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Abstract

Grant Number:	1R43HL073491-01
PI Name:	SCHULMAN, HOWARD
PI Email:	hschulman@surromed.com
PI Title:
Project Title:	Prolonging Annexin Antithrombotic Activity

Abstract: DESCRIPTION (provided by applicant): There is need to develop an agent that can be used to prevent or treat arterial or venous thrombosis without increasing hemorrhage. The human placental anticoagulant protein annexin V inhibits coagulation by binding to phosphatidylserine on the outer surface of activated platelets in which phospholipid asymmetry is lost. Recombinant human annexin V decreases arterial and venous thrombosis in experimental animal models without increasing hemorrhage. However, annexin V (32 kDa) rapidly passes from the circulation into the urine limiting its usefulness as an anti-thromobic agent. The investigators propose to increase the molecular weight of annexin V by conjugation with polyethylene glycol. It is predicted that this modification will prolong the half-life of annexin V in the circulation and its anticoagulant activity, thereby producing a clinically useful anti-thrombotic agent. Pegylated annexin V may also attenuate reperfusion injury. The investigators' milestone for Phase I is development of a pegylated annexin with significantly prolonged serum half-life and which retains its intrinsic anticoagulant activity; clinical efficacy in thrombosis will be tested in a subsequent SBIR-Phase II proposal.

Thesaurus Terms:
annexin, anticoagulant, drug design /synthesis /production, molecular weight, recombinant protein, thrombosis
blood circulation, blood coagulation, chemical conjugate, hemorrhage, method development, pharmacokinetics, platelet, polyethylene glycol, protein binding, thromboplastin
laboratory mouse, laboratory rabbit, protein purification, prothrombin time

Institution:	SURROMED, INC.
	2375 GARCIA AVE
	MOUNTAIN VIEW, CA 940431104
Fiscal Year:	2003
Department:
Project Start:	29-SEP-2003
Project End:	31-AUG-2004
ICD:	NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG:	ZRG1

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