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GENERATION OF PF4 POLYETHYLENE GLYCOL CONJUGATES

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 16431
Amount: $27,274.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1991
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
One Kendall Square, Building 7 00
Cambridge, MA 02139
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 Lai, Chee K
 Principal Investigator
 (617) 225-6000
Business Contact
 1 R43 CA55423-01
Phone: () -
Research Institution
N/A
Abstract

ANGIOGENESIS IS A COMPLEX PROCESS INVOLVING THE PROLIFERATION, MIGRATION, AND PRECISE THREE DIMENSIONAL ALIGNMENT OF ENDOTHELIAL CELLS. A WIDE RANGE OF DISEASE PROCESSES INCLUDING SOLID TUMOR GROWTH, DIABETIC RETINOPATHY, INFLAMMATORY ARTHRITIS, AND PSORIASIS ARE ASSOCIATED WITH ABERRANT ANGIOGENESIS. IF RELATIVELY NON-TOXIC AGENTS WERE AVAILABLE TO INHIBIT ANGIOGENESIS SPECIFICALLY; MANAGEMENT OF THESE "ANGIOGENIC DISEASES" COULD BE GREATLY IMPROVED. IT HAS BEEN SHOWN IN PREVIOUS INVESTIGATIONS THAT RECOMBINANT HUMAN PLATELET FACTOR FOUR (RPF4) INTERFERES WITH SEVERAL STEPS IN THE NEOVASCULARIZATION PROCESS AND INHIBITS ANGIOGENESIS IN VIVO. IF INJECTED DIRECTLY INTO SOLID TUMORS IN SEVERAL MURINE MODELS RPF4 INHIBITS TUMOR GROWTH, PROBABLY BY INHIBITING TUMOR NEOVASCULARIZATION. THE SHORT SERUM HALF-LIFE OF RPF4, HOWEVER, LIMITS ITS SYSTEMIC UTILITY. CONJUGATION OF SEVERAL THERAPEUTICALLY USEFUL PROTEINS TO POLYETHYLENE GLYCOL (PEG) HAVE BEEN SHOWN TO EXTEND THEIR SERUM HALF-LIVES WHILE MAINTAINING BIOLOGICAL ACTIVITY. IT IS ANTICIPATED THAT CONJUGATION OF RPF4 TO PEG WILL EXTEND THE CIRCULATION HALF-LIFE OF THIS PROTEIN AND MAY YIELD A USEFUL, SYSTEMICALLY ADMINISTERED ANGIOSTATIC AGENT.

* Information listed above is at the time of submission. *

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