteen (15) business days of the date of execution of this Agreement by both Parties. 5.2 Milestones. (a) OBI agrees to make the following payments to CURIS upon the first occurrence of each milestone event for the Licensed Product. If a Licensed Product is replaced by OBI with another Licensed Product (a "Replacement Compound"), OBI shall not be obligated to make the same milestone payments for the Replacement Compound as it already made in connection with the Licensed Product which was replaced. It is understood that in no event shall OBI be obligated to make the payment due on any milestone more than once with respect to the same Licensed Product (or its Replacement Compound) in connection with either the Renal Indication or the Neural Indication, regardless of the number of indications with the Renal Indication or Neural Indication for which such Licensed Product is developed. (b) The amounts shown are the amounts to be received by CURIS, net of any withholding taxes, due on every milestone payment, which shall be the responsibility of OBI. (c) Upon the achievement of the following milestones in connection with a Renal Indication for Licensed Product as follows: (i) $[**] upon acceptance by FDA or the regulatory authority of a Major European Country of the first IND (or its foreign equivalent); (ii) $[**] upon completion of the First POP and an affirmative decision by OBP to continue a post-POP development program for Regulatory Approval; (iii) $[**] upon the dosing of the 10th patient in the first Phase III clinical trial; (iv) $30,000,000 upon the US Regulatory Approval of the Licensed Product; and 13 (v) $[**] upon EMEA Regulatory Approval or approval in the first Major European Country of Licensed Product. (d) Upon the achievement of the following milestones in connection with a Neural Indication for Licensed Product as follows: (i) $[**] upon the dosing of the 10th patient in the first Phase III clinical trial; (ii) $[**] upon US Regulatory Approval of Licensed Product; and (iii) $[**] upon EMEA Regulatory Approval or approval in the first Major European Country of Licensed Product. 5.3 Earned Royalties For Licensed Products. (a) OBI shall pay CURIS a royalty of [**]% of Net Sales of Licensed Product sold by or for OBI, its Affiliates or Sublicensees. (b) Royalties shall be paid in respect of a given Licensed Product, on country-by-country basis, for a period of the later of (i) ten (10) years from the Date of First Sale of the Licensed Product in a given country or (ii) the expiration of the last to expire of any Valid Patent Claim covering the Licensed Product in such country, provided that, if in any Royalty Reporting Period during such period, (1) a third Party commences selling a Product which is a Generic Equivalent of the Licensed Product in a country in the Territory and (2) such Unlicensed Unit Sales (as defined below) amount to the following percentages of OBI's Unit Sales in units of the Licensed Product in such country in the same Royalty Reporting Period, the royalty rate applied in such country shall be reduced by the following percentages, as long as the Unlicensed Unit Sales amount to the particular percentage of OBI's unit sales in units of the Licensed Product in such country in the same Royalty Reporting Period. Unlicensed Unit Sales as a Royalty Rate Reduction* (% of OBI Unit Sales) (% of Royalty Rate) less than [**]% [**]% [**]% - [**]% [**]% more than [**]% [**]% For purposes of this Section 6.5 (b) "Unlicensed Unit Sales" and "OBI Unit Sales" shall be deemed to mean the total grams of BMP-7 contained in the Third Party product (irrespective of dosage form) and the Licensed Product (irrespective of dosage form), respectively, as reflected on the label of each such Licensed Product and Third Party product; and (ii) Unlicensed Unit Sales shall be determined by the sales reports of IMS America Ltd. of Plymouth Meeting, 14 Pennsylvania ("IMS") or any successor to IMS or any other independent sales auditing firm selected by OBI and reasonably acceptable to CURIS. OBI shall bear all costs of providing CURIS with such information. If OBI is entitled to a royalty reduction based on Unlicensed Unit Sales pursuant to this Section 5.3(b) for any Royalty Reporting Period, OBI shall submit the sales report of IMS or such other independent firm, as applicable, for the relevant Royalty Reporting Period to CURIS, together with OBI's or its Sublicensees' sales report for the relevant Royalty Reporting Period. Such sales reports for each Royalty Reporting Period in which OBI is entitled to such royalty reduction shall be submitted with the royalty report for such Royalty Reporting Period submitted pursuant to Section 5.7. 5.4 Third Party Patents. If a Patent or Patents of a Third Party should be in force in any country during the term of this Agreement covering the manufacture, use or sale of any Licensed Product, and if it should prove in OBI's reasonable judgment, after consultation with CURIS, impractical or impossible for OBI or any Affiliate to continue the activity or activities licensed hereunder without obtaining a royalty bearing license from such Third Party under such Patent or Patents in said country, then OBI shall be entitled to a credit against the royalty payments due under Section 5.3 of an amount equal to the royalty paid to such Third Party, not to exceed [**] percent ([**]%) of the royalty due under this Agreement, arising from the manufacture, use or sale of the Licensed Product in said country. Notwithstanding the above, the royalty due to CURIS under Section 5.3 shall never be reduced by more than [**] percent ([**]%). 5.5 Compulsory License. If at any time and from time to time a Third Party in any country shall, under the right of a compulsory license granted or ordered to be granted by a competent governmental authority, manufacture, use or sell any Licensed Product, with respect to which royalties would be payable pursuant to Section 5.3 hereof, then OBI may reduce the royalty on sales in such country of such Licensed Product, to an amount no greater than the amount payable by said Third Party as consideration for the compulsory license, except that the royalty payable to CURIS shall not be reduced to less than [**] percent ([**]%) of the amount that would be payable to CURIS in such country under provisions of Section 5.4, and in no event lower than [**]. 5.6 Currency Restrictions. Except as herein provided in this Section 5.6, all royalties shall be paid in Dollars. If, at any time, legal restrictions prevent the prompt remittance of part of or all royalties with respect to any country where Licensed Products are sold, OBI shall document such restrictions to CURIS and shall then have the right and option to make such payments by depositing the amount thereof in local currency to CURIS' accounts in a bank or depository designated by CURIS in such country. 5.7 Reports and Records. 15 (a) During the term of this Agreement and commencing with the Date of First Sale of a Licensed Product, OBI shall furnish, or cause to be furnished to CURIS, written reports, including royalty payment due, within thirty (30) days following the end of each calendar quarter for which royalties are due, showing: (i) the Net Sales of each Licensed Product sold by each of OBI, its Affiliates and its Sublicensees in each country of the Territory, during the calendar quarter and the total for all quarters of the current Calendar Year; (ii) the units of each product form of each Licensed Product sold by each of OBI, its Affiliates and its Sublicensees in each country of the Territory, during the calendar quarter and the total for all quarters of the current Calendar Year; (iii) the royalties payable in Dollars, which shall have accrued hereunder in respect to such Net Sales; (iv) the royalties, if any, paid or due to be paid to each Third Party under provisions of this Agreement on Net Sales during the calendar quarter. (b) All payments to be made by OBI to CURIS shall be made in Dollars by same day wire transfer within thirty (30) days following the end of each calendar quarter, except as provided in Section 5.6. In the case of sales outside the United States, royalty payments by OBI to CURIS shall be converted to Dollars in accordance with OBI's current customary and usual procedures for calculating same which are the following: the rate of currency conversion shall be calculated using a simple monthly period average of the end "spot rates" provided by Brown Brothers Harriman, 59 Wall Street, NY, NY 10005, for each quarter, or if such rates are not available, the same computation using the spot rates as published by a leading United States commercial bank for such accounting period. These methods of conversion are consistent with OBI's current accounting methods. OBI shall give CURIS prompt written notice of any proposed changes to OBI's customary and usual procedures for currency conversion, which shall only apply after such notice has been delivered to and approved by CURIS, provided that such changes continue to maintain a set methodology for currency conversion. (c) Each report shall be made within thirty (30) days from the end of each calendar quarter. OBI shall keep accurate records in sufficient detail to enable royalties and other payments payable hereunder to be determined. OBI shall be responsible for all royalties and late payments that are due to CURIS that have not been paid by OBI, its Affiliates and Sublicensees. (d) OBI shall maintain complete and accurate records, in accordance with U.S. generally accepted accounting practices, which are relevant to costs, 16 expenses and payments under this Agreement and such records shall be open during reasonable business hours for a period of five (5) years from creation of individual records for examination at CURIS' expense and not more often than once each year by a certified public accountant or other representative selected by CURIS and acceptable to OBI for the sole purpose of verifying the correctness of calculations or such costs, expenses or payments made under this Agreement. In the absence of material discrepancies (in excess of 2%) in any request for reimbursement resulting from such audit, the accounting expense shall be paid by CURIS. If material discrepancies do result, OBI shall bear the reasonable audit expense. Any records or accounting information received from OBI shall be Confidential Information for purposes of Article VII. (e) OBI shall grant access to such records to Stryker Corporation's independent accountant for purposes of auditing Net Sales which is used in the computation of royalties due Stryker Corporation, by CURIS, subject to any obligations of confidentiality that Stryker has to CURIS which shall also apply to OBI. 5.8 Taxes. (a) OBI will make all payments to CURIS under this Agreement without deduction or withholding for taxes except to the extent that any such deduction or withholding is required by law in effect at the time of payment. (b) Any tax required to be withheld on amounts payable under this Agreement will promptly be paid by OBI on behalf of CURIS to the appropriate governmental authority, and OBI will furnish CURIS with proof of payment of such tax. Any such tax required to be withheld will be an expense of and borne by CURIS. (c) OBI and CURIS will cooperate with respect to all documentation required by any taxing authority or reasonably requested by OBI to secure a reduction in the rate of applicable withholding taxes. (d) If OBI had a duty to withhold taxes in connection with any payment it made to CURIS under this Agreement but OBI failed to withhold, and such taxes were assessed against and paid by OBI, then CURIS will indemnify and hold harmless OBI from and against such taxes (including interest). If OBI makes a claim under this Section 5.8 (d), it will comply with the obligations imposed by Section 5.8 (b) as if OBI had withheld taxes from a payment to Curis. 5.9 Sublicenses. Should any sublicenses granted hereunder by OBI result in CURIS owing Biogen, Inc, Genetics Institute or any party under the Ludwig Agreement, additional royalties, milestone payments or other payments that it would not have otherwise owed such parties, but for such sublicense, OBI shall 17 be responsible for any such additional expenses and shall compensate CURIS accordingly. ARTICLE VI - MANUFACTURE 6.1 OBI's Responsibility. OBI shall be solely responsible for making or having made Licensed Products. ARTICLE VII - PUBLICATIONS 7.1 Confidentiality; Exceptions. Except to the extent expressly authorized by this Agreement or otherwise agreed in writing, CURIS agrees that, for the time royalties are due and for five (5) years thereafter, CURIS shall keep confidential and shall not publish or otherwise disclose or use for any purpose other than as provided for in this Agreement any Information and other confidential and proprietary information and materials furnished to it by or for OBI including but not limited to royalty reports and other financial information, except to the extent that it can be established by CURIS that such Confidential Information: (i) was in the lawful knowledge and possession of the receiving Party prior to the time it was disclosed to, or learned by, the receiving Party, or was otherwise developed independently by the receiving Party, as evidenced by written records kept in the ordinary course of business, or other documentary proof of actual use by the receiving Party; (ii) was generally available to the public or otherwise part of the public domain at the time of its disclosure to the receiving Party; (iii) became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving Party in breach of this Agreement; or (iv) was disclosed to the receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the disclosing Party not to disclose such information to others. 7.2 Authorized Disclosure. Except as expressly provided otherwise in this Agreement, CURIS may disclose Confidential Information of OBI as follows: (i) to Third Parties under appropriate terms and conditions including confidentiality provisions substantially equivalent to those in this Agreement as is reasonably necessary to exercise the rights granted herein; provided, however, that if CURIS is required by law or regulation to make any such disclosure of OBI's Confidential Information it will give reasonable advance notice to OBI of such disclosure requirement will use its reasonable efforts to secure confidential treatment of such Confidential Information required to be disclosed. 7.3 Publications. Notwithstanding any other provision of this Agreement, including, but not limited to the provisions of Section 7.4, CURIS may not publish the results of any of its or its Third Party collaborator's research and development 18 activities relating to BMP-7 in the Field without the prior written consent of OBI, provided, however, publication permitted under R&D Agreements already in force shall not be restricted if permitted in such Agreements. 7.4 Public Announcements. Neither Party shall originate any publicity, news release or public announcements, written or oral, whether to the public or press, stockholders or otherwise, relating to this Agreement, including its existence, the subject matter to which it relates, performance under it or any of its terms, to any amendment hereto or performances hereunder without the prior written consent of the other Party, save only such announcements that are required by law to be made or that are otherwise agreed by the Parties. All such announcements shall be brief and factual. If a Party decides to make an announcement required by law, it will give the other Party at least ten (10) business days advance notice, where possible, of the text of the announcement so that the other Party will have an opportunity to comment upon the announcement. To the extent that the receiving Party reasonably requests that any information in the materials proposed to be disclosed or deleted, the disclosing Party shall request confidential treatment of such information pursuant to Rule 406 of the Securities Act of 1933 or Rule 24b-2 of the Securities Exchange Act of 1934 as amended, as applicable (or any other applicable regulation relating to the confidential treatment of information) so that there be omitted from the materials that are publicly filed any information that the receiving Party reasonably requests to be deleted, unless in the opinion of the disclosing Party's legal counsel such Confidential Information is legally required to be fully disclosed. Except for customary discussions with current or prospective investors and analysts, or at securities, industry or similar conferences or as required under applicable laws or regulations or as advised by CURIS' counsel, each Party shall give the other Party a reasonable opportunity (not to exceed 10 days) to review the content of any oral announcement before it is made. Notwithstanding the foregoing, however, where urgent, unusual and rare circumstances require immediate disclosure in the opinion of the Party's counsel, the Party will, unless impossible because of legal reasons, provide at least three (3) days advance notice. Notwithstanding the above, the Parties agree that CURIS may announce the signing of this Agreement, the achievement of each milestone in this Agreement. ARTICLE VIII - PURCHASED ASSETS AND OWNERSHIP OF INTELLECTUAL PROPERTY AND PATENT RIGHTS 8.1 Purchased Assets. On the Effective Date, CURIS shall sell, transfer, assign, convey and deliver, or cause to be sold, transferred, assigned, conveyed 19 and delivered, to OBI all of CURIS' right, title and interest in the assets listed below (the "Purchased Assets"): a. CURIS Know-How b. biological, pharmaceutical and medical materials and supplies relating to BMPs, including the Cell Lines. c. assays for detection of BMP-7 d. books, records, files, correspondence, data, reports, and other information, whether in written, electronic or other form, including, product specifications, quality control records and manuals, research and development files, records and laboratory books e. rights, claims or causes of action accruing on or after the Effective Date under or with respect to the Purchased Assets f. R&D Agreements as described in Schedule F, but only under the following conditions: The Parties agree that the R&D Agreements will be assigned to OBI, at OBI's request, following the Effective Date. To the extent that assignment of any R&D Agreement requires Third Party consent, CURIS agrees to use commercially reasonable efforts to obtain any and all such Third Party consents. To the extent that OBI does not elect assignment of an R&D Agreement or if the Third Party consent cannot be obtained, all CURIS' rights including Patent and know-how under the R&D Agreement shall be licensed to OBI pursuant to the terms of Section 4.1 of this Agreement. OBI shall also have the option to obtain assignment of one or more Third Party Agreements after the Effective Date and CURIS hereby agrees to effect such assignment upon request from OBI. CURIS shall bear the costs associated with any such assignments. 8.2. Patent Prosecution and Related Matters. Following the Effective Date, OBI shall be responsible for and shall bear the responsibilities and Patent Costs of filing, prosecuting and maintaining all CURIS Patents incurred after the Effective Date, to the same extent that CURIS currently bears such responsibilities and costs prior to the Effective Date. It is understood that CURIS and therefore OBI hereunder have no obligation to pay Patent Costs associated with the Patents listed in Schedule B, which Patent Costs are solely borne by Stryker Corporation. CURIS shall execute (or cause to be executed) all documents that are necessary to permit OBI to file, prosecute and maintain the CURIS Patents, except for those listed on Schedule B, at no charge, including but not limited to powers of attorney. If any such executions cannot be secured after reasonable efforts, CURIS hereby appoints OBI as its attorney in fact to take all actions OBI deems reasonably necessary to exercise the rights set forth 20 in this Section 8.2. As of the Effective Date, OBI shall have the exclusive right to respond to, defend or prosecute any actions, challenges, infringements, invalidity, oppositions, reexaminations, misappropriations or proceedings by or against a Third Party alleging infringement, misappropriation or violation of any of the CURIS Patent Rights , to the extent that CURIS has the right to respond to, defend or prosecute any of the foregoing by or against a Third Party alleging infringement, misappropriation or violation of such CURIS Patent Rights. In such event, CURIS shall cooperate with OBI and their respective legal counsel, join in suits or actions that may be brought by OBI and be available at OBI's reasonable requests to be an expert witness or otherwise to assist in such proceedings. CURIS also agrees to promptly provide OBI with any notices or communications it receives from Stryker under any of the Stryker Agreements (as described in Schedule G) or from a Third Party under other Agreement relating to any of the CURIS Patents licensed hereunder including notices or communications relating to infringement or validity of such Patents or Oppositions filed against such Patents. ARTICLE IX - REPRESENTATIONS AND WARRANTIES; EXCLUSIVITY. 9.1 Representations and Warranties. Each of the Parties hereby represents and warrants and covenants as follows: This Agreement is a legal and valid obligation binding upon such Party and enforceable in accordance with its terms. The execution, delivery and performance of the Agreement by such Party does not conflict with any agreement, instrument or understanding, oral or written, to which it is a Party or by which it is bound, nor violate any law or regulation of any court, governmental body or administrative or other agency having jurisdiction over it. CURIS owns or otherwise Controls all of the rights, title and interest in and to CURIS Know-How. 9.2 Patents and Know-How Warranties. To the best of its knowledge as of the Effective Date, CURIS represents and warrants that (i) any Patent, know-how or other intellectual property right owned or controlled by CURIS that is applicable to this Agreement is not currently being infringed by any Third Party, and (ii) that the practice of such rights does not infringe any valid property right of any Third Party and (iii) that it has the right to license and/or sublicense the Curis Patents listed in Schedules A, B, C, D and E and (iv) that the Patents listed in Schedules A,B,C,D and E are the entire patent estate that relate to BMP-7 in the Field to which CURIS has the right to license or assign. 9.3 CURIS Representations and Warranties. Curis represents and warrants to OBI and agrees as follows: (a) That inventions that were created by Third Parties pursuant to the R&D Agreements, of which Curis had notice and exercised its rights prior to the 21 Effective Date, have resulted in patents that are either owned by Curis or co-owned by Curis and are listed as Curis Patents on Schedules A, C and D. (b) That all inventions that were created prior to the Effective Date or those inventions that may be created after the Effective Date, under the R&D Agreements, in either instance, which Curis had no notice of prior to the Effective Date, are subject to J&J's rights that are granted to it by Curis, under this Agreement, pursuant to Section 4.1 (which describes the license to Curis Licensed Third Party Patent Rights) and Section 8.1 (g) (which describes the process whereby Curis agrees to assign R&D Agreements to J&J, at J&J's election). (c) That Curis has granted no rights, under the Curis Patent Rights or Ludwig Patent Rights to Third Parties pursuant to the R&D Agreements, except to the extent that such Third Parties are co-owners of a Curis Patent as of the Effective Date and as listed in this Agreement. (d) That Curis has no payment or funding obligations to Third Parties under the R&D Agreements or the Ludwig Agreement. (e) That any other obligation, or liability, such as indemnification, that may exist under the R&D Agreements, is the sole responsibility of Curis. (f) That there are no restrictions in any of the Third Party Agreements of Schedule G or R & D Agreements of Schedule F that would restrict OBI from using its technology. ARTICLE X TERM AND TERMINATION 10.1. Term. This Agreement shall commence on the Effective Date and shall remain in effect until the expiration of OBI's obligation to pay royalties for any Licensed Product, unless earlier terminated as provided in this Article X. 10.2 Termination For Breach. Either Party may terminate this Agreement in the event the other Party shall have materially breached or defaulted in the performance of any of its material obligations hereunder, and such default shall have continued for ninety (90) days after written notice thereof was provided to the breaching party by the non-breaching party. Any termination shall become effective at the end of such ninety (90) day period unless the breaching party (or any other party on its behalf) has cured any such breach or default prior to the expiration of the ninety (90) day period. 10.3 Termination For Bankruptcy. Either Party hereto shall have the right to terminate this Agreement forthwith by written notice to the other Party (i) if the other Party is declared insolvent or bankrupt by a court of competent jurisdiction, (ii) if a voluntary or involuntary petition in bankruptcy is filed in any court of 22 competent jurisdiction against the other Party and such petition is not dismissed within ninety (90) days after filing, or (iii) if the other Party shall make or execute an assignment of substantially all of its assets for the benefit of creditors. 10.4 Results of Termination by OBI for Cause. In the event of termination of this Agreement by OBI pursuant to Sections 10.2 or 10.3, the licenses granted to OBI in Article V hereof, shall survive termination. In addition, the royalties rates recited in Paragraph 5.4 shall each be amended and reduced by 50%. Sections 5.3 through 6.9, and all relevant definitions in Article I shall survive termination. 10.5 Results of Termination by CURIS for Cause. In the event of termination of this Agreement by CURIS pursuant to Sections 10.2, 10.3 or 10.6, the licenses granted to OBI hereunder shall terminate. Upon such termination, OBI shall provide CURIS at no cost to CURIS copies of all OBI internal reports, reports from Third Parties, and notes of communications and correspondence with and reports submitted to regulatory agencies pertaining to Licensed Products. 10.6 Termination by OBI. OBI shall have the right to terminate this Agreement for any reason upon ninety (90) days written notice to CURIS. 10.7 OBI shall have the right to terminate this Agreement upon thirty days prior written notice should CURIS breach the representation and warranty recited in section 9.3 (f). In the event of termination under this Section 10.7, OBI shall receive a credit for any payments made to CURIS hereunder as of the date of termination, which OBI may apply to any future Agreement that the Parties may enter into. In addition, should the breach by CURIS of such representation and warranty result in any liabilities to OBI under any lawsuit brought by a Third Party against OBI relating to OBI's alleged violation of any the restrictions referred to in the representation and warranty in section 9.3 (f), CURS shall indemnify and hold harmless OBI for any damages suffered by OBI and it's attorney's fees in defending such lawsuit. 10.8 Surviving Rights. Sections 5.8, 5.9, 7.1 and 7.2 and any relevant definitions in Article I shall survive the expiration and any termination of this Agreement for any reason. 10.9 Accrued Rights, Surviving Obligations. Termination, relinquishment or expiration of the Agreement for any reason shall be without prejudice to any obligations which shall have accrued prior to such termination, relinquishment or expiration, including, without limitation, the payment obligations under Section 2.5 and Article 6 hereof and any and all damages arising from any breach hereunder. Such termination, relinquishment or expiration shall not relieve either Party from obligations that are expressly indicated to survive termination or expiration of the Agreement. 23 10.10 Termination Not Sole Remedy. Termination is not the sole remedy under this Agreement and, whether or not termination is effected, all other remedies will remain available except as agreed to otherwise herein. ARTICLE XI - INDEMNIFICATION 11.1 Research and Development Indemnification. Each Party (the "Indemnifying Party") shall indemnify, defend and hold the other Party (the "Indemnified Party") harmless from and against any and all liabilities, claims, damages, costs, expenses or money judgments incurred by or rendered against the Indemnified Party and its Affiliates incurred in the defense or settlement of a Third Party lawsuit or in a satisfaction of a Third Party judgment arising out of any injuries to person and/or damage to property resulting from (i) negligent acts of the Indemnifying Party performed in carrying out the Research hereunder, including failure by the Indemnifying Party to provide the Indemnified Party with any Information of the Indemnifying Party's which, if timely received, would have avoided injury, death or damage, provided such failure to provide such know-how is due to negligence of the part of the Indemnifying Party, and (ii) personal injury to the Indemnified Party employees or agents or damage to the Indemnified Party's property resulting from acts performed by, under the direction of, or at the request of the Indemnifying Party in carrying out activities contemplated by this Agreement. 11.2 Indemnification for Licensed Products. With respect to Licensed Products covered by this Agreement: (a) OBI hereby agrees to save, defend and hold CURIS and its agents, directors, officers and employees harmless from and against any and all suits, claims, actions, demands, liabilities, expenses and/or loss, including reasonable legal expense and attorney's fees ("Losses") resulting directly from the manufacture, use, handling, storage, sale or other disposition of chemical agents or Licensed Products by OBI, its Affiliates and agents except to the extent such Losses result from the negligence of CURIS. (b) In the event that CURIS is seeking indemnification under Sections 11.1 or 11.2(a), it shall inform OBI of a claim as soon as reasonably practicable after it receives notice of the claim, shall permit OBI to assume direction and control of the defense of the claim (including the right to settle the claim solely for monetary consideration), and shall cooperate as requested (at the expense of OBI) in the defense of the claim. (c) CURIS hereby agrees to save, defend and hold OBI and its agents, directors, officers and employees harmless from and against any and all suits, claims, actions, demands, liabilities, expenses and/or loss, including reasonable legal expense and attorneys' fees ("Losses") resulting directly from the manufacture, use, handling, storage, sale or other disposition of chemical agents 24 or Licensed Products by CURIS, its Affiliates, agents or Sublicensees, except to the extent such Losses result from the negligence of OBI. (d) CURIS agrees to save, defend and hold OBI and its agents, directors, officers and employees harmless from and against any and all suits, claims, actions, demands, liabilities, expenses and/or loss, including reasonable legal expense and attorney's fees ("Losses") resulting directly from any breach of the representations and warranties described in Section 9.3. (e) In the event OBI is seeking indemnification under Sections 11.1 or 11.2(c), it shall inform CURIS of a claim as soon as reasonably practicable after it receives notice of the claim, shall permit CURIS to assume direction and control of the defense of the claim (including the right to settle the claim solely for monetary consideration), and shall cooperate as requested (at the expense of CURIS) in the defense of the claim. ARTICLE XII - DISPUTE RESOLUTION 12.1 Dispute Resolution and Arbitration. In the case of any disputes between the Parties arising from this Agreement, and in case this Agreement does not provide a solution for how to resolve such disputes, the Parties shall discuss and negotiate in good faith a solution acceptable to both Parties and in the spirit of this Agreement. If after negotiating in good faith pursuant to the foregoing sentence, the Parties fail to reach agreement within sixty (60) days, then the President of CURIS and the President of OBI shall discuss in good faith an appropriate resolution to the dispute. If these executives fail, after good faith discussions, to reach an amicable agreement within sixty (60) days, then either Party may upon written notice to the other submit the dispute to binding arbitration pursuant to Section 12.2. 12.2 Arbitration. Any claim, dispute or controversy arising out of or in connection with or relating to this Agreement, (including, without limitation, disputes with respect to the rights and obligations of the Parties following termination) not settled by the procedures set forth in Section 13.1 above or the breach or alleged breach of a material provision of this Agreement shall be adjudicated by arbitration in accordance with the Arbitration Proceedings as set forth in Exhibit A attached hereto. ARTICLE XIII - MISCELLANEOUS 13.1 Relationship of Parties. For the purposes of this Agreement, each party is an independent contractor and not an agent or employee of the other party. Neither party shall have authority to make any statements, representations, or commitments of any kind, or to take any action which shall be binding on the 25 other party, except as may be explicitly provided for herein or authorized in writing. 13.2 Counterparts. This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, and all of which together shall be deemed to be one and the same instrument. 13.3 Headings. All headings in this Agreement are for convenience only and shall not affect the meaning of any provision hereof. 13.4 Binding Effect. This Agreement shall inure to the benefit of and be binding upon the parties and their respective lawful successors and assigns. 13.5 Assignment. Neither party may assign this Agreement without the prior written consent of the other party, except that a party may assign this Agreement to an Affiliate or to a successor in connection with the merger, consolidation, or sale of all or substantially all of its assets or that portion of its business pertaining to the subject matter of this Agreement. 13.6 Amendment and Waiver. This Agreement may be amended, supplemented, or otherwise modified at any time, but only by means of a written instrument signed by both parties. Any waiver of any rights or failure to act in a specific instance shall relate only to such instance and shall not be construed as an agreement to waive any rights or fail to act in any other instance, whether or not similar. 13.7 Governing Law. This Agreement and the legal relations among the parties shall be governed by and construed in accordance with the laws of the State of New York, USA, irrespective of any choice of laws or conflict of laws principles. 13.8 Severability. In the event that any provision of this Agreement shall, for any reason, be held to be invalid or unenforceable in any respect, such invalidity or unenforceability shall not affect any other provision hereof, and this Agreement shall be construed as if such invalid or unenforceable provision had not been included herein. 13.9 Entire Agreement. This Agreement constitutes the entire agreement between the parties with respect to the subject matter hereof and supersedes any and all prior or contemporaneous oral and prior written agreements and understandings. 13.10 Advice of Counsel. OBI and CURIS have each consulted counsel of their choice regarding this Agreement, and each acknowledges and agrees that this Agreement shall not be deemed to have been drafted by one party or another and will be construed accordingly. 26 13.11 Consents Not Unreasonably Withheld. Whenever provision is made in this Agreement for either Party to secure the consent or approval of the other, that consent or approval shall not unreasonably be withheld, and whenever in this Agreement provision is made for one Party to object to or disapprove a matter, such objection or disapproval shall not unreasonably be exercised. 13.12 Retained Rights. Nothing in this Agreement shall limit in any respect the right of either Party to conduct research and development with respect to and market products outside the Field using such Party's know-how. 13.13 Force Majeure. Neither Party shall lose any rights hereunder or be liable to the other Party for damages or losses on account of failure of performance by the defaulting Party if the failure is occasioned by government action, war, fire, explosion, flood, strike, lockout, embargo, act of God, or any other similar cause beyond the control of the defaulting Party, provided that the Party claiming force majeure has exerted all reasonable efforts to avoid or remedy such force majeure; provided, however, that in no event shall a Party be required to settle any labor dispute or disturbance. Notwithstanding the foregoing, this Section 14.13 shall not operate to relieve either Party from performance of any obligation for more than ninety (90) days. 13.14 Further Actions. Each Party agrees to execute, acknowledge and deliver such further instruments, and to do all such other acts, as may be necessary or appropriate in order to carry out the purposes and intent of this Agreement. 13.15 No Trademark Rights. Except as otherwise provided herein, no right, express or implied, is granted by the Agreement to use in any manner the name "CURIS" or "OBI", or any other trade name or trademark of the other Party or its Affiliates in connection with the performance of the Agreement. 13.16 Notices. All notices hereunder shall be in writing and shall be deemed given if delivered personally or by facsimile transmission (receipt verified), email (receipt acknowledged), mailed by registered or certified mail (return receipt requested), postage prepaid, or sent by express courier service, to the Parties at the following address (or at such other address for a Party as shall be specified by like notice; provided, that notices of a change of address shall be effective only upon receipt thereof). If to CURIS, addressed to: CURIS Inc. 61 Moulton Street Cambridge, MA 02138 Attention: General Counsel Facsimile: 617 ###-###-#### Email: ***@*** 27 If to OBI: addressed to: Ortho Biotech Products, L.P. Route 22 East P.O. Box 6914 Bridgewater, NJ 0880709814 Attention: President Facsimile: Email: With a copy to: Office of General Counsel Johnson & Johnson One Johnson & Johnson Plaza New Brunswick, NJ 08933 Facsimile: 732 ###-###-#### Email: ***@*** Each of the Parties consent to the personal jurisdiction of the U.S. Federal Courts and agree to accept any legal process served upon such Party at the addresses specified above for such Party. 13.17 Waiver. Except as specifically provided for herein, the waiver from time to time by either of the Parties of any of their rights or their failure to exercise any remedy shall not operate or be construed as a continuing waiver of same or of any other of such Party's rights or remedies provided in this Agreement. 13.18 Compliance with Laws. The Parties shall comply with all applicable laws, rules, regulations and orders of the United States and applicable European countries and supra-governmental organizations and all jurisdictions and any agency or court thereof in connection with this Agreement and the transactions contemplated thereby. 13.19 Bankruptcy. All rights and licenses granted under or pursuant to this Agreement by each Party as a licensor are, and shall otherwise be deemed to be, for purposes of Section 365(n) of Title ll, U.S. Code (the "Bankruptcy Code"), licenses of rights to "intellectual property" as defined under section 101(35A) of the Bankruptcy Code. The Parties agree that each licensee of such rights under this Agreement, shall retain and may fully exercise all rights and elections it would have in the case of a licensor bankruptcy under the Bankruptcy Code. 28 Each Party agrees during the term of this Agreement to create or maintain current copies, or if not amenable to copying, detailed descriptions or other appropriate embodiments, of all such intellectual property licensed to the other Party. 13.20 Confidential Treatment. CURIS agrees to give this Agreement "Confidential Treatment" in any filings it makes with the U.S. Securities & Exchange Commission including redacting all financial terms, except to the extent that (a) such financial information is disclosed in CURIS financial statements and (b) that the financial information has been previously disclosed in the press release that has been approved by OBI 13.21 Governmental Authority Consents. No consents of any Governmental Authority having jurisdiction over CURIS is required to be obtained by CURIS in order to authorize the execution by CURIS of this Agreement or the performance by CURIS of the terms hereof and consents, if any, required pursuant to the HSR Act. 29 IN WITNESS WHEREOF, the undersigned have duly executed and delivered this Agreement as a sealed instrument effective as of the date first above written. ORTHO BIOTECH PRODUCTS, L.P. by: Ortho Biotech, Inc. its general partner /S/ Gary M. Reedy - -------------------------- By: Gary M. Reedy President CURIS, INC. /S/ Daniel R. Passeri - -------------------------- By: Daniel R. Passeri President and CEO 30 Exhibit A Dispute Resolution a. Any dispute, claim or controversy arising from or related in any way to this Agreement or the interpretation, application, breach, termination or validity thereof, including any claim of inducement of this Agreement by fraud or otherwise, will be submitted for resolution to arbitration pursuant to the rules then pertaining of the CPR Institute for Dispute Resolution for Non-Administered Arbitration (available at www.cpradr.org/arb-rules.htm), or successor ("CPR"), except where those rules conflict with these provisions, in which case these provisions control. The arbitration will be held in New York City, New York. b. The panel shall consist of three arbitrators chosen from the CPR Panels of Distinguished Neutrals (or, by agreement, from another provider of arbitrators) each of whom is a lawyer with at least 15 years experience with a law firm or corporate law department of over 25 lawyers or who was a judge of a court of general jurisdiction. In the event the aggregate damages sought by the claimant are stated to be less than $5 million, and the aggregate damages sought by the counterclaimant are stated to be less than $5 million, and neither side seeks equitable relief, then a single arbitrator shall be chosen, having the same qualifications and experience specified above. Each arbitrator shall be neutral, independent, disinterested, impartial and shall abide by The CPR-Georgetown Commission Proposed Model Rule for the Lawyer as Neutral available at www.cpradr.org/cpr-george.html. c. The parties agree to cooperate (1) to attempt to select the arbitrator(s) by agreement within 45 days of initiation of the arbitration, including jointly interviewing the final candidates, (2) to meet with the arbitrator(s) within 45 days of selection and (3) to agree at that meeting or before upon procedures for discovery and as to the conduct of the hearing which will result in the hearing being concluded within no more than nine (9) months after selection of the arbitrator(s) and in the award being rendered within 60 days of the conclusion of the hearings, or of any post-hearing briefing, which briefing will be completed by both sides within 45 days after the conclusion of the hearings. d. In the event the parties cannot agree upon selection of the arbitrator(s), the CPR will select arbitrator(s) as follows: CPR shall provide the parties with a list of no less than 25 proposed arbitrators (15 if a single arbitrator is to be selected) having the credentials referenced above. Within 25 days of receiving such list, the parties shall rank at least 65% of the proposed arbitrators on the initial CPR list, after exercising cause challenges. The parties may then interview the five candidates (three if a single arbitrator is to be selected) with the highest combined rankings for no more than one hour each and, following the interviews, may exercise one peremptory challenge each. The panel will consist of the remaining three candidates (or one, if one arbitrator is to be selected) with the highest combined rankings. In the event these procedures fail to result in selection of the required number of arbitrators, CPR shall select the appropriate number of arbitrators from among the members of the various CPR Panels of 31 Distinguished Neutrals, allowing each side challenges for cause and three peremptory challenges each. e. In the event the parties cannot agree upon procedures for discovery and conduct of the hearing meeting the schedule set forth in paragraph c above, then the arbitrator(s) shall set dates for the hearing, any post-hearing briefing, and the issuance of the award in accord with the paragraph c schedule. The arbitrator(s) shall provide for discovery according to those time limits, giving recognition to the understanding of the parties that they contemplate reasonable discovery, including document demands and depositions, but that such discovery be limited so that the paragraph c schedule may be met without difficulty. In no event will the arbitrator(s), absent agreement of the parties, allow more than a total of ten days for the hearing or permit either side to obtain more than a total of 40 hours of deposition testimony from all witnesses, including both fact and expert witnesses, or serve more than 20 individual requests for documents, including subparts, or 20 individual requests for admission or interrogatories, including subparts. Multiple hearing days will be scheduled consecutively to the greatest extent possible. f. The arbitrator(s) must render their award by application of the substantive law of New York and are not free to apply "amiable compositeur" or "natural justice and equity." The arbitrator(s) shall render a written opinion setting forth findings of fact and conclusions of law with the reasons therefor stated. A transcript of the evidence adduced at the hearing shall be made and shall, upon request, be made available to either party. The arbitrator(s) shall have power to exclude evidence on grounds of hearsay, prejudice beyond its probative value, redundancy, or irrelevance and no award shall be overturned by reason of such ruling on evidence. To the extent possible, the arbitration hearings and award will be maintained in confidence. g. In the event the panel's award exceeds $5 million in monetary damages or includes or consists of equitable relief, or rejects a claim in excess of that amount or for that relief, then the losing party may obtain review of the arbitrators' award or decision by a single appellate arbitrator (the "Appeal Arbitrator") selected from the CPR Panels of Distinguished Neutrals by agreement or, failing agreement within seven working days, pursuant to the selection procedures specified in paragraph d above. If CPR cannot provide such services, the parties will together select another provider of arbitration services that can. No Appeal Arbitrator shall be selected unless he or she can commit to rendering a decision within forty-five days following oral argument as provided in this paragraph. Any such review must be initiated within thirty (30) days following the rendering of the award referenced in f above. h. The Appeal Arbitrator will make the same review of the arbitration panel's ruling and its bases that the U.S. Court of Appeals of the Circuit where the arbitration hearings are held would make of findings of fact and conclusions of law rendered by a district court after a bench trial and then modify, vacate or affirm the arbitration panel's award or decision accordingly, or remand to the panel for further proceedings. The Appeal Arbitrator will consider only the arbitration panel's findings of fact and conclusions of law, pertinent portions of 32 the hearing transcript and evidentiary record as submitted by the parties, opening and reply briefs of the party pursuing the review, and the answering brief of the opposing party, plus a total of no more than four (4) hours of oral argument evenly divided between the parties. The party seeking review must submit its opening brief and any reply brief within seventy-five (75) and one hundred thirty (130) days, respectively, following the date of the award under review, whereas the opposing party must submit its responsive brief within one hundred ten (110) days of that date. Oral argument shall take place within five (5) months after the date of the award under review, and the Appeal Arbitrator shall render a decision within forty-five (45) days following oral argument. That decision will be final and not subject to further review, except pursuant to the Federal Arbitration Act. i. The parties consent to the jurisdiction of the Federal District Court for the district in which the arbitration is held for the enforcement of these provisions and the entry of judgment on any award rendered hereunder (including after review by the Appeal Arbitrator where such an appeal is pursued). Should such court for any reason lack jurisdiction, any court with jurisdiction shall act in the same fashion. j. Each party has the right before or, if the arbitrator(s) cannot hear the matter within an acceptable period, during the arbitration to seek and obtain from the appropriate court provisional remedies such as attachment, preliminary injunction, replevin, etc. to avoid irreparable harm, maintain the status quo, or preserve the subject matter of the arbitration. k. EACH PARTY HERETO WAIVES ITS RIGHT TO TRIAL OF ANY ISSUE BY JURY. l. EACH PARTY HERETO WAIVES ANY CLAIM TO PUNITIVE, EXEMPLARY OR MULTIPLIED DAMAGES FROM THE OTHER. m. EACH PARTY HERETO WAIVES ANY CLAIM OF CONSEQUENTIAL DAMAGES FROM THE OTHER. n. EACH PARTY HERETO WAIVES ANY CLAIM FOR ATTORNEYS' FEES AND COSTS AND PREJUDGMENT INTEREST FROM THE OTHER. 33 SCHEDULE A Curis BMP Portfolio (Worldwide) Licensed to Stryker

Page 1 of 10 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003CPFW2 CRP-059CPFW2 Method for modulating inflammatory 05/22/1995 08/445,467 Issued 6,077,823 Curis US response - ------------------------------------------------------------------------------------------------------------------------------------ CBM- CRP-059Div Method for reducing tissue damage 06/20/2000 09/597,517 Pending Curis US 003CPFW2DIV associate with ischemia-reperfusion or hypoxia injury - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003DE CRP-059DE Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis DE Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003EP CRP-059EP Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis EP Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003ES CRP-059ES Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis ES Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003FR CRP-059FR Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis FR Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003FWC2 CRP-059FW2 Method for modulating inflammatory 03/30/1995 08/414,033 Issued 6,194,376 Curis US response comprising administering morphogen - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003GB CRP-059GB Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis UK Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003IE CRP-059IE Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis IE Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003IT CRP-059IT Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis IT Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003JP CRP-059JP Method for modulating inflammatory 08/28/1992 05-505344 Pending Curis JP response following ischemic reperfusion injury - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003LU CRP-059LU Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis LU Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003MC CRP-059MC Morphogen-Induced Modulation of 08/28/1992 92919544.4 In Opposition 0601106 Curis MC Inflammatory Response B1 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-003PC CRP-059PC Method for modulating inflammatory 08/28/1992 PCT/US93/04692 Completed Curis PCT response following ischemic National reperfusion injury Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004AU CRP-070AU Morphogen Induced Nerve Regeneration 07/29/1993 47971/93 Issued 681,594 Curis AU and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004C2DV CRP-070DV Morphogen-Induced Nerve Regeneration 05/31/1995 08/456,033 Allowed Curis US and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004C2US CRP-070FW2 Morphogen Induced Nerve Regeneration 06/16/1994 08/260,675 Pending Curis US and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004C3US CRP-070FWCN2 Morphogen-Induced Nerve Regeneration 09/25/1997 08/937,756 Pending Curis US and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004CA CRP-070CA Morphogen Induced Nerve Regeneration 07/29/1993 2,141,554 Allowed CA and Repair

Page 2 of 10 Schedule A Curis BMP Portfolio (Worldwide) Licensed to Stryker - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004EP CRP-070EP Morphogen Induced Nerve Regeneration 07/29/1993 93918560.9 Pending Curis EP and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004JP CRP-070JP Morphogen Induced Nerve Regeneration 07/29/1993 6-505485 Pending Curis JP and Repair - ------------------------------------------------------------------------------------------------------------------------------------ CBM-004PC CRP-070PC Morphogen Induced Nerve Regeneration 07/29/1993 PCT/US93/07231 Completed Curis PCT and Repair National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-008 CRP-128 Methods and Compositions for the 09/25/1997 08/938,622 Allowed Curis US Treatment and Prevention of Parkinson's Disease - ------------------------------------------------------------------------------------------------------------------------------------ CBM-010EP CRP-141EP Methods and Compositions for 01/21/1999 99903241 Pending EP 1047443 Curis EP Enhancing Cognitive Function Using Morphogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ CBM-010PC CRP-141PC Methods and Compositions for 01/21/1999 PCT/US99/01232 Completed Curis PCT Enhancing Cognitive Function Using National Stage Morphogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ CBM-010US CRP-141 Methods and Compositions for 01/23/1998 09/012,846 Pending Curis US Enhancing Cognitive Function Using Morphogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ CBM-011US CRP-155 Methods and Compositions for the 09/25/1997 08/937,755 Pending Curis US Treatment of Motor Neuron Injury and Neuropathy - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013AUD2 CRP-118AUD2 Morphogen Treatment for Chronic Renal 05/06/1997 38887/01 Pending Curis AU Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013CA CRP-118CA Morphogen Treatment for Chronic Renal 05/06/1997 2,254,954 Pending Curis CA Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013CPA CRP-118CPA Morphogen Treatment for Chronic Renal 05/06/1996 08/643,321 Allowed Curis US Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013CUS CRP-118 Morphogen Treatment for Chronic Renal 08/28/2002 Not yet assigned Pending Curis US Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013EP CRP-118EP Morphogen Treatment for Chronic Renal 05/06/1997 97922726.1 Pending Curis EP Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013JP CRP-118JP Morphogen Treatment for Chronic Renal 05/06/1997 9-540211 Pending Curis JP Failure - ------------------------------------------------------------------------------------------------------------------------------------ CBM-013PC CRP-118PC Morphogen Treatment for Chronic Renal 05/06/1997 PCT/US97/07816 Completed Curis PCT Failure National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014AU CRP-144AU Therapies for Acute Renal Failure 05/05/1998 72443/98 Issued 743510 Curis AU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014AUD CRP-144AU Therapies for Acute Renal Failure 05/05/1998 34339/02 Pending 743510 Curis AU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014CA CRP-144CA Therapies for Acute Renal Failure 05/05/1998 2,289,123 Pending Curis CA - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014EP CRP-144EP Therapies for Acute Renal Failure 05/05/1998 98919715.7 Pending Curis EP - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014JP CRP-144JP Therapies for Acute Renal Failure 05/05/1998 10-548048 Pending Curis JP
Page 3 of 10 Curis BMP Portfolio (Worldwide) Licensed to Stryker - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014PC CRP-144PC Therapies for Acute Renal failure 05/05/1998 PCT/US98/03197 Completed Curis PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-014US CRP-144 Therapies for acute renal failure 05/05/1998 09/445,328 Pending Curis US - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015AUD CRP-145AUD Novel Therapies for Chronic Renal Failure 05/06/1997 71419/00 Pending Curis AU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015AUD2 CRP-145AUD2 Novel Therapies for Chronic Renal Failure 05/06/1997 Pending Curis AU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015CA CRP-145CA Novel Therapies for Chronic Renal Failure 05/06/1997 2,254,953 Pending Curis CA - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015EP CRP-145EP Novel Therapies for Chronic Renal Failure 05/06/1997 97923567.8 Pending Curis EP - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015JP CRP-145JP Novel Therapies for Chronic Renal Failure 05/06/1997 9-540150 Pending Curis JP - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015PC CRP-145PC Therapies for Chronic Renal Failure 05/06/1997 PCT/US97/07655 Completed Curis PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-015US CRP-145 Novel Therapies for Chronic Renal Failure 02/11/2000 08/851,628 Pending Curis US - ------------------------------------------------------------------------------------------------------------------------------------ CBM-016FW2 CRP-068 Morphogen Treatment of Organ Transplants 06/07/1995 08/480,515 Issued 6,090,776 Curis US - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017AT CRP-072AT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis AT - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017AU CRP-072AU Morphogen Induced Liver Regeneration 09/16/1993 51623/93 Issued 681,356 Curis AU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017CA CRP-072CA Morphogen Induced Liver Regeneration 09/16/1993 2,144,514 Issued 2,144,514 Curis CA - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017CH CRP-072CH Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis CH - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017DE CRP-072DE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis DE - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017DK CRP-072DK Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis DK - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017EP CRP-072EP Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis EP - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017ES CRP-072ES Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis ES - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017FR CRP-072FR Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis FR - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017FW2 CRP-072FW2 Morphogen Induced Liver Regeneration 05/22/1995 08/445,468 Issued 5,849,686 Curis US - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017GR CRP-072GR Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis GR - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017IE CRP-072IE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis IE - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017IT CRP-072IT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis IT - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017JP CRP-072JP Morphogen Induced Liver Regerneration 09/16/1993 06-508342 Pending Curis JP - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017LU CRP-072LU Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis LU - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017MC CRP-072MC Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis MC - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017NL CRP-072NL Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis NL - ------------------------------------------------------------------------------------------------------------------------------------ CBM-017PC CRP-072PC Morphogen Induced Liver Regeneration 09/16/1993 PCT/US93/08808 Completed Curis PCT National Stage

Page 4 of 10 Curis BMP Portfolio (Worldwide) Licensed to Stryker - --------------------------------------------------------------------------------------------------------------------------------- CBM-017PT CRP-072PT Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis PT - --------------------------------------------------------------------------------------------------------------------------------- CBM-017SE CRP-072SE Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis SE - --------------------------------------------------------------------------------------------------------------------------------- CBM-017UK CRP-072UK Morphogen Induced Liver Regeneration 09/16/1993 93922700.5 Issued 0661987 B1 Curis UK - --------------------------------------------------------------------------------------------------------------------------------- CBM-018CN CRP-074CN Morphogen treatment of Gastrointestinal 06/05/1995 08/462,623 Issued 5,739,107 Curis US Ulcers - --------------------------------------------------------------------------------------------------------------------------------- CBM-018DV CRP-074DV Morphogen Treatment for Limiting 06/05/1995 08/461,113 Issued 6,399,569 Curis US Proliferation of Epithelial Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-018FW2 CRP-074FW2 Morphogen Treatment of Gastrointestinal 06/05/1995 08/461,397 Issued 5,972,884 Curis US Ulcers - --------------------------------------------------------------------------------------------------------------------------------- CBM-019 CPUS CRP-123 Treatment of Mammalian Myocardium with 12/03/1999 09/331,375 Pending Curis US Morphogen Locally, Or with Morphogenically-Treated Myogenic Precursor Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-019AU CRP-123AU Treatment of Mammalian Myocardium with 12/19/1997 57119/98 Issued 741350 Curis AU Morphogen Locally, Or with Morphogenically-Treated Myogenic Precursor Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-019CA CRP-123CA Treatment of Mammalian Myocardium with 12/19/1997 2,275,436 Pending Curis CA Morphogen Locally, Or with Morphogenically-Treated Myogenic Precursor Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-019EP CRP-123EP Treatment of Mammalian Myocardium with 12/19/1997 97953356.9 Pending Curis EP Morphogen Locally, Or with Morphogenically-Treated Myogenic Precursor Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-019JP CRP-123JP Treatment of Mammalian Myocardium with 12/19/1997 10-528998 Pending Curis JP Morphogen Locally, Or with Morphogenically-Treated Myogenic Precursor Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-020CP2AU CRP-160CP2AU Methods for Maintaining or Restoring 12/16/1998 19218/99 Pending Curis AU Tissue-Appropriate Phenotype of Soft Tissue Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-020CP2CA CRP-160CP2CA Methods for Maintaining or Restoring 12/16/1998 2,314,821 Pending Curis CA Tissue-Appropriate Phenotype of Soft Tissue Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-020CP2EP CRP-160CP2EP Methods for Maintaining or Restoring 12/16/1998 98964007.3 Pending 1 040 126 Curis EP Tissue-Appropriate Phenotype of Soft Tissue Cells - --------------------------------------------------------------------------------------------------------------------------------- CBM-020CP2JP CRP-16OCP2JP Methods for Maintaining or Restoring 12/16/1998 2000-539059 Pending Curis JP Tissue-Appropriate Phenotype of Soft Tissue Cells

Page 5 of 10 - ------------------------------------------------------------------------------------------------------------------------------------ CBM-020CP2PC CRP-160CP2PC Methods for Maintaining or 12/16/1998 PCT/US98/26788 Completed Curis PCT Restoring Tissue-Appropriate National Phenotype of Soft Tissue Cells Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-020CP2US CRP-160CP2US Methods for Maintaining or 12/16/1998 09/581,770 Pending Curis US Restoring Tissue-Appropriate Phenotype of Soft Tissue Cells - ------------------------------------------------------------------------------------------------------------------------------------ CBM-021CIP CRP-166 CIP Method for Alleviating Cancer 11/13/1998 09/191,239 Pending Curis US Symptoms - ------------------------------------------------------------------------------------------------------------------------------------ CBM-021CPCA~ CRP-166CPCA Method for Alleviating Cancer 11/12/1999 2,349,038 Pending Curis CA Symptoms - ------------------------------------------------------------------------------------------------------------------------------------ CBM-021CPEP~ CRP-166CPEP Method for Alleviating Cancer 11/12/1999 99958892.4 Pending 1,131,087 Curis EP Symptoms - ------------------------------------------------------------------------------------------------------------------------------------ CBM-021CPJP~ CRP-166CPJP Method for Alleviating Cancer 11/12/1999 2000-582058 Pending Curis JP Symptoms - ------------------------------------------------------------------------------------------------------------------------------------ CBM-021CPPC~ CRP-166CPPC Method for Alleviating Cancer 11/12/1999 PCT/US99/26636 Completed Curis PCT Symptoms National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022AU CRP-060AU Osteogenic Proteins in the 08/28/1992 31762/93 Issued 670558 Curis AU Treatment of Bone Diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022CA CRP-060CA Treatment to prevent loss of 08/28/1992 2,116,559 Pending Curis CA and/or increase bone mass in metabolic bone diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022CN CRP-060CN Treatment to prevent loss of 03/20/1995 08/406,672 Issued 5,674,844 Curis US and/or increase bone mass in metabolic bone diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022CP FWC CN CRP-060CPFWC CN Treatment to Prevent Loss of 10/13/1998 09/170,936 Issued 6,333,312 Curis US and/or Increase Bone Mass in Metabolic Bone Diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022CPFWC CN2 CRP-060CPFWC CN2 Treatment to Prevent Loss of 09/13/2001 09/952,318 Pending Curis US and/or Increase Bone Mass in Metabolic Bone Diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022EP CRP-060EP Treatment to prevent loss of 08/28/1992 93900497.4 Pending Curis EP and/or increase bone mass in metabolic bone diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022JP CRP-060JP Treatment to prevent loss of 08/28/1992 05-506066 Pending Curis JP and/or increase bone mass in metabolic bone diseases - ------------------------------------------------------------------------------------------------------------------------------------ CBM-022PC CRP-060PC Osteogenic Proteins in the 08/28/1992 PCT/US92/07432 Completed Curis PCT Treatment of Bone Diseases National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-035AT CRP-058AT Morphogenic Protein 08/28/1992 92921799 Issued EP 0601129 Curis AT Screening Method B1

Page 6 of 10 SCHEDULE A Curis BMP Portfolio (Worldwide) Licensed to Stryker - ------------------------------------------------------------------------------------------------------------------------------- CBM-035AU CRP-058AU Morphogenic Protein Screening Method 08/28/1992 28624/92 Issued 678,345 Curis AU - ------------------------------------------------------------------------------------------------------------------------------- CBM-035AUDV CRP-058AUDV Morphogenic Protein Screening Method 08/28/1992 36040/97 Issued 696,364 Curis AU II - ------------------------------------------------------------------------------------------------------------------------------- CBM-035BE CRP-058BE Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis BE B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CA CRP-058CA Morphogenic Protein Screening Method 08/28/1992 2,116,560 Issued 2,116,156 Curis CA - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CH CRP-058CH Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis CH B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CN CRP-058 Morphogenic Protein Screening Method 05/26/1995 08/451,953 Issued 5,741,641 Curis US - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CN2 CRP-058 Method of Diagnosing Renal Tissue 05/06/1996 08/643,563 Issued 5,707,810 Curis US Damage or Disease - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CNDV CRP-058 Morphogenic Protein Screening Method 08/15/1997 08/912,088 Issued 5,994,131 Curis US - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CPC CRP-058CPC Morphogenic Protein Screening Method 08/28/1992 PCT/US92/07359 Completed Curis PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------- CBM-035CPFW CRP-058 Morphogenic Protein Screening Method 07/20/1994 08/278,729 Issued 5,650,276 Curis US - ------------------------------------------------------------------------------------------------------------------------------- CBM-035DE CRP-058DE Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis DE B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035DK CRP-058DK Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis DK B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035EP CRP-058EP Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 Curis EP B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035EPD CRP-058EPDV Morphogenic Protein Screening Method 08/28/1992 97202681.9 Pending Curis EP - ------------------------------------------------------------------------------------------------------------------------------- CBM-035EPD2 CRP-058EPDIV Morphogenic Protein Screening Method 08/28/1992 100232.8 Pending 1 033 574 Curis EP - ------------------------------------------------------------------------------------------------------------------------------- CBM-035ES CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 ES B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035FR CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 FR B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035GB CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 UK B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035GR CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 GR B1 - ------------------------------------------------------------------------------------------------------------------------------- CBM-035IE CRP-058 Morphogenic Protein Screening Method 08/28/1992 92921799 Issued EP 0601129 IE B1
Page 7 of 10 SCHEDULE A Curis BMP Portfolio (Worldwide) Licensed to Slryker - ----------------------------------------------------------------------------------------------------------------------------------- CBM-035IT CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 IT B1 - ----------------------------------------------------------------------------------------------------------------------------------- CBM-035JP CRP-058JP Morphogenic Protein Screening Method 8/28/1992 05-505345 Pending Curis JP - ----------------------------------------------------------------------------------------------------------------------------------- CBM-035LU CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 LU B1 - ----------------------------------------------------------------------------------------------------------------------------------- CBM-035MC CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 MC B1 - ----------------------------------------------------------------------------------------------------------------------------------- CBM-035NL CRP-058 Morphogenic Protein Screening Method 8/28/1992 92921799 Issued EP 0601129 NL B1 - ----------------------------------------------------------------------------------------------------------------------------------- CBM-036DV1 CRP-073 Morphogen Cell Surface Receptor 6/2/1995 08/459,009 Issued 5,861,479 Curis US - ----------------------------------------------------------------------------------------------------------------------------------- CBM-036DV2 CRP-073 Novel Morphogen Cell Surface Receptor 6/2/1995 08/459,951 Issued 6,093,547 Curis US - ----------------------------------------------------------------------------------------------------------------------------------- CBM-036FW CRP-073 Morphogen Cell Surface Receptor 12/16/1994 08/357,533 Issued 5,831,050 Curis US - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037AU CRP-091AU Methods and Compositions for 6/7/1995 28223/95 Issued 703445 AU Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037AUD CRP-091AUD Methods and Compositions for 6/24/1999 36757/99 Allowed 743067 AU Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037AUD2 CRP-091AUD2 Methods and Compositions for 4/17/2002 34387/02 Pending AU Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037CA CRP-091CA Methods and Compositions for 6/7/1995 2,191,583 Pending CA Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037CP CRP-091CP Methods and Compositions for 6/7/1995 08/486,343 Issued 6,071,695 Curis US Modulating Morphogenic Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037EP CRP-091EP Methods and Compositions for 6/7/1995 95923784.3 Pending EP Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037JP CRP-091JP Methods and Compositions for 6/7/1995 8-501323 Pending JP Modulating Protein Expression - ----------------------------------------------------------------------------------------------------------------------------------- CBM-037PC CRP-091PC Methods and Compositions for 6/7/1995 PCT/US95/07349 Completed Curis PCT Modulating Protein Expression National Stage - ----------------------------------------------------------------------------------------------------------------------------------- CBM-038 CRP-107 Methods and Compositions for 7/26/1995 08/507,598 Issued 5,834,188 Curis US Identifying Morphogen Analogs - ----------------------------------------------------------------------------------------------------------------------------------- CBM-039 CRP-116 Morphogen-Responsive Regulatory 7/26/1995 08/507,750 Issued 5,932,716 Curis US Elements - ----------------------------------------------------------------------------------------------------------------------------------- CBM-039DV CRP-116DV Methods and Compositions for 6/11/1997 08/872,859 Issued 6,110,460 Curis US Identifying Morphogen Analogs - ----------------------------------------------------------------------------------------------------------------------------------- CBM-040 CRP-126CP Methods and Compositions for 12/12/1996 08/764,522 Issued 6,090,544 Curis US Identifying Morphogen Analogs - ------------------------------------------------------------------------------------------------------------------------------------ CBM-040Div CRP-126CPD1 Methods and Compositions for 7/10/2000 09/613,177 Pending Curis US Identifying Morphogen Analogs
Page 8 of 10 SCHEDULE A Curis BMP Portfolio (Worldwide) Licensed to Stryker - ------------------------------------------------------------------------------------------------------------------------------------ CBM-041 CRP-127 Methods and Compositions for 12/12/1996 08/764,528 Issued 6,103,491 Curis US Identifying Morphogen Analogs - ------------------------------------------------------------------------------------------------------------------------------------ CBM-041Div CRP-127 Methods and Compositions for 08/14/2000 09/638,489 Pending Curis US Identifying Morphogen Analogs - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043 CRP-148 Modulators Of Morphogen Expression 11/15/1999 09/423,821 Pending Curis US And Methods Of Identifying The Same - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043AU CRP-148AU Modulators Of Morphogen Expression 05/28/1998 77073/98 Issued 745514 Curis AU And Methods Of Identifying The Same - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043CA CRP-148CA Modulators Of Morphogen Expression 05/28/1998 2,291,510 Pending Curis CA And Methods Of Identifying The Same - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043EP CRP-148EP Modulators Of Morphogen Expression 05/28/1998 98925035.2 Pending Curis EP And Methods Of Identifying The Same - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043JP CRP-148JP Modulators Of Morphogen Expression 05/28/1998 11-500978 Pending Curis JP And Methods Of Identifying The Same - ------------------------------------------------------------------------------------------------------------------------------------ CBM-043PC CRP-148PC Modulators Of Morphogen Expression 05/28/1998 PCT/US98/11025 Completed Curis PCT And Methods Of Identifying The Same National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058 US CRP-131 Morphogens and GDNF/NGF 09/09/1998 09/508,254 Pending Curis US Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058AU CRP-131AU Morphogens and GDNF/NGF 09/09/1998 94759/98 Issued 749454 Curis AU Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058CA CRP-131CA Synergistic Effects of OP/BMP 09/09/1998 2,303,460 Pending Curis CA Morphogens and GDNF/NGF Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058EP CRP-131EP Morphogens and GDNF/NGF 09/09/1998 98948122.1 Pending Curis EP Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058HK CRP-131HK Morphogens and GDNF/NGF 09/09/1998 108400.7 Pending Curis HK Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058JP CRP-131JP Morphogens and GDNF/NGF 09/09/1998 2000-510457 Pending Curis JP Neurotrophic Factors. - ------------------------------------------------------------------------------------------------------------------------------------ CBM-058PC CRP-131PC Morphogens and GDNF/NGF 09/09/1998 PCT/US98/18772 Completed Curis PCT Neurotrophic Factors. National Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-070CA CRP-125CA Methods for Tissue Morphogenesis and 05/29/1998 2,291,514 Pending Curis CA Methods for Evaluating Morphogenic Activity - ------------------------------------------------------------------------------------------------------------------------------------ CBM-070EP CRP-125EP Methods for Tissue Morphogenesis and 05/29/1998 98926115.1 Pending Curis EP Methods for Evaluating Morphogenic Activity - ------------------------------------------------------------------------------------------------------------------------------------ CBM-070JP CRP-125JP Methods for Tissue Morphogenesis and 05/29/1998 11-500923 Pending Curis JP Methods for Evaluating Morphogenic Activity
Page 9 of 10 SCHEDULE A Curis BMP Portfolio (Worldwide) Licensed to Stryker CBM-070PC CRP-125PC Methods for Tissue Morphogenesis and 5/29/1998 PCT/US98/10909 Completed Curis PCT Methods for Evaluating Morphogenic National Activity Stage - ------------------------------------------------------------------------------------------------------------------------------------ CBM-070US CRP-165US Methods for Tissue Morphogenesis and 5/29/1998 09/423,943 Pending Curis US Methods for Evaluating Morphogenic Activity - ------------------------------------------------------------------------------------------------------------------------------------ CUR-566CP2US Morphogen Analogs of Bone 06/06/2002 10/164,279 Pending Curis US Morphogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ CUR-566CPUS Morphogen Analogs of Bone 04/10/2002 60/371,298 Pending Curis US Morphogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ CUR-566US Morphogen Analogs of OP-1 02/05/2002 60/354,820 Pending Curis US - ------------------------------------------------------------------------------------------------------------------------------------

Page 10 of 10 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker Stryker Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee Country of Filing - ----------------------------------------------------------------------------------------------------------------------------------- STK-001 Osteogenic Proteins and Polypeptides 04/08/1988 07/179,406 Issued 4,968,590 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001AT Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker AT - ----------------------------------------------------------------------------------------------------------------------------------- STK-001AT4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker AT - ----------------------------------------------------------------------------------------------------------------------------------- STK-001AU1 Osteogenic Devices 04/07/1989 35305/89 Issued 618,357 Stryker AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-001AU2 Biosynthetic Osteogenic Proteins and 04/07/1989 34449/89 Issued 628,050 Stryker AU Osteogenic Devices Containing Them - ----------------------------------------------------------------------------------------------------------------------------------- STK-001AU4 Osteogenic Devices 10/15/1990 66481/90 Issued 648,997 Stryker AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-001BE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker BE - ----------------------------------------------------------------------------------------------------------------------------------- STK-001BE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker BE - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CA1 Osteogenic Devices 04/07/1989 596,143 Pending Stryker CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CA1DV Osteogenic Devices 04/07/1989 617,121 Pending Stryker CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CA2 Biosynthetic Osteogenic Proteins and 04/07/1989 596,144 Issued 1,338,663 Stryker CA Osteogenic Devices Containing Them - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CA4 Osteogenic Devices 10/15/1990 2,042,577-6 Pending Stryker CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CH1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker CH - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP2 Osteogenic Device 02/23/1989 07/315,342 Issued 5,011,691 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP2DV2 Osteogenic Proteins 09/24/1992 07/950,229 Issued 5,324,819 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP2DV3 Cartilage and Bone-Inducing Proteins 11/01/1993 08/145,812 Issued 5,750,651 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP2DVFW Osteogenic Proteins 12/22/1992 07/995,345 Issued 5,258,494 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP6 Osteogenic Proteins 02/21/1992 07/841,646 Issued 5,266,683 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP6DV2 Antibodies to Osteogenic Proteins 11/01/1993 08/147,023 Issued 5,468,845 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP6DV3 Method of Selectively Extracting 05/23/1995 08/447,570 Issued 5,714,589 Stryker US Osteogenic Protein - ----------------------------------------------------------------------------------------------------------------------------------- STK-001CP6DV4 Nucleic Acids Encoding Osteogenic Proteins 05/23/1995 08/449,700 Issued 5,863,758 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001DE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker DE - ----------------------------------------------------------------------------------------------------------------------------------- STK-001DE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker DE - ----------------------------------------------------------------------------------------------------------------------------------- STK-001DK4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker DE - ----------------------------------------------------------------------------------------------------------------------------------- STK-001DV2 Osteogenic Devices 01/28/1992 07/827,052 Issued 5,250,302 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-001EP1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-001EP1DV Osteogenic Proteins 07/07/1995 95 20 1872.9 Allowed Stryker EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-001EP2DV Biosynthetic Osteogenic Proteins and 04/07/1989 96 20 0044.4 Allowed Stryker EP Osteogenic Devices Containing Them - ----------------------------------------------------------------------------------------------------------------------------------- STK-001EP4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-001ES4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker ES - ----------------------------------------------------------------------------------------------------------------------------------- STK-001FR1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker FR - ----------------------------------------------------------------------------------------------------------------------------------- STK-001FR4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker FR - ----------------------------------------------------------------------------------------------------------------------------------- STK-001GB1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker GB
Page 1 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ------------------------------------------------------------------------------------------------------------------------------------ STK-001GB4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker UK - ------------------------------------------------------------------------------------------------------------------------------------ STK-001GR4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker GR - ------------------------------------------------------------------------------------------------------------------------------------ STK-001IT1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker IT - ------------------------------------------------------------------------------------------------------------------------------------ STK-001IT4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker IT - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP1 Osteogenic Devices 04/07/1989 1-504771 Issued ###-###-#### Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP1DV Osteogenic Devices 04/07/1989 Aug-35 Issued ###-###-#### Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP2DV Osteogenic Devices 04/07/1989 7-263371 Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP4 Osteogenic Devices 10/15/1990 515578/90 Issued ###-###-#### Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP4DV Osteogenic Devices 07/02/1997 177440/97 Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP4DV2 Osteogenic Devices 08/24/2000 200-254562 Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001JP4DV3 Osteogenic Devices Not yet assigned Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-001LU1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker LU - ------------------------------------------------------------------------------------------------------------------------------------ STK-001LU4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker LU - ------------------------------------------------------------------------------------------------------------------------------------ STK-001NL1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker NL - ------------------------------------------------------------------------------------------------------------------------------------ STK-001NL4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker NL - ------------------------------------------------------------------------------------------------------------------------------------ STK-001PC1 Osteogenic Devices 04/07/1989 PCT/US89/01453 Completed Stryker PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ STK-001PC2 Biosynthetic Osteogenic Proteins and 04/07/1989 PCT/US89/01469 Completed Stryker PCT Osteogenic Devices Containing Them National Stage - ------------------------------------------------------------------------------------------------------------------------------------ STK-001PC4 Osteogenic Devices 10/15/1990 PCT/US90/05903 Completed Stryker PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ STK-001SE1 Osteogenic Proteins and Polypeptides 04/07/1989 89 90 4986.0 Issued 0 362 367 B Stryker SE - ------------------------------------------------------------------------------------------------------------------------------------ STK-001SE4 Osteogenic Devices 10/15/1990 90 91 6655.5 Issued 0 448 704 B Stryker SE - ------------------------------------------------------------------------------------------------------------------------------------ STK-008 Nucleotide Sequences Encoding 01/20/1995 08/375,901 Issued 6,261,835 Stryker US Osteogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ STK-008CN DNA sequences encoding osteogenic 01/03/2001 09/754,831 Pending Stryker US protein - ------------------------------------------------------------------------------------------------------------------------------------ STK-009 Method for Recombinant Production of 01/20/1995 08/376,731 Issued 5,670,336 Stryker US Osteogenic Protein OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ STK-042AU Bone Collagen Matrix for Xenogenic 02/22/1990 51747/90 Issued 627,850 AU Implants - ------------------------------------------------------------------------------------------------------------------------------------ STK-042CA Bone Collagen Matrix for Xenogenic 02/22/1990 2,027,259-7 Issued 2,027,259-7 CA Implants - ------------------------------------------------------------------------------------------------------------------------------------ STK-042DE Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 DE Implants - ------------------------------------------------------------------------------------------------------------------------------------ STK-042EP Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 EP Implants
Page 2 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ----------------------------------------------------------------------------------------------------------------------------------- STK-042FR Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 FR Implants - ----------------------------------------------------------------------------------------------------------------------------------- STK-042GB Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 UK Implants - ----------------------------------------------------------------------------------------------------------------------------------- STK-042IT Bone Collagen Matrix for Xenogenic 02/22/1990 90 90 4002.4 Issued 0 411 105 IT Implants - ----------------------------------------------------------------------------------------------------------------------------------- STK-042JP Bone Collagen Matrix for Xenogenic 02/22/1990 504059/90 Issued 2113455 JP Implants - ----------------------------------------------------------------------------------------------------------------------------------- STK-042PC Bone Collagen Matrix for Xenogenic 02/22/1990 PCT/US90/00912 Completed PCT Implants National Stage - ----------------------------------------------------------------------------------------------------------------------------------- STK-049AU Synthetic Bone Matrix 05/22/1991 79614/91 Issued 639,574 AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-049CA Synthetic Bone Matrix 05/22/1991 2,082,946-0 Issued 2,082,946 CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-049EP Synthetic Bone Matrix 05/22/1991 91 91 1588.1 Grant 0 608 211 EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-049JP Synthetic Bone Matrix 05/22/1991 03-510269 Issued ###-###-#### JP - ----------------------------------------------------------------------------------------------------------------------------------- STK-049PC Synthetic Bone Matrix 05/22/1991 PCT/US91/03603 Completed PCT National Stage - ----------------------------------------------------------------------------------------------------------------------------------- STK-056AU Osteogenic Peptides 10/18/1991 89000/91 Issued 663,689 AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-056CA Osteogenic Peptides 10/18/1991 2,094,027 Issued 2,094,027 CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-056DE Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 DE - ----------------------------------------------------------------------------------------------------------------------------------- STK-056EP Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-056FR Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 FR - ----------------------------------------------------------------------------------------------------------------------------------- STK-056GB Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 UK - ----------------------------------------------------------------------------------------------------------------------------------- STK-056IT Osteogenic Proteins 10/18/1991 91 91 9612.1 Issued 0 643 767 IT - ----------------------------------------------------------------------------------------------------------------------------------- STK-056JP Osteogenic Peptides 10/18/1991 03-518322 Pending JP - ----------------------------------------------------------------------------------------------------------------------------------- STK-056JPDV Osteogenic Peptides 10/18/1991 10-352101 Pending JP - ----------------------------------------------------------------------------------------------------------------------------------- STK-056PC Osteogenic Peptides 10/18/1991 PCT/US91/07635 Completed PCT National Stage - ----------------------------------------------------------------------------------------------------------------------------------- STK-058AU CRP-076AU OP-3 Induced Morphogenesis 11/02/1993 55900/94 Issued 681,362 Stryker AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-058CA CRP-076CA OP-3 Induced Morphogenesis 11/02/1993 2,147,598 Pending Stryker CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-058DV CRP-076DV OP-3 Induced Morphogenesis 06/07/1995 08/479,666 Issued 5,652,337 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-058DV2 CRP-076DV2 OP-3 Induced Morphogenesis 07/28/1997 08/901,200 Issued 5,854,071 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-058DV3 CRP-076DV3 OP-3-Induced Morphogenesis 12/23/1998 09/219,391 Issued 6,153,583 Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-058EP CRP-076EP OP-3 Induced Morphogenesis 11/02/1993 94 90 1244.7 Pending 0672064 A Stryker EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-058FW CRP-076FW Nucleic Acid Encoding a Novel 06/07/1995 08/480,528 Issued 5,652,118 Stryker US Morphogenic Protein OP-3
Page 3 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ------------------------------------------------------------------------------------------------------------------------------------ STK-058JP CRP-076JP OP-3 Induced Morphogenesis 11/02/1993 6-511392 Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------------ STK-059 CRP-080 Single Chain Analogs of the TGF-Beta 10/01/1998 08/478,097 Issued 6,040,431 Stryker US Superfamily (Morphons) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059PC CPR-080PC Single Chain Analogs of the TGF-B 06/06/1996 PCT/US96/09293 Completed Stryker PCT Superfamily (Morphons) National Stage - ------------------------------------------------------------------------------------------------------------------------------------ STK-059AU CRP-080AU Single Chain Analogs of the TGF-B 06/06/1996 61570/96 Issued 717811 Stryker AU Superfamily (Morphogen) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059AUDV CRP-080AUDV Single Chain Analogs of the TGF-B 06/06/1996 43748/00 Pending Stryker AU Superfamily (Morphogen) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059CA CRP-080CA Single Chain Analogs TGF-B Superfamily 06/06/1996 2,223,292 Pending Stryker CA (Morphogen) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059CN CRP-080CN Single Chain Analogs of the TGF-Beta 02/02/2000 09/496,398 Pending Stryker US Superfamily (Morphons) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059EP CRP-080EP Single Chain Analogs of the TGF-B 06/06/1996 96 9 1 9162.6 Pending 833844 Stryker EP Superfamily (Morphogen) - ------------------------------------------------------------------------------------------------------------------------------------ STK-059JP CPR-080JP Single Chain Analogs of the TGF-B 06/06/1996 09-501647 Pending 11-510686 Stryker JP Superfamily (Morphogen) - ------------------------------------------------------------------------------------------------------------------------------------ STK-060AU CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 47951/93 Issued 678,380 Stryker AU of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060CA CRP-081 - Novel Morphogenic Protein Compositions 07/29/1993 2,141,555 Pending Stryker CA of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060DV CRP-081 Novel Morphogenic Protein Compositions 06/02/1995 08/459,346 Issued 5,834,179 Stryker US of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060DVCN CRP-081 Novel Morphogenic Protein Compositions 07/08/1997 08/889,419 Issued 6,071,708 Stryker US of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060EP CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 93918529.4 Pending 0652953 A Stryker EP of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060FW CRP-081FW Novel Morphogenic Protein Compositions 03/13/1995 08/402,542 Issued 6,395,883 Curis US of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060JP CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 6-505462 Pending Stryker JP of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060KR CRP-081 Novel Morphogenic Protein Compositions 07/29/1993 700360/1995 Pending Stryker KR of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-060PC CPR-081PC Novel Morphogenic Protein Compositions 07/29/1993 PCT/US93/07189 Completed Stryker PCT of Matter National Stage - ------------------------------------------------------------------------------------------------------------------------------------ STK-061 CRP-082 Lipid Modified Serum Free Media 09/22/1993 08/124,676 Issued 5,631,159 Stryker US of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-061AU CRP-082 Lipid Modified Serum Free Media 09/21/1994 80717/94 Issued 698633 Stryker AU of Matter - ------------------------------------------------------------------------------------------------------------------------------------ STK-061CA CRP-082 Lipid Modified Serum Free Media 09/21/1994 2,170,761 Issued 2,170,761 Stryker CA of Matter - ------------------------------------------------------------------------------------------------------------------------------------
Page 4 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker - ------------------------------------------------------------------------------------------------------------------------------- STK-061DE CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker DE - ------------------------------------------------------------------------------------------------------------------------------- STK-061EP CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker EP - ------------------------------------------------------------------------------------------------------------------------------- STK-061FR CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker FR - ------------------------------------------------------------------------------------------------------------------------------- STK-061GB CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker UK - ------------------------------------------------------------------------------------------------------------------------------- STK-061IT CRP-082 Lipid Modified Serum Free Media 09/21/1994 94 93 1761.4 Issued 0 720 648 Stryker IT - ------------------------------------------------------------------------------------------------------------------------------- STK-061JP CRP-082 Lipid Modified Serum Free Media 09/21/1994 7-509936 Pending Stryker JP - ------------------------------------------------------------------------------------------------------------------------------- STK-061PC CRP-082 Lipid Modified Serum Free Media 09/21/1994 PCT/US94/10736 Completed Stryker PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------- STK-062 CRP-084 Methods and Compositions for High 10/25/1993 08/143,497 Issued 5,585,237 Stryker US Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062AU CRP-084 Methods and Compositions for High 10/21/1994 80859/94 Issued 685188 Stryker AU Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062CA CRP-084 Methods and Compositions for High 10/21/1994 2,171,759 Pending Stryker CA Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062DV CRP-084 Methods and Compositions for High 06/05/1995 08/461,666 Issued 5,614,385 Stryker US Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062DVCN CRP-084 Methods and Compositions for High 11/27/1996 08/757,300 Issued 5,712,119 Stryker US Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062EP CRP-084 Methods and Compositions for High 10/21/1994 94 93 1958.6 Pending Stryker EP Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062JP CRP-084 Methods and Compositions for High 10/21/1994 7-512727 Pending Stryker JP Protein Production from Recombinant DNA - ------------------------------------------------------------------------------------------------------------------------------- STK-062PC CRP-084 Methods and Compositions for High 10/21/1994 PCT/US94/12063 Completed Stryker PCT Protein Production from Recombinant National DNA Stage - ------------------------------------------------------------------------------------------------------------------------------- STK-064 CRP-096 Compositions and Methods for 03/04/1994 08/206,864 Issued 5,610,021 Stryker US Identification and Use of Soluble Complex Forms of Osteogenic Proteins - ------------------------------------------------------------------------------------------------------------------------------- STK-064AU CRP-096 Methods and Compositions for 03/04/1994 63588/94 Issued 682,176 AU Recombinant Osteogenic Protein Production
Page 5 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker - ----------------------------------------------------------------------------------------------------------------------------------- STK-064CA CRP-096 Methods and Compositions for 03/04/1994 2,157,387 Issued 2,157,387 CA Recombinant Osteogenic Protein Production - ----------------------------------------------------------------------------------------------------------------------------------- STK-064EP CRP-096 Methods and Compositions for 03/04/1994 94 91 0830.2 Pending EP Recombinant Osteogenic Protein Production - ----------------------------------------------------------------------------------------------------------------------------------- STK-064JP CRP-096 Methods and Compositions for 03/04/1994 6-520181 Pending JP Recombinant Osteogenic Protein Production - ----------------------------------------------------------------------------------------------------------------------------------- STK-064PC CRP-096 Method and Compositions for 03/04/1994 PCT/US94/02335 Completed PCT Recombinant Osteogenic Protein National Production Stage - ----------------------------------------------------------------------------------------------------------------------------------- STK-075 Modified TGF-Beta Superfamily Proteins 08/16/1999 09/375,333 Pending Stryker US - ----------------------------------------------------------------------------------------------------------------------------------- STK-075AU Modified TGF-Beta Superfamily Proteins 10/07/1999 11039/00 Pending Stryker AU - ----------------------------------------------------------------------------------------------------------------------------------- STK-075CA Modified TGF-Beta Superfamily Proteins 10/07/1999 2,345,024 Pending Stryker CA - ----------------------------------------------------------------------------------------------------------------------------------- STK-075EP Modified TGF-Beta Superfamily Proteins 10/07/1999 99954772.2 Pending Stryker EP - ----------------------------------------------------------------------------------------------------------------------------------- STK-075JP Modified TGF-Beta Superfamily Proteins 10/07/1999 2000-574560 Pending Stryker JP - ----------------------------------------------------------------------------------------------------------------------------------- STK-075PC Modified TGF-Beta Superfamily Proteins 10/07/1999 PCT/US99/23372 Completed Stryker PCT National Stage - ----------------------------------------------------------------------------------------------------------------------------------- STK-076 Modified Proteins and DNAs of the TGF- 08/16/1999 09/374,958 Pending Stryker US Beta Superfamily, Including Morphogenic Proteins - ----------------------------------------------------------------------------------------------------------------------------------- STK-076AU Modified Proteins and DNAs of the TGF- 10/07/1999 11038/00 Pending Stryker AU Beta Superfamily, Including Morphogenic Proteins - ----------------------------------------------------------------------------------------------------------------------------------- STK-076CA Modified Proteins and DNAs of the TGF- 10/07/1999 2,344,974 Pending Stryker CA Beta Superfamily, Including Morphogenic Proteins - ----------------------------------------------------------------------------------------------------------------------------------- STK-076EP Modified Proteins and DNAs of the TGF- 10/07/1999 99954771.4 Pending Stryker EP Beta Superfamily, Including Morphogenic Proteins - ----------------------------------------------------------------------------------------------------------------------------------- STK-076JP Modified Proteins and DNAs of the TGF- 10/07/1999 2000-574702 Pending Stryker JP Beta Superfamily, Including Morphogenic Proteins
Page 6 of 7 Schedule B Curis BMP Portfolio (Worldwide) Licensed from Stryker
- ---------------------------------------------------------------------------------------------------------- STK-076PC Modified Proteins and DNAs of the TGF- 10/07/1999 PCT/US99/23371 Completed Stryker PCT Beta Superfamily, including Morphogenic National Proteins Stage - ---------------------------------------------------------------------------------------------------------- STK-077 Modified Proteins and DNAs of the TGF- 08/16/1999 09/374,936 Pending Stryker US Beta Superfamily, including Modified Morphogenic Proteins - ---------------------------------------------------------------------------------------------------------- STK-077AU Modified Proteins and DNAs of the TGF- 10/07/1999 11037/00 Pending Stryker AU Beta Superfamily, including Modified Morphogenic Proteins - ---------------------------------------------------------------------------------------------------------- STK-077CA Modified Proteins and DNAs of the TGF- 10/07/1999 2,345,287 Pending Stryker CA Beta Superfamily, including Modified Morphogenic Proteins - ---------------------------------------------------------------------------------------------------------- STK-077EP Modified Proteins and DNAs of the TGF- 10/07/1999 99954770.6 Pending Stryker EP Beta Superfamily, including Modified Morphogenic Proteins - ---------------------------------------------------------------------------------------------------------- STK-077JP Modified Proteins and DNAs of the TGF- 10/07/1999 2000-574686 Pending Stryker JP Beta Superfamily, including Modified Morphogenic Proteins - ---------------------------------------------------------------------------------------------------------- STK-077PC Modified Proteins and DNAs of the TGF- 10/07/1999 PCT/US99/23370 Completed Stryker PCT Beta Superfamily, including Modified National Morphogenic Proteins Stage - ----------------------------------------------------------------------------------------------------------
Page 7 of 7 Schedule C Curis BMP Patent Portfolio (Worldwide) Co-Owned with Ludwig Institute for Cancer Research and Licensed to Stryker Corporation
Country of Curis Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee Filing - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023CP1US CRP-097CP1 Morphogen Protein 06/02/1995 08/448,371 Allowed Curis, Ludwig US Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023CP1CUS CRP-097CP1C Morphogen Protein 10/18/2001 09/982,543 Pending Curis, Ludwig US Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023CP2US CRP-097CP2 Methods of antagonizing 06/02/1995 08/481,337 Issued 5,863,738 Curis, Ludwig US OP-1 binding to a Institute for Cell Surface receptor Cancer Research utilizing ALK polypeptides - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023PC CRP-097PC Morphogen Protein 04/28/1995 PCT/US95/05467 Completed Curis, Ludwig PCT Specific Cell National Institute for Surface Receptors Stage Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023AU CRP-097AU Morphogenic Protein 04/28/1995 24662/95 Issued 702163 Curis, Ludwig AU Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023CA CRP-097CA Morphogen Protein 04/28/1995 2,187,902 Pending Curis, Ludwig CA Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023EP CRP-097EP Morphogen Protein 04/28/1995 95918920 Pending Curis, Ludwig EP Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-023JP CRP-097JP Morphogenic Protein 04/28/1995 7-528497 Pending Curis, Ludwig JP Specific Cell Institute for Surface Receptors Cancer Research and Uses Therefor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-024US CRP-117 Method and Device for 08/13/1996 08/696,268 Issued 5,968,752 Curis, Ludwig US Identifying an OP-1 Institute for Analog Which Binds Cancer Research An Alk-1 Receptor - ---------------------------------------------------------------------------------------------------------------------------------- CBM-024PC CRP-117PC Binding of OP-1 08/13/1996 PCT/US97/12078 Completed Curis, Ludwig PCT and Analogs Thereof National Institute for to the Cell surface Stage Cancer Research Receptor ALK-1 and Analogs Thereof - ---------------------------------------------------------------------------------------------------------------------------------- CBM-024EP CRP-117EP Binding of Osteogenic 08/13/1996 96928166.6 Pending Curis, Ludwig EP Protein (OP-1) Institute for and Analogs Thereof Cancer Research to the Cell Surface Receptor ALK-1 and Analogs Thereof - ---------------------------------------------------------------------------------------------------------------------------------- CBM-024JP CRP-117JP Binding of Osteogenic 08/13/1996 9-509445 Pending Curis, Ludwig JP Protein (OP-1) Institute for and Analogs Thereof Cancer Research to the Cell Surface Receptor ALK-1 and Analogs Thereof - ----------------------------------------------------------------------------------------------------------------------------------
Page 1 of 1 Schedule D Curis BMP Patent Portfolio (Worldwide) Co-Owned with Other Institutions and Licensed to Stryker Corporation (except as indicated)
- ----------------------------------------------------------------------------------------------------------------------------------- Country Curis Case No. CRP No. Title Filing Date Serial No. Status Patent No. Assignee of Filing - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005 CP US* CRP-069 Methods for Enhancing 03/21/1997 08/828,281 Issued ###-###-#### Curis, MGH US Functional Recovery Following Central Nervous System Ischemia or Trauma - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005 CPCUS* CRP-069 Methods for Enhancing 02/01/2002 10/062,370 Pending Curis, MGH US Functional Recovery Following Central Nervous System Ischemia or Trauma - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005AU* CRP-069AU Methods for Enhancing 03/21/1997 25823/97 Issued 725341 Curis, MGH AU Functional Recovery Following Central Nervous System Ischemia or Trauma - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005CA* CRP-069CA Methods for Enhancing 03/21/1997 2,249,596 Pending Curis, MGH CA Functional Recovery Following Central Nervous System Ischemia or Trauma - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005PC* CRP-069PC Methods for Enhancing 03/21/1997 PCT/US97/04177 Completed Curis, MGH PCT Functional Recovery National Following Central Nervous Stage System Ischemia or Trauma - ----------------------------------------------------------------------------------------------------------------------------------- CBM-005EP* CRP-069EP Methods for Enhancing 03/21/1997 97917532 Pending Curis, MGH EP Functional Recovery Following Central Nervous System Ischemia or Trauma - ------------------------------------------------------------------------------------------------------------------------------------ CBM-005JP* CRP-069JP Methods for Enhancing 03/21/1997 9-533583 Pending Curis, MGH JP Functional Recovery Following Central Nervous System Ischemia or Trauma - ------------------------------------------------------------------------------------------------------------------------------------ CBM-007US* CRP-098 Morphogen Induced Dendritic 08/18/1994 08/292,782 Pending Curis, SUNY US Growth at Buffalo - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066 C2US* CRP-102 Computer System and Methods 02/22/2001 09/791,946 Pending Curis, US for Producing Analogs of Brandeis Human OP-1 (as amended) University - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066 CPFWUS* CRP-102 Computer System and Methods 01/22/1997 08/786,284 Issued 6,273,598 Curis, US for Producing Analogs of B1 Brandeis Human OP-1 (as amended) University - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066AU* CRP-102AU Computer Systems and Methods 01/22/1997 22449/97 Issued 725295 Curis, AU and Compositions for Brandeis Producing Morphogen Analogs University - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066AUD* CRP-102AUD Computer Systems and Methods 07/22/1997 53497/00 Pending Curis, AU and Compositions for Brandeis Producing Morphogen Analogs University - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066CA* CRP-102CA Computer Systems and Methods 01/22/1997 2,244,228 Pending Curis, CA and Compositions for Brandeis Producing Morphogen Analogs University - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066EP* CRP-102EP Computer Systems and Methods 01/22/1997 97905604.1 Pending Curis, EP and Compositions for Brandeis Producing Morphogen Analogs University - ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 2 Schedule D Curis BMP Patent Portfolio (Worldwide) Co-Owned with Other Institutions and Licensed to Stryker Corporation (except as indicated)
- ------------------------------------------------------------------------------------------------------------------------------------ CBM-066JP* CRP-102JP Computer Systems and Methods 01/22/1997 09-526303 Pending Curis, Brandeis JP and Compositions for University Producing Morphogen Analogs - ------------------------------------------------------------------------------------------------------------------------------------ CBM-066PC* CRP-102PC Computer Systems and Methods 01/22/1997 PCT/US97/01071 Completed National Curis, Brandeis PCT and Compositions for Stage University Producing Morphogen Analogs - ------------------------------------------------------------------------------------------------------------------------------------ CUR-599US# Cojoint Administration of 08/28/2002 60/406,431 Pending Curis, Washington US Morphogens and ACE Univ. (St. Louis) Inhibitors in Treatment of Chronic Renal Failure - ------------------------------------------------------------------------------------------------------------------------------------ * Licensed to Stryker # Not Licensed to Stryker
Page 2 of 2 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide)
- ------------------------------------------------------------------------------------------------------------------------------------ Country of Curis Case No Filing Date Serial No Title Status Patent No Issue Date Filing - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001 US 07/01/1986 06/880,776 Abandoned - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001AT 06/30/1987 87905023 Novel osteoinductive compositions Issued 141928 09/15/1996 AT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001AU 06/30/1987 77835 Novel osteoinductive compositions Issued 613314 08/01/1991 AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001CP2US 03/26/1987 07/031,346 Osteoinductive factors -- BMP-1 protease 4,877,864 10/31/1989 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001CPUS 12/17/1986 06/943,332 Abandoned - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001DE 06/30 ###-###-#### Novel osteoinductive compositions Issued ###-###-#### 10/02/1996 DE - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001DK 02/29/1988 1062 Novel osteoinductive compositions Issued 172275 02/16/1998 DK - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001EP 06/30/1987 87905023 Novel osteoinductive compositions Issued 313578 08/28/1996 EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001ES 06/30 ###-###-#### Novel osteoinductive compositions Issued ###-###-#### 07/01/1989 ES - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001GR 06/30/1987 871028 Novel osteoinductive compositions Issued 871028 01/11/1988 GR - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001IE 06/29/1987 1739 Novel osteoinductive compositions Issued 75881 09/24/1997 IE - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001IL 06/26/1987 83003 Novel osteoinductive compositions Issued 83003 12/20/1987 IL - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001JP 06/30/1987 504617/87 Novel osteoinductive compositions Issued 2500241T2 02/01/1990 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001KR 02/29/1988 700231/88 Novel osteoinductive compositions Issued ###-###-#### KR - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001MX 06/30/1987 7140 Novel osteoinductive compositions Issued 170919 09/22/1993 MX - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001MXDIV 09/21/1993 93/5743 Novel osteoinductive compositions MX - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001MY 06/30/1987 PI ###-###-#### Novel osteoinductive compositions Issued 102505 MX - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001NO 02/29/1988 88071 Novel osteoinductive compositions Issued 309531 02/12/2001 NO - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001NODiv 02/29/1988 88071 Novel osteoinductive compositions Issued 310029 05/07/2001 NO - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001NODiv2 02/29/1988 88071 Novel osteoinductive compositions Issued 310030 05/07/2001 NO - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001NZ 06/30/1987 220894 Novel osteoinductive compositions Issued 220894 NZ - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001PC 06/30/1987 PCT/US87/01537 Novel osteoinductive compositions Completed National Stage PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001PH 07/01/1987 35484 Novel osteoinductive compositions PH - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001PT 07/01/1987 85225 Novel osteoinductive compositions Issued 85225 PT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001TW 07/29/1987 76104439 Novel osteoinductive compositions Issued 45626 PT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-001ZA 06/29/1987 87/4681 Novel osteoinductive compositions Issued 87/4681 ZA - ------------------------------------------------------------------------------------------------------------------------------------ AHP-002 07/31/1990 07/5561,496 DNA sequences encoding BMP-1 products 5,108,922 04/28/1992 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-003CPUS 03/20/1987 07/179,100 DNA sequences encoding osteoinductive products 5,013,649 05/07/1991 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-004 PC 04/07/1989 PCT/US89/01464 DNA sequences encoding BMP-3 Completed National Stage PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-004 US 04/08/1988 179,197 DNA sequences encoding BMP-3 Abandoned US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-004AU 04/07/1989 34487 DNA sequences encoding BMP-3 Issued 645244 AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-004CPUS 04/26/1991 692,827 DNA sequences encoding BMP-3 5,116,738 05/26/1992 US - ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-004EP 04/07/1989 89904945.6 DNA sequences encoding BMP-3 408649 A1 EP AHP-004JP 04/07/1989 504776/89 DNA sequences encoding BMP-3 Issued ###-###-#### T2 08/15/1991 EP AHP-004KR 12/07/1989 702291/89 DNA sequences encoding BMP-3 Issued 08/15/1991 KR AHP-005 06/23/1989 07/370,547 DNA sequences encoding BMP-5 proteins Abandoned 5,106,748 04/21/1992 US AHP-005 03/28/1989 329,610 DNA sequenes encoding BMP-5 proteins Abandoned US AHP-005CPC2Div 06/05/1995 08/469,935 Bone morphogenetic protein 5 (BMP-5) compositions Issued 5,635,373 06/03/1997 US AHP-005CPC2DivCP 01/23/1997 08/788,729 Methods of Administering BMP-5 Proteins Issued 5,939,388 08/17/1999 US AHP-005CPC2US 09/07/1993 08/116,425 Bone morphogenetic protein 5 (BMP-5) compositions Issued 5,543,394 08/06/1996 US AHP-005CPEP 09/26/1991 91917761 Bone morphogenetic protein 5 (BMP-5) compositions Completed National Stage 550625 A1 EP AHP-005CPPC 09/26/1991 PCT/US91/07069 Bone morphogenetic protein 5 (BMP-5) compositions Completed National Stage PCT AHP-005CPUS 09/26/1990 588,227 Bone morphogenetic protein 5 (BMP-5) compositions Abandoned US AHP-006 03/07/1990 07/490,033 DNA sequences encoding BMP-6 proteins 5,187,076 02/16/1993 US AHP-006D2C2 11/09/1998 09/189,157 BMP-6 Proteins Issued 6,207,813 03/27/2001 US AHP-006D2C2DV 03/23/2001 09/816,299 BMP-6 Proteins Pending US AHP-006D2CUS 06/05/1995 08/469,936 BMP-6 Issued 5,849,880 12/15/1998 US AHP-006D2US 05/27/1994 08/251,069 BMP-6 proteins Issued 5,459,047 10/17/1995 US AHP-007 US 11/17/1989 07/438,919 DNA Encoding BMP-7 Protein 5,141,905 08/25/1992 US AHP-007CPAU 03/27/1990 53577/90 Osteoinductive Compositions AU AHP-007CPCA 03/27/1990 ###-###-####.5 Osteoinductive Compositions CA AHP-007CPEP 03/27/1990 90805830.7 Osteoinductive Compositions EP AHP-007CPJP 03/27/1990 505549/90 Osteoinductive Compositions JP AHP-007CPKR 03/27/1990 702523/90 Osteoinductive Compositions KR AHP-007CPPC 03/27/1990 PCT/US90/01630 Osteoinductive Compositions PCT AHP-008 US 09/24/1991 07/764,731 Methods for producing BMP-7s 5,366,875 11/22/1994 US AHP-009 US 03/18/1991 655,579 BMP-2 Products Issued 5,618,924 04/08/1997 US AHP-010 US 07/11/1989 07/387,537 DNA sequences encoding the osteoinductive proteins Issued 5,166,058 11/24/1992 AHP-010AU 08/19/1994 78682 Neural Regeneration using Human Bone Morphogenetic Proteins Issued 677866 05/08/1997 AU
Page 2 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010CA 08/19/1994 2,169,191 Neural Regeneration using Human 05/08/1997 CA Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010CP2C2US 06/12/2001 09/804,625 BMP-4 Products Pending 06/12/2001 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010CP2CUS 09/09/1997 08/925,779 BMP-4 Products Issued 6,245,889 06/12/2001 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010CP2US 06/14/1991 07/721,847 BMP products Issued 6,150,328 11/21/2000 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010EP 08/19/1994 94929728 Neural Regeneration using Human Pending 716610 05/08/1997 EP Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010FI 08/19/1994 960809 Neural Regeneration using Human Pending 05/08/1997 FI Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010JP 08/19/1994 507663 Neural Regeneration using Human Issued ###-###-#### T2 05/08/1997 JP Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010NO 08/19/1994 960711 Neural Regeneration using Human 05/08/1997 NO Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010OAPI 08/19/1994 60780 Neural Regeneration using Human 05/08/1997 OAPI Bone Morphogenetic Proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-010PC 08/19/1994 PCT/US94/09330 Neural Regeneration using Human Completed PCT Bone Morphogenetic Proteins National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-011 09/07/1993 118,363 Compositions comprising bone Issued 5,631,142 05/20/1997 US morphogenetic protein -2 (BMP-2) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-012 09/05/1997 08/927,124 BMP-3 Products Issued 6,177,406 01/23/2001 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-013 US 04/02/1991 07/679,451 Production of recombinant bone- Issued 5,318,898 06/07/1994 US inducing proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-013PC 03/27/1992 PCT/US92/02474 Improved production of PCT recombinant bone-inducing proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-014 US 01/27/1994 08/187,921 Production of bone-inducing Issued 5,516,654 05/14/1996 US proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015 US 06/18/1990 07/539,756 Osteoinductive pharmaceutical Issued 5,364,839 11/15/1994 US formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015AT 06/18/1991 Osteoinductive pharmaceutical AT formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015CA 06/18/1991 2,085,750 Osteoinductive pharmaceutical CA formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015CA 06/18 ###-###-#### Osteoinductive pharmaceutical 535091 CA formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015DE 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 DE formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015DK 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 DK formulations - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015EP 06/18/1991 91911720.1 Osteoinductive pharmaceutical 535091 EP formulations
Page 3 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015GB 06/18/1991 Osteoinductive pharmaceutical formulations GB - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015JP 06/18/1991 511544/91 Osteoinductive pharmaceutical formulations JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-015PC 06/18/1991 PCT/US91/04337 Osteoinductive pharmaceutical formulations PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-016 US 09/19/1994 08/308,787 Formulations for delivery of osteogenic proteins Issued 5,520,923 05/28/1996 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-016AU 07/24/1995 31042/95 Formulations for delivery of osteogenic proteins AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-016PC 07/24/1995 PCT/US95/09325 Formulations for delivery of osteogenic proteins PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-017 US 12/07/1993 08/163,877 Mutants of bone morphogenetic proteins Issued 5,399,677 03/21/1995 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-017EP 11/15/1994 95903116.2 Mutants of bone morphogenetic proteins EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-017PC 11/15/1994 PCT/US94/13181 Mutants of bone morphogenetic proteins PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018 US 09/10/1993 08/119,772 Formulations for delivery of osteogenic proteins Issued 5,385,887 01/31/1995 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018AU 09/02/1994 79537/94 Formulations for delivery of osteogenic proteins 695374B2 AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018AU 09/02/1994 79537/94 Formulations for delivery of osteogenic proteins AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018CA 09/02/1994 2,169,362 Formulations for delivery of osteogenic proteins CA - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018EP 09/02/1994 961037 Formulations for delivery of osteogenic proteins EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018FI 09/02/1994 961037 Formulations for delivery of osteogenic proteins FI - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018JP 09/02/1994 508729 Formulations for delivery of osteogenic proteins 9502368T2 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018JP 09/02/1994 508729/1995 Formulations for delivery of osteogenic proteins JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018KR 03/08/1996 701202/1996 Formulations for delivery of osteogenic proteins KR - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018NO 09/02/1994 P960905 Formulations for delivery of osteogenic proteins NO - ------------------------------------------------------------------------------------------------------------------------------------ AHP-018PC 09/02/1994 PCT/US94/09870 Formulations for delivery of osteogenic proteins PCT
Page 4 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019 US 10/11/1991 07/776,514 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins 5,171,579 12/15/1992 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019AU 10/09/1992 27885/92 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019EP 10/09/1992 92921634.9 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins 608313 EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019JP 10/09/1992 507211/93 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019KR 10/09/1992 701180/94 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins KR - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019MX 10/09/1992 92/5805 Formulations of blood clot-polymer matrix for delivery of osteogenic proteins MX - ------------------------------------------------------------------------------------------------------------------------------------ AHP-019PC 10/09/1992 PCT/US92/08628 Formulations of blood clot-polymer Completed matrix for delivery of osteogenic National proteins Stage PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-020CPUS 05/05/1995 08/435,120 Neural regeneration using human bone morphogenetic proteins Issued 5,756,457 05/26/1998 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPAU 05/12/1994 69107 BMP-10 compositions Issued 677849 05/08/1997 AU - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPBR 05/12 ###-###-#### BMP-10 compositions BR - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPDiv 05/30/1995 08/453,942 Bone morphogenetic protein-10 (BMP-10) compositions Issued 5,703,043 12/30/1997 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPDivCon 09/10/1997 08/926,885 Antibodies to bone morphogenetic protein-10 (BMP-10) Issued 5,932,216 08/03/1999 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPEP 05/12/1994 94917363 BMP-10 compositions 698095 EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPFI 05/12/1994 955420 BMP-10 compositions FI - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPJP 05/12/1994 525699 BMP-10 compositions ###-###-#### T2 02/10/1997 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPKR 05/12 ###-###-#### BMP-10 compositions 231640 B1 12/01/1999 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPNO 05/12/1994 954525 BMP-10 compositions NO - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPOA 05/12/1994 60736 BMP-10 compositions OA - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPPC 05/12/1994 PCT/US94/05290 BMP-10 compositions Completed National Stage PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPUS 05/20/1994 247,908 DNA molecules encoding bone morphogenetic protein-10 Issued 5,637,480 06/10/1997

Page 5 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-021CPUS 05/20/1994 247,908 DNA molecules encoding bone Issued 5,637,480 06/10/1997 morphogenetic protein-10 - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022 CP3CUS 10/06/1994 08/319,831 Bone and cartilage inductive proteins Pending US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022 CP3US 11/26/1991 07/800,364 Bone and cartilage inductive proteins Issued 5,688,678 11/18/1997 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022AT 05/15/1991 9.19111E+13 Bone and cartilage inductive proteins Issued 12/15/2001 AT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022CA 05/15 ###-###-#### Bone and cartilage inductive proteins 12/15/2001 CA - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022DE 05/15/1991 69132823 Bone and cartilage inductive proteins Issued 69132823 01/03/2002 DE - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022EP 05/15/1991 91911807 Bone and cartilage inductive proteins Issued 536186 11/21/2001 EP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022JP 05/15/1991 510213 Bone and cartilage inductive proteins Issued ###-###-#### T2 01/27/1994 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022JPD 01/24/2001 2001016118 Bone and cartilage inductive proteins 2001245682 A2 01/27/1994 JP - ------------------------------------------------------------------------------------------------------------------------------------ AHP-022PC 05/15/1991 PCT/US91/03388 Bone and cartilage inductive proteins Completed PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-023CP2CUS 06/06/1994 08/750,222 BMP-9 compositions Issued 6,034,061 03/07/2000 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-023CP2PC 06/05/1995 PCT/US95/07084 BMP-9 compositions Completed PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-023CP2US 06/06/1994 08/254,353 BMP-9 compositions Issued 6,287,816 B1 09/11/2001 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-023CPUS 06/25/1992 08/050,132 BMP-9 compositions Issued 5,661,007 08/26/1997 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-023PC 06/25/1992 PCT/US92/05374 BMP-9 compositions Completed PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-024EP 06/22/1992 92914339 Pharmaceutical formulations 591392B1 EP of osteogeneic proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-024PC 06/22/1992 PCT/US92/05309 Pharmaceutical formulations of osteogenic proteins PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-024US 06/22/1992 08/081,378 Pharmaceutical formulations Issued 5,597,897 01/28/1997 US of osteogeneic proteins - ------------------------------------------------------------------------------------------------------------------------------------ AHP-025CP2CUS 06/06/1995 469,411 Recombinant bone morphogenetic 6,190,880 02/20/2001 US protein heterodimers - ------------------------------------------------------------------------------------------------------------------------------------ AHP-025CP2US 11/27/1992 07/989,847 Recombinant bone morphogenetic protein Issued 5,866,364 02/02/1999 US heterodimers, compositions and methods of use - ------------------------------------------------------------------------------------------------------------------------------------ AHP-025PC 11/02/1992 PCT/US92/09430 Recombinant bone morphogenetic protein PCT heterodimers, compositions and methods of use - ------------------------------------------------------------------------------------------------------------------------------------ AHP-026CP4DivUS 808,324 Tendon-inducing compositions Issued 6,284,872 09/04/2001 US
Page 6 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - ------------------------------------------------------------------------------------------------------------------------------------ AHP-026CP4US 12/22/1994 362,670 Methods of inducing formation Issued 5,658,882 08/19/1997 US of tendon and/or ligament tissue comprising administering BMP-12, BMp-13 and/or MP-52 - ------------------------------------------------------------------------------------------------------------------------------------ AHP-026CP5US 11/02/1994 08/333,576 BMP-12 and BMP-13 proteins Issued 6,027,919 06,27,0919 US and DNA encoding them - ------------------------------------------------------------------------------------------------------------------------------------ AHP-026PC 12/06/1994 PCT/US94/14030 BMP-12, BMP-13 and tendon- Completed PCT inducing compositions National thereof Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-027 US 09/17/1993 08/123,934 Activin receptors-like Issued 6,291,206 09/18/2001 US kinase (ALK) belonging to the TGF receptor family and/or the BMP receptor family - ------------------------------------------------------------------------------------------------------------------------------------ AHP-027PC 09/07/1994 PCT/US94/10080 Activin receptors-like Completed kinase (ALK) belonging National to the TGF receptor Stage family and/or the BMP receptor family - ------------------------------------------------------------------------------------------------------------------------------------ AHP-028CPDiv 05/30/1995 452,772 BMP-11 compositions Issued 5,700,911 12/23/1997 PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-028CPDivCPC2US 11/07/1997 919,850 Neuronal uses of BMP-11 Issued 6,340,668 01/22/2001 PCT - ------------------------------------------------------------------------------------------------------------------------------------ AHP-028CPUS 05/20/1994 08/247,907 BMP-11 compositions Issued 5,639,638 06/17/1997 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-028PC 05/12/1994 PCT/US94/05288 BMP-11 compositions Completed PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-029PC 01/27/1995 PCT/US95/01110 Methods and compositions Completed PCT for treatment of periodontal National disease and repair of Stage periodontal lesions - ------------------------------------------------------------------------------------------------------------------------------------ AHP-029US 01/27/1995 379,813 Methods and compositions PCT for treatment of periodontal disease and repair of periodontal lesions - ------------------------------------------------------------------------------------------------------------------------------------ AHP-030 01/12/1994 PCT/US94/00657 GDF-5 Completed PCT National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-030 US 01/12/1994 455,559 GDF-5 Issued ###-###-#### 09/01/1998 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-030 US 09/01/1998 145,060 GDF-5 Issued ###-###-#### 06/12/2001 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-031 PC 07/08/1994 PCT/US94/07762 GDF-6 Completed US National Stage - ------------------------------------------------------------------------------------------------------------------------------------ AHP-031 US 04/15/1996 581,529 GDF-6 Issued 5,770,444 06/23/1998 US - ------------------------------------------------------------------------------------------------------------------------------------ AHP-032 US 04/15/1996 581,528 GDF-7 Issued 5,986,058 11/16/1999 US

Page 7 of 8 SCHEDULE E Curis Patent Portfolio Licensed from American Home Products (Worldwide) - -------------------------------------------------------------------------------- AHP-032PC 07/08/1994 PCT/US94/07799 GDF-7 Completed PCT National Stage - -------------------------------------------------------------------------------- Page 8 of 8
SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ MATERIAL TRANSFER AGREEMENTS - ------------------------------------------------------------------------------------------------------------------------------------ Burger, Elisabeth Academic Center for Dentistry Amsterdam MTA 9/6/91 Stryker; Dentin: Embryonic Long bone development - ------------------------------------------------------------------------------------------------------------------------------------ Minnear, Fred Albany Medical College MTA 4/20/98 Morphogens; Lung: lung cell-based assays - ------------------------------------------------------------------------------------------------------------------------------------ Minnear, Fred Albany Medical College MTA 10/1/98 Morphogens; Lung: cell-based assays - ------------------------------------------------------------------------------------------------------------------------------------ Mehler, Mark Albert Einstein Coll Medicine. MTA 3/31/94 Morphogens: in vivo studies on cytokins, receptors and proteins - ------------------------------------------------------------------------------------------------------------------------------------ Frenz, Dorothy Albert Einstein College of Medicine MTA 6/16/98 Morphogens; Ocular: role of BMPs in otic capsule formation in the mouse inner ear - ------------------------------------------------------------------------------------------------------------------------------------ Laurencin, Cato Allegheny University Hospital MTA 9/30/97 Osteoporosis: effect of OP-1 on cellular activity and phenotypic expression of senescent osteoblasts in osteoporosis - ------------------------------------------------------------------------------------------------------------------------------------ MacPhee, Martin American Red Cross MTA 10/6/92 Morphogens; Wound healing: examine the efficacy of Fibrin Sealant, supplemented with PDGF-bb, EGF-1 or OP-1 in promoting wound healing - ------------------------------------------------------------------------------------------------------------------------------------ Hruska, Keith Barnes Jewish Hospital MTA 3/13/97 Renal: Chronic failure & renal osteodystrophy - ------------------------------------------------------------------------------------------------------------------------------------ Hruska, Keith Barnes Jewish Hospital MTA 4/2/99 Renal: Chronic failure & renal osteodystrophy - amendment to expand sample - ------------------------------------------------------------------------------------------------------------------------------------ Hruska, Keith Barnes Jewish Hospital MTA 11/28/01 Research pertaining to the mechanisms of action of BMP-7 with respect to preservation of renal and vascular structure and function in animal disease models - ------------------------------------------------------------------------------------------------------------------------------------ Beresford, Jon Bath Institute MTA 6/29/94 Morphogens: regulation of MSX2 homeobox genes in transfected cells - ------------------------------------------------------------------------------------------------------------------------------------ Kim, Isaac Yi Baylor College MTA 3/11/99 Morphogens; Cancer: the role of BMP-6 and morphogenic proteins in the treatment of prostate and other cancers - amendment - ------------------------------------------------------------------------------------------------------------------------------------ Kim, Isaac Yi Baylor College MTA 3/4/98 Morphogens; Cancer: OP-1 in (renal & prostate) carcinoma - ------------------------------------------------------------------------------------------------------------------------------------ Morton, Ronald Baylor College of Medicine MTA 3/4/98 Morphogens; Cancer: OP-1 in carcinomas (renal & prostate) - ------------------------------------------------------------------------------------------------------------------------------------ Rosen, Jeffrey Baylor College of Medicine MTA 5/26/93 Morphogens: mammary glands - ------------------------------------------------------------------------------------------------------------------------------------ Ratan, Rajiv Beth Israel Deaconess Hospital MTA 6/19/99 Neuro: The transcriptional regulation of cell death and survival factors in neuronal cultures - ------------------------------------------------------------------------------------------------------------------------------------ Sukhatme, Vikas Beth Israel Deaconess Hospital MTA 11/22/93 Renal: Delivery of OP-1 for chronic renal disease - ------------------------------------------------------------------------------------------------------------------------------------
Page 1 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Suva, Larry Beth Israel Deaconess Hospital MTA 3/22/93 Small Molecules: Characterization of the cbfa1 gene promoter - ------------------------------------------------------------------------------------------------------------------------------------ Hollenberg, Tony Beth Israel Deaconess Medical Center MTA 6/3/99 Morphogens: The role of morphogens in the thyroid - ------------------------------------------------------------------------------------------------------------------------------------ LaMont, J. Thomas Beth Israel Deaconess Medical Center MTA 4/27/99 Morphogen: Gastro: Role of morphogens in intestinal inflammation - ------------------------------------------------------------------------------------------------------------------------------------ Pothoulakis, Beth Israel Deaconess Medical Center MTA 6/19/99 Morphogens: Gastro: screen the BMPs in Charalabos a model of bowel inflammation - ------------------------------------------------------------------------------------------------------------------------------------ Muller-Beckmann, B. Boehringer Mannheim GmbH MTA 3/25/94 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Wulff, Karl Boerhringer Mannheim MTA 3/25/94 - ------------------------------------------------------------------------------------------------------------------------------------ Stafford, Walter Boston BioMedical Research Institute MTA 11/15/94 Formulations: Efforts to Characterize the Physical State of OP-1 in Solution: Effects of PH, Protein, Buffer components - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Boston Scientific Corporation MTA 9/22/99 - ------------------------------------------------------------------------------------------------------------------------------------ Farmer, Steve Boston University MTA 8/28/95 Morphogens: adipogenesis and myogenesis and overall tissue morphogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Graves, Dana Boston University MTA 3/25/99 Morphogens: adipogenesis and myogenesis; effect of OP-1 on osteoblastic cells (amendment) - ------------------------------------------------------------------------------------------------------------------------------------ Graves, Dana Boston University MTA 11/8/95 Morphogens: adipogenesis and myogenesis; effect of OP-1 on osteoblastic cells - ------------------------------------------------------------------------------------------------------------------------------------ Gerstenfeld, Louis Boston University Medical School MTA 2/1/00 Molecular Therapeutics: transcrptional factors determining osteogenesis, for use in developing BMP analogs for soft tissue therapeutics - ------------------------------------------------------------------------------------------------------------------------------------ Carlson, William Brandeis University MTA 10/30/92 - ------------------------------------------------------------------------------------------------------------------------------------ Carlson, William Brandeis University MTA 1/21/93 Small Molecule: Structure determination of OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Ren, Ruibao Brandeis University MTA 2/20/98 Morphogens; Hematopoiesis: OP-1 in hematopoiesis & leukemogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Sen, Ranjan Brandeis University MTA 6/1/98 Small Molecule: Plasmids and Extracts - ------------------------------------------------------------------------------------------------------------------------------------ Maas, Richard Brigham & Woman's Hospital MTA 12/1/95 Morphogens; Ocular: OP-1 in ocular development - ------------------------------------------------------------------------------------------------------------------------------------ MacKenzie, Harold Brigham & Women's Hospital MTA 9/8/99 Renal: Effect of sBMP-7 treatment +/- enalapril beginning 5 weeks after 5/6 nephrectomy - ------------------------------------------------------------------------------------------------------------------------------------ Nigam, Sanjay Brigham & Women's Hospital MTA 6/19/96 Renal: nephrogenic differentiation - ------------------------------------------------------------------------------------------------------------------------------------
Page 2 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Sayegh, Mohamed Hassan Brigham & Women's Hospital MTA 5/19/99 Renal: role of BMPs in the regulation of allo- and auto-immune responses using in vitro and in vivo models - ------------------------------------------------------------------------------------------------------------------------------------ Fausto, Nelson Brown University MTA 7/16/91 Morphogens; Liver: the role of OP-1 in liver cell differentiation and liver regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Patterson, Paul CA Institute of Tech. MTA 10/16/95 Neuro: differentiate between dendrite bearing or dendrite-less neurons & response to OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Garcia Castro, Martin California Institute of MTA 6/30/99 Morphogens: to the role of morphogens on the induction Technology of Neural Crest cells during development - ------------------------------------------------------------------------------------------------------------------------------------ Wise, Donald Cambridge Scientific Inc. MTA 5/12/93 Formulations: OP-1 and biodegradable polymers - ------------------------------------------------------------------------------------------------------------------------------------ Lein, Pamela Canisius College MTA 8/14/97 Neuro: Dendritic growth in sympathetic neurons - ------------------------------------------------------------------------------------------------------------------------------------ Ballock, R. Tracy Case Western Reserve MTA 6/2/95 Neuro: Effectiveness of OP-1 on the development of University neurons in culture - ------------------------------------------------------------------------------------------------------------------------------------ Hopfer, Ulrich Case Western Reserve MTA 2/2/00 University - ------------------------------------------------------------------------------------------------------------------------------------ ten Dijke, Peter Catholic University MTA 2/16/94 Small Molecules: OP-1 receptors & interactions with ligands - ------------------------------------------------------------------------------------------------------------------------------------ D'Amore, Patricia Children's Hospital MTA 10/22/90 Morphogens: effect of OP-1 on cultured smooth muscle cells, endothelial vessel cells, other cells - ------------------------------------------------------------------------------------------------------------------------------------ D'Amore, Patricia Children's Hospital MTA 5/4/98 Morphogens: growth & differentiation factor effects on vascular development - ------------------------------------------------------------------------------------------------------------------------------------ D'Amore, Patricia Children's Hospital MTA 9/22/88 - ------------------------------------------------------------------------------------------------------------------------------------ D'Amore, Patricia Children's Hospital MTA 7/28/98 Morphogens: growth & differentiation factor effects on vascular development - ------------------------------------------------------------------------------------------------------------------------------------ Golden, Jeff Children's Hospital - MTA 9/16/98 Morphogens; Development: the role of OP-1 in the Philadelphia developing chick embryo on dorsal-ventral patterning of the forebrain - ------------------------------------------------------------------------------------------------------------------------------------ Greenberg, Michael Children's Hospital-Boston MTA 10/9/97 Neuro: role of OP-1 in growth and differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Harris, William Children's Hospital-Boston MTA 11/1/93 Renal: IMCD cells (MTA); Role of OP-1 in kidney and brain (SRA) - ------------------------------------------------------------------------------------------------------------------------------------ Hauschka, Peter Children's Hospital-Boston MTA 9/11/90 Osteoporosis: Basic research on the mechanisms of Osteogenic protein action in bone - ------------------------------------------------------------------------------------------------------------------------------------ Klagsbrun, Michael Children's Hospital-Boston MTA 12/10/98 Morphogens: Effect of BMPs on the expression of neuropilin in a number of cell types including endothelial, tumor and neuronal cells - ------------------------------------------------------------------------------------------------------------------------------------ Kreidber, Jordan Children's Hospital-Boston MTA 11/6/95 Morphogens: In situ hybridization /test for OP-1 expression in WT-1 mutant embryos - ------------------------------------------------------------------------------------------------------------------------------------
Page 3 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Smith, Lois Children's Hospital-Boston MTA 12/2/98 Ocular: the role of OP-1 and related morphogens in ocular repair and regeneration during development and disease - ------------------------------------------------------------------------------------------------------------------------------------ Kohtz, Jhumku Children's Memorial Institute MTA 4/27/99 Morphogen: the role of BMPs in forebrain development for Education and Research - ------------------------------------------------------------------------------------------------------------------------------------ Muschler, George Cleveland Clinic Foundation MTA 2/7/94 Stryker: effect of OP-1 in the isolation of osteoblastic cells from primary bone aspirates - ------------------------------------------------------------------------------------------------------------------------------------ Nawa, Hiroyuki Cold Spring Harbor Lab MTA 3/7/95 Neuro: factors regulating neuronal plasticity in developing brain - ------------------------------------------------------------------------------------------------------------------------------------ Svoboda, Karel Cold Spring Harbor Laboratory MTA 6/19/99 Neuro: to the effects of BMPs on the dynamics of dendritic spine and filopodia formation/retraction in hippocampal neurons - ------------------------------------------------------------------------------------------------------------------------------------ Le Douarin, Nicole College de France MTA 4/26/98 Morphogens: embryological development - ------------------------------------------------------------------------------------------------------------------------------------ Chen, Theresa College of Notre Dame MTA 3/9/98 Osteoporosis: OP-1 & Skeleton Aging - ------------------------------------------------------------------------------------------------------------------------------------ Chen, Theresa College of Notre Dame MTA 1/27/98 Osteoporosis: OP-1 & Skeleton Aging - ------------------------------------------------------------------------------------------------------------------------------------ Barasch, Jon Columbia University MTA 8/29/96 Renal: role of OP-1 in nephrogenic induction - ------------------------------------------------------------------------------------------------------------------------------------ Dodd, Jane Columbia University MTA 3/20/98 Neuro: role of OP-1, BMP-6 and GDF's in neurogenesis, in particular forebrain patterning in central nervous system & axonal guidance in spinal cord - ------------------------------------------------------------------------------------------------------------------------------------ Jessell, Thomas Columbia University (Howard MTA 9/16/96 Neuro: role of OP-1 in neural tube induction and Hughes Institute) differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Beall, Melissa Cornell University MTA 9/22/99 Molecular Therapeutics: Analysis of Schistomsoma mansoni TGF-B-like type I receptor SmRK1 and it's role in BMP signalling - ------------------------------------------------------------------------------------------------------------------------------------ Silver, Randi Cornell University MTA 10/21/96 Renal: role of OP-1 on ion transport and acid/base balance in the principal and inercalated cells of cortical collecting duct - ------------------------------------------------------------------------------------------------------------------------------------ Pearce, Edward J. Cornell University, College of MTA 9/22/99 Research on Schistomsoma mansoni TGF-Beta-like Veterinary Medicine receptor, SmRK1, and the potential role of these factors as ligands for the parasite receptor - ------------------------------------------------------------------------------------------------------------------------------------ Gee, Connie Dana Farber Cancer Institute MTA 3/25/91 Small Molecule: effect of OP-1 on pp60c-src protein tryrosine kinase activity in macrophage cultures - isolation of OP-1 receptors - ------------------------------------------------------------------------------------------------------------------------------------ Franzen, Asa Dept. of Genetics & Pathology, MTA 3/13/00 : BMP-7 cDNAs pertaining to BMP expression in Unit of Pathology, Rudbecklab, anaplastic thyroid carcinoma cell lines Uppsala Sweden - ------------------------------------------------------------------------------------------------------------------------------------
Page 4 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Diacrin, Inc. MTA 8/15/99 Morphogens: the expansion of liver cell lines in vitro for therapeutic uses - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Diacrin, Inc. MTA 8/15/99 Morphogens: expansion of liver cell lines in vitro for therapeutic uses - ------------------------------------------------------------------------------------------------------------------------------------ Dean, Richard Diatech, Inc. MTA 11/26/90 Morphogens: in vivo imaging of target tissues in animal models - ------------------------------------------------------------------------------------------------------------------------------------ Quarles, L. Darryl Duke University Medical MTA 8/18/93 Morphogens: role of OP-1 in ostoeblast cell lines and Center helix-loop-helix proteins - ------------------------------------------------------------------------------------------------------------------------------------ Wang, Xiao-Fan Duke University Medical MTA 10/10/95 Small Molecules: signal pathways of TGF-B superfamily Center members - ------------------------------------------------------------------------------------------------------------------------------------ Prochiantz, Alain Ecole Normale Superieure MTA 10/20/98 Small Molecule: Role of BMPs in regulation of homeogene expression during neuronal development - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Eli Lilly and Company MTA 7/31/98 Neuro: Stroke studies - ------------------------------------------------------------------------------------------------------------------------------------ Benedetti, Luca Fidia Advanced Biopolymers MTA 2/8/93 Formulations: hyaluronic acid polymers - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Fisions Applied Sensor MTA 11/11/93 Assay development: development of assays to Technologies quatntiate OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Bernstein, Erwin Fred Hutchinson Cancer Center MTA 6/10/94 Morphogens: hemopoietic stem cells - ------------------------------------------------------------------------------------------------------------------------------------ Funa, Keiko Goteborg University MTA 7/29/99 Neuro: The effect of morphogens on dopaminergic neurons in culture and in animal models of Parkinson's Disease (amendment for expanded sample) - ------------------------------------------------------------------------------------------------------------------------------------ Funa, Keiko Goteborg University MTA 6/18/99 Neuro: The effect of morphogens on dopaminergic neurons in culture and in animal models of Parkinson's Disease - ------------------------------------------------------------------------------------------------------------------------------------ Funa, Keiko Goteborg University, Institute MTA 12/28/00 To use BMP in rat model of Parkinson's Disease of Anatomy and Cell Biology - ------------------------------------------------------------------------------------------------------------------------------------ Kojima, Itaru Gunma University MTA 11/25/97 Renal: OP-1 on the tubulogenesis of the kidney - ------------------------------------------------------------------------------------------------------------------------------------ Davis, Kevin Hammersmith Hospital MTA 3/25/93 - ------------------------------------------------------------------------------------------------------------------------------------ Shoskes, Daniel Harbor-UCLA Medical Center MTA 2/3/00 Renal: studies on the effect of BMP-7 in established models of oxidant stress - ------------------------------------------------------------------------------------------------------------------------------------ Bignami, Amico Harvard Medical School MTA 10/9/90 Neuro: localization of OP-1 and BMP-2 in nerve tissue - ------------------------------------------------------------------------------------------------------------------------------------ Hollenbeck, Peter Harvard Medical School MTA 7/26/96 Neuro: intracellular transport in neurons - ------------------------------------------------------------------------------------------------------------------------------------ Lassar, Andrew Harvard Medical School MTA 12/22/98 Morphogens: role of BMPs in somite chondrogenesis of the developing chick embryo - ------------------------------------------------------------------------------------------------------------------------------------ Tabin, Cliff Harvard Medical School MTA 12/22/98 Morphogens: Role of GDF5 and GDF6 in bone development and limb patterning in the developing chick - ------------------------------------------------------------------------------------------------------------------------------------
Page 5 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Whitman, Malcolm Harvard Medical School MTA 12/22/98 Small Molecule: the role of BMP's in the regulation or modification of cell specification and differentiation during frog embryogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Whitman, Malcom Harvard Medical School MTA 1/4/01 Role of BMP signaling in frog embryos - ------------------------------------------------------------------------------------------------------------------------------------ Robertson, Elizabeth Harvard University MTA 10/11/99 Morphogens: Use of BMP-7/LacZ Transgenic Mouse for characterization of OP-1 expression and screening of morphogen analogs - ------------------------------------------------------------------------------------------------------------------------------------ Robertson, Elizabeth Harvard University MTA 8/22/95 Morphogens: effects of OP-1 during embryonic development - ------------------------------------------------------------------------------------------------------------------------------------ Robertson, Elizabeth Harvard University MTA 12/8/98 Morphogens: Use of BMP-7/LacZ Transgenic Mouse for characterization of OP-1 expression and screening of morphogen analogs - ------------------------------------------------------------------------------------------------------------------------------------ Bar-Shavit, Zvi Hebrew University MTA 9/28/93 Osteoporosis: Modulation of proenkephalin expression in osteoblasts - ------------------------------------------------------------------------------------------------------------------------------------ Rao, D. Sudhaker Henry Ford Hospital MTA 11/15/95 Renal: study OP-1 as marker of renal osteodystrophy and renal function - ------------------------------------------------------------------------------------------------------------------------------------ Lechleider, Robert Henry M. Jackson MTA 6/17/99 Small Molecules: The role of Smads in vascular and Foundation for hematopoietic biology Advancement of Military Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Rosenblum, Norman Hospital for Sick MTA 12/2/98 Renal: Role of OP-1 in branching morphogenesis Children during kidney development - amendment - ------------------------------------------------------------------------------------------------------------------------------------ Rosenblum, Norman Hospital for Sick MTA 1/26/96 Renal: Role of OP-1 in branching morphogenesis Children during kidney development - ---------------------------------------------------------------------------------------------------------------------------------- Wrana, Jeff Hospital for Sick MTA 7/10/95 Small Molecule: OP-1 signaling pathways; smads; Children Amendment to NDA 12/3/97 - ------------------------------------------------------------------------------------------------------------------------------------ Pelletier, Jean-Pierre Hospital Notre-Dame MTA 10/18/88 Cartilage: involvement of metalloprotease in the destruction of the extracellular matrix of human osteoarthritis cartilage (TIMP gene) - ------------------------------------------------------------------------------------------------------------------------------------ Miralles, F. Hospital Robert Debre MTA 11/23/97 Morphogens: OP-1 in pancreatic differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Goff, Stephen Howard Hughes Medical MTA 8/28/98 Morphogens; Hematopoesis: the role of Abelson Institute/Columbia tyrosine kinase in response to BMP's University - ------------------------------------------------------------------------------------------------------------------------------------ Vander Eynder-Van Hubrecht Laboratory MTA 3/20/95 Morphogens: role of OP-1 in mouse mesoderm induction Raay, A.J.M. using tissue culture studies - ------------------------------------------------------------------------------------------------------------------------------------ Binderman, Itzhak ICHILOV Hospital MTA 3/5/91 Dental: Role of OP-1 in tooth regeneration in dogs - ------------------------------------------------------------------------------------------------------------------------------------ Massey, Richard IGEN, Inc MTA 6/10/96 Process Development: receipt of materials to quantitate matrix containing bovine OP-1 - ------------------------------------------------------------------------------------------------------------------------------------
Page 6 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Wharton, John Imperial College of Medicine MTA 10/5/00 To study the effects of BMP-4 and BMP-7 on the pulmonary artery smooth muscle cells derived from patients with primary and secondary pulumonary hypertension and controls - ------------------------------------------------------------------------------------------------------------------------------------ Broxmeyer, Hal Indiana University MTA 6/2/99 Morphogens: Hematopoesis: Role of morphogens on hematopoietic precursor cells in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Chen, Yan Indiana University School of MTA 6/2/99 Small Molecule: the involvement of Smads in morphogen Medicine signaling and the development morphogens for soft tissue applications - ------------------------------------------------------------------------------------------------------------------------------------ Ronco, P. Inserm U64-Hopit Tevon MTA 10/19/95 Renal: OP-1 pattern expression in human glomerular defects - ------------------------------------------------------------------------------------------------------------------------------------ Sautier, Jean-Michel Institut Biomedical des MTA 1/6/99 Small Molecule: phenotypic changes in response to Cordeliers BMPs for the purpose of developing screening assays for BMP activity in soft tissue applications - ------------------------------------------------------------------------------------------------------------------------------------ Mallein-Gerin, Institut de Biologie et Chimie MTA 1/25/96 Morphogens: role of OP-1 in immortilized cell lines Frederic des Proteines - ------------------------------------------------------------------------------------------------------------------------------------ Nifuji, Akira Institut Pasteur MTA 12/10/92 Morphogens: role of OP-1 in the differentiation of osteogenic / chondrogenic C1 cells - ------------------------------------------------------------------------------------------------------------------------------------ Querol, Sergie Institute de Recerca Oncologica MTA 6/28/99 Morphogen: The role of morphogens in proliferation and differentiation of stem cells - ------------------------------------------------------------------------------------------------------------------------------------ Krokan, Hans Institute of Cancer Research MTA 2/8/00 Morphogens:cancer: To study the role of BMP's and Molecular Biology induction of apoptosis and growth arrest of myeloma cells - ------------------------------------------------------------------------------------------------------------------------------------ Ishii, Shunsuke Institute of Phy.& Chem. MTA 1/16/96 Small Molecules: role of OP-1 on several Research, Riken Tsukuba transcription factors involved in cellular growth Center control - ------------------------------------------------------------------------------------------------------------------------------------ Bovolenta, Paola Instituto Cajal MTA 6/5/98 Morphogens; Ocular: Effect of OP-1 on expression of Otx2 in retina - ------------------------------------------------------------------------------------------------------------------------------------ Tokunaga, Hideo Iwate Medical University MTA 3/19/01 Expression of BMP-7 in Human Renal Cell Carcinomal Cell Lines - ------------------------------------------------------------------------------------------------------------------------------------ Johnson, Ken Jackson Research Lab MTA 3/28/95 Morphogens: OP-1 cDNA probes - ------------------------------------------------------------------------------------------------------------------------------------ Jos van Kampen, G.P. Jan van Breemen Inst MTA 9/10/93 Cartilage: in vitro model of osteoarthritis - ------------------------------------------------------------------------------------------------------------------------------------ Shimomura, Ryuichi Japan Tobacco Inc. MTA 6/3/94 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Miyazono, Kohei Japanese Foundation for MTA 12/16/98 Small Molecules: BMP receptors (amendment) Cancer Research - ------------------------------------------------------------------------------------------------------------------------------------ Miyazono, Kohei Japanese Foundation for MTA 9/26/96 Small Molecules: BMP receptors Cancer Research - ------------------------------------------------------------------------------------------------------------------------------------
Page 7 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Lein, Pamela Johns Hopkins MTA 5/26/99 Neuro: The role of morphogens in dendrite formation - ------------------------------------------------------------------------------------------------------------------------------------ Campochiaro, Peter Johns Hopkins Hospital MTA 10/22/98 Morphogens; Ocular: The role of morphogens in ocular pathologies - ------------------------------------------------------------------------------------------------------------------------------------ Adler, Ruben Johns Hopkins University MTA 4/15/99 Morphogens; Ocular: Role of BMPs in retinal development - ------------------------------------------------------------------------------------------------------------------------------------ Racusen, Lorraine Johns Hopkins University MTA 8/30/95 Morphogens: Adeno-12 SV40 HPT (from Johns Hopkins) - ------------------------------------------------------------------------------------------------------------------------------------ Reddi, A.H. Johns Hopkins University MTA 7/13/92 Stryker and Osteoporosis: femoral head study - ------------------------------------------------------------------------------------------------------------------------------------ Rothstein, Jeffery Johns Hopkins University MTA 5/25/99 Neuro: The role of Morphogens in the treatment of ALS - ------------------------------------------------------------------------------------------------------------------------------------ Shapiro, Jay Johns Hopkins University MTA 5/9/94 Osteoporosis: effects of hOP-1 on control osteoblasts and osteoblasts from patients with osteogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Sakou, Takashi Kagoshima University MTA 4/14/95 Osteoporosis: expression of OP-1 and receptors in OPLL patients - ------------------------------------------------------------------------------------------------------------------------------------ Sakou, Takashi Kagoshima University MTA 3/16/98 Osteoporosis: mechanism of fracture healing and bone formation with regards osteoporosis and other metabolic bone diseases - ------------------------------------------------------------------------------------------------------------------------------------ Lee, Chang-Ho Kangnung National University MTA 2/10/96 Osteoporosis: osteoblast differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Kouegawa, Junick Kirin Brewery Co., Ltd. MTA 11/11/93 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Sakamoto, Choitsu Kobe University School of MTA 6/27/96 Morphogens; Gastrointestinal: role of OP-1 in Medicine mechanism of GI ulcer healing; follistatin-like cell surface OP-1 binding protein - ------------------------------------------------------------------------------------------------------------------------------------ Abe, Shin-ichi Kumamoto University MTA 2/8/00 Renal: BMP-7 and BMP-6 to be used to test activity on the testes by using in vitro culture system. - ------------------------------------------------------------------------------------------------------------------------------------ Kitamoto, Yasunori Kumamoto University MTA 12/8/97 Renal: OP-1 in metanephric mesenchyme differentiation to glomerulogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Ito, Yoshiaki Kyoto University MTA 11/12/98 Small Molecule: PEBP2aA/Cbfa1 expression in osteoblast progenitors and osteoblasts in vitro and in vivo - ------------------------------------------------------------------------------------------------------------------------------------ Nijweide, Peter Lab. of Cell Biol. & Hist. MTA 11/8/91 Cartilage: effect of OP-1 on osteoclast formation and the differentiation of osteoblasts, cartilage cells and osteocytes in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Wall, Nancy Lawrence University MTA 2/28/98 Morphogens: the effects of BMP-7 on differentiation, cell proliferation and apoptosis of 1st and 2nd branchial arch mesenchyme in chick embryos - ------------------------------------------------------------------------------------------------------------------------------------ McColl, Shaun Le Centre Hospitalier MTA 8/16/91 Morphogens: expression of OP-1 by synoviocytes - ------------------------------------------------------------------------------------------------------------------------------------ Baylink, David Loma Linda University MTA 1/24/92 Osteoporosis: development of serum assays to assess bone metabolism; - ------------------------------------------------------------------------------------------------------------------------------------
Page 8 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Baylink, David Loma Linda University MTA 10/1/90 Osteoporosis: role of OP-1 on the growth and maintenance of human osteoblasts in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Bidani, Anil K. Loyola University-Chicago, VA MTA 1/8/97 Renal: role of OP-1 in the mechanisms of Hospital @ Hines progressive glomerular injury and nephron loss - ------------------------------------------------------------------------------------------------------------------------------------ ten Dijke, Peter Ludwig Institute for Cancer MTA 8/3/93 Small Molecule: Alks cDNA's Research - ------------------------------------------------------------------------------------------------------------------------------------ ten Dijke, Peter Ludwig Institute for Cancer MTA 10/13/92 Small Molecule: TGFb receptors & signalling Research molecules; binding assays on cells transfected with clones - ------------------------------------------------------------------------------------------------------------------------------------ Heinegard, Dick Lund University MTA 1/29/96 Morphogens: interaction between OP-1 and matrix proteins - ------------------------------------------------------------------------------------------------------------------------------------ Karsenty, Gerard M.D. Anderson Cancer Center MTA 10/11/96 Use of morphogenic proteins, BMP-2,3,6,7,8 and GDF 5,6, and 7 in experimental studies relating to osteoblast differentiation. - ------------------------------------------------------------------------------------------------------------------------------------ Thorlacius, Henrik Malmo University Hospital MTA 8/8/98 Morphogens; Angiogenesis: Role of BMP on angiogenesis in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Thorlacius, Henrik Malmo University Hospital MTA 7/18/98 Morphogens; Angiogenesis: Role of BMP on angiogenesis in vitro - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Marion Merrell Dow MTA 5/5/93 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Behar, Oded Massachusetts General MTA 12/15/97 Morphogens: Interactions between semaphorins Hospital and BMPs - ------------------------------------------------------------------------------------------------------------------------------------ Bonventre, Joseph Massachusetts General MTA 10/10/91 Renal: Role of OP-1 in recovery from acute Hospital renal failure - ------------------------------------------------------------------------------------------------------------------------------------ DiFiglia, Marian Massachusetts General MTA 3/18/93 Neuro: localization of OP-1 expression in the Hospital brain and it's role in neuronal growth (Huntington's & Parkinson's disease) - ------------------------------------------------------------------------------------------------------------------------------------ Drummond, Iain Massachusetts General MTA 12/19/97 Renal: Kidney development in fish Hospital - ------------------------------------------------------------------------------------------------------------------------------------ Finklestein, Seth Massachusetts General MTA 7/17/91 Neuro: role of OP-1 in stroke/brain injury Hospital - ------------------------------------------------------------------------------------------------------------------------------------ Katagiri, Take Massachusetts General MTA 4/1/98 Osteoporosis: endochondral Hospital ossification/interaction with PTHrP & PTH - ------------------------------------------------------------------------------------------------------------------------------------ Schneyer, Alan Massachusetts General MTA 4/16/96 Morphogens: role of OP-1 in tissue formation Hospital and embryonic development - ------------------------------------------------------------------------------------------------------------------------------------ Wang, Tongwen Massachusetts General MTA 12/9/97 Small Molecule: Characterization of signal Hospital transduction pathway of OP-1 & activation of signaling proteins such as Smads & Myx - ------------------------------------------------------------------------------------------------------------------------------------ Page 9 of 25
SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF FFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Sklar, Robert Massachusetts General MTA 10/10/91 Morphogens: effect of BMP's on human muscle Hospital-East development in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Schneider, Gerald Massachusetts Institute of MTA 3/3/93 Neuro: axon regeneration Technology - ------------------------------------------------------------------------------------------------------------------------------------ Rohrer, Hermann Max-Planck Institute for Brain MTA 1/3/94 Neuro: sympathetic neurons Research - ------------------------------------------------------------------------------------------------------------------------------------ Rohrer, Hermann Max-Planck Institute for Brain MTA 3/15/99 Neuro: sympathetic neurons - (amendment) Research - ------------------------------------------------------------------------------------------------------------------------------------ Kessel, Michael Max-Planck-Institut fur MTA 5/31/99 Neuro: role of BMPs in neural plate development Biophysikalische Chemie - ------------------------------------------------------------------------------------------------------------------------------------ Bolander, Mark Mayo Clinic MTA 8/1/91 Stryker: expression of OP-1 in the fracture callous - ------------------------------------------------------------------------------------------------------------------------------------ Schwartz, Robert Mayo Clinic MTA 7/20/94 Morphogens; Cardiovascular: effect of OP-1 in pig coronary arteries and myocardium injuries - ------------------------------------------------------------------------------------------------------------------------------------ Kumar, Rajiv Mayo Foundation MTA 12/15/95 Renal: chronic renal failure animal models - ------------------------------------------------------------------------------------------------------------------------------------ Riggs, B. Lawrence Mayo Foundation MTA 12/18/98 Osteoporosis: Effect of BMPs in models of osteoporosis using a conditionally immortalized human marrow stromal cell line - ------------------------------------------------------------------------------------------------------------------------------------ de Crommbrugge, MD Anderson Cancer Center MTA 1/15/92 Small Molecule: TGFb receptors Benoit - ------------------------------------------------------------------------------------------------------------------------------------ Pavenstadt, Hermann Med. Universitatesklinik MTA 2/28/01 Study involves work on the biological role of Freiburg, Department of podocytes, the effects of OP-1 on podocytes function Nephrology by stimulating podocytes with OP-1 and perform cDNA expression analysis, and whether OP-1 prevents proteinuria in a mouse model of glomerulonephritis - ------------------------------------------------------------------------------------------------------------------------------------ Lucas, Paul Medical Center-Central GA MTA 5/7/92 - ------------------------------------------------------------------------------------------------------------------------------------ Abd-Al-Fattah, Anwar Medical College of VA MTA 11/11/91 Morphogens; Cardiovascular: cardiac myocyte regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Wornom, Isaac Medical College of VA MTA 9/18/90 Stryker; Cranio-facial: effect of OP-1 on onlay bone grafts to the facial skeleton in rabbits - ------------------------------------------------------------------------------------------------------------------------------------ Furley, Placzek Medical Research Council MTA 11/29/94 Morphogens: induction of floorplate by notochord - ------------------------------------------------------------------------------------------------------------------------------------ Triffitt, James Medical Research Council MTA 4/2/91 Osteoporosis: role of OP-1 in bone differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Nakaoka, Takashi Medical University of South MTA 9/10/97 Morphogens; Cardiovascular: vascular smooth muscle Carolina proliferation - ------------------------------------------------------------------------------------------------------------------------------------ Massague, Joan Memorial Sloan-Kettering MTA 7/9/93 Small Molecule: Small Molecule: TGFb Receptors - ------------------------------------------------------------------------------------------------------------------------------------
Page 10 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Detmer, Kristina Mercer University School MTA 7/27/99 Morphogens: the effects of morphogens on the of Medicine differentiation of human hematopoietic progenitor cells - ------------------------------------------------------------------------------------------------------------------------------------ Detmer, Kristina Mercer University School MTA 4/30/96 Morphogens: role of OP-1 in skin development of Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Young, Henry Mercer University School MTA 3/25/92 of Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Rodan, Gideon Merck & Co., Inc. MTA 2/10/94 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Seyfried, Christoph Merck KgaA Biomedical MTA 6/19/00 : evaluation of mBMP-7 in stroke models Research - ------------------------------------------------------------------------------------------------------------------------------------ Paredes, Ana Miami Children's Hospital MTA 6/10/98 Renal: effect of rhOP-1 in bone cells from Research Institute children with chronic renal failure - ------------------------------------------------------------------------------------------------------------------------------------ Paredes, Ana Miami Children's Hospital MTA 8/27/97 Renal: effect of OP-1 on acute renal failure Research Institute - ----------------------------------------------------------------------------------------------------------------------------------- Khouri, Roger Miami Hand Center MTA 8/28/96 Cartilage: repair of bone and cartilage - ------------------------------------------------------------------------------------------------------------------------------------ Miles, Inc., Miles Inc. MTA 1/11/93 Osteoporosis: model systems - ------------------------------------------------------------------------------------------------------------------------------------ Hobson, Grace Namours Research MTA 11/25/95 Osteoporosis: Effect of OP-1 on the treatment of certain bone diseases characterized by abnormal bone growth - ------------------------------------------------------------------------------------------------------------------------------------ Covarrubias, Luis National Autonomous Univ. MTA 8/12/98 Morphogens: Effect of BMPs on cell proliferation, of Mexico differentiation and survival using model systems of EFG responsive neuro progenator cells and epidermal cells - ------------------------------------------------------------------------------------------------------------------------------------ Ruscetti, Francis National Cancer Institute MTA 11/13/90 - ------------------------------------------------------------------------------------------------------------------------------------ Liang, Tony National Institute for Aging MTA 12/12/95 Osteoporosis: Ability of OP-1 to induce osteoblast lineage in marrow ablation models - ------------------------------------------------------------------------------------------------------------------------------------ Ueno, Naoto National Institute for Basic MTA 10/23/98 Small Molecule: Determination of binding constant Biology of OP-1 to follistatin by surface plasm on resonance - ------------------------------------------------------------------------------------------------------------------------------------ Smith, James National Institute for Medical MTA 3/22/94 Morphogens: Effect of OP-1 in it's ability to induce Research mesoderm - ------------------------------------------------------------------------------------------------------------------------------------ Donkersloot, Jacob / National Institute of Dental MTA 12/13/95 Cartilage: Production of recombinant cartilage-derived Luyten, Frank Research morphogenetic proteins and evalution of their biological functions - ------------------------------------------------------------------------------------------------------------------------------------ Kopp, Jeffrey National Institute of Health MTA 6/1/98 Renal: Role of OPs in renal development and disease - amendment - ------------------------------------------------------------------------------------------------------------------------------------ Kopp, Jeffrey National Institute of Health MTA 4/22/99 Renal: Over-expression of BMP7 in the liver modulates hepatocyte proliferation or recovery of differentiated function following partial hepatectomy - ------------------------------------------------------------------------------------------------------------------------------------
Page 11 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Kopp, Jeffrey National Institute of Health MTA 10/5/96 Renal: Role of OPs in renal development and disease - ------------------------------------------------------------------------------------------------------------------------------------ Kneller, Robert National Institute of Health, NCI MTA 12/26/95 Osteoporosis: Effect of OP-1 in stimulating bone formation and differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Donovan, Peter NCI: Advanced Bioscience Lab., Inc. MTA 7/1/98 Renal: The effects of OP-1 on embryonic mysenchymal tubual differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Scharp, David Neocrin Company MTA 10/4/96 Assay development: Encapsulated cells - ------------------------------------------------------------------------------------------------------------------------------------ ten dijke, Peter Netherlands Cancer Institute MTA 8/28/02 Molecular Therapeutics: characterization of BMP signaling path - ------------------------------------------------------------------------------------------------------------------------------------ ten dijke, Peter Netherlands Cancer Institute MTA 5/16/00 Molecular Therapeutics: characterization of BMP signaling path - ------------------------------------------------------------------------------------------------------------------------------------ Pereira, Miercio New England Medical Center MTA 10/13/95 Small Molecules: OP-1 and activin signalling in trypanosome invasion of cells - ------------------------------------------------------------------------------------------------------------------------------------ Newman, Stuart New York Medical Coll MTA 4/13/92 Morphogens: role of OP-1 on limb-bud mesenchymal differentiation with respect to pattern formation - ------------------------------------------------------------------------------------------------------------------------------------ LeRoux, Peter New York University MTA 8/11/97 Neuro: role of OP-1in neurons in culture - ------------------------------------------------------------------------------------------------------------------------------------ Fishell, Gordon New York University Medical Center MTA 7/21/98 Morphogens: the role of OP-1 in development & regionalization of telencephalon - ------------------------------------------------------------------------------------------------------------------------------------ Nawa, Hiroyuki Nigata University MTA 7/24/95 Neuro: factors regulating neuronal plasticity in developing brain - ------------------------------------------------------------------------------------------------------------------------------------ Roberts, Anita NIH MTA 8/13/98 Small Molecule: Target gene regulation by BMP-7 - ------------------------------------------------------------------------------------------------------------------------------------ Miller, William North Carolina State University MTA 12/4/98 Small Molecule: role of BMPs in stimulating follicle- stimulating hormone expression - ------------------------------------------------------------------------------------------------------------------------------------ Stern, Paula Northwestern University MTA 12/16/94 Osteoporosis: Role of OP-1 in remodeling - ------------------------------------------------------------------------------------------------------------------------------------ Woodruff, Teresa Northwestern University MTA 9/13/99 Morphogens, Reproduction: the mechanism of BMP regulation of FSH expression in the pituitary. - ------------------------------------------------------------------------------------------------------------------------------------ Sauter, Andre Novartis Pharma AG MTA 2/23/99 Neuro: Novartis's internal evaluation of the use of OP-1 in Novartis's stroke model - ------------------------------------------------------------------------------------------------------------------------------------ Hollinger, Jeffrey Oregon Health Sciences University MTA 6/5/98 Morphogens; Liver: OP-1 in hepatic repair & regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Hollinger, Jeffrey Oregon Health Sciences University MTA 8/19/98 Morphogens; Liver: OP-1 in hepatic repair & regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Hollinger, Jeffrey Oregon Health Sciences University MTA 3/23/98 Morphogens; Liver: OP-1 in hepatic repair & regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Withers, Ginger Oregon Health Sciences University MTA 5/13/99 Neuro: the role of morphogens in the expression of dendritic and synaptic structural plasticity - ------------------------------------------------------------------------------------------------------------------------------------
Page 12 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Komori, Toshihisa Osaka University Medical MTA 5/16/97 Osteoporosis: Role of OP-1 in osteogenesis School - ------------------------------------------------------------------------------------------------------------------------------------ Gordon, Neal Perseptive Biosystems MTA 4/7/94 Assay Development: Construction of affinity columns - ------------------------------------------------------------------------------------------------------------------------------------ Flowers, John Protein Polymer Technologies MTA 1/21/94 Morphogens: Extracellular matrix components for hard and soft tissue repair and regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Ashton, Brian R. Jones & A. Hunt Hospital MTA 3/19/92 Osteoporosis: Role of OP-1 in marrow differentiation and marrow induced endochondral bone formation in vivo - ------------------------------------------------------------------------------------------------------------------------------------ Essery, John R.W. Johnson Pharmaceutical MTA 3/14/94 Osteoporosis: model systems for bone and mineral Res. Institute metabolism - ------------------------------------------------------------------------------------------------------------------------------------ Bizios, Rena Rensselaer Polyt Institute MTA 10/13/93 Osteoporosis: Role of OP-1 on osteoblast proliferation and cell population motility on substrates modified with covalently-bound bioactive, adhesive peptides. - ------------------------------------------------------------------------------------------------------------------------------------ Schwartz, Edith Rhode Island Hospital MTA 12/19/91 Osteoporosis: Study the effects of OP-1 on osteoblast cell lines - ------------------------------------------------------------------------------------------------------------------------------------ Rivas, Miriam Rockefeller University MTA 7/13/98 Morphogens: the role of OP-1 in psoriatic skin - ------------------------------------------------------------------------------------------------------------------------------------ McK. Ciombor, Deborah Roger Williams Hospital MTA 1/5/94 Morphogens: mesenchymal cell differentition - ------------------------------------------------------------------------------------------------------------------------------------ Rehbein, Steven Roswell Park Cancer Institute MTA 1/14/94 Morphogens; Hematopoiesis: differentiation of hemopoietic progenitor cells in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Chester, Kerry Royal Free Hospital MTA 1/16/95 Cancer: tumor imaging - ------------------------------------------------------------------------------------------------------------------------------------ Kruse, Friedrich Ruprecht-Karls-Universitat MTA 7/5/98 Morphogens; Ocular: Role of OP-1 and BMP-5 in cornea Heidelberg development - ------------------------------------------------------------------------------------------------------------------------------------ Kuettner, Klaus Rush-Presb-St. Luke's MTA 5/3/93 Cartilage: role of OP-1 in cell metabolism and differentiation of chondrocytes or modulation of their phenotype - ------------------------------------------------------------------------------------------------------------------------------------ Wientroub, Shlomo Sackler School of Medicine MTA 3/8/92 Morphogens: Effect of OP-1 mouse marrow celll ines - ------------------------------------------------------------------------------------------------------------------------------------ Tschannen, Ronald Sandoz Pharma Ltd. MTA 4/14/94 Osteoporosis: models systems - ------------------------------------------------------------------------------------------------------------------------------------ Saeki, Masanori Sankyo Co., Ltd. MTA 11/1/93 Osteoporosis: models systems - ------------------------------------------------------------------------------------------------------------------------------------ Halpain, Shelley Scripps Research Institute MTA 10/22/98 Neuro: the effect of BMPs on MAP2 and the dendritic cytoskelton - ------------------------------------------------------------------------------------------------------------------------------------ - --------------- Shield Diagnostics Ltd MTA 1/19/94 Assay Development: development of assays to quantitate OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Walsh, Kenneth St. Elizabeth's Medical Center MTA 11/17/98 Morphogens; Cardiac: Effect of BMPs on pressure overload cardiac hypertrophy - ------------------------------------------------------------------------------------------------------------------------------------
Page 13 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF FFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Martin, Kevin St. Louis University MTA 4/22/99 Renal: studies on the relationship between BMP expression and circulating levels and metabolic bone pathologies seen in renal disease, for the purpose of generating systemic therapies for osteoporosis - ------------------------------------------------------------------------------------------------------------------------------------ Martin, Kevin St. Louis University MTA 3/18/99 Renal: studies on the relationship between BMP expression and circulating levels and metabolic bone pathologies seen in renal disease, for the purpose of generating systemic therapies for osteoporosis - ------------------------------------------------------------------------------------------------------------------------------------ Barres, Barbara Stanford University MTA 9/20/95 Neural: development of neuronal and glial cells in culture - ------------------------------------------------------------------------------------------------------------------------------------ Hsueh, Aaron Stanford University Medical Center MTA 4/21/99 Morphogen: the effects of BMPs on ovarian follicle development - ------------------------------------------------------------------------------------------------------------------------------------ Cho, Moon-Il State University of New York at MTA 6/10/99 Small Molecule: the development of in vitro assays Buffalo using periodontal ligament fibroblast cell lines, to facilitate the development of soft tissue applications for CDMPs - ------------------------------------------------------------------------------------------------------------------------------------ Rohrer, Lucia Swiss Federal Institute of MTA 8/5/98 Morphogens: Role of BMPs in blood vessel formation Technology Zurich by endothelial cells - ------------------------------------------------------------------------------------------------------------------------------------ Brand, Thomas Technische University Brschwg MTA 10/4/95 Morphogens; Cardiovascular: early heart dev. - ------------------------------------------------------------------------------------------------------------------------------------ Ishizuka, Seiichi Teijin Institute MTA 8/23/94 Osteoporosis: role of OP-1 in bone formation by vitamin D3 analogues in vitro and in vivo - ------------------------------------------------------------------------------------------------------------------------------------ Bleiberg, Ilan Telaviv University/Sackler School MTA 12/23/93 Morphogens: effects of OP-1 on clonal cell lines of of Medicine DBM implants - ------------------------------------------------------------------------------------------------------------------------------------ Sires, Bryan The Eye Institute MTA 6/24/93 Ocular: role of OP-1 in choriodal osetomas in eyes - ------------------------------------------------------------------------------------------------------------------------------------ Oakley, Robert The George Washington University MTA 8/11/99 Morphogens: Studies on cell death in the developing Medical Center chick limb - ------------------------------------------------------------------------------------------------------------------------------------ Hirschberg, Raimund The Harbor-UCLA Research & Education MTA 3/27/00 Renal: The role of BMP's in renal interstitial Institute fibrosis - ------------------------------------------------------------------------------------------------------------------------------------ Bhatia, Mick The John P. Robarts Research MTA 10/19/98 Morphogens; Hematopoiesis: the role of BMP's in Institute hematopoiesis - ------------------------------------------------------------------------------------------------------------------------------------ Bhatia, Mick The John P. Robarts Research MTA 2/16/98 Morphogens; Hematopoiesis: the role of BMP's in Institute hematopoiesis - ------------------------------------------------------------------------------------------------------------------------------------ Rutherford, Bruce The Regents of the University of MTA 4/16/02 OP-1 in an assay of the Osteoblastic conversion of Michigan fibroblasts in response to secreted OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Choe, Senyon The Salk Institute MTA 4/27/00 BMP-7: To ascertain the structure of BMP-7 associated with Type II receptors. - ------------------------------------------------------------------------------------------------------------------------------------
Page 14 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Johnson, Mary The University of Arizona MTA 1/18/99 The study of the ability of OP-1 to reverse the effect of ethanol, nicotine and barbituates on dendritic branching - ------------------------------------------------------------------------------------------------------------------------------------ Sharma, Kumar Thomas Jefferson University MTA 10/15/98 Morphogens; Renal: role of BMPs in diabetic kidney disease - ------------------------------------------------------------------------------------------------------------------------------------ Ohtaka, Akihiko Tohoku University School of MTA 7/23/98 Renal: the role of OP-1 in tubulogenesis of Medicine metanephric mesenchyme and glomerulogenesis in animal models of nephritis - ------------------------------------------------------------------------------------------------------------------------------------ Nifuji, Akira Tokyo Medical and Dental MTA 8/19/98 Morphogens: Patterning in development Institute - ------------------------------------------------------------------------------------------------------------------------------------ Asahina, Izumi Tokyo Medical/Dental MTA 12/27/93 Osteogenesis: OP-1 induced endochondral University osteogenesis model system in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Noda, Masaki Tokyo Medical/Dental MTA 8/26/93 Osteoporosis: effects of OP-1 on bone metabolism University - ------------------------------------------------------------------------------------------------------------------------------------ Noda, Masaki Tokyo Medical/Dental MTA 7/8/98 Osteoporosis: Differentiation & Determination of University Skeletal Tissue Using Mouse Cells & Chicken Embryo - ------------------------------------------------------------------------------------------------------------------------------------ Albertini, David Tufts University School of MTA 8/2/99 Morphogen: reproduction: The role of morphogens in Medicine ovarian function - ------------------------------------------------------------------------------------------------------------------------------------ Libby, Peter Tufts University School of MTA 1/5/88 Morphogens; Cardiovascular: PDGH Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Hata, Akiko Tufts University School of MTA 2/14/01 Studies of regulation of BMP target genes through Medicine OAZ protein involved in the BMP-4 dependent gene expression. - ------------------------------------------------------------------------------------------------------------------------------------ Hata, Akiko Tufts University School of MTA-Amendment 3/18/02 Studies of regulation of BMP target genes through Medicine OAZ protein involved in the BMP-4 dependent gene expression. - ------------------------------------------------------------------------------------------------------------------------------------ Bermek, Engin Turkish Sci Tech Res Institute MTA 10/5/93 Morphogens: mice embryos - ------------------------------------------------------------------------------------------------------------------------------------ Maxian, Suzanne UMD, New Jersey MTA 4/11/94 Formulations: evaluate resorbable hydroxyapatite coatings in osteointegration studies - ------------------------------------------------------------------------------------------------------------------------------------ Zeevalk, Gail UMDNJ-Robert Wood Johnson MTA 2/7/00 Neuro: the effects of BMPs on the metabolic Med. School processes and phenotype in cultured dopaminergic ventral midbrain neurons (relating to Parkinson's Disease) - ------------------------------------------------------------------------------------------------------------------------------------ Boitani, Carla Universita di Roma "La MTA 7/13/98 Morphogens: Role of BMPs on Sertoli cell and Sapienza" spermatogonial cell proliferation and differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Luyten, Frank Universitaire Ziekenhuizen MTA 8/17/98 Osteoporosis: the role of OP-1 and related BMP's Leuven in osteoporosis - ------------------------------------------------------------------------------------------------------------------------------------ Ambrosio, Santiago Universitat de Barcelona MTA 4/25/96 Neuro: role of OP-1 in promoting survival of fetal mesencephalic cells - ------------------------------------------------------------------------------------------------------------------------------------
Page 15 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Reiriz, Julia Universitat de Barcelona MTA 7/2/98 Neuro: Effect of BMPs as protective agents against excitotoxicity in primary neuronal cultures - ------------------------------------------------------------------------------------------------------------------------------------ Ventura, Francesc Universitat de Barcelona MTA 1/18/99 Small Molecule: studies on the effect of BMPs on the transcriptional regulation of the junB and TIEG promoters differentiation of C2C12 cells - ------------------------------------------------------------------------------------------------------------------------------------ Thomsen, G.H. University at Stony Brook MTA 3/24/95 Morphogens: role of OP-1 in Xenopus development - ------------------------------------------------------------------------------------------------------------------------------------ Shepard, Pierre University Clinic of Cologne MTA 7/26/00 Research pertaining to research on wound healing in the skin using mice as a model, focusing on the expression of BMPs and their receptors during the healing process - ------------------------------------------------------------------------------------------------------------------------------------ Murphy, Madeline University College of Dublin MTA 1/8/01 Examine the ability of BMP-7 to modulate gremlin function in primary human mesangial and primary human renal proximal tubular cells, for studying pathological mechanisms in diabetic neuropathy - ------------------------------------------------------------------------------------------------------------------------------------ Hurle, Juan University de Cantabria, MTA 6/28/95 Morphogens: analyzing mechanisms accounting for Facultad de Med Avda., establishment of interdigital spaces in the chick leg bud - ------------------------------------------------------------------------------------------------------------------------------------ Hurle, Juan University de Cantabria, MTA 9/17/98 Morphogens: role of BMPs in chick limb skeletogenesis Facultad de Med Avda., - ------------------------------------------------------------------------------------------------------------------------------------ Johnson, Mary University of Arizona MTA 2/10/99 Neuro: study of the ability of OP-1 to reverse the effects of ethanol, nicotine and barbituates on dendritic branding - ------------------------------------------------------------------------------------------------------------------------------------ Szivek, John University of Arizona MTA 11/17/93 Morphogens: techniques for attaching strain gauges - ------------------------------------------------------------------------------------------------------------------------------------ Szivek, John University of Arizona Health MTA 11/17/93 Osteoporosis: techniques for attaching strain gauges Sciences Ctr. - ------------------------------------------------------------------------------------------------------------------------------------ Gaddy-Kurten, Dana University of Arkansas MTA 12/16/96 Morphogens: Role of OP-1 in bone cell differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Higgins, Dennis University of Buffalo, State MTA 12/16/93 Neuro: role of OP-1 in sympathetic neurons University of New York - ------------------------------------------------------------------------------------------------------------------------------------ Szabo, Sandor University of CA-Irvine MTA 2/3/95 - ------------------------------------------------------------------------------------------------------------------------------------ Cross, James University of Calgary MTA 2/26/01 Research pertaining to the testing of OP-1 effects in vitro sing murine and human placental trophoblast cell and tissue culture systems - ------------------------------------------------------------------------------------------------------------------------------------ Reddi, A.H. University of California, Davis MTA 9/8/98 Morphogens: tissue regeneration & morphogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Horie, Kuniko University of California, MTA 4/17/98 Morphogens: role of OP-1 in C2C12 myoblasts San Diego - ------------------------------------------------------------------------------------------------------------------------------------ Shimasaki, Shunichi University of California, MTA 11/5/98 Morphogens: the effect of OP-1 on the control of San Diego ovarian follicle growth - ------------------------------------------------------------------------------------------------------------------------------------
Page 16 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Shanahan, Catherine University of Cambridge MTA 12/11/98 Morphogens: BMP expression in vascular smooth muscle cells - ------------------------------------------------------------------------------------------------------------------------------------ Roberts, Veronica University of CA-SD MTA 4/23/97 Small molecule: pax-6 expression in immortalized immature pituitary cell lines - ------------------------------------------------------------------------------------------------------------------------------------ Mobley, William University of CA-SF MTA 11/19/97 Neuro: in vitro/in vivo studies - ------------------------------------------------------------------------------------------------------------------------------------ Kelly, Katrina University of Cincinnati MTA 7/31/96 Renal: role of OP-1 in kidney disease - ------------------------------------------------------------------------------------------------------------------------------------ Hoffer, Barry University of Colorado MTA 10/5/94 Neuro: role of OP-1 in spinal cord injury - ------------------------------------------------------------------------------------------------------------------------------------ Hoffman, Stephen University of Colorado MTA 10/8/93 Morphogens: effects of OP-1 on melanoma cells and keratinocytes - ------------------------------------------------------------------------------------------------------------------------------------ Fouty, Brian University of Colorado Health MTA 12/19/00 Studies involve proliferation of pulmonary artery smooth muscle cells in response to hypoxia and mitogens, and the effects of BMP-7 on smooth muscle cell proliferation in the pulmonary circulation - ------------------------------------------------------------------------------------------------------------------------------------ Bickford, Paula University of Colorado Health Science Center MTA 9/24/97 Neuro: Parkinson's Disease - ------------------------------------------------------------------------------------------------------------------------------------ Granholm-Bentley, University of Colorado Health Science Center MTA 9/23/97 Neuro: effects of OP-1 on motoneurons Ann-Charlotte - ------------------------------------------------------------------------------------------------------------------------------------ Rutherford, Bruce University of Conn. Health Center. MTA 12/20/90 Dental: effect of OP-1 on ROS, periodontal ligament fibroblast and pulp fibroblast cell cultures - ------------------------------------------------------------------------------------------------------------------------------------ Maxwell, Gerald University of Connecticut MTA 4/27/93 Neuro: the mechanism of precursor cells development - ------------------------------------------------------------------------------------------------------------------------------------ Brandi, Maria University of Florence MTA 8/16/91 Morphogens: effect of OP-1 on growth and differentiation of bone endothelial cells - ------------------------------------------------------------------------------------------------------------------------------------ Brandt, Roland University of Heidelberg MTA 6/3/98 Neuro: mechanisms of dendritic sprouting in cultured human neurons - ------------------------------------------------------------------------------------------------------------------------------------ Solursh, Michael University of Iowa MTA 7/6/90 Morphogens: cellular responses of cultured mesenchymal cells to OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Maenpaa, P. University of Kuopio MTA 11/26/92 Morphogens: regulation of osteocalcin synthesis in cultured human osteosarcoma cells by steroid hormones and related vitamins - ------------------------------------------------------------------------------------------------------------------------------------ Ferguson, Mark University of Manchester MTA 8/20/96 Morphogens: role of OP-1 and related proteins to augment wound repair in fetus and post-fetal life - ------------------------------------------------------------------------------------------------------------------------------------ Greenberger, Joel University of Massachusetts Medical Center MTA 7/1/91 Morphogens: effect of OP-1 on bone marrow cell differentiation in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Rusckowski, Mary University of Massachusetts Medical Center MTA 2/4/98 Morphogens: Biodistribution of Tc-OP-1 in normal mice - ------------------------------------------------------------------------------------------------------------------------------------
Page 17 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Dietrich, W.D. University of Miami MTA 8/11/98 Neuro: traumatic brain injury models - ------------------------------------------------------------------------------------------------------------------------------------ Dietrich, W.D. University of Miami MTA 3/4/97 Neuro: traumatic brain injury models - ------------------------------------------------------------------------------------------------------------------------------------ Paredes, Ana University of Miami MTA 11/30/94 Renal: role of OP-1 in renal models - ------------------------------------------------------------------------------------------------------------------------------------ Franceschi, Renny University of Michigan MTA 5/18/00 - ------------------------------------------------------------------------------------------------------------------------------------ Franceschi, Renny University of Michigan MTA 5/29/92 - ------------------------------------------------------------------------------------------------------------------------------------ Franceschi, Renny University of Michigan MTA 9/28/93 Osteoporosis: expresssion of osteoblast phenotypes in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Oegema, Theodore University of Minnesota MTA 11/18/88 Morphogens: herniated disk model of osteogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Sanders, Michel University of Minnesota MTA 12/15/98 Morphogens: examining the differential expression of OP-1 in diverse tissues in the chicken - ------------------------------------------------------------------------------------------------------------------------------------ McKee, Marc University of Montreal MTA 7/29/93 Morphogens: role of OP-1 in bone cell differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Nanci, Antonio University of Montreal MTA 7/29/93 Morphogens: role of OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Echevarria, Diego University of Murcia MTA 4/30/99 Neuro: the role of morphogens in the early regionalization of the forebrain - ------------------------------------------------------------------------------------------------------------------------------------ Cooper, Lyndon University of N. Carolina MTA 4/8/94 Morphogens: OP-1 in osteoblastic cells for wound healing - ------------------------------------------------------------------------------------------------------------------------------------ Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 3/29/99 Morphogens; Gastro: role of BMP-6 and morphogenic proteins in the treatment of inflammatory bowel disease - amendment to expand Sample - ------------------------------------------------------------------------------------------------------------------------------------ Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 12/11/98 Morphogens; Gastro: effects of OP-1 on intestinal epithelial cell proliferation - ------------------------------------------------------------------------------------------------------------------------------------ Sartor, R. Balfour University of North Carolina at Chapel Hill MTA 1/29/99 Morphogens; Gastro: role of BMP-6 and morphogenic proteins in the treatment of inflammatory bowel disease - amendment - ------------------------------------------------------------------------------------------------------------------------------------ Langille, Robert University of Ottawa MTA 8/15/95 Morphogens: role of OP-1 in mandibular development - ------------------------------------------------------------------------------------------------------------------------------------ Vaananen, Kalvervo University of Oulu MTA 11/2/90 morphogens: effect of OP-1 in osteoclast mediated bone resorption - ------------------------------------------------------------------------------------------------------------------------------------ Emerson, Charles University of Pennsylvania MTA 12/15/95 Morphogens: Cell culture model for study of MyoD regulation - ------------------------------------------------------------------------------------------------------------------------------------ Leboy, Phoebe University of Pennsylvania MTA 8/16/91 Osteoporosis: Osteoblast differentiation: effect of OP-1 on rat stromal cell cultures - ------------------------------------------------------------------------------------------------------------------------------------ Fabisiak, James University of Pittsburg MTA 1/30/92 Morphogens: ability of OP-1 to protect the lung after oxidant-induced injury in rat model - ------------------------------------------------------------------------------------------------------------------------------------ Patel, Ketan University of Reading MTA 7/30/99 Molecular Therapeutics: role of BMPs in the development and positioning of the muscle masses during chick limb and thorax development - ------------------------------------------------------------------------------------------------------------------------------------ O'Keefe, Regis University of Rochester MTA 3/11/99 Small Moleucle: the role of BMPs in limb patterning signaling - ------------------------------------------------------------------------------------------------------------------------------------ Lee, Amy University of S. California MTA 3/12/92 Production: GRP78 producing CHO cell line - ------------------------------------------------------------------------------------------------------------------------------------
Page 18 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Wuthier, Roy University of S. Carolina MTA 7/18/91 Cartilage: effect of OP-1 on avian growth plate chondrocytes in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Andrews, Peter University of Sheffield MTA 2/24/93 Morphogens: cancer: role of OP-1 in the de-differentiation of human transformed cells - ------------------------------------------------------------------------------------------------------------------------------------ Nishimoto, S. Ken University of Tennessee MTA 11/11/92 Morphogens: effects of OP-1 on the regulation of MGP synthesis in chondrosarcoma, chondrocytes, osteoblasts and kidney cells - ------------------------------------------------------------------------------------------------------------------------------------ Raghow, Rajendra University of Tennessee MTA 3/15/91 Renal: effect of OP-1 and BMP-2A on type I collagen gene expression in synovial, dermal & pulmonary mesenchymal cells in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Abboud, Hanna University of Texas MTA 11/20/94 Renal: role of OP-1 in kidney function - ------------------------------------------------------------------------------------------------------------------------------------ D'Souza, Rena University of Texas MTA 3/15/94 Morphogens: recombinant OP-1, monoclonal and polyclonal antibodies, cDNA probes to hard tissue repair - ------------------------------------------------------------------------------------------------------------------------------------ Olson, Merle (cbm University of Texas MTA 7/8/96 Renal: role of OP-1 in kidney refusd) - ------------------------------------------------------------------------------------------------------------------------------------ Talpaz, Moshe University of Texas MTA 5/3/93 Cancer: de-differentiation of transformed cells - ------------------------------------------------------------------------------------------------------------------------------------ Venkatachalam, M. A. University of Texas MTA 1/6/97 Small Molecule: expression of pax-2 - ------------------------------------------------------------------------------------------------------------------------------------ Yoneda, Toshiyuki University of Texas MTA 10/24/95 Morphogens; Cancer: role of OP-1 on cancer metastasis - ------------------------------------------------------------------------------------------------------------------------------------ Jester, James University of Texas MTA 7/8/99 Morphogens: Role of morphogens on corneal keratocyte Southwestern Medical Center differentiation and growth in in vitro models of corneal wound healing - ------------------------------------------------------------------------------------------------------------------------------------ Karsenty, Gerard University of Texas, MD MTA 10/26/94 Morphogens: BMP's in development Anderson Cancer Center - ------------------------------------------------------------------------------------------------------------------------------------ Nagarajan, Lalitha University of Texas, MD MTA 12/8/98 Small Molecule: Smad5 response to BMPs Anderson Cancer Center - ------------------------------------------------------------------------------------------------------------------------------------ Noji, Sumihare University of Tokushima MTA 10/18/95 Morphogens: function of OP-1 in limb bud formation, role of shh - ------------------------------------------------------------------------------------------------------------------------------------ Asashima, Makoto University of Tokyo MTA 11/27/97 Renal: tissue differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Kurabayashi, Masahiko University of Tokyo MTA 3/3/97 Morphogens: Cardiovascular - ------------------------------------------------------------------------------------------------------------------------------------ Yamashita, Hidetoshi University of Tokyo MTA 11/25/94 Morphogens; Ocular: effects of OP-1 on ocular tissue - ------------------------------------------------------------------------------------------------------------------------------------ Sodek, Jaro University of Toronto MTA 11/13/92 Osteoporosis: in vivo induction of bone formation - ------------------------------------------------------------------------------------------------------------------------------------
Page 19 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ EFFECTIVE DATE OF PRINCIPAL TYPE OF ORIGINAL INVESTIGATOR INSTITUTE AGREEMENT AGREEMENT FIELD OF AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Sodek, Jaro University of Toronto MTA 10/15/98 Osteoporosis: in vivo induction of bone formation - amendment - ------------------------------------------------------------------------------------------------------------------------------------ Harkonen, Pirkko University of Turku MTA 11/23/93 Morphogens; Cancer: effects and expression of OP-1 in human breast and prostate cancer cell lines - ------------------------------------------------------------------------------------------------------------------------------------ Rao, Mahendra University of Utah Medical MTA 5/12/99 Neuro: stem cell differentiation in the nervous system Center - ------------------------------------------------------------------------------------------------------------------------------------ Erlacher, Ludwig University of Vienna MTA 5/5/98 Cartilage: Postnatal human articular chondrocytes & other in vitro cell-based assays - ------------------------------------------------------------------------------------------------------------------------------------ Balian, Gary University of Virginia MTA 3/13/91 Osteoporosis: effect of OP-1 on clonal bone marrow stromal cell lines - ------------------------------------------------------------------------------------------------------------------------------------ Banker, Gary University of Virginia MTA 8/18/95 Neuro: role of OP-1 on Dendritic outgrowth - ------------------------------------------------------------------------------------------------------------------------------------ Phillips, Aled University of Wales College of MTA 1/2/00 Renal: studies on renal mechanism of action Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Hauschka, Stephen University of Washington MTA 7/28/93 Morphogens: role of OP-1 in muscle differentiation and regeneration - ------------------------------------------------------------------------------------------------------------------------------------ Reh, T.A. University of Washington MTA 11/19/98 Morphogens; Ocular: role of BMPs in auditory function - ------------------------------------------------------------------------------------------------------------------------------------ Reh, T.A. University of Washington MTA 7/23/97 Morphogens; Ocular: role of BMP's in formation of vertebrate eye during embryonic development - ------------------------------------------------------------------------------------------------------------------------------------ Stone, Jennifer University of Washington MTA 2/25/98 Morphogens; Auditory: OP-1 in regeneration of sensory tissues in the ear - ------------------------------------------------------------------------------------------------------------------------------------ Stone, Jennifer University of Washington MTA 5/25/99 Morphogens; Auditory: OP-1 in regeneration of sensory tissues in the ear (amended to expand Sample) - ------------------------------------------------------------------------------------------------------------------------------------ Thomas, Regi University of Washington MTA 2/10/98 Morphogens; Cancer: Role of OP-1 in prostate cancer - ------------------------------------------------------------------------------------------------------------------------------------ D'Souza, Sudhir University of Western Ontario MTA 4/7/00 Renal: To examine the role of BMP-7 in an in vitro model of proximal tubule injury - ------------------------------------------------------------------------------------------------------------------------------------ Hoffmann, Michael University of Wisconsin MTA 1/17/94 Morphogens: role of dpp/BMP family in Drosophila development - ------------------------------------------------------------------------------------------------------------------------------------ Baas, Peter University of Wisconsin, MTA 7/26/96 Madison School of Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Fallon, John University of Wisconsin-Madison MTA 4/14/99 Morphogens: the role of BMPs in the pattern formation - ------------------------------------------------------------------------------------------------------------------------------------ Ripamonti, Ugo University of Witwatersrand MTA 7/22/94 Stryker: craniofacial reconstruction - ------------------------------------------------------------------------------------------------------------------------------------ Vukicevic, Slobodan University of Zagreb MTA 2/5/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: Role of BMP's in the regulation of bone mass - ------------------------------------------------------------------------------------------------------------------------------------
Page 20 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Vukicevic, Slobodan University of Zagreb MTA 7/22/91 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: Localization of OP-1 and related BMPs on human fetal sections and the induction of second messengers in chondrocytes and osteoblasts in vitro - ------------------------------------------------------------------------------------------------------------------------------------ Vukicevic, Slobodan University of Zagreb MTA 4/20/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: Role of BMP-3 in inductin of mesonephric mesenchyme and the development of fetal lungs - ------------------------------------------------------------------------------------------------------------------------------------ Vukicevic, Slobodan University of Zagreb MTA 7/14/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: Role of BMP-6 in kidney development and repair - ------------------------------------------------------------------------------------------------------------------------------------ Vukicevic, Slobodan University of Zagreb MTA 7/14/98 Renal/Stryker/Cartilage/Osteoporosis/Morphogens: The role of morphogens and growth factors in the prevention/repair or gastro-intestinal disorders - ------------------------------------------------------------------------------------------------------------------------------------ Mohler, Hanns University of Zurich/ MTA 8/15/98 Neuro: to the role of OP-1 in enhancing the Institute of Pharmacology regenerative plasticity of epileptogenic tissue in vivo - ------------------------------------------------------------------------------------------------------------------------------------ Wong, Sui-Lam University Technologies MTA 9/14/92 Morphogens: WB600 strain; THEIRS International Inc. - ------------------------------------------------------------------------------------------------------------------------------------ Ebendal, Ted Uppsala Universitet MTA 12/9/96 Neuro: neuro/ocular: role of OP-1 in retinal neurons - ------------------------------------------------------------------------------------------------------------------------------------ Nimni, Marcel USC/Children's Hospital-LA MTA 12/9/93 Osteoporosis: mineralization and maturation process of resobable porous hydroxyapatite in rats; capability of DBM carrier to stimulate bone marrow derived cells to transform osteoblasts - ------------------------------------------------------------------------------------------------------------------------------------ Fu, Y.H. Florence V.A. Medical Center MTA 10/29/92 Cartilage: chondrocyte differentiation - ------------------------------------------------------------------------------------------------------------------------------------ Szabo, Sandor V.A. Medical Center MTA 2/3/95 Morphogens: Gastroinstestinal - ------------------------------------------------------------------------------------------------------------------------------------ Conger, John V.A. Medical Center (MTA/CA), Denver MTA 5/22/96 Renal: Effects of OP-1 in Acute Renal Failure Research Institute (SRA) - ------------------------------------------------------------------------------------------------------------------------------------ Frantz, Frazier VA Commonwealth University MTA 5/31/91 Morphogens: role of OP-1 in fetal healing - ------------------------------------------------------------------------------------------------------------------------------------ Hogan, Brigid Vanderbilt University MTA 10/30/90 Morphogens: embryogenesis - ------------------------------------------------------------------------------------------------------------------------------------ Pang, Roy Verax Corp MTA 2/22/93 Osteoporosis: study the effect of OP-1 & other growth factors on bone marrow culture - ------------------------------------------------------------------------------------------------------------------------------------ Wang, Tongwen Virginia Mason Research Center MTA 7/28/00 - ------------------------------------------------------------------------------------------------------------------------------------ Charness, Michael W. Roxbury VA Medical Center MTA 8/31/92 Neuro: NCAM expression - ------------------------------------------------------------------------------------------------------------------------------------
Page 21 of 25 SCHEDULE F Research and Development Agreements
- ----------------------------------------------------------------------------------------------------------------------------------- PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ----------------------------------------------------------------------------------------------------------------------------------- Perides, George W. Roxbury VA Medical Center MTA 6/30/92 Neuro: NCAM regulation by BMPs - ------------------------------------------------------------------------------------------------------------------------------------ Khouri, Roger WA University School MTA 9/25/92 Cartilage: repair of bone and cartilage of Medicine - ------------------------------------------------------------------------------------------------------------------------------------ Weeks, Paul WA University School of Medicine MTA 12/21/90 Cartilage: effect of growth factors on rate & quality of tendon healing in vivo - ------------------------------------------------------------------------------------------------------------------------------------ Liapis, Helen Washington University School MTA 3/3/00 Renal: The role of BMP-7 in animal models of of Medicine obstructive nephropathy in the newborn. - ------------------------------------------------------------------------------------------------------------------------------------ Jaenisch, Rudolf Whitehead Institute MTA 2/15/94 Renal: organ cultures - ------------------------------------------------------------------------------------------------------------------------------------ Kreidberg, Jordan Whitehead Institute MTA 2/15/94 Renal: organ cultures - ------------------------------------------------------------------------------------------------------------------------------------ Andrews, Peter Wistar Institute MTA 1/8/91 Morphogens; Cancer: carcinoma cells - ------------------------------------------------------------------------------------------------------------------------------------ Levine, Elliot Wistar Institute MTA 5/21/98 Osteoporosis: Matrix formation and osteogenesis with regards to osteoporosis in cultured human cells - ------------------------------------------------------------------------------------------------------------------------------------ Levine, Elliot Wistar Institute MTA 8/6/98 Osteoporosis: Matrix formation and osteogenesis with regards to osteoporosis in cultured human cells - ------------------------------------------------------------------------------------------------------------------------------------ Lewis, Alan Wyeth-Ayerst MTA 6/11/91 Morphogens: animal models - ------------------------------------------------------------------------------------------------------------------------------------ Baron, Roland Yale University MTA 9/10/90 Osteoporosis: effect of OP-1 on osteoclast-mediated bone resorption - ------------------------------------------------------------------------------------------------------------------------------------ Vignery, Agnes Yale University MTA 11/4/92 Morphogens: T-cell proliferation assays - ------------------------------------------------------------------------------------------------------------------------------------ - ------------------------------------------------------------------------------------------------------------------------------------ SPONSORED RESEARCH AGREEMENTS - ----------------------------------------------------------------------------------------------------------------------------------- Barnes Jewish Keith Hruska Research 5/8/98 The Role of OP-1 in Urinary Obstruction Models in Rat Hospital Agreement + Amendments - ------------------------------------------------------------------------------------------------------------------------------------ Beth Israel Raghu Kalluri Research 2/20/98 The Role of OP-1 in Rat Kidney Fibrosis Model Deaconess Agreement - ------------------------------------------------------------------------------------------------------------------------------------ Beth Israel Raghu Kalluri Research 1/5/00 The role of BMP-7 in alpha 3 (type IV collagen) KO Deaconess Agreement mice - ------------------------------------------------------------------------------------------------------------------------------------ Beth Israel Vikas Suthatme Research 1/1/97 Evaluation of a gene therapy based approach for Deaconess Agreement delivery of OP-1 and related genes in the area of chronic renal disease/gene delivery of OP-1 - ------------------------------------------------------------------------------------------------------------------------------------ Beth Israel Larry Suva Research 3/16/94 Characterization of the CBFA1 Gene Promoter Deaconess Agreement + Amendment - ------------------------------------------------------------------------------------------------------------------------------------
Page 22 of 25 SCHEDULE F Research and Development Agreements
- ----------------------------------------------------------------------------------------------------------------------------------- PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ----------------------------------------------------------------------------------------------------------------------------------- Boston Biomedical Walter F. Stafford Research 5/5/97 Efforts to Characterize the Physical State of Research Institute Agreement OP-1 in Solution: Effects of pH, Protein, Buffer Components - ----------------------------------------------------------------------------------------------------------------------------------- Brandeis University William D. Carlson Research and 10/1/90 OP-1 Dimer Structure License Agreement - ----------------------------------------------------------------------------------------------------------------------------------- Brandeis University William D. Carlson Research 12/20/95 OP-1 3D structures used in drug design for Agreement bone disorders - ----------------------------------------------------------------------------------------------------------------------------------- Harvard College Claire Doerschuk Research 9/15/98 OP-1 and its therapeutic potential in Agreement Bleomycin-Induced Lung Injury - ----------------------------------------------------------------------------------------------------------------------------------- Harvard College Malcolm Whitman Research 11/15/98 Identifying Genomic Targets for BMP and Agreement + Smad1 Signals Amendments - ----------------------------------------------------------------------------------------------------------------------------------- Indiana University Bruce Molitoris Research 6/1/99 In vitro studies concerning the mechanism of Agreement morphogen action in the kidney - ----------------------------------------------------------------------------------------------------------------------------------- Johns Hopkins David Blake Research 5/2/94 Metabolic Fate of Systemic OP-1: Binding and University Agreement Sequestration Administration - ----------------------------------------------------------------------------------------------------------------------------------- Loma Linda Univrsity David J. Baylink Research 11/29/93 Effects of OP-1 in ischemia Agreement - ----------------------------------------------------------------------------------------------------------------------------------- Ludwig Institute for Dr. Kohei Miyazono Research 6/1/97 Type I receptors ALK-1, ALK-2, ALK-3 and ALK-6 Cancer Agreement antibodies with OP-1 for drug development or Research/Japanese discovery Foundation of Cancer/CBMI - ----------------------------------------------------------------------------------------------------------------------------------- Massachusetts Seth Finklestein Research 9/1/93 The Effects of OP-1 in ischemia General Hospital Agreement - ----------------------------------------------------------------------------------------------------------------------------------- Massachusetts Dr. Joseph V. Bonventre Research 8/1/95 OP-1 in recovery from Acute Renal Failure General Hospital Agreement - ----------------------------------------------------------------------------------------------------------------------------------- Massachusetts Robert H. Brown Research 12/15/98 OP-1 as a candidate therapeutic in ALS mice General Hospital Agreement - ----------------------------------------------------------------------------------------------------------------------------------- Miami Children's Ana Paredes Research 2/25/98 Effect of mOP-1: Time course of disease Hospital Agreement progression in the rat remnant kidney model - ----------------------------------------------------------------------------------------------------------------------------------- Sierra Biomedical Contract Research 1/18/99 Non-human primate toxicology studies - -----------------------------------------------------------------------------------------------------------------------------------
Page 23 of 25 SCHEDULE F Research and Development Agreements
- ----------------------------------------------------------------------------------------------------------------------------------- PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ----------------------------------------------------------------------------------------------------------------------------------- The University of R. Bruce Rutherford Research 4/15/92 OP-1 to induce secondary dentin formation Connecticut Health Agreement Center - ----------------------------------------------------------------------------------------------------------------------------------- University of Miami Ana Paredes Research 4/1/96 Effect of rbOsteogenic Protein-1 Agreement - ----------------------------------------------------------------------------------------------------------------------------------- University of Miami W. Dalton Dietrich Research 9/12/97 Effects of OP-1 Administration following Agreement severe traumatic brain injury in rats - ----------------------------------------------------------------------------------------------------------------------------------- University of Miami W. Dalton Dietrich Research 4/27/98 Effects of OP-1 Administration following Agreement middle cerebral artery occlusion in rats - ----------------------------------------------------------------------------------------------------------------------------------- University of Miami W. Dalton Dietrich Research 9/4/98 Role of BMPs in neuronal development Agreement - ----------------------------------------------------------------------------------------------------------------------------------- University of NY at Dennis Higgins Research 4/1/98 OP-1 on dendritic growth in vivo,OP-1 Buffalo, SUNY Agreement transported by neurons in vivo, OP-1 mediates neurotrophi interactions in tissue culture - ----------------------------------------------------------------------------------------------------------------------------------- University of NY at Dennis Higgins Amendment to 9/11/98 OP-1 on dendritic growth in vivo,OP-1 transported Buffalo, SUNY Research by neurons in vivo, OP-1 mediates neurotrophi Agreement dated interactions in tissue culture April 1, 1998 - ----------------------------------------------------------------------------------------------------------------------------------- University of NY at Dennis Higgins Amendment to OP-1 on dendritic growth in vivo,OP-1 transported by Buffalo, SUNY Research neurons in vivo, OP-1 mediates neurotrophi interactions Agreement dated in tissue culture April 1, 1998 and September 11,1998 - ----------------------------------------------------------------------------------------------------------------------------------- University of F. Michael Hoffman Research 4/1/94 Structure-function Analysis of BMPs Wisconsin-Madison Agreement Medical School - ----------------------------------------------------------------------------------------------------------------------------------- Uppsala University Ted Ebendal Collaboration 12/20/96 OP-1 effects in the nervous system Agreement - ----------------------------------------------------------------------------------------------------------------------------------- University of Thomas Reh Research 9/21/98 Role of BMPs in delaying or rescuing rod photoreceptors Washington Agreement in animal models of retinal degenerative diseases - ----------------------------------------------------------------------------------------------------------------------------------- Washington Ted Ebendal Research 1/15/00 BMP-7 on the progression of renal disease in a mouse University Agreement model of Alport syndrome - -----------------------------------------------------------------------------------------------------------------------------------
SBIR Grants Page 24 of 25 SCHEDULE F Research and Development Agreements
- ------------------------------------------------------------------------------------------------------------------------------------ PRINCIPAL INSTITUTE TYPE OF EFFECTIVE FIELD OF AGREEMENT INVESTIGATOR AGREEMENT DATE OF ORIGINAL AGREEMENT - ------------------------------------------------------------------------------------------------------------------------------------ Creative Biomolecules Dattatreyamurty Bosukonda SBIR Grant 1 R43 AR44140-01 12/12/96 OP-1 3D Structure Used in Drug Design for Bone Disorders - ------------------------------------------------------------------------------------------------------------------------------------ Creative Biomolecules Paul L. Kaplan SBIR Grant 1 R43 NS37970-01 8/1/98 OP-1 Treatment for Parkinson's Disease - ------------------------------------------------------------------------------------------------------------------------------------
Page 25 of 25 SCHEDULE G Third Party Agreements Company Date of Agreement Stryker Corporation Master Restructuring Agreement October 15, 1998 Creative Irrevocable License Agreement November 20, 1998 Stryker Irrevocable License Agreement November 20, 1998 First Amendment to Master Restructuring Agreement November 2, 2001 First Amendment to Stryker License Agreement November 2, 2001 First Amendment to Creative License Agreement November 2, 2001 Second Amendment to Master Restructuring Agreement October 1, 2002 Assignment October 1, 2002 Genetics Institute / Stryker Corporation Cross-License Agreement July 15, 1996 Biogen Corporation Research Collaboration and License Agreement December 9, 1996 Amendment Agreement December 30, 1998 Ludwig Institute for Cancer Research Agreement June 1, 1997 34