Anti-TIGIT Antibodies
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.