Anti-ox40 antibodies and methods of use

Abstract

The invention provides anti-OX40 antibodies and methods of using the same.

1 - 70 . (canceled) 
     
     
         71 . A method of treating an individual having cancer comprising administering to the individual an effective amount of an anti-human OX40 agonist antibody, wherein the antibody comprises:
 (1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:2; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:3; and (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:4; and   (2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; and (f) an HVR-L3 comprising an amino acid sequence of SEQ ID NO:7.   
     
     
         72 . The method of  claim 71 , further comprising administering an additional therapeutic agent. 
     
     
         73 . The method of  claim 72 , wherein the additional therapeutic agent comprises a chemotherapeutic agent. 
     
     
         74 . The method of  claim 72 , wherein the additional therapeutic agent comprises a PD-1 axis binding antagonist. 
     
     
         75 . A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an anti-angiogenesis agent and an OX40 binding agonist; wherein the OX40 binding agonist is an anti-human OX40 agonist antibody comprising:
 (1) a heavy chain variable domain (VH) comprising (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:2; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:3; and (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:4; and   (2) a light chain variable domain (VL) comprising (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; and (f) an HVR-L3 comprising an amino acid sequence of SEQ ID NO:7.   
     
     
         76 . (canceled) 
     
     
         77 . (canceled) 
     
     
         78 . The method of  claim 75 , wherein the anti-angiogenesis agent is an anti-angiogenesis antibody. 
     
     
         79 . The method of  claim 78 , wherein the anti-angiogenesis antibody is a monoclonal antibody. 
     
     
         80 . The method of  claim 78 , wherein the anti-angiogenesis antibody is a human or humanized antibody. 
     
     
         81 . The method of  claim 75 , wherein the anti-angiogenesis agent is a VEGF antagonist. 
     
     
         82 - 90 . (canceled) 
     
     
         91 . The method of  claim 81 , wherein the VEGF antagonist is an anti-VEGF antibody. 
     
     
         92 . The method of  claim 91 , wherein the anti-VEGF antibody is a human or humanized antibody. 
     
     
         93 - 107 . (canceled) 
     
     
         108 . The method of  claim 71 , wherein the OX40 agonist antibody is a full-length human IgG1 antibody. 
     
     
         109 . The method of  claim 71 , wherein the OX40 agonist antibody depletes cells that express human OX40. 
     
     
         110 . The method of  claim 109 , wherein the cells are CD4+ effector T cells. 
     
     
         111 . The method of  claim 109 , wherein the cells are Treg cells. 
     
     
         112 . The method of  claim 109 , wherein the depleting is by ADCC or phagocytosis. 
     
     
         113 . The method of  claim 112 , wherein the depleting is by ADCC. 
     
     
         114 - 146 . (canceled) 
     
     
         147 . The method of  claim 71 , wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO: 56. 
     
     
         148 . The method of  claim 71 , wherein the OX40 agonist antibody comprises a VL sequence of SEQ ID NO: 57. 
     
     
         149 . The method of  claim 71 , wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO:56 and a VL sequence of SEQ ID NO: 57. 
     
     
         150 - 156 . (canceled) 
     
     
         157 . The method of  claim 71 , wherein the cancer is lung cancer, glioblastoma, cervical cancer, ovarian cancer, breast cancer, colon cancer, colorectal cancer, fallopian tube cancer, peritoneal cancer, kidney cancer, renal cancer, non-Hodgkins lymphoma, prostate cancer, pancreatic cancer, soft-tissue sarcoma, kaposi's sarcoma, carcinoid carcinoma, head and neck cancer, mesothelioma, multiple myeloma, non-small cell lung cancer, neuroblastoma, melanoma, gastric cancer, or liver cancer. 
     
     
         158 . The method of  claim 71 , wherein the cancer is a gynecologic cancer. 
     
     
         159 . The method of  claim 71 , wherein the cancer is advanced, refractory, recurrent, chemotherapy-resistant, and/or platinum-resistant. 
     
     
         160 . The method of  claim 75 , wherein the individual has cancer or has been diagnosed with cancer. 
     
     
         161 . The method of  claim 71 , wherein the treatment results in a sustained response in the individual after cessation of the treatment. 
     
     
         162 . The method of  claim 75 , wherein the OX40 binding agonist is administered before the anti-angiogenesis agent, simultaneous with the anti-angiogenesis agent, or after the anti-angiogenesis agent. 
     
     
         163 . The method of  claim 71 , wherein the individual is a human. 
     
     
         164 . The method of  claim 75 , wherein the anti-angiogenesis agent and/or the OX40 binding agonist are administered intravenously, intramuscularly, subcutaneously, intracerobrospinally, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, intra-articularly, intrasynovially, or intranasally. 
     
     
         165 . The method of  claim 75 , further comprising administering a chemotherapeutic agent for treating or delaying progression of cancer. 
     
     
         166 - 173 . (canceled) 
     
     
         174 . The method of  claim 75 , wherein the OX40 agonist antibody is a full-length human IgG1 antibody. 
     
     
         175 . The method of  claim 75 , wherein the OX40 agonist antibody depletes cells that express human OX40. 
     
     
         176 . The method of  claim 75 , wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO: 56. 
     
     
         177 . The method of  claim 75 , wherein the OX40 agonist antibody comprises a VL sequence of SEQ ID NO: 57. 
     
     
         178 . The method of  claim 75 , wherein the OX40 agonist antibody comprises a VH sequence of SEQ ID NO:56 and a VL sequence of SEQ ID NO: 57. 
     
     
         179 . The method of  claim 75 , wherein the cancer is lung cancer, glioblastoma, cervical cancer, ovarian cancer, breast cancer, colon cancer, colorectal cancer, fallopian tube cancer, peritoneal cancer, kidney cancer, renal cancer, non-Hodgkins lymphoma, prostate cancer, pancreatic cancer, soft-tissue sarcoma, kaposi's sarcoma, carcinoid carcinoma, head and neck cancer, mesothelioma, multiple myeloma, non-small cell lung cancer, neuroblastoma, melanoma, gastric cancer, or liver cancer. 
     
     
         180 . The method of  claim 75 , wherein the cancer is a gynecologic cancer 
     
     
         181 . The method of  claim 75 , wherein the cancer is advanced, refractory, recurrent, chemotherapy-resistant, and/or platinum-resistant. 
     
     
         182 . The method of  claim 75 , wherein the treatment results in a sustained response in the individual after cessation of the treatment. 
     
     
         183 . The method of  claim 75 , wherein the individual is a human.