Icos binding proteins

Abstract

The present invention relates to an ICOS binding protein or antigen binding portion thereof that is an agonist to human ICOS and does not induce complement, ADCC, or CDC when placed in contact with a T cell in vivo and methods of treating cancer, infectious disease and/or sepsis with said ICOS binding protein or antigen binding portion thereof. Further the ICOS binding proteins or antigen binding portions thereof of the present invention are capable of activating a T cell when placed in contact with said T cell; stimulating T cell proliferation when placed in contact with said T cell and/or inducing cytokine production when placed in contact with said T cell. The present invention relates to ICOS binding proteins or antigen binding portions thereof comprising one or more of: SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID NO:5; and/or SEQ ID NO:6.

1 . A method of treating cancer in a human in need thereof, which method comprises administering an ICOS binding protein or antigen binding portion thereof to said human, wherein the ICOS binding protein or antigen binding portion thereof competes for binding to human ICOS with a reference antibody or antigen binding portion thereof comprising a V H  domain comprising an amino acid sequence set forth in SEQ ID NO:7 and a V L  domain comprising the amino acid sequence set forth in SEQ ID NO:8, and administering an anti-CTLA4 antibody or antigen binding portion thereof to said human. 
     
     
         2 . A method of treating cancer in a human in need thereof, which method comprises administering an ICOS binding protein or antigen binding portion thereof to said human, wherein the ICOS binding protein or antigen binding portion thereof competes for binding to human ICOS with a reference antibody or antigen binding portion thereof comprising a V H  domain comprising an amino acid sequence set forth in SEQ ID NO:7 and a V L  domain comprising the amino acid sequence set forth in SEQ ID NO:8, and administering an anti-PD-L1 antibody or antigen binding portion thereof to said human. 
     
     
         3 . A method of treating cancer in a human in need thereof, which method comprises administering an ICOS binding protein or antigen binding portion thereof to said human, wherein the ICOS binding protein or antigen binding portion thereof competes for binding to human ICOS with a reference antibody or antigen binding portion thereof comprising a V H  domain comprising an amino acid sequence set forth in SEQ ID NO:7 and a V L  domain comprising the amino acid sequence set forth in SEQ ID NO:8, and administering a chemotherapeutic agent to said human. 
     
     
         4 . The method of  claim 1 , wherein the anti-CTLA4 antibody is ipilimumab. 
     
     
         5 . The method of  claim 3 , wherein the chemotherapeutic agent is an alkylating agent, antimetabolite, antibiotic, topoisomerase inhibitor, anti-mitotic agent, hormone, or hormone analog. 
     
     
         6 . The method of  claim 3 , wherein the chemotherapeutic agent is selected from: paclitaxel, docetaxel, gemcitabine, carboplatin, busulfan, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, melphalan, 5-fluorouracil, mercaptopurine, floxuridine, fludarabine, hydroxyurea, methotrexate, daunorubicin, doxorubicin, actinomycin, bleomycin, topotecan, irinotecan, etoposide, teniposide, vinblastine, vincristine, vinorelbine, prednisone, and prednisolone. 
     
     
         7 . The method of  claim 3 , wherein the chemotherapeutic agent is selected from: paclitaxel, docetaxel, gemcitabine, and carboplatin. 
     
     
         8 . The method of  claim 1 , wherein the ICOS binding protein is a monoclonal antibody. 
     
     
         9 . The method of  claim 1 , wherein the ICOS binding protein comprises reduced antibody dependent cell mediated cytotoxicity (ADCC) or reduced complement activation functionality. 
     
     
         10 . The method of  claim 1 , wherein the cancer is a solid tumor. 
     
     
         11 . The method of  claim 1 , wherein the cancer is selected from: colorectal cancer (CRC), esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell carcinoma, EC squamous cell, non-small cell lung carcinoma, mesothelioma, prostate cancer, and gastric cancer. 
     
     
         12 . The method of  claim 2 , wherein the ICOS binding protein is a monoclonal antibody. 
     
     
         13 . The method of  claim 2 , wherein the ICOS binding protein comprises reduced antibody dependent cell mediated cytotoxicity (ADCC) or reduced complement activation functionality. 
     
     
         14 . The method of  claim 2 , wherein the cancer is a solid tumor. 
     
     
         15 . The method of  claim 2 , wherein the cancer is selected from: colorectal cancer (CRC), esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell carcinoma, EC squamous cell, non-small cell lung carcinoma, mesothelioma, prostate cancer, and gastric cancer. 
     
     
         16 . The method of  claim 3 , wherein the ICOS binding protein is a monoclonal antibody. 
     
     
         17 . The method of  claim 3 , wherein the ICOS binding protein comprises reduced antibody dependent cell mediated cytotoxicity (ADCC) or reduced complement activation functionality. 
     
     
         18 . The method of  claim 3 , wherein the cancer is a solid tumor. 
     
     
         19 . The method of  claim 3 , wherein the cancer is selected from: colorectal cancer (CRC), esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell carcinoma, EC squamous cell, non-small cell lung carcinoma, mesothelioma, prostate cancer, and gastric cancer.