Anti-cmet antagonists

Abstract

The invention provides therapeutic anti-c-met antibodies, and compositions comprising and methods of using these antibodies.

1 . A method of modulating a disease associated with dysregulation of the HGF/c-met signaling axis, said method comprising administering to a subject an effective amount of an anti-c-met antibody, wherein the anti-c-met antibody comprises (a) a heavy chain variable domain comprising HVR1-HC, HVR2-HC and HVR3-HC sequence depicted in  FIG. 13  (SEQ ID NO: 191-193); and (b) a light chain variable domain comprising HVR1-LC, HVR2-LC and HVR3-LC sequence depicted in  FIG. 13  (SEQ ID NO: 183-185). 
     
     
         2 : A method of treating a subject having cancer, said method comprising administering to the subject an effective amount of an anti-c-met antibody, wherein the anti-c-met antibody comprises (a) a heavy chain variable domain comprising HVR1-HC, HVR2-HC and HVR3-HC sequence depicted in  FIG. 13  (SEQ ID NO: 191-193); and (b) a light chain variable domain comprising HVR1-LC, HVR2-LC and HVR3-LC sequence depicted in  FIG. 13  (SEQ ID NO: 183-185). 
     
     
         3 . The method of  claim 2 , wherein the cancer is lung cancer, brain cancer, kidney cancer, gastric cancer, colorectal cancer, pancreatic cancer, liver cancer, head and neck cancer, bladder cancer, cervical cancer, thyroid cancer and/or prostate cancer. 
     
     
         4 : A method of treating a proliferative disorder in a subject, said method comprising administering to the subject an effective amount of an anti-c-met antibody, wherein the anti-c-met antibody comprises (a) a heavy chain variable domain comprising HVR1-HC, HVR2-HC and HVR3-HC sequence depicted in  FIG. 13  (SEQ ID NO: 191-193); and (b) a light chain variable domain comprising HVR1-LC, HVR2-LC and HVR3-LC sequence depicted in  FIG. 13  (SEQ ID NO: 183-185). 
     
     
         5 : (canceled) 
     
     
         6 : The method of  claim 1 ,  2 , or  4 , wherein the heavy chain variable domain comprises FR1-HC, FR2-HC, FR3-HC and FR4-HC sequence depicted in  FIG. 13  (SEQ ID NO: 187-90). 
     
     
         7 : The method of  claim 1 ,  2 , or  4 , wherein the light chain variable domain comprises FR1-LC, FR2-LC, FR3-LC and FR4-LC sequence depicted in  FIG. 13  (SEQ ID NO: 179-182). 
     
     
         8 : The method of  claim 1 ,  2 , or  4 , wherein the heavy chain variable domain comprises FR1-HC, FR2-HC, FR3-HC and FR4-HC sequence depicted in  FIG. 13  (SEQ ID NO: 187-90) and the light chain variable domain comprises FR1-LC, FR2-LC, FR3-LC and FR4-LC sequence depicted in  FIG. 13  (SEQ ID NO: 179-182). 
     
     
         9 : The method of  claim 8 , wherein the antibody comprises CH1 sequence depicted in  FIG. 13  (SEQ ID NO: 194). 
     
     
         10 : The method of  claim 8 , wherein the antibody comprises CL1 sequence depicted in  FIG. 13  (SEQ ID NO: 186). 
     
     
         11 : The method of  claim 8 , wherein the antibody comprises Fc sequence depicted in  FIG. 13  (SEQ ID NO: 195). 
     
     
         12 : The method of  claim 8 , wherein the antibody is monovalent and comprises a Fc region, wherein the Fc region comprises a first and a second polypeptide, wherein the first polypeptide comprises the Fc sequence depicted in  FIG. 13  (SEQ ID NO: 195) and the second polypeptide comprises the sequence depicted in  FIG. 14  (SEQ ID NO: 196). 
     
     
         13 : The method of  claim 1 ,  2 , or  4 , wherein the antibody is monovalent and comprises an Fc region. 
     
     
         14 : The method of  claim 2 m further comprising treatment with a second therapeutic agent. 
     
     
         15 : The method of  claim 14 , wherein the second therapeutic agent is a chemotherapeutic agent, an anti-angiogenic agent, or a growth inhibitory agent. 
     
     
         16 : The method of  claim 15 , wherein the anti-angiogenic agent is an anti-VEGF antibody. 
     
     
         17 : The method of  claim 14  wherein administration is combined administration. 
     
     
         18 : The method of  claim 14 , wherein administration is separate administration. 
     
     
         19 : The method of  claim 18 , wherein separate administration of the anti-cmet antibody is prior to and/or following administration of the second therapeutic agent.