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 . An ICOS binding protein or antigen binding portion thereof comprising 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 specifically binds to human ICOS. 
     
     
         2 . The ICOS binding protein or antigen binding portion thereof of  claim 1  comprising heavy chain CDRs having the amino acid sequences set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 and light chain CDRs having the amino acid sequences set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. 
     
     
         3 . The ICOS binding protein or antigen binding portion thereof of  claim 1  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. 
     
     
         4 . The ICOS binding protein or antigen binding portion thereof of  claim 1  that is an agonist to human ICOS. 
     
     
         5 . The ICOS binding protein or antigen binding portion thereof of  claim 1  further comprising an IgG4 isotype scaffold or variant thereof. 
     
     
         6 . The ICOS binding protein or antigen binding portion thereof of  claim 1  further comprising a hIgG4PE scaffold. 
     
     
         7 . The ICOS binding protein or antigen binding portion thereof of  claim 1  wherein said ICOS binding protein is a humanized monoclonal antibody. 
     
     
         8 . A pharmaceutical composition comprising the ICOS binding protein or antigen binding portion thereof of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         9 . A method of treating a disease selected from cancer, infectious disease, or sepsis in a human in need thereof which method comprises the step of administering a pharmaceutical composition of  claim 8  to said human. 
     
     
         10 . The method of  claim 9  further comprising administering at least one anti-neoplastic agent, at least one second immuno-modulatory agent, and/or at least one immunostimulatory adjuvant to said human. 
     
     
         11 . The method of  claim 10  wherein said second immuno-modulatory agent is selected from:
 an anti-CTLA4 antibody, an anti-PD-1 antibody, an anti-PDL1 antibody and an anti-OX40 antibody. 
 
     
     
         12 . The method of  claim 11  wherein the disease is cancer. 
     
     
         13 . The method of  claim 12  wherein said cancer is selected from colorectal cancer (CRC), esophageal, cervical, bladder, breast, head and neck, ovarian, melanoma, renal cell carcinoma (RCC), EC squamous cell, non-small cell lung carcinoma, mesothelioma, and prostate cancer. 
     
     
         14 . The method of  claim 9 , wherein the disease is infectious disease. 
     
     
         15 . The method of  claim 14 , wherein the infectious disease is HIV. 
     
     
         16 . The method of  claim 9 , wherein the disease is sepsis. 
     
     
         17 . A method of stimulating T cell proliferation, inducing T cell activation and/or inducing cytokine production in a human comprising administering a pharmaceutical composition of  claim 8  to said human. 
     
     
         18 . A polynucleotide encoding the ICOS binding protein or antigen binding portion thereof of  claim 1 . 
     
     
         19 . An ICOS binding protein or antigen binding portion thereof, wherein the ICOS binding protein or antigen binding portion thereof cross-competes for binding to human ICOS with a reference antibody or antigen binding portion thereof comprising 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.