Anti-icos antibodies

Abstract

Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Methods of producing anti-ICOS antibodies, including species cross-reactive antibodies, using transgenic knock-out mice.

1 - 113 . (canceled) 
     
     
         114 . A method of treating cancer in a human patient, the method comprising administering to the patient an antibody that binds the extracellular domain of human ICOS, the antibody comprising a variable heavy (VH) domain amino acid sequence SEQ ID NO: 408 and a variable light (VL) domain amino acid sequence SEQ ID NO: 415. 
     
     
         115 . The method of claim  1 , wherein the antibody comprises a human heavy and/or light chain constant region. 
     
     
         116 . The method of claim  1 , wherein the antibody comprises an Fc effector positive constant region. 
     
     
         117 . The method of  claim 116 , wherein the Fc region has enhanced ADCC, ADCP and/or CDC function compared with a native human Fc region. 
     
     
         118 . The method of claim  1 , wherein the antibody comprises a heavy chain amino acid sequence SEQ ID NO: 410 and a light chain amino acid sequence SEQ ID NO: 417. 
     
     
         119 . The method of claim  1 , wherein the antibody is an IgG1. 
     
     
         120 . The method of claim  1 , wherein the antibody is afucosylated. 
     
     
         121 . The method of claim  1 , wherein the cancer is a solid tumor. 
     
     
         122 . The method of claim  1 , wherein the cancer is renal cell cancer, head and neck cancer, melanoma, non small cell lung cancer or diffuse large B-cell lymphoma. 
     
     
         123 . The method of claim  1 , wherein the cancer is melanoma. 
     
     
         124 . The method of claim  1 , wherein the cancer cancer is a haemotological liquid tumor. 
     
     
         125 . The method of claim  1 , wherein the cancer is B cell lymphoma, or a T lymphocyte. 
     
     
         126 . The method of claim  1 , wherein the cancer is or has been characterised as being refractory to treatment with an immunooncology drug, e.g., anti-CTLA-4 antibody, anti-PD1 antibody, anti-PD-L1 antibody, anti-CD137 antibody or anti-GITR antibody. 
     
     
         127 . The method of claim  1 , wherein the cancer is not responsive to prior treatment with an immunooncology drug. 
     
     
         128 . The method of claim  1 , wherein the cancer is resistant to treatment with an anti-CD20 antibody. 
     
     
         129 . The method of  claim 128 , wherein the anti-CD20 antibody is rituximab. 
     
     
         130 . The method of claim  1 , wherein the cancer tumor is high in regulatory T cells. 
     
     
         131 . The method of claim  1 , wherein the cancer is or has been characterised as being positive for expression of ICOS ligand and/or FOXP3. 
     
     
         132 . The method of claim  1 , wherein the patient has an increased level of ICOS-positive regulatory T cells following treatment with another therapeutic agent. 
     
     
         133 . The method of claim  1 , wherein the antibody is conjugated to a cytotoxic drug or pro-drug.