ICOS binding proteins
The present invention relates to an ICOS binding protein or antigen binding portion thereof that is an agonist 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 a disease selected from cancer and infectious disease in a human in need thereof which method comprises the step of 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.
2. The method of claim 1 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.
3. The method of claim 2 wherein said second immuno-modulatory agent is selected from: an anti-CTLA4 antibody, an anti-PD-1 antibody, an anti-PDL1antibody and an anti-OX40 antibody.
4. The method of claim 3 wherein the disease is cancer.
5. The method of claim 4 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.
6. The method of claim 1 wherein the disease is infectious disease.
7. The method of claim 6 wherein the infectious disease is HIV.
8. A method of stimulating T cell proliferation, inducing T cell activation and/or inducing cytokine production in a human 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.
9. The method of claim 1 wherein the disease is cancer.
10. The method of claim 1 wherein said ICOS binding protein is a monoclonal antibody.
11. The method of claim 10 wherein the monoclonal antibody is humanized.
12. The method of claim 11 wherein the antibody 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 as set forth in SEQ ID NO:8.
13. The method of claim 12 wherein the antibody comprises a scaffold selected from human IgG1 isotype or variant thereof and human IgG4 isotype or variant thereof.
14. The method of claim 12 wherein the antibody comprises a scaffold, wherein the scaffold is a human IgG4 isotype and comprises an Fc region comprising a S 22 8P mutation and a L235E mutation.
15. The method of claim 2 wherein the immunostimulatory adjuvant is a TLR4 agonist.
16. The method of claim 15 wherein the TLR4 agonist comprises CRX-601
17. The method of claim 3 wherein the anti-PD-1 antibody is pembrolizumab or nivolumab.
18. The method of claim 17 wherein the anti-PD-1 antibody is pembrolizumab.
19. The method of claim 3 wherein the anti-CTLA4 antibody is ipilimumab.
20. A method of treating cancer in a human in need thereof which method comprises the step of administering a pharmaceutical composition comprising a monoclonal antibody that specifically binds to human ICOS and a pharmaceutically acceptable carrier to said human, wherein the monoclonal antibody comprises a V H domain comprising an amino acid sequence set forth in SEQ ID NO:7; and a V L domain comprising an amino acid sequence set forth in SEQ ID NO:8 and wherein said antibody comprises a scaffold, wherein the scaffold is a human IgG4 isotype and comprises an Fc region comprising a S228P mutation and a L235E mutation.