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, the method comprising administering a pharmaceutical composition comprising an ICOS binding protein or antigen binding portion thereof and a pharmaceutically acceptable carrier to said human, wherein the ICOS binding protein or antigen binding portion thereof comprises a V H  domain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:7; and a V L  domain comprising an amino acid sequence at least 90% identical to the amino acid sequence as set forth in SEQ ID NO:8 wherein said ICOS binding protein or antigen binding portion thereof specifically binds to human ICOS, and administering at least one anti-neoplastic agent selected from the group consisting of docetaxel, paclitaxel, gemcitabine, and carboplatin to said human. 
     
     
         2 . The method of  claim 1 , wherein said 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 (RCC), EC squamous cell, non-small cell lung carcinoma, mesothelioma, urothelial cancer, and prostate cancer. 
     
     
         3 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion thereof comprises one or more of: CDRH1 as set forth in SEQ ID NO:1; CDRH2 as set forth in SEQ ID NO:2; CDRH3 as set forth in SEQ ID NO:3; CDRL1 as set forth in SEQ ID NO:4; CDRL2 as set forth in SEQ ID NO:5 and/or CDRL3 as set forth in SEQ ID NO:6 or a direct equivalent of each CDR wherein a direct equivalent has no more than two amino acid substitutions in said CDR. 
     
     
         4 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion thereof is an ICOS agonist. 
     
     
         5 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion comprises a heavy chain variable region comprising SEQ ID NO:1; SEQ ID NO:2; and SEQ ID NO:3, and a light chain variable region comprising SEQ ID NO:4; SEQ ID NO:5; and SEQ ID NO:6. 
     
     
         6 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion thereof comprises a V H  domain comprising the 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. 
     
     
         7 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion thereof comprises a scaffold selected from human IgG1 isotype and human IgG4 isotype. 
     
     
         8 . The method of  claim 1 , wherein the ICOS binding protein or antigen binding portion thereof comprises an hIgG4PE scaffold. 
     
     
         9 . The method of  claim 1 , wherein the ICOS binding protein is a monoclonal antibody. 
     
     
         10 . The method of  claim 11 , wherein the monoclonal antibody is humanized. 
     
     
         11 . The method of  claim 11 , wherein the monoclonal antibody comprises heavy chain CDRs comprising the amino acid sequences set forth in SEQ ID NO:1; SEQ ID NO:2; and SEQ ID NO:3 and light chain CDRs comprising the amino acid sequences set forth in SEQ ID NO:4; SEQ ID NO:5; and SEQ ID NO:6. 
     
     
         12 . The method of  claim 11 , wherein the monoclonal antibody is an agonist to human ICOS and comprises an IgG4 isotype scaffold. 
     
     
         13 . The method of  claim 11 , wherein the monoclonal antibody comprises a hIgG4PE scaffold. 
     
     
         14 . The method of  claim 1  further comprising administering an anti-PD1 antibody to said human. 
     
     
         15 . The method of  claim 15 , wherein the anti-PD1 antibody is pembrolizumab. 
     
     
         16 . The method of  claim 14 , wherein the anti-PD1 antibody is nivolumab. 
     
     
         17 . The method of  claim 1 , wherein the anti-neoplastic agent is docetaxel. 
     
     
         18 . The method of  claim 1 , wherein the anti-neoplastic agent is paclitaxel. 
     
     
         19 . The method of  claim 1 , wherein the anti-neoplastic agent is gemcitabine. 
     
     
         20 . The method of  claim 1 , wherein the anti-neoplastic agent is carboplatin.