ANTI-TIGIT ANTIBODIES AND APPLICATION THEREOF
Provided are antibodies that bind specifically to TIGIT or antigen binding fragments of the antibodies and a composition thereof. Also provided are a nucleic acid molecule coding the antibodies or the antigen binding fragments thereof, an expression vector and a host cell for expressing the antibodies or the antigen binding fragments thereof, and therapeutic and diagnostic uses of the antibodies.
1 . An isolated anti-TIGIT antibody or an antigen-binding fragment thereof, wherein the anti-TIGIT antibody or the antigen-binding fragment thereof comprises:
(1) 1 to 3 heavy chain complementarity determining regions selected from heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, wherein the HCDR1 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 1 or 11, the HCDR2 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 2 or 12, and the HCDR3 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 3 or 13; and/or
(2) 1 to 3 light chain complementarity determining regions selected from light chain complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein the LCDR1 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 6 or 16, the LCDR2 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 7 or 17, and the LCDR3 comprises an amino acid sequence identical to or having at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 8 or 18.
2 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3 and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein:
(1) the HCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 1, the HCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 2, the HCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 3, the LCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 6, the LCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 7, and the LCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 8; or
(2) the HCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 11, the HCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 12, the HCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 13, the LCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 16, the LCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 17, and the LCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 18.
3 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
the VH comprises an amino acid sequence identical to or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to any amino acid sequence selected from SEQ ID NOs: 4, 14, 21, 23, 25, 27 and 29; and/or
the VL comprises an amino acid sequence identical to or having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to any amino acid sequence selected from SEQ ID NOs: 9, 19, 22, 24, 26, 28 and 30.
4 . The antibody or the antigen-binding fragment thereof according to claim 3 , wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and the antibody is selected from:
(1) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 4 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 9;
(2) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 14 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 19;
(3) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 21 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 22;
(4) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 23 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 24;
(5) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 25 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 26;
(6) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 27 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 28; and
(7) an antibody in which a VH comprises an amino acid sequence set forth in SEQ ID NO: 29 and a VL comprises an amino acid sequence set forth in SEQ ID NO: 30.
5 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein an amino acid sequence of a heavy chain of the antibody is set forth in SEQ ID NO: 31 or 33, and/or an amino acid sequence of a light chain of the antibody is set forth in SEQ ID NO: 32 or 34.
6 . The antibody or the antigen-binding fragment thereof according to claim 5 , wherein the amino acid sequence of the heavy chain of the antibody is set forth in SEQ ID NO: 31, and the amino acid sequence of the light chain of the antibody is set forth in SEQ ID NO: 32; or the amino acid sequence of the heavy chain of the antibody is set forth in SEQ ID NO: 33, and the amino acid sequence of the light chain of the antibody is set forth in SEQ ID NO: 34.
7 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is a murine antibody, a chimeric antibody, a humanized antibody or a fully human antibody.
8 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody or the antigen-binding fragment thereof is a complete antibody, a single-chain antibody, a Fab antibody, a Fab′ antibody, a (Fab′)2 antibody or a bispecific (multi specific) antibody.
9 . The antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is of any IgG subtype, such as IgG1, IgG2, IgG3 or IgG4.
10 . An isolated nucleic acid molecule, encoding an anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 .
11 . An isolated nucleic acid molecule of claim 10 , encoding an anti-TIGIT antibody or the antigen-binding fragment comprising the amino acid sequence set forth in any of SEQ ID NOs: 1-4, 6-9, 11-14, 16-19, and 21-34.
12 . An isolated nucleic acid molecule of claim 10 , wherein the isolated nucleic acid molecule is selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 10, SEQ ID NO: 15, and SEQ ID NO: 20.
13 . A pharmaceutical composition, comprising a composition of the antibody or the antigen-binding fragment thereof according to claim 1 and a pharmaceutically acceptable carrier or excipient.
14 . The pharmaceutical composition according to claim 13 , further comprising a PD-1 axis antagonist.
15 . A method for treating and/or preventing a TIGIT-mediated disease or disorder in a subject, comprising: administering to the subject an effective amount of anti-TIGIT antibody or the antigen-binding fragment thereof according to claim 1 , the isolated nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, or a pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof or the isolated nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof, wherein preferably, the disease or disorder is cancer.
16 . The method according to claim 15 , further comprising: co-administering to the subject one or more therapies comprising surgical treatment and/or radiation therapy, and/or administering one or more other therapeutic agents comprising a chemotherapeutic agent, a PD-1 axis antagonist and an anti-angiogenic agent.
17 . The method according to claim 16 , wherein the therapeutic agent is a PD-1 axis antagonist, wherein preferably, the anti-PD-1 axis antagonist is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody.
18 .- 20 . (canceled)