RESEARCH AGREEMENTResearch and Development Agreement |
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EXHIBIT 10.4
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UNITED STATES DEPARTMENT OF AGRICULTURE RESEARCH AGREEMENT |
TYPE OF RESEARCH AGREEMENT Cooperative Research and Development Agreement |
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AGREEMENT NO. 58-3K95-3-0967 |
TYPE OF ACTION Amendment No. 3 |
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AGENCY (Name and Address) Agricultural Research Service 1400 Independence Avenue SW Washington, D.C. 20250-0302 |
PERIOD OF AGREEMENT 10/01/02 through 9/30/07 |
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FEDERAL OBLIGATION $ 0 |
CHANGE IN FEDERAL OBLIGATION |
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This Agreement is authorized by the Federal Technology Transfer Act, 15 USC 3710a, et seq., and is governed by its terms. |
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Items |
1 Descriptions |
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1. Technology Transfer Coordinator |
Harry D. Danforth |
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2. Cooperator |
Hepalife Technologies, Inc. Suite 216 - 1628 West 1 st Ave, Vancouver, BC, V6J 1G1 Tax ID # |
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3. Principal Investigator |
Harmel Rayat, Director |
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4. USDA Laboratory |
Growth Biology Laboratory 10300 Baltimore Ave. Beltsville, MD 20705-2350 |
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5. USDA Researcher (ADODR) |
Neil Talbott, Thomas Caperna |
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6. National Program Leader & Area |
First & Last Name of NPL |
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7. Accounting Code |
X91-1265-356 |
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8. Amount |
$807,828.00 (total for 5 years) |
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9. Finance Office |
Budget & Fiscal Office USDA-ARS-BA Bldg. 003, Room 306, BARC-West Beltsville, MD 20705-2350 |
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10. Cris No. |
1365-31000-087-01T |
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11. Title of Project |
OPTIMIZATION OF THE ARS-PICM-19 CELL LINE FOR AN IN VITRO MODEL OF PIG LIVER FUNCTION AND APPLICATION TO AN EXTRACORPOREAL LIVER ASSIST DEVICE |
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12. Log # |
22659 |
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This Agreement is amended, as follows: The duration of the Agreement is extended for three (3) years through September 30, 2007. ARS will receive a total of $807,828.00 in funds of which $153,600.00 has been paid. The Statement of Work and Clause 9 have been changed and are incorporated herein. The Title of Project has been changed. ALL OTHER TERMS AND CONDITIONS REMAIN THE SAME. |
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FOR THE UNITED STATES DEPARTEMENT OF AGRICULTURE |
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SIGNATURE /s/ Richard Brenner |
TYPED NAME RICHARD J. BRENNER Authorized Departmental Officer |
DATE May 19, 2004 |
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FOR THE COOPERATOR (Signature of person(s) authorized by the governing body of the COOPERATOR to incur contractual obligations) |
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SIGNATURE /s/ Harmel Rayat |
TYPED NAME AND TITLE HARMEL RAYAT |
DATE May 24, 2004 |
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Clause 9
9.1
HEPALIFE shall have the first option to prepare and prosecute patent or Plant Variety Protection Certificate applications, foreign and domestic, on Subject Inventions owned or co-owned by the U.S. Government, subject to the following conditions:
a.
All documents shall be submitted to ARS sufficiently in advance of filing to allow ARS a reasonable opportunity to review and make recommendations thereon;
b.
Copies of all correspondence from the U.S. Patent and Trademark Office or Plant Variety Protection Office and foreign equivalent offices shall be provided promptly to ARS;
c.
The following USDA personnel shall be given an associate power of attorney or be listed as an attorney of record:
Patent Advisor
Patent Attorney
Evelyn Rabin
John Fado
USDA-ARS-OTT
USDA-OGC Rm. 3311
5601 Sunnyside Avenue
South Agriculture Bldg.
Beltsville MD
Washington, D.C. 20250-1415
Registration Number
Registration No. 27876
Tel: 301-504-4781
Tel.: 202-720-2421
Fax: 301-504-5060
Fax: 202-720-8706
9.2
The act of preparing and/or filing documents, per se , shall not entitle HEPALIFE to any rights in such Inventions or the reimbursement of costs incident to patent prosecution.
9.3
ARS shall have the right at any time, at its sole discretion, concerning Inventions solely owned by the U.S. Government, to: (1) assume responsibility for prosecuting any such application; and (2) permit any application to become abandoned or issued patent/certificate to expire, subject to the provisions of any license agreement relating to the subject matter.
9.4
ARS agrees to provide HEPALIFE consultation and advice in the preparation, filing, and prosecution of patent or Plant Variety Protection Certificate applications on Subject Inventions.
STATEMENT OF WORK
A.
Introduction/Background
ARS has developed several in-vitro model systems to investigate various aspects of hepatic gene expression and metabolic regulation. These systems encompass both established cell lines and primary liver cell cultures. One stem-like cell line, derived from porcine epiblast (embryonic) tissue is the ARS PICM-19 cell line (ARS patent #5,532,156), has been partially characterized and is a non-transformed immortal cell line that possesses many characteristics similar to that of intact liver parenchymal cells. ARS interests would be greatly enhanced by further characterization and improvements in the culture technology that would ultimately result in the cell line not requiring feeder cell support and growth in a completely serum-free defined medium. These advancements would facilitate our understanding of regulatory events in pig liver gene/proteome expression and in regulation of nutrient metabolism. Further, it has already been demonstrated that the unique hepatic characteristics of the ARS-PICM-19 cell line would have potential application for use in the production of a rescue device for human patients in liver failure (ARS patent # 5,866,420; “Artificial Liver Device”, granted to ARS on 2/2/1999). To date, the cellular components of artificial liver devices that are being tested by other institutions are based on freshly isolated porcine hepatocytes, human transformed tumor cells, or poorly defined stem-like cells prepared from fresh human adult liver tissue. It is widely recognized that the greatest hindrance to the development of a completely functional artificial liver rescue device is the lack of an appropriate defined cell line that will provide the functions of an intact liver. The primary interest of Hepalife is to explore the possibility that the ARS PICM-19 cell line is indeed the most appropriate cell line to use in such a device.
B.
Objective
The overall objective of the work is to optimize the patented ARS-PICM-19 cell line as an in-vitro model of the pig liver. The first objective is to investigate and discover culture conditions for the ARS-PICM-19 cell line, or modifications of the ARS-PICM-19 cell line technology itself, that will optimize function, i.e., culture conditions or cell line modifications that will enable, as closely as possible, the reproduction of normal pig liver functions in an in-vitro environment. Directly related to the first objective will be the second and third objectives. The second objective is adapting and applying the optimized ARS-PICM-19 cell line technology to the development of an extracorporeal liver assist device as described in patent #5,866,420. The third objective is to use the ARS-PICM-19 cell line in the development of in






