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.

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 . (canceled) 
   
   
       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. 
   
   
       11 . The mAb of  claim 10  which completely inhibits growth of a human tumor xenograft in a mouse. 
   
   
       12 . The mAb of  claim 1  which is a Fab or F(ab′) 2  fragment or single-chain antibody. 
   
   
       13 . The mAb of  claim 1  which specifically binds HGF with a binding affinity of at least 10 8  M −1 . 
   
   
       14 . A chimeric or humanized L2G7 mAb. 
   
   
       15 . An antibody that competes for binding to human HGF with an antibody of  claim 14 . 
   
   
       16 . A cell line producing a mAb of  claim 1 . 
   
   
       17 . A pharmaceutical composition comprising a mAb of  claim 14 . 
   
   
       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.