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Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44HL059705-02
Agency Tracking Number: HL059705
Amount: $0.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Solicitation Year: N/A
Award Year: 2002
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
YORK, PA 17404
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (717) 843-0300
Business Contact
Phone: (717) 843-0300
Research Institution

To prevent heparin-induced bleeding, protamine is used in nearly 2,000,000 cardiac/vascular operations to reverse the anticoagulant effects of heparin. Intravenous use of protamine, however, can cause life-threatening adverse reactions. In fact, the combined use of heparin and protamine was suggested as the major cause of morbidity and mortality for patients undergoing such surgeries. Although many attempts have been made, to date, protamine remains as the sole clinical heparin antidote; due to its unmatched reliability, efficacy, and low costs. A recent authoritative review by clinicians concluded that the ideal heparin-neutralizing agent should be a compound that provided all advantages and yet lacked anaphylactic potential of protamine. An explicit examination of the mechanism of heparin neutralization and protamine toxicity by us suggests that complete heparin neutralization may require only a small arginine-rich fragment in protamine, whereas the toxicity of protamine is attributed primarily to its polycationic and polymeric nature. Thus, a chain-shortened low molecular weight protamine (LMWP), if it can be derived from protamine to contain only the heparin-neutralizing domain, could be this ideal heparin- neutralizing agent. Further, this LMWP may also be devoid of antigenicity and immunogenicity; both are known to contribute significantly to protamine toxicity. The ultimate goal of this SBIR project is therefore to develop LMWP to be a non-toxic, wholesale protamine substitute. During the Phase I work, the feasibility of this approach was successfully demonstrated. In this Phase II application, the focus is to demonstrate the utility of the approach in aborting all patients, either diabetic or non-diabetic, with or without pre- development of anti-protamine antibodies in their system, from possible attack of protamine allergy. In Phase III, ISTN will team up with identified industrial partners to proceed FDA-approved clinical trials, standarization of the compound under GMP, and commercialization of the final LMWP products.

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

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