Cleveland State University

University of Vermont and State Agricultural College

University of Vermont

Michael Kalafatis

Kenneth G Mann

Joseph Wiencek

Cornelis Van't Veer

Katherine Turner

Joesph Wiencek

During the process of coagulation, prothrombin is activated to α-thrombin by prothrombinase. Key residues in the structure of prothrombin allow for modulation of the activation of prothrombin. In certain embodiments, a recombinant prothrombin with at least one point mutation or deletion is provided.

Recombinant prothrombin analogues and uses thereof

Disclosed are methods and compositions for identifying and treating certain conditions and diseases. In certain instances, the general inventive concepts provide methods for determining rhTRAIL sensitivity of a sample and/or methods and compositions for inducing apoptosis to treat conditions and diseases with rhTRAIL.

Death receptors as markers for rhTRAIL-sensitivity

During the process of coagulation, prothrombin is activated to &#x3b1;-thrombin by prothrombinase. Key residues in the structure of prothrombin allow for modulation of the activation of prothrombin. In certain embodiments, a recombinant prothrombin with at least one point mutation or deletion is provided.

Peptides derived from amino acids 307 to 356 of the human blood coagulation factor Va are provided. Such peptides comprise: i) a length of between 3 and 50 amino acids, ii) a minimum of 3 contiguous amino acids from the 307&#x2013;356 heavy chain region of factor Va, excluding peptide segments comprising amino acids 311 to 325 and amino acids 321 to 335, iii) optional additional amino acids at one or both ends of the contiguous amino acids such that the entire peptide is at least 60% identical to a sequence within 307 to 356 of factor Va, and iv) have an ICof between 50 nM to 500 &#x3bc;M for inhibition of prothrombinase. The present invention also provides a pharmaceutical composition comprising one or more prothrombinase-inhibiting peptide segments. The present invention also provides administration of the pharmaceutical composition to human subjects for the purpose of preventing thrombotic disorders.

Thrombin generation inhibitors

Peptides derived from amino acids 307 to 356 of the human blood coagulation factor Va are provided. Such peptides comprise: i) a length of between 3 and 50 amino acids, ii) a minimum of 3 contiguous amino acids from the 307-356 heavy chain region of factor Va, excluding peptide segments comprising amino acids 311 to 325 and amino acids 321 to 335, iii) optional additional amino acids at one or both ends of the contiguous amino acids such that the entire peptide is at least 60% identical to a sequence within 307 to 356 of factor Va, and iv) have an IC of between 50 nM to 500 &mgr;M for inhibition of prothrombinase. The present invention also provides a pharmaceutical composition comprising one or more prothrombinase-inhibiting peptide segments. The present invention also provides administration of the pharmaceutical composition to human subjects for the purpose of preventing thrombotic disorders.

Persons having the Factor V,mutation and a lower than average plasma level of TFPI have been found to be at elevated risk of thrombosis. Prophylactic methods for reducing the risk of thrombosis employ the administration of TFPI to achieve higher levels in the plasma.

Thrombosis prophylaxis for factor Vleiden carriers

Persons having the Factor V.sup.LEIDEN mutation and a lower than average plasma level of TFPI have been found to be at elevated risk of thrombosis. Prophylactic methods for reducing the risk of thrombosis employ the administration of TFPI to achieve higher levels in the plasma.

Thrombosis prophylaxis for factor V.sup.LEIDEN carriers

The present invention is directed to immunochemical detection procedures, e.g., using both Western blotting and direct immunoassays, for fragments of Factor Va, which can thus be used; (a) in a predictive manner to evaluate the existence and/or extent of a thrombotic complication; (b) to monitor the efficacy of prophylaxis for a thrombotic condition; and (c) as a means to evaluate potential risk of hemorrhage during thrombolytic therapy.

Growing community of inventors

Shaker Heights, OH, United States of America

Michael Kalafatis