Antibodies Against Tissue Factor Pathway Inhibitor (TFPI)

Abstract

The invention relates to antibodies that specifically bind to tissue factor pathway inhibitor (TFPI) and that reduce clotting time in (a) human FVIII-deficient plasma and/or (b) human whole blood. Such antibodies have utility in the treatment of bleeding disorders and in the stimulation of blood clotting.

1 . An isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 and a light chain comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein the heavy chain CDR comprises an amino acid residues 98 to 107 of SEQ ID NO: 6. 
     
     
         2 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 1 , wherein a heavy chain comprises an amino acid sequence having 90% identity to SEQ ID NO: 6. 
     
     
         3 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 2 , wherein a light chain comprises an amino acid sequence having 90% identity to SEQ ID NO: 3. 
     
     
         4 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 3  that reduces clotting time in vivo without significantly reducing platelet levels. 
     
     
         5 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 3 , wherein the antibody is a monoclonal antibody. 
     
     
         6 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 3 , wherein the antibody reduces clotting time in human FVIII-deficient plasma. 
     
     
         7 . The isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 3 , wherein the antibody reduces clotting time in human FVIII-deficient whole blood. 
     
     
         8 . A pharmaceutical composition comprising the isolated antibody that specifically binds to tissue factor pathway inhibitor (TFPI) of  claim 1  and a pharmaceutically acceptable carrier or diluent. 
     
     
         9 . A method of treating a bleeding disorder in a subject or for stimulating blood clotting in a subject, the method comprising administering to said subject the isolated antibody according to  claim 1  for treatment of a bleeding disorder or the stimulation of blood clotting.