Modulators of hepatocyte growth factor activator

Abstract

The invention provides methods and compositions for modulating hepatocyte growth factor activator function.

1 . An isolated antibody that binds human hepatocyte growth factor activator (HGFA).  
     
     
         2 . The antibody of  claim 1 , wherein the antibody binds to an active site of HGFA.  
     
     
         3 . The antibody of  claim 1 , wherein the antibody binds to HGFA at a position other than an active site of HGFA.  
     
     
         4 . The antibody of  claim 1  which is a blocking antibody.  
     
     
         5 . The antibody of  claim 4  which blocks HGFA proteolytic activity.  
     
     
         6 . The antibody of  claim 5  which blocks HGFA proteolysis of single chain HGF.  
     
     
         7 . The antibody of  claim 1  which inhibits HGF/c-met signaling.  
     
     
         8 . The antibody of  claim 7  which inhibits cell proliferation.  
     
     
         9 . The antibody of  claim 7  which inhibits angiogenesis.  
     
     
         10 . The antibody of  claim 1 , wherein the antibody is an allosteric inhibitor of HGFA enzymatic activity.  
     
     
         11 . The antibody of  claim 1 , wherein the antibody is a complete or partial competitive inhibitor of HGFA enzymatic activity.  
     
     
         12 . A method treating a disease associated with dysregulation of HGF/c-met signaling in a subject, comprising administering to the subject an effective amount of an antibody that binds HGFA in accordance with any of the preceding claims.  
     
     
         13 . The method of  claim 10  wherein the disease is cancer.  
     
     
         14 . The method of  claim 10  wherein the disease is associated with dysregulation of angiogenesis.  
     
     
         15 . The method of  claim 10  wherein the disease is immune related.  
     
     
         16 . An isolated antibody that specifically binds human hepatocyte growth factor activator, wherein the antibody comprises a heavy chain CDR sequence comprising the respective H1, H2 and/or H3 sequences depicted in  FIG. 1A .  
     
     
         17 . The antibody of  claim 16 , wherein the H1, H2 and/or H3 sequences are as depicted in  FIGS. 1B, 1C  and/or  1 D.