Methods of reducing hemorrhage due to surgical procedure
The invention concerns glycosylated proteins having human factor VIII activity. In a preferred embodiment, the protein is glycosylated with oligosaccharides that include an alpha-(2,6)-linked sialic acid and a bisecting GlcNAc linked to a core beta-mannose.
1. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the isolated Factor VIII comprises the amino acid sequence of SEQ ID NO: 1 and an N-linked oligosaccharide comprising an alpha-(2,6)-linked sialic acid.
2. The method of claim 1 , wherein the pharmaceutical composition is administered to the patient preoperatively.
3. The method of claim 2 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
4. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the isolated Factor VIII comprises the amino acid sequence of SEQ ID NO: 1 and an N-linked oligosaccharide comprising a bisecting GlcNAc linked to a core beta-mannose.
5. The method of claim 4 , wherein the pharmaceutical composition is administered to the patient preoperatively.
6. The method of claim 4 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
7. The method of claim 4 , wherein the isolated Factor VIII further comprises an N-linked oligosaccharide comprising an alpha-(2,6)-linked sialic acid.
8. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the amino acid sequence of the isolated Factor VIII is at least 95% identical to SEQ ID NO: 1 and the isolated Factor VIII further comprises an N-linked oligosaccharide comprising alpha-(2,6)-linked sialic acid.
9. The method of claim 8 , wherein the pharmaceutical composition is administered to the patient preoperatively.
10. The method of claim 8 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
11. The method of claim 8 , wherein the isolated Factor VIII further comprises an N-linked oligosaccharide comprising a bisecting GlcNAc linked to a core beta-mannose.
12. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the amino acid sequence of the isolated Factor VIII is at least 95% identical to SEQ ID NO: 1 and the isolated Factor VIII further comprises an N-linked oligosaccharide comprising a bisecting GlcNAc linked to a core beta-mannose.
13. The method of claim 12 , wherein the pharmaceutical composition is administered to the patient preoperatively.
14. The method of claim 12 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
15. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the isolated Factor VIII has the amino acid sequence of SEQ ID NO: 1 and the isolated Factor VIII comprises an N-linked oligosaccharide comprising alpha-(2,6)-linked sialic acid.
16. The method of claim 15 , wherein the pharmaceutical composition is administered to the patient preoperatively.
17. The method of claim 15 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
18. A method of reducing hemorrhage in a hemophilic patient due to a surgical procedure comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising isolated Factor VIII, wherein the isolated Factor VIII has the amino acid sequence of SEQ ID NO: 1 and the isolated Factor VIII comprises an N-linked oligosaccharide comprising a bisecting GlcNAc linked to a core beta-mannose.
19. The method of claim 18 , wherein the pharmaceutical composition is administered to the patient preoperatively.
20. The method of claim 18 , further comprising the step of re-administering the pharmaceutical composition 6 to 12 hours after the initial administration.
21. The method of claim 18 , wherein the isolated Factor VIII further comprises an N-linked oligosaccharide comprising alpha-(2,6)-linked sialic acid.