Modified vitamin K-dependent polypeptides
The invention provides vitamin k-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.
1. A protein C polypeptide or activated protein C polypeptide wherein said polypeptide comprises a modified GLA domain, said modified GLA domain comprising the amino acid sequence of SEQ ID NO:1 with one, two, three, four, or five amino acid substitutions at positions selected from the group consisting of residues 10,11, 28, 32, and 33.
2. The protein C or activated protein C polypeptide of claim 1 , wherein residue 32 of SEQ ID NO:1 is glutamic acid.
3. The protein C or activated protein C polypeptide of claim 1 , wherein residue 33 of SEQ ID NO:1 is aspartic acid.
4. A pharmaceutical composition comprising said protein C or activated protein C polypeptide of any one of claims 1 to 3 and a pharmaceutically acceptable cater.
5. The composition of claim 4 for use in treating thrombosis in a mammal.
6. The composition of claim 4 for use in decreasing clot formation in a mammal.
7. The composition of claim 5 , wherein said composition is formulated for parenteral administration to a human patient.
8. The composition of claim 6 , wherein said composition is formulated for parenteral administration to a human patient.