Polypeptide compounds for inhibiting angiogenesis and tumor growth

Abstract

In certain embodiments, this present invention provides polypeptide compositions, and methods for inhibiting Ephrin B2 or EphB4 activity. In other embodiments, the present invention provides methods and compositions for treating cancer or for treating angiogenesis-associated diseases.

1 - 62 . (canceled) 
     
     
         63 . A method for reducing the growth rate of a tumor, comprising administering an amount of an isolated monoclonal antibody, or a fragment thereof, sufficient to reduce the growth rate of the tumor, wherein the antibody or fragment thereof binds to the extracellular domain of EphB4 and inhibits an activity of EphB4. 
     
     
         64 . The method of  claim 63 , wherein the tumor comprises cells expressing a higher level of EphB4 and/or EphrinB2 than noncancerous cells of a comparable tissue. 
     
     
         65 . A method for treating a patient suffering from a cancer, comprising administering to the patient an isolated monoclonal antibody, or a fragment thereof, that binds to the extracellular domain of EphB4 and inhibits an activity of EphB4. 
     
     
         66 . The method of  claim 65 , wherein the cancer comprises cancer cells expressing EphrinB2 and/or EphB4 at a higher level than noncancerous cells of a comparable tissue. 
     
     
         67 . The method of  claim 65 , wherein the cancer is metastatic cancer. 
     
     
         68 . The method of  claim 65 , wherein the tumor is selected from colon carcinoma, breast tumor, mesothelioma, prostate tumor, squamous cell carcinoma, Kaposi sarcoma, and leukemia. 
     
     
         69 . The method of  claim 65 , wherein the cancer is an angiogenesis-dependent cancer. 
     
     
         70 . The method of  claim 65 , wherein the cancer is an angiogenesis-independent cancer. 
     
     
         71 . The method of  claim 65 , wherein the antibody inhibits the interaction between EphrinB2 and EphB4. 
     
     
         72 . The method of  claim 65 , wherein the antibody inhibits clustering of EphrinB2 or EphB4. 
     
     
         73 . The method of  claim 65 , wherein the antibody inhibits phosphorylation of EphrinB2 or EphB4. 
     
     
         74 . The method of  claim 65 , wherein the antibody is formulated with a pharmaceutically acceptable carrier. 
     
     
         75 . The method of  claim 65 , further including administering at least one additional anti-cancer chemotherapeutic agent that inhibits cancer cells in an additive or synergistic manner with the antibody. 
     
     
         76 . A method for inhibiting angiogenesis, comprising contacting a cell with an amount of an isolated monoclonal antibody, or a fragment thereof, sufficient to inhibit angiogenesis, wherein the antibody or fragment thereof binds to the extracellular domain of EphB4 and inhibits an activity of EphB4. 
     
     
         77 . The method of  claim 76 , wherein the cell expresses EphB4 or EphrinB2. 
     
     
         78 . A method for treating a patient suffering from an angiogenesis-associated disease, comprising administering to the patient an isolated monoclonal antibody, or a fragment thereof, that binds to the extracellular domain of EphB4 and inhibits an activity of EphB4. 
     
     
         79 . The method of  claim 78 , wherein the antibody is formulated with a pharmaceutically acceptable carrier. 
     
     
         80 . The method of  claim 78 , wherein the angiogenesis-associated disease is selected angiogenesis-dependent cancer, benign tumors, inflammatory disorders, chronic articular rheumatism, psoriasis, ocular angiogenic diseases, Osler-Webber Syndrome, myocardial angiogenesis, plaque neovascularization, telangiectasia, hemophiliac joints, angiofibroma, wound granulation, wound healing, scleroderma, pyogenic granuloma, coronary collaterals, ischemic limb angiogenesis, rubeosis, arthritis, diabetic neovascularization, fractures, vasculogenesis, and hematopoiesis. 
     
     
         81 . The method of  claim 78 , further including administering at least one additional anti-angiogenesis agent that inhibits angiogenesis in an additive or synergistic manner with the antibody.