Snake factor V and methods of use thereof as a procoagulant
Compositions and Methods for the treatment of coagulation disorders using Factor V variants are provided. Preferred disorders include hemophilia A and B.
1. A method for the treatment of a blood coagulation disorder in a patient in need thereof, comprising administering an effective amount of an activated form of isolated snake factor V (FV) encoded by the nucleic acid having the nucleotide sequence SEQ ID NO: 1 or SEQ ID NO: 2, thereby enhancing clot formation in said patient and ameliorating the symptoms of said blood coagulation disorder.
2. The method of claim 1 , for the treatment of hemophilia A.
3. The method of claim 1 , for the treatment of hemophilia B.
4. The method of claim 1 , wherein said activated form of FV is delivered intravenously or topically.
5. The method of claim 1 , wherein said disorder is selected from the group consisting of hemophilia A and B, hemophilia A and B associated with inhibitory antibodies, coagulation factor deficiency, vitamin K epoxide reductase C1 deficiency, gamma-carboxylase deficiency, bleeding associated with trauma, injury, thrombosis, thrombocytopenia, stroke, coagulopathy, disseminated intravascular coagulation (DIC); over-anticoagulation treatment disorders, Bernard Soulier syndrome, Glanzman thromblastemia, and storage pool deficiency.
6. The method of claim 5 , wherein said over-anticoagulation treatment disorder results from administration of heparin, low molecular weight heparin, pentasaccharide, warfarin, small molecule antithrombotics, and FXa inhibitors.
7. The method of claim 1 , wherein said variant is administered intravenously at least once a day at a dosage between about 10 and 500 μg/kg.
8. The isolated nucleic acid of SEQ ID NO: 2 encoding snake Factor V.
9. The nucleic acid of claim 8 contained in an expression vector.
10. An isolated host cell comprising the nucleic acid of claim 9 .
11. The isolated snake Factor V protein encoded by the nucleic acid of SEQ ID NO: 1.
12. The protein of claim 11 contained in a liposome or micelle.
13. A pharmaceutical composition comprising the protein of claim 11 contained in a pharmaceutically acceptable excipient.