Anti-TIGIT Antibodies

Abstract

Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.

1 - 52 . (canceled) 
     
     
         53 . An isolated antibody or antigen binding fragment thereof that specifically binds to human TIGIT, the antibody or antigen binding fragment comprising:
 a) amino acid sequences of complementarity determining regions (CDRs), HCDR1, HCDR2, and HCDR3, of a heavy chain variable domain (VH) comprising the amino acid sequence of SEQ ID NO: 221; and   b) amino acid sequences of CDRs, LCDR1 and LCDR3, of a light chain variable domain (VL) comprising the amino acid sequence of SEQ ID NO: 222.   
     
     
         54 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the amino acid sequence of HCDR1, HCDR2, HCDR3, LCDR1 and LCDR3 is defined according to the method of Kabat, Chothia, or MacCallum. 
     
     
         55 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the HCDR1 comprises amino acid residues selected from the group consisting of: amino acid residues 27-35, amino acid residues 31-35, amino acid residues 26-32, and amino acid residues 30-35 of SEQ ID NO: 221. 
     
     
         56 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the HCDR2 comprises amino acid residues selected from the group consisting of: amino acid residues 51-58, amino acid residues 50-65, amino acid residues 53-55, and amino acid residues 47-58 of SEQ ID NO: 221. 
     
     
         57 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the HCDR3 comprises amino acid residues selected from the group consisting of: amino acid residues 97-110, amino acid residues 95-102, amino acid residues 96-101, and amino acid residues 93-101 of SEQ ID NO: 221. 
     
     
         58 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the LCDR1 comprises amino acid residues selected from the group consisting of: amino acid residues 24-35, amino acid residues 24-34, amino acid residues 26-32, and amino acid residues 30-36 of SEQ ID NO: 222. 
     
     
         59 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the LCDR3 comprises amino acid residues selected from the group consisting of: amino acid residues 90-98, amino acid residues 89-97, amino acid residues 91-96, and amino acid residues 89-96 of SEQ ID NO: 222. 
     
     
         60 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the antibody or antigen binding fragment further comprises an LCDR2 amino acid sequence of a VL comprising the amino acid sequence of SEQ ID NO: 222. 
     
     
         61 . The isolated antibody or antigen binding fragment according to  claim 60 , wherein the LCDR2 comprises amino acid residues selected from the group consisting of: amino acid residues 51-57, amino acid residues 50-56, amino acid residues 50-52, and amino acid residues 46-55 of SEQ ID NO: 222. 
     
     
         62 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the antibody or antigen binding fragment further comprises a methionine (M) to threonine (T) substitution at amino acid residue 116 in VH framework 4 (FR4) region, wherein the M-T substitution improves stability of the antibody or antigen binding fragment compared to an antibody or antigen binding fragment not comprising the substitution. 
     
     
         63 . The isolated antibody or antigen binding fragment thereof according to  claim 53 , wherein the antibody or antigen binding fragment comprises a fragment of a human immunoglobulin. 
     
     
         64 . The isolated antibody or antigen binding fragment thereof according to  claim 63 , wherein the fragment of a human immunoglobulin is a fragment of human IgG. 
     
     
         65 . The isolated antibody or antigen binding fragment thereof according to  claim 53 , wherein the antibody is a human IgG1 antibody. 
     
     
         66 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the antibody or antigen binding fragment selectively depletes TIGIT-expressing Treg cells. 
     
     
         67 . The isolated antibody or antigen binding fragment according to  claim 53 , wherein the antibody or antigen binding fragment decreases expression of TIGIT on CD8 T cells and/or on Treg cells. 
     
     
         68 . A pharmaceutical composition comprising an effective amount of the isolated antibody or antigen binding fragment according to  claim 53 , and a pharmaceutically acceptable carrier. 
     
     
         69 . The pharmaceutical composition of  claim 68 , wherein the antibody or antigen binding fragment comprises a fragment of a human immunoglobulin, wherein the fragment of a human immunoglobulin is a fragment of human IgG. 
     
     
         70 . The pharmaceutical composition of  claim 68 , wherein the antibody is a human IgG1 antibody. 
     
     
         71 . The pharmaceutical composition of  claim 68 , wherein the antibody or antigen binding fragment selectively depletes TIGIT-expressing Treg cells. 
     
     
         72 . The pharmaceutical composition of  claim 68 , wherein the antibody or antigen binding fragment decreases expression of TIGIT on CD8 T cells and/or on Treg cells.