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US 6,207,419 B1Granted
Thrombin inhibitory agents and methods of using same
AssigneeThe University of North Carolina at Chapel Hill
InventorsFrank C. Church, Susannah J. Bauman
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AssigneeThe University of North Carolina at Chapel Hill
InventorsFrank C. Church, Susannah J. Bauman
Estimating the term…
The present invention describes heparin cofactor II mutants comprising a carboxyl-terminal amino acid extension with enhanced anti-thrombotic effects. Preferred are amino acid extensions comprising His of from about 2 to 20 amino acids. Most preferred are heparin cofactor II proteins comprising (His)6 and (His)5Pro carboxyl terminal extensions. Further described are isolated nucleic acids encoding the inventive heparin cofactor II mutants, and vectors and host cells containing the same. Also provided are pharmaceutical formulations containing the inventive heparin cofactor II mutants, preferably in the presence of a polyanion cofactor. As another aspect of the present invention are methods of inhibiting thrombin activity so as to inhibit blood coagulation, regulate wound healing, tissue repair, and/or inhibit inflammation in a subject in need thereof.
An isolated DNA encoding a mutant heparin cofactor II comprising, in combination, a heparin cofactor II and a carboxyl terminal amino acid extension, wherein said carboxyl terminal amino acid extension comprises a histidine residue and confers enhanced anti-thrombin activity to said mutant heparin cofactor II.
An isolated DNA encoding a mutant heparin cofactor II comprising, in combination, a heparin cofactor II and a carboxyl terminal amino acid extension, wherein said carboxyl terminal amino acid extension consists of histidine residues and confers enhanced anti-thrombin activity to said mutant heparin cofactor II.
The isolated DNA of claim having the sequence given as SEQ ID NO:4.
An isolated DNA encoding a mutant heparin cofactor II comprising, in combination, a heparin cofactor II and a carboxyl terminal amino acid extension, wherein said carboxyl terminal amino acid extension consists of histidine residues and a carboxyl terminal proline residue and confers enhanced anti-thrombin activity to said mutant heparin cofactor II.
Dependencies are inferred from the claim text.