Treatment of coagulation disease by administration of recombinant VWF

1. A method for treating Von Willebrand Disease or Hemophilia A in a subject in need thereof, the method comprising: intravenously administering to the subject a composition comprising recombinant Von Willebrand Factor (rVWF) wherein endogenous Factor VIII half-life is extended as compared to a subject administered plasma derived Von Willebrand Factor, wherein the rVWF is not modified with a water soluble polymer, wherein the composition is a high molecular weight VWF multimer composition comprising at least 20% VWF decamers or higher order multimers, and wherein the rVWF has a higher specific activity than plasma derived Von Willebrand Factor, and the higher order rVWF multimers are stable for at least 3 hours post-administration.

2. The method of claim 1 , wherein the method comprises co-administering to the subject said composition comprising recombinant Von Willebrand Factor (rVWF) and a composition comprising recombinant Factor VIII (rFVIII).

3. The method of claim 2 , wherein the rVWF and rFVIII are administered together in a single composition.

4. The method according to claim 1 , wherein the subject is administered between 1.0 IU/kg VWF:RCo and 150 IU/kg VWF:RCo per dose.

5. The method of claim 4 , wherein the subject is administered between 2 IU/kg VWF:RCo and 50 IU/kg VWF:RCo per dose.

6. The method of claim 4 , wherein the subject is administered between 5 IU/kg VWF:RCo and 40 IU/kg VWF:RCo per dose.

7. The method of claim 4 , wherein the subject is administered between 10 IU/kg VWF:RCo and 20 IU/kg VWF:RCo per dose.

8. The method according to claim 1 , wherein the rVWF is matured in vitro by treatment with Furin.

9. The method according to claim 1 , wherein the rVWF is produced through expression in a Chinese Hamster Ovary (CHO cell culture).

10. The method according to claim 2 , wherein the rFVIII and rVWF are produced through expression in the same cell culture.

11. The method according to claim 1 , wherein the subject is administered rVWF no more than once every other day.

12. The method of claim 11 , wherein the subject is administered rVWF no more than twice a week.

13. The method according claim 1 , wherein the Factor VIII half-life is extended by at least 5 hours.

14. The method of claim 13 , wherein the Factor VIII half-life is extended by at least 12 hours.

15. The method of claim 13 , wherein the Factor VIII half-life is extended by at least 24 hours.

16. The method of claim 13 , wherein the Factor VIII half-life is extended by at least 36 hours.

17. The method of claim 13 , wherein the Factor VIII half-life is extended by at least 48 or 72 hours.

18. The method of claim 2 , wherein the ratio of procoagulant activity (IU FVIII:C) of the administered FVIII to Ristocetin cofactor activity (IU rVWF:RCo) of the administered rVWF is between 2:1 and 1:4.

19. The method of claim 18 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) is between 3:2 and 1:3.

20. The method of claim 18 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) is between 1:1 and 1:2.

21. The method of claim 18 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) is about 3:4.

22. The method of claim 1 , wherein the rVWF has a specific activity of about 20-150 mU/μg.

23. The method of claim 1 , wherein the high molecular weight VWF multimer composition comprises at least 30% VWF decamers or higher order multimers.

24. The method of claim 1 , wherein the high molecular weight VWF multimer composition comprises at least 40% VWF decamers or higher order multimers.

25. The method of claim 1 , wherein the high molecular weight VWF multimer composition comprises at least 50% VWF decamers or higher order multimers.

26. The method of claim 1 , wherein the high molecular weight VWF multimer composition comprises at least 60% VWF decamers or higher order multimers.

27. The method of claim 1 , wherein the high molecular weight VWF multimer composition comprises at least 70% VWF decamers or higher order multimers.

28. A method for treating Hemophilia A or Von Willebrand Disease in a subject in need thereof, the method comprising: administering to the subject a composition comprising recombinant Von Willebrand Factor (rVWF) wherein Factor VIII half-life is extended as compared to a subject administered plasma derived Von Willebrand Factor, wherein: (a) the rVWF has a higher specific activity than plasma derived Von Willebrand Factor, wherein the specific activity of rVWF is about 20-150 mU/g; (b) the FVIII half-life is at least 1.5 times higher as compared to FVIII half-life in a subject administered plasma derived Von Willebrand Factor; and (c) the rVWF is not modified with a water soluble polymer; and (d) the rVWF is a high molecular weight VWF multimer composition comprising at least 20% VWF decamers or higher order multimers, wherein the higher order rVWF multimers are stable for at least 3 hours post-administration.

29. A method for treating Hemophilia A or Von Willebrand Disease in a subject in need thereof, the method comprising: administering to the subject a composition comprising recombinant Von Willebrand Factor (rVWF) wherein Factor VIII half-life is extended as compared to a subject administered plasma derived Von Willebrand Factor, wherein: (a) the composition is a high molecular weight VWF multimer composition comprising at least 20% VWF decamers or higher order multimers, (b) the rVWF has a higher specific activity than plasma derived Von Willebrand Factor, wherein the specific activity of rVWF is at least about 20-150 mU/g; (c) the FVIII half-life is at least 1.5 times higher as compared to FVIII half-life in a subject administered plasma derived Von Willebrand Factor; and (d) the rVWF is not modified with a water soluble polymer; and (e) the rVWF is a high molecular weight VWF multimer composition comprising at least 20% VWF decamers or higher order multimers, wherein the higher order rVWF multimers are stable for at least 3 hours post-administration.

30. The method of claim 1 , 28 or 29 , wherein the method is a method for treating Von Willebrand Disease Type 3.

31. The method of claim 1 , 28 or 29 , wherein the level of Factor VIII procoagulant activity (FVIII:C) in the plasma of the subject 24 hours post-administration is at least 90% of the level of FVIII:C activity present in the plasma 1 hour post-administration.

32. The method of claim 1 , 28 or 29 wherein said water soluble polymer is PEG.