This Clinical Trial Agreement ("Agreement") is entered into as of the 28 day of August, 1996 (the "Effective Date"), by and among Aastrom Biosciences, Inc. ("Aastrom"), located at 24 Frank Lloyd Wright Dr., Lobby L, Ann Arbor, MI48105, and Loyola University Medical Center Cancer Center (the "Institution"), located at 2160 South First Avenue, Maywood, IL 60153. Definitions shall have the meaning as set forth in Exhibit A.

RECITALS

WHEREAS, Aastrom is the developer, manufacturer and/or licensee of medical devices and materials, such as a Cell Production System ("CPS") device and related materials and device, which have potential medical application for use in subjects care and research;

WHEREAS, Aastrom desires to conduct a human clinical trial ("Study") of the CPS in subjects in accordance with a protocol entitled "A Pilot Trial of Autologous Transplantation For Patients With Advanced Breast Cancer Using Marrow Cells Expanded Ex Vivo"("Protocol") which is incorporated herein by reference as Exhibit B attached hereto;

WHEREAS, the Institution has research, clinical and medical facilities, technical capabilities and expertise in order to conduct the Study in accordance with the Protocol;

WHEREAS, the Study contemplated by this Agreement is of mutual interest and benefit to the Institution and to Aastrom such that the parties hereto desire to have the Institution conduct the Study under the qualified direction of Patrick J. Stiff, M.D. (the "Principal Investigator"); and

WHEREAS, Aastrom and the Institution agree to conduct the Study in accordance with the terms and conditions hereinafter set forth.

AGREEMENT

I. CLINICAL TRIAL DESCRIPTION

The Institution agrees to undertake and complete the Study described in the Protocol (Exhibit B) in compliance with all applicable laws, rules and regulations relating to the Study, including without limitation, all laws, rules and regulations concerning or promulgated by the Food and Drug Administration ("FDA").

Aastrom agrees to provide the Institution the laboratory and clinical equipment listed in the Schedule of Laboratory and Clinical Equipment on Exhibit C which are reasonably necessary for the Institution to conduct the Study. Aastrom shall retain title to all such equipment which shall promptly be returned to Aastrom upon request by Aastrom.

II. FUNDING

Aastrom shall provide payments to the Institution in accordance with the terms contained in the Clinical Trial Budget (Exhibit D) and the Schedule of Clinical Trial Milestone Payments (Exhibit D) incorporated herein.

III. CONDUCT OF STUDY

A. Facilities

The Study shall be conducted only at the following locations: Loyola University Medical Center Cancer Center, 2160 South First Avenue, Maywood, IL 60153. The CPS and other Study materials may not be transferred to any other location or to any third party without the prior written consent of Aastrom.

B. Investigator

The Institution agrees that the Study will be conducted under the direction of the Principal Investigator in accordance with the Protocol and the Investigator Agreement (see Section 13.0 of the Clinical Protocol) and incorporated herein by reference. The Principal Investigator may, subject to the prior written consent of Aastrom, designate a clinical coordinator and one or more subinvestigators to assist in conducting the Study. The Institution acknowledges that the Principal Investigator and subinvestigators have each executed an Investigator Agreement, copies of which are included in Exhibit E. In the event that additional subinvestigators are added to the Study, such subinvestigators must execute and deliver an Investigator Agreement which shall be deemed incorporated by reference into this Agreement. In the event the Principal Investigator can no longer function in such capacity, then Aastrom and the Institution shall attempt to agree on a replacement. If a mutually acceptable replacement cannot be agreed upon, this Agreement and the Study at the Institution shall terminate. The Institution agrees that it will use its best efforts to recruit qualified subjects for enrollment in the Study consistent with the guidelines contained in the Protocol and the best interest of the subject; however, no subjects shall be enrolled in the Study if they are currently enrolled in another investigational study without the prior written consent of Aastrom.

C. Compliance with Protocol

Any changes to the Protocol may only be made with the prior written agreement of Aastrom; provided that during the Study, if the Principal Investigator feels that it is necessary to deviate from the ProtoColin order to protect the life or physical well-being of a Study subject before written approval can be obtained, he/she may do so in accordance with the procedures detailed in the Protocol.

D. Institutional Review Board Approval and Informed Consent

The Institution will obtain: (i) the approval of the governing Institutional Review Board ("IRB") prior to initiating the Study and thereafter as required by applicable laws, rules and regulations; and (ii) prior written informed consent of all subjects and/or their legal guardians in a form that is substantially the same as provided in the Protocol and satisfactory to both the governing IRB and Aastrom and in compliance with applicable laws, rules and regulations.

E. Adverse Events

The Institution shall immediately notify Aastrom (Thomas E. Muller, Ph.D., Vice President Regulatory Affairs at 313/930-5555 and/or by fax at 313/930-5520) of any unanticipated adverse effect, whether ascribed to the investigational device or not, in accordance with the instructions provided in the Protocol.

IV. STUDY MONITORING AND ACCESS TO FACILITIES

Aastrom's designated representatives and/or authorized representatives of regulatory agencies may, at all reasonable times, visit the Institution in order to: (i) determine the adequacy of the facilities, (ii) validate case reports against original data in the subject medical records and the files of the Principal Investigator, and (iii) monitor the conduct of the Study to determine whether the Study is being conducted in compliance with the Protocol and all applicable laws, rules and regulations. The Institution agrees to obtain any required subject release (s) to allow Aastrom's designated representatives, and/or authorized representatives of regulatory agencies, to conduct such review prior to enrolling each subject in the Study.

V. REPORTS

The Institution agrees to have the Principal Investigator submit reports to Aastrom and the reviewing IRB in accordance with the Protocol and all applicable laws, rule and regulations.

VI. PROPRIETARY RIGHTS

A. Data and Materials

The Institution understands and agrees that the underlying rights to the CPS and other intellectual property and materials which are the subject of the Protocol belong to Aastrom. The parties agree that the Institution shall retain control over the CPS and Study materials, and further agree not to allow access to, disclose the existence or nature of, or transfer the CPS or Study materials to third parties without advance written approval of Aastrom. Aastrom reserves the right to distribute the CPS and Study materials to others and to use them for its own purposes. Title to the CPS andStudy materials shall remain with Aastrom. Further, the Institution agrees that data and materials derived as a direct result of the Study described in the Protocol (hereinafter referred to as "Clinical Trial Information") whether generated by the Institution, the Principal Investigator, and/or their agents or employees, either solely or jointly with others, is the property of Aastrom; provided that the Institution and the Principal Investigator may utilize the Clinical Trial Information in furtherance of academic publications authorized by this Agreement and for subject care purposes.

B. Patent Ownership and Related Matters

The Institution agrees that the Study results and any inventions or discoveries by the Institution, the Principal Investigator or their agents or employees during the Study that are modifications, improvements or new uses applicable to the CPS or that are a direct result of the performance of the Study in accordance with the detailed testing Protocol provided by Aastrom to Institution and which are dependent on, or relate to, the Study, the claims of Aastrom's patentable inventions, the use of the cells processed through the CPS or Aastrom's Confidential Information shall be the property of Aastrom. Any invention arising out of the work performed under this Study solely by the Institution and not covered in the previous sentence shall be the exclusive property of the Institution (the "Institution Invention") and shall not be considered a part of Aastrom's Confidential Information. The Institution shall promptly disclose each such Institution Invention and the terms under which the Institution would be prepared to license it. Aastrom shall have a right of first refusal to exclusively develop, license and commercialize such Institution Invention. Aastrom shall have sixty (60) days after receipt of such disclosure to exercise its right of first refusal, and if so exercised, the parties shall thereafter negotiate a mutually acceptable licensing agreement in good faith. If the Institution at any time offers such Institution Invention on terms different than those disclosed to Aastrom, the Institution shall offer such Institution Invention to Aastrom on such different terms in accordance with the first right refusal herein. The Institution and Principal Investigator shall not obtain, or attempt to obtain, patent coverage on the CPS or its.......

详文见附件