Conjugated Factor VIII Molecules

Abstract

The present invention relates to B-domain truncated Factor VIII molecules with a modified circulatory half-life, said molecule being covalently conjugated with a hydrophilic polymer. The invention furthermore relates to methods for obtaining such molecules as well as use of such molecules.

What is claimed: 
     
         1 . A Factor VIII molecule with a modified circulatory half-life comprising a FVIII molecule with a truncated B-domain consisting of amino acids 741-760 of SEQ ID N0:2, wherein the FVIII molecule is covalently conjugated to a hydrophilic polymer via an O-linked oligosaccharide on a serine residue corresponding to position 750 of SEP ID N0:2. 
     
     
         2 . The FVIII molecule of  claim 1  made by a process comprising: a) transfecting a mammalian host cell with a vector encoding the FVIII molecule of  claim 1 ; b) culturing the host cell of step (a) under conditions suitable to express the FVIII molecule in the host cell; c) harvesting the FVIII molecule from the host cell culture of step (b); and d) covalently conjugating the FVIII molecule with the hydrophilic polymer via an O-linked oligosaccharide on the serine residue corresponding to position 750 of SEQ ID N0:2. 
     
     
         3 . The FVIII molecule of  claim 1 , wherein the hydrophilic polymer is a polysaccharide. 
     
     
         4 . The FVIII molecule of  claim 1 , wherein the hydrophilic polymer is heparin. 
     
     
         5 . The FVIII molecule of  claim 2 , wherein the mammalian host cell is a CHO cell. 
     
     
         6 . A pharmaceutical composition comprising the FVIII molecule of  claim 1 . 
     
     
         7 . A pharmaceutical composition comprising the FVIII molecule of  claim 2 . 
     
     
         8 . A method of treating a haemophilic disease comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 6 . 
     
     
         9 . A method of treating a haemophilic disease comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of  claim 7 . 
     
     
         10 . A method according to  claim 8 , wherein the pharmaceutical composition is administered subcutaneously. 
     
     
         11 . A method according to  claim 9 , wherein the pharmaceutical composition is administered intravenously. 
     
     
         12 . The FVIII molecule of  claim 2 , wherein the hydrophilic polymer is a polysaccharide. 
     
     
         13 . The FVIII molecule of  claim 2 , wherein the hydrophilic polymer is heparin.