Compounds Suitable for Treatment of Haemophilia

Abstract

The present invention relates to VWF compounds as well as compositions suitable for treatment of blood clotting diseases.

1 . A pharmaceutical composition comprising: (i) a von Willebrand factor (VWF) fragment comprising up to 1200 amino acids, wherein said VWF fragment comprises the TIL′ domain and the E′ domains; and (ii) a FVIII molecule. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the B domain of said FVIII molecule comprises 15-30 amino acids 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment comprises less than 600 amino acids. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment comprises between 500 and 600 amino acids. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment comprises amino acids 764-1268 (SEQ ID NO 16). 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein said VWF fragment furthermore comprises repetitive elements. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment comprises one or two amino acid substitution(−s) of the 1099 and/or 1142 cysteine(s−). 
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment is part of a dimer. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein said VWF fragment is a monomer. 
     
     
         10 . The pharmaceutical composition according to  claim 1 , wherein the bioavailability of said FVIII molecule is at least 5%.following subcutaneous administration. 
     
     
         11 . The pharmaceutical composition according to  claim 1 , wherein the molar ratio between said FVIII and said VWF fragment is 1:1. 
     
     
         12 . The pharmaceutical formulation according to  claim 1 , wherein the concentration of FVIII is at least 500 IU/ml. 
     
     
         13 . The pharmaceutical formulation according to  claim 1 , wherein the amount of said FVIII bound to said VWF fragment is at least 70% of the total amount of said FVIII in said formulation. 
     
     
         14 . A method of treating haemophilia comprising: administering to a subject in need of such treatment a pharmaceutically effective amount of the pharmaceutical composition according to  claim 1 , wherein said pharmaceutical composition is administered subcutaneously. 
     
     
         15 . A method of treating von Willebrand disease comprising: administering intravenously or subcutaneously to a subject in need of such treatment a pharmaceutically effective amount of the pharmaceutical composition according to  claim 1 .