Cooperative Research And Development Agreement

EXHIBIT 10.62 Confidential Treatment Requested Cooperative Research and
Development Agreement (CRADA 02177) Cooperative and Research Development Agreement for the
Development of Introgen Proprietary Vectors and
Recombinants for the Treatment of Cancer Steven A. Rosenberg, M.D., Ph.D.
Surgery Branch
Center for Cancer Research
National Cancer Institute Robert E. Sobol, M.D.
Introgen Therapeutics, Inc. Prepared by
Technology Transfer Branch
National Cancer Institute


PUBLIC HEALTH SERVICE COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
FOR INTRAMURAL-PHS CLINICAL RESEARCH This Agreement is based on the model Cooperative Research and Development Agreement (" CRADA" ) adopted by the U.S. Public Health Service (" PHS" ) Technology Transfer Policy Board for use by components of the National Institutes of Health (" NIH" ), the Centers for Disease Control and Prevention (" CDC" ), and the Food and Drug Administration (" FDA" ), which are agencies of the PHS within the Department of Health and Human Services (" HHS" ).This Cover Page identifies the Parties to this CRADA:The U.S. Department of Health and Human Services, as represented by
the National Cancer Institute
an Institute, Center, or Division (hereinafter referred to as the " ICD" ) of the
National Institutes of HealthandIntrogen Therapeutics, Inc.,
hereinafter referred to as the " Collaborator" ,
having offices at 2250 Holcombe Blvd. Houston, Texas 77030,
created and operating under the laws of Delaware. PHS ICT-CRADA Model Adopted 2005Page 1 of 20


COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
FOR INTRAMURAL-PHS CLINICAL RESEARCH Article 1. Introduction This CRADA between ICD and Collaborator will be effective when signed by the Parties, which are identified on both the Cover Page and the Signature Page (page 18). The official contacts for the Parties are identified on the Contacts Information Page (page 19). Publicly available information regarding this CRADA appears on the Summary Page (page 20). The research and development activities that will be undertaken by ICD and Collaborator in the course of this CRADA are detailed in the Research Plan, attached as Appendix A. The staffing, funding, and materials contributions of the Parties are set forth in Appendix B. Any changes to the model CRADA are set forth in Appendix C. Article 2. Definitions The terms listed in this Article will carry the meanings indicated throughout the CRADA. To the extent a definition of a term as provided in this Article is inconsistent with a corresponding definition in the applicable sections of either the United States Code (U.S.C.) or the Code of Federal Regulations (C.F.R.), the definition in the U.S.C. or C.F.R. will control." Adverse Drug Experience" or " ADE" means an Adverse Event associated with the use of the Test Article, that is, an event where there is a reasonable possibility that the Test Article may have caused the event (a relationship between the Test Article and the event cannot be ruled out), in accordance with the definitions of 21 C.F.R. Part 310, 305, or 312, or other applicable regulations." Adverse Event" or " AE" means any untoward medical occurrence in a Human Subject administered Test Article. An AE does not necessarily have a causal relationship with the Test Article, that is, it can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the Test Article, whether or not it is related to it. See FDA Good Clinical Practice Guideline (FDA GCP, from International Conference on Harmonisation (ICH) E6: " Good Clinical Practice: Consolidated Guidance, 62 Federal Register 25, 691 (1997))." Affiliate" means any corporation or other business entity controlled by, controlling, or under common control with Collaborator at any time during the term of the CRADA. For this purpose, " control" means direct or indirect beneficial ownership of at least fifty percent (50%) of the voting stock or at least fifty percent (50%) interest in the income of the corporation or other business entity." Annual Report" means the report of progress of an IND-associated investigation that ICD, as the IND Sponsor, must submit to the FDA within sixty (60) days of the anniversary of the effective date of the IND (pursuant to 21 C.F.R. a7 312.33)." Background Invention" means an Invention conceived and first actually reduced to practice before the Effective Date." Clinical Investigator" means, in accordance with 21 C.F.R. a7 312.3, an individual who actually conducts a clinical investigation, that is, who directs the administration or dispensation of Test Article to a subject, and who assumes responsibility for studying Human Subjects, for recording PHS ICT-CRADA Model Adopted 2005Page 2 of 20


and ensuring the integrity of research data, and for protecting the welfare and safety of Human Subjects." Collaborator Materials" means all tangible materials not first produced in the performance of this CRADA that are owned or controlled by Collaborator and used in the performance of the Research Plan. The term " Collaborator Materials" does not include " Test Article" (defined below)." Confidential Information" means confidential scientific, business, or financial information provided that the information does not include: (a) information that is publicly known or that is available from public sources; (b) information that has been made available by its owner to others without a confidentiality obligation; (c) information that is already known by the receiving Party, or information that is independently created or compiled by the receiving Party without reference to or use of the provided information; or (d) information that relates to potential hazards or cautionary warnings associated with the production, handling, or use of the subject matter of the Research Plan." Cooperative Research and Development Agreement" or " CRADA" means this Agreement, entered into pursuant to the Federal Technology Transfer Act of 1986, as amended (15 U.S.C. a7 3710a et seq .), and Executive Order 12591 of April 10, 1987." CRADA Data" means all recorded information first produced in the performance of the Research Plan." CRADA Materials" means all tangible materials first produced in the performance of the Research Plan other than CRADA Data." CRADA Principal Investigator(s)" or " CRADA PI(s)" means the person(s) designated by the Parties who will be responsible for the scientific and technical conduct of the Research Plan. The CRADA PI may also be a Clinical Investigator." CRADA Subject Invention" means any Invention of either or both Parties, conceived or first actually reduced to practice in the performance of the Research Plan." Drug Master File" or " DMF" is described in 21 C.F.R. Part 314.420. A DMF is a submission to the FDA that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs." Effective Date" means the date of the last signature of the Parties executing this Agreement." Government" means the Government of the United States of America." Human Subject" means, in accordance with the definition in 45 C.F.R. a7 46.102(f), a living individual about whom an investigator conducting research obtains: (a) data through intervention or interaction with the individual; or (b) Identifiable Private Information. PHS ICT-CRADA Model Adopted 2005Page 3 of 20


" ICD Materials" means all tangible materials not first produced in the performance of this CRADA that are owned or controlled by ICD and used in the performance of the Research Plan." IND" means an " Investigational New Drug Application" , filed in accordance with 21 C.F.R. Part 312 under which clinical investigation of an experimental drug or biologic (Test Article) is performed in Human Subjects in the United States or intended to support a United States licensing action." Identifiable Private Information" or " IPI" about a Human Subject means private information from which the identity of the subject is or may readily be ascertained. Regulations defining and governing this information include 45 C.F.R. Part 46 and 21 C.F.R. Part 50." Institutional Review Board" or " IRB" means, in accordance with 45 C.F.R. Part 46, 21 C.F.R. part 56, and other applicable regulations, an independent body comprising medical, scientific, and nonscientific members, whose responsibility is to ensure the protection of the rights, safety, and well-being of the Human Subjects involved in a study." Invention" means any invention or discovery that is or may be patentable or otherwise protected under Title 35 of the United States Code, or any novel variety of plant which is or may be protectable under the Plant Variety Protection Act, 7 U.S.C. a7a7 2321 et seq ." Investigator' s Brochure" means, in accordance with the definition in 21 C.F.R. a7 312.23(a)(5), a document containing information about the Test Article, including animal screening, preclinical toxicology, and detailed pharmaceutical data, including a description of possible risks and side effects to be anticipated on the basis of prior experience with the drug or related drugs, and precautions, such as additional monitoring, to be taken as part of the investigational use of the drug." Patent Application" means an application for patent protection for a CRADA Subject Invention with the United States Patent and Trademark Office (" U.S.P.T.O." ) or the corresponding patent issuing authority of another nation." Patent" means any issued United States patent, any international counterpart(s), and any corresponding grant(s) by a non-U.S. government in place of a patent." Placebo" means an inactive substance identical in appearance to the material being tested that is used to distinguish between drug action and suggestive effect of the material under study." Protocol" means the formal, detailed description of a study to be performed as provided for in the Research Plan. It describes the objective(s), design, methodology, statistical considerations, and organization of a trial. For the purposes of this CRADA, the term, Protocol, for clinical research involving Human Subjects, includes any and all associated documents, including informed consent forms, to be provided to Human Subjects and potential participants in the study." Raw Data" means the primary quantitative and empirical data first collected from experiments and clinical trials conducted within the scope of this CRADA." Research Plan" means the statement in Appendix A of the respective research and development commitments of the Parties. The Research Plan should describe the provisions for sponsoring the IND, clinical and safety monitoring, and data management. PHS ICT-CRADA Model Adopted 2005Page 4 of 20


" Sponsor" means, in accordance with the definition in 21 C.F.R. a7 312.3, an organization or individual who assumes legal responsibility for supervising or overseeing clinical trials with Test Articles, and is sometimes referred to as the IND holder." Steering Committee" means the research and development team whose composition and responsibilities with regard to the research performed under this CRADA are described in Appendix A." Summary Data" means any extract or summary of the Raw Data, generated by, or on behalf of, ICD or by, or on behalf of, Collaborator. Summary Data will not include extracts or summaries that incorporate IPI." Test Article" means, in accordance with 21 C.F.R. 50.3 (j), any drug (including a biological product), medical device, food additive, color additive, electronic product, or any other Article subject to regulation under the Federal Food, Drug, and Cosmetic Act that is intended for administration to humans or animals, including a drug or biologic as identified in the Research Plan and Appendix B, that is used within the scope of the Research Plan. The Test Article may also be referred to as Investigational Agent, Study Material, or Study Product. Article 3. Cooperative Research and Development 3.1 Performance of Research and Development . The research and development activities to be carried out under this CRADA will be performed solely by the Parties identified on the Cover Page, unless specifically stated elsewhere in the Agreement. The CRADA PIs will be responsible for coordinating the scientific and technical conduct of this project on behalf of their employers. Any Collaborator employees who will work at ICD facilities will be required to sign a Guest Researcher or Special Volunteer Agreement appropriately modified in view of the terms of this CRADA.3.2 Research Plan . The Parties recognize that the Research Plan describes the collaborative research and development activities they will undertake and that interim research goals set forth in the Research Plan are good faith guidelines. Should events occur that require modification of these goals, then by mutual agreement the Parties can modify them through an amendment, according to Paragraph 13.6.3.3 Use and Disposition of Collaborator Materials and ICD Materials . The Parties agree to use Collaborator Materials and ICD Materials only in accordance with the Research Plan and Protocol(s), not to transfer these materials to third parties except in accordance with the Research Plan and Protocol(s) or as approved by the owning or providing Party, and, upon expiration or termination of the CRADA, to dispose of these materials as directed by the owning or providing Party.3.4 Third Party Rights in Collaborator' s CRADA Subject Inventions . If Collaborator has received (or will receive) support of any kind from a third party in exchange for rights in any of Collaborator' s CRADA Subject Inventions, Collaborator agrees to ensure that its obligations to the third party are both consistent with Articles 6-8 and subordinate to Article 7 of this CRADA.3.5 Disclosures to ICD . Prior to execution of this CRADA, Collaborator agrees to disclose to ICD all instances in which outstanding royalties are due under a PHS license agreement and in which Collaborator had a PHS license terminated in accordance with 37 C.F.R. a7 404.9. These PHS ICT-CRADA Model Adopted 2005Page 5 of 20


disclosures will be treated as Confidential Information upon request by Collaborator in accordance with Paragraphs 2.4, 8.3, and 8.4.3.6 Clinical Investigator Responsibilities . The Clinical Investigator will be required to submit, or to arrange for submission of, each Protocol associated with this CRADA to the IRB. In addition to the Protocol all associated documents, including informational documents and advertisements, must be reviewed and approved by the IRB before starting the research. The research will be done in strict accordance with the Protocol(s) and no substantive changes in a finalized Protocol will be made unless mutually agreed upon by the Parties. Research will not commence (or will continue unchanged, if already in progress) until each substantive change to a Protocol, including those required by either the FDA or the IRB, has been integrated in a way acceptable to the Parties, submitted to the FDA and approved by the IRB.3.7 Investigational Applications .3.7.1 If an IND is required, ICD will be the IND Sponsor and will submit an IND. All Clinical Investigators must have completed registration documents on file (1572 forms).3.7.2 When ICD files the IND, Collaborator agrees to provide ICD background data and information necessary to support the IND. Collaborator further agrees to provide a letter of cross-reference to all pertinent regulatory filings sponsored by Collaborator. Collaborator' s employees will be reasonably available to respond to inquiries from the FDA regarding information and data contained in the Collaborator' s IND, DMF, other filings, or other information and data provided to ICD by the Collaborator pursuant to this Article 3.3.7.3 If Collaborator supplies Confidential Information to ICD in support of an IND filed by ICD, this information will be protected in accordance with the corresponding confidentiality provisions of Article 8.3.7.4 Collaborator may sponsor its own clinical trials and hold its own IND for studies performed outside the scope of this CRADA. These studies, however, should not adversely affect the ability to accomplish the goal of the Research Plan, for example, by competing for the same study population. All data from those clinical trials are proprietary to Collaborator for purposes of this CRADA.3.8 Test Article Information and Supply . Collaborator agrees to provide ICD without charge and on a schedule that will ensure adequate and timely performance of the research, a sufficient quantity of formulated and acceptably labeled, clinical-grade Test Article (and, as required by the Protocol(s), Placebo) to complete the clinical trial(s) agreed to and approved under this CRADA. Collaborator will provide a Certificate of Analysis to ICD for each lot of the Test Article provided.3.9 Test Article Delivery and Usage . Collaborator will ship the Test Article and, if required, Placebo to ICD in containers marked in accordance with 21 C.F.R. a7 312.6. ICD agrees that the Clinical Investigators will keep appropriate records and take reasonable steps to ensure that the Test Article is used in accordance with the Protocol(s) and applicable FDA regulations. In addition, ICD agrees that the Test Article (and all Confidential Information supplied by Collaborator relating to the Test Article) will be used solely for the conduct of the CRADA research and development activities. Furthermore, ICD agrees that no analysis or modification of the Test Article will be performed without Collaborator' s prior written consent. At the completion of the Research Plan, any unused quantity of Test Article will be returned to Collaborator or disposed as directed by Collaborator. Pharmacy contacts at ICD will be determined by ICD and communicated to Collaborator. PHS ICT-CRADA Model Adopted 2005Page 6 of 20


3.10 Monitoring . Subject to the restrictions in Article 8 concerning IPI, and with reasonable advance notice and at reasonable times, ICD will permit Collaborator or its designee(s) to monitor the conduct of the research, as well as to audit source documents containing Raw Data, to the extent necessary to verify compliance with FDA Good Clinical Practice (International Conference on Harmonisation (ICH) E6: A Good Clinical Practice: Consolidated Guidance; 62 Federal Register 25, 691 (1997)) and the Protocol(s).3.11 FDA Meetings/Communications . All meetings with the FDA concerning any clinical trial within the scope of the Research Plan will be discussed by Collaborator and ICD in advance. Each Party reserves the right to take part in setting the agenda for, to attend, and to participate in these meetings. ICD will provide Collaborator with copies of FDA meeting minutes, all transmittal letters for IND submissions, IND safety reports, formal questions and responses that have been submitted to the FDA, Annual Reports, and official FDA correspondence, pertaining either to the INDs under this CRADA or to the Clinical Investigators on Protocols performed in accordance with the Research Plan, except to the extent that those documents contain the proprietary information of a third party or dissemination is prohibited by law. Article 4. Reports 4.1 Interim Research and Development Reports . The CRADA PIs should exchange information regularly, in writing. This exchange may be accomplished through meeting minutes, detailed correspondence, circulation of draft manuscripts, Steering Committee reports, copies of Annual Reports and any other reports updating the progress of the CRADA research. However, the Parties must exchange updated Investigator' s Brochure, formulation and preclinical data, and toxicology findings, as they become available.4.2 Final Research and Development Reports . The Parties will exchange final reports of their results within [*] after the expiration or termination of this CRADA. These reports will set forth the technical progress made; any publications arising from the research; and the existence of invention disclosures of potential CRADA Subject Inventions and/or any corresponding Patent Applications.4.3 Fiscal Reports . If Collaborator has agreed to provide funding to ICD under this CRADA and upon the request of Collaborator, then concurrent with the exchange of final research and development reports according to Paragraph 4.2, ICD will submit to Collaborator a statement of all costs incurred by ICD for the CRADA. If the CRADA has been terminated, ICD will specify any costs incurred before the date of termination for which ICD has not received funds from Collaborator, as well as for all reasonable termination costs including the cost of returning Collaborator property or removal of abandoned Collaborator property, for which Collaborator will be responsible.4.4 Safety Reports . In accordance with FDA requirements ICD, as the IND Sponsor, will establish and maintain records and submit safety reports to the FDA, as required by 21 C.F.R. a7 312.32 and 21 C.F.R. 812.150(b)(1), or other applicable regulations. In the conduct of research under this CRADA, the Parties will comply with specific ICD guidelines and policies for reporting ADEs and AEs, as well as procedures specified in the Protocol(s). ICD must provide Collaborator with copies of all Safety Reports concurrently with their submission to the FDA, and with any other information affecting the safety of Human Subjects in research conducted under this CRADA. [*] Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portion. PHS ICT-CRADA Model Adopted 2005Page 7 of 20


4.5 Annual Reports . ICD will provide Collaborator a copy of the Annual Report concurrently with the submission of the Annual Report to the FDA. Annual Reports will be kept confidential in accordance with Article 8. Article 5. Staffing, Financial, and Materials Obligations 5.1 ICD and Collaborator Contributions . The contributions of any staff, funds, materials, and equipment by the Parties are set forth in Appendix B. The Federal Technology Transfer Act of 1986, 15 U.S.C. a7 3710a(d)(1) prohibits ICD from providing funds to Collaborator for any research and development activities under this CRADA.5.2 ICD Staffing . No ICD employees will devote 100% of their effort or time to the research and development activities under this CRADA. ICD will not use funds provided by Collaborator under this CRADA for ICD personnel to pay the salary of any permanent ICD employee. Although personnel hired by ICD using CRADA funds will focus principally on CRADA research and development activities, Collaborator acknowledges that these personnel may nonetheless make contributions to other research and development activities, and the activities will be outside the scope of this CRADA.5.3 Collaborator Funding . Collaborator acknowledges that Government funds received by Collaborator from an agency of the Department of Health and Human Services may not be used to fund ICD under this CRADA. If Collaborator has agreed to provide funds to ICD then the payment schedule appears in Appendix B and Collaborator will make payments according to that schedule. If Collaborator fails to make any scheduled payment, ICD will not be obligated to perform any of the research and development activities specified herein or to take any other action required by this CRADA until the funds are received. ICD will use these funds exclusively for the purposes of this CRADA. Each Party will maintain separate and distinct current accounts, records, and other evidence supporting its financial obligations under this CRADA and, upon written request, will provide the other Party a Fiscal Report according to Paragr ...