Anti-Galectin-9 antibodies and uses thereof
Disclosed herein are anti-Galectin-9 antibodies and methods of using such for inhibiting a signaling pathway mediated by Galectin-9 or eliminating pathologic cells expressing Galectin-9. Such anti-Galectin-9 antibodies may also be used to diagnose and/or to treat diseases associated with Galectin-9, such as autoimmune diseases and solid tumors.
1. An isolated antibody, which binds human galactin-9, wherein the antibody comprises a heavy chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 361, a heavy chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 388, and a heavy chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 406 and/or comprises a light chain complementarity determining region 1 (CDR1) set forth as SEQ ID NO: 328, a light chain complementary determining region 2 (CDR2) set forth as SEQ ID NO: 329, and a light chain complementary determining region 3 (CDR3) set forth as SEQ ID NO: 352.
2. The isolated antibody of claim 1 , wherein the antibody binds to an epitope in a carbohydrate recognition domain (CRD) of galectin-9.
3. The isolated antibody of claim 2 , wherein the CRD is CRD2.
4. The isolated antibody of claim 3 , wherein the CRD2 consists of the amino acid sequence of SEQ ID NO: 4.
5. The isolated antibody of claim 1 , which is a full-length antibody or an antigen-binding fragment thereof.
6. The isolated antibody of claim 1 , which is a single chain antibody.
7. The isolated antibody of claim 1 , which is a human antibody or a humanized antibody.
8. The isolated antibody of claim 1 , wherein the antibody comprises a VH set forth as SEQ ID NO: 55 and a VL set forth as SEQ ID NO: 54.
9. The isolated antibody of claim 8 , wherein the antibody binds to an epitope in a carbohydrate recognition domain (CRD) of galectin-9, wherein the CRD is CRD2.
10. The isolated antibody of claim 8 , which is a full-length antibody or an antigen-binding fragment thereof.
11. The isolated antibody of claim 8 , which is a single chain antibody.
12. The isolated antibody of claim 8 , which is a human antibody or a humanized antibody.
13. The isolated antibody of claim 8 , which is an IgG molecule.
14. The isolated antibody of claim 13 , wherein the antibody is an IgG1 or IgG4 molecule.
15. The isolated antibody of claim 14 , wherein the antibody is an IgG4 molecule, wherein the IgG4 has a S228P mutation.
16. The isolated antibody of claim 14 , wherein the antibody comprises a heavy chain constant region set forth as SEQ ID NO: 422, and/or a light chain constant region set forth as SEQ ID NO: 418.
17. The isolated antibody of claim 8 , wherein the antibody comprises a V H set forth as SEQ ID NO: 55 and a V L set forth as SEQ ID NO: 54, and has a heavy chain constant region set forth as SEQ ID NO: 422 and a light chain constant region set forth as SEQ ID NO: 418.
18. The isolated antibody of claim 17 , wherein the antibody comprises a heavy chain set forth as SEQ ID NO: 316 and a light chain set forth as SEQ ID NO:108.
19. The isolated antibody of claim 18 , wherein the antibody is G9.2-17.
20. The isolated antibody of claim 19 , wherein the antibody binds to an epitope in a carbohydrate recognition domain (CRD) of galectin-9, wherein the CRD is CRD2.
21. A pharmaceutical composition comprising the antibody of claim 19 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the antibody of claim 17 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier.
24. The isolated antibody of claim 1 , which is an IgG molecule.
25. The isolated antibody of claim 24 , wherein the antibody is an IgG1 or IgG4 molecule.
26. The isolated antibody of claim 25 , wherein the antibody is an IgG4 molecule, wherein the IgG4 has a S228P mutation.
27. The isolated antibody of claim 25 , wherein the antibody comprises a heavy chain constant region set forth as SEQ ID NO: 422, and/or a light chain constant region set forth as SEQ ID NO: 418.
28. The isolated antibody of claim 1 , wherein the antibody has a V L CDR1 set forth as SEQ ID NO: 328, a V L CDR2 set forth as SEQ ID NO: 329, a V L CDR3 set forth as SEQ ID NO: 352, a V H CDR1 set forth as SEQ ID NO: 361, a V H CDR2 set forth as SEQ ID NO: 388, a V H CDR3 set forth as SEQ ID NO: 406, and has a heavy chain constant region set forth as SEQ ID NO: 422 and a light chain constant region set forth as SEQ ID NO: 418.
29. The isolated antibody of claim 1 , wherein the antibody comprises a heavy chain set forth as SEQ ID NO: 316 and/or a light chain set forth as SEQ ID NO:108.
30. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.