SPECIFIC ASSAY FOR FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS

THIS PROJECT WILL DEVELOP A HIGHLY SPECIFIC AND RAPID ASSAY FOR DETECTION AND QUANTITATION OF FIBRINOGEN AND FIBRIN DEGRADATION PRODUCTS IN PLASMA TO AID IN THE EFFECTIVE DIAGNOSIS OF THROMBOSIS AND MONITOR THROMBOLYTIC THERAPY BY IDENTIFICATION OF THE PRODUCTS OF THROMBOLYSIS. THIS IMMUNOASSAY WILL BE BASED UPON A UNIQUE EPITOPE WITHIN THE DEGRADATION PRODUCTS, FG-DNEO, THAT IS EXPRESSED BY NEITHER FIBRINOGEN NOR FIBRIN. THE CHARACTERISTICS OF THIS CLEAVAGE-ASSOCIATED NEOANTIGEN PERMIT ACCURATE DETECTION AND A PRECISE QUANTITATION OF DEGRADATION PRODUCTS ON A MOLAR BASIS EVEN IN THE PRESENCE OF PLASMA FIBRINOGEN. AS SUCH, AN FG-DNEO IMMUNOASSAY OFFERS SUBSTANTIAL ADVANTAGES OVER ALL EXISTING ASSAYS FOR FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS BECAUSE IT IS DEGRADATION-SPECIFIC. IN PHASE I, MONOCLONAL ANTIBODIES WITH FG-DNEO SPECIFICITY WILL BE DEVELOPED AND SELECTED BY TWO DISTINCT APPROACHES. ONE APPROACH IS PROPRIETARY AND ENTAILS IMMUNIZATION WITH A SYNTHETIC PEPTIDE PREDICTED TO CONTAIN THE FG-DNEO EPITOPE. IN PHASE II, SELECTED MONOCLONAL ANTIBODIES WILL BE EVALUATED FOR GREATEST EFFICACY IN A CLINICAL ASSAY FOR FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS. A VERY RAPID FG-DNEO ASSAY WILL BE DEVELOPED FOR USE IN DIAGNOSIS OF THROMBOSIS/THROMBOLYSIS AND IN MONITORING EFFICACY AND SAFETY DURING ONGOING THROMBOLYTIC THERAPY.