Factor VIII Fusion Protein

Abstract

The present invention relates to modified coagulation factors. In particular, the present invention relates to conjugated Factor VIII molecules fused to a polypeptide such as e.g. an antibody binding protein or a Fc domain.

1 . A FVIII molecule fused to a fusion partner, wherein the fusion partner replaces the A3-domain of the Factor VIII molecule, is inserted into the B-domain of Factor VIII, or is inserted in the C-terminal end of the C2 domain in Factor FVIII. 
     
     
         2 . The FVIII molecule according to  claim 1 , wherein the fusion partner is albumin. 
     
     
         3 . The FVIII molecule according to  claim 2 , wherein said molecule is conjugated with a side group. 
     
     
         4 . The FVIII molecule according to  claim 1 , wherein said FVIII molecule is a B domain truncated variant comprising a B domain having the sequence as set forth in SEQ ID NO: 2, and wherein the fusion partner is an Fc domain that is inserted in the C-terminal end of the C2 domain in Factor FVIII. 
     
     
         5 . The FVIII molecule according to  claim 4 , wherein said Fc domain is a mutated Fc domain having reduced effector functions and/or increased affinity to the neonatal Fc receptor. 
     
     
         6 . The FVIII molecule according to  claim 1 , wherein the Factor VIII molecule is fused to an Fc receptor. 
     
     
         7 . The FVIII molecule according to  claim 6 , wherein said Fc receptor is FcγRI. 
     
     
         8 . The FVIII molecule according to  claim 1 , wherein the Factor VIII molecule has reduced vWF binding capacity. 
     
     
         9 . The FVIII molecule according to  claim 1 , wherein the FVIII fusion protein is conjugated with a side group. 
     
     
         10 . The FVIII molecule according to  claim 9 , wherein the side group is selected from one or more of the list group consisting of: hydrophilic polymers, peptides and hydrophobic side groups. 
     
     
         11 . A method of making a molecule according to  claim 1 , wherein said method comprises incubating a host cell encoding said molecule under appropriate conditions. 
     
     
         12 . A method for treatmenting of haemophilia comprising administering an effective amount of the molecule of  claim 1  to a subject in need thereof. 
     
     
         13 . A pharmaceutical composition comprising a molecule according to  claim 1 .