Therapeutic factor viii antibodies

Abstract

The present invention relates to therapeutic FVIII antibodies. In particular, the present invention relates to FVIII antibodies having the ability to prolong the circulatory half life of FVIII. The present invention furthermore relates to use of such antibodies in treatment and prophylaxis of haemophilia A.

1 . A monoclonal Factor VIII antibody having the ability to bind to activated human Factor VIII, wherein said antibody, upon binding to activated Factor VIII, reduces dissociation of the A2 domain, and wherein said antibody does not interfere with vWF binding. 
     
     
         2 . The monoclonal antibody according to  claim 1 , wherein said antibody does not accelerate thrombin activation. 
     
     
         3 . The antibody according to  claim 1 , wherein said antibody binds to the A2 domain. 
     
     
         4 . The antibody according to  claim 1 , wherein said antibody binds to the A3 domain. 
     
     
         5 . The antibody according to  claim 1 , wherein said antibody binds to an epitope identical with or overlapping with the peptide fragment 407-428 (SEQ ID NO 15) and/or 591-602 (SEQ ID NO: 16). 
     
     
         6 . The antibody according to  claim 1 , wherein said antibody binds to an epitope identical with or overlapping with the peptide fragment 1965-1976 (SEQ ID NO: 17). 
     
     
         7 . The antibody according to  claim 1 , wherein the antibody competes with binding to the 4F143 antibody. 
     
     
         8 . The antibody according to  claim 1 , wherein said antibody comprises one or more CDR sequences having at least 95% identity with one or more of the CDR sequences selected from the list consisting of: SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 12, and SEQ ID NO: 13. 
     
     
         9 . The antibody according to  claim 5 , wherein said antibody comprises a VL sequence having at least 95% identity with the SEQ ID NO: 9 and a VH sequence having at least 95% identity with SEQ ID NO: 10. 
     
     
         10 . A method for treating haemophilia A comprising administering an antibody according to  claim 1  to a subject in need thereof. 
     
     
         11 . The method for treating haemophilia A of  claim 10  comprising administering the antibody in combination with a Factor VIII molecule. 
     
     
         12 . A pharmaceutical composition comprising an antibody according to  claim 1 . 
     
     
         13 . The pharmaceutical composition according to  claim 12 , further comprising a Factor VIII molecule. 
     
     
         14 . The pharmaceutical composition according to  claim 12 , wherein said composition is for subcutaneous administration. 
     
     
         15 . A method of making an antibody according to  claim 1 , wherein said method comprises incubation of a host cell encoding such antibody under conditions suitable for expressing said antibody.