Treatment of coagulation disease by administration of recombinant vwf

Abstract

The present invention provides methods of treating coagulation disease, including hemophilia and von Willebrand disease by administering recombinant von Willebrand Factor alone or in combination with Factor VIII.

1 .- 31 . (canceled) 
     
     
         32 . A method for treating Von Willebrand Disease or Hemophilia A comprising administering a Recombinant Von Willebrand Factor (rVWF), wherein the rVWF comprises a high molecular weight VWF multimer composition comprising at least 40% VWF decamers or higher order multimers. 
     
     
         33 . The method of  claim 32 , wherein the rVWF is matured in vitro by treatment with Furin. 
     
     
         34 . The method of  claim 32 , wherein the rVWF has a specific activity of about 20 to 150 mU/μg. 
     
     
         35 . The method of  claim 34 , wherein the rVWF has a specific activity of about 30 to 120 mU/μg. 
     
     
         36 . The method of  claim 32 , wherein the high molecular weight VWF multimer composition comprises at least 50% VWF decamers or higher order multimers. 
     
     
         37 . The method of  claim 32 , wherein the high molecular weight VWF multimer composition comprises at least 60% VWF decamers or higher order multimers. 
     
     
         38 . The method of  claim 32 , wherein the high molecular weight VWF multimer composition comprises at least 70% VWF decamers or higher order multimers. 
     
     
         39 . The method of  claim 32 , wherein the subject is to be administered between 1.0 IU/kg VWF:RCo and 150 IU/kg VWF:RCo per dose. 
     
     
         40 . The method of  claim 39 , wherein the subject is administered between 2 IU/kg VWF:RCo and 50 IU/kg VWF:RCo per dose. 
     
     
         41 . The method of  claim 39 , more preferred wherein the subject is administered between 5 IU/kg VWF:RCo and 40 IU/kg VWF:RCo per dose. 
     
     
         42 . The method of  claim 39 , wherein the subject is administered between 10 IU/kg VWF:RCo and 20 IU/kg VWF:RCo per dose. 
     
     
         43 . The method of  claim 32 , wherein the rVWF is administered no more than once daily, no more than once every other day, no more than once every third day, no more than once every fourth day, no more than once every fifth day, no more than twice a week, no more than once a week, no more than once every two weeks, or no more than once a month. 
     
     
         44 . The method of  claim 32 , wherein the rVWF is administered in multiple administrations. 
     
     
         45 . The method of  claim 32 , wherein the method is a method for treating Von Willebrand Disease Type 3. 
     
     
         46 . The method of  claim 32 , wherein the method comprises co-administering to the subject rVWF and Factor VIII (FVIII). 
     
     
         47 . The method of  claim 46 , wherein the FVIII is plasma derived FVIII. 
     
     
         48 . The method of  claim 46 , wherein the FVIII is recombinant FVIII. 
     
     
         49 . The method of  claim 46 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) to be administered to the subject is between 2:1 and 1:4. 
     
     
         50 . The method of  claim 46 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) to be administered to the subject is between 3:2 and 1:3. 
     
     
         51 . The method of  claim 46 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) to be administered to the subject is between 1:1 and 1:2. 
     
     
         52 . The method of  claim 46 , wherein the ratio of FVIII procoagulant activity (IU FVIII:C) to rVWF Ristocetin cofactor activity (IU rVWF:RCo) to be administered to the subject is about 3:4. 
     
     
         53 . The method of  claim 48 , wherein the rVWF is produced through expression in a Chinese Hamster Ovary (CHO cell culture). 
     
     
         54 . The method of  claim 53 , wherein the rFVIII and rVWF are produced through expression in the same cell culture. 
     
     
         55 . The method of  claim 46 , wherein the rVWF and FVIII are administered together in a single composition. 
     
     
         56 . The method of  claim 46 , wherein the method is a method for treating Von Willebrand Disease Type 3. 
     
     
         57 . A composition comprising recombinant Von Willebrand Factor (rVWF), wherein the rVWF comprises a high molecular weight VWF multimer composition comprising at least 40% VWF decamers or higher order multimers. 
     
     
         58 . The composition of  claim 57 , wherein the composition further comprises FVIII. 
     
     
         59 . The composition of  claim 58 , wherein the FVIII is plasma derived FVIII. 
     
     
         60 . The composition of  claim 58 , wherein the FVIII is recombinant FVIII. 
     
     
         61 . The composition of  claim 60 , wherein the rVWF is produced through expression in a Chinese Hamster Ovary (CHO cell culture). 
     
     
         62 . The composition of  claim 61 , wherein the rFVIII and rVWF are produced through expression in the same cell culture.