Monoclonal antibodies to hepatocyte growth factor

Abstract

The present invention is directed toward a neutralizing monoclonal antibody to hepatocyte growth factor, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.

We claim:  
     
         1 . A monoclonal antibody (mAb) that binds and neutralizes human Hepatocyte Growth Factor (HGF).  
     
     
         2 . The mAb of  claim 1  which is chimeric.  
     
     
         3 . The mAb of  claim 1  which is humanized.  
     
     
         4 . The mAb of  claim 1  which is human.  
     
     
         5 . The mAb of  claim 1  which inhibits binding of HGF to cMet by at least 50%.  
     
     
         6 . The mAb of  claim 1  which inhibits HGF-induced scattering of Madin-Darby canine kidney cells.  
     
     
         7 . The mAb of  claim 1  which inhibits HGF-induced proliferation of HUVEC cells.  
     
     
         8 . The mAb of  claim 1  which inhibits HGF-induced angiogenesis.  
     
     
         9 . The mAb of  claim 1  which neutralizes all biological activities of HGF.  
     
     
         10 . The mAb of  claim 1  which inhibits growth of a human tumor xenograft in a mouse when used as a single agent.  
     
     
         11 . The mAb of  claim 1  which is a Fab or F(ab′) 2  fragment or single-chain antibody.  
     
     
         12 . An anti-HGF mAb selected from the group of L1H4, L2C7 and L2G7.  
     
     
         13 . A chimeric or humanized L2G7 mAb.  
     
     
         14 . A cell line producing a mAb of  claim 1 .  
     
     
         15 . A cell line producing a mAb of  claim 13 .  
     
     
         16 . A pharmaceutical composition comprising a mAb of  claim 1 .  
     
     
         17 . A pharmaceutical composition comprising a mAb of  claim 13 .  
     
     
         18 . A method of treating cancer in a patient comprising administering to the patient a pharmaceutical composition comprising a neutralizing anti-HGF mAb.  
     
     
         19 . A method of  claim 18  wherein said cancer is glioblastoma.  
     
     
         20 . The method of  claim 18  wherein said mAb is a chimeric or humanized L2G7 mAb.