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 galectin-9, wherein the antibody comprises:
(a) a heavy chain that comprises a heavy chain variable region (VH), which comprises a heavy chain complementarity determining region 1 (CDR1) comprising FTVSSSSIH (SEQ ID NO: 361), a heavy chain complementary determining region 2 (CDR2) comprising YISSSSGYTYYADSVKG (SEQ ID NO: 388), and a heavy chain complementary determining region 3 (CDR3) comprising YWSYPSWWPYRGMDY (SEQ ID NO: 406); and
(b) a light chain that comprises a light chain variable region, which comprises a light chain complementarity determining region 1 (CDR1) comprising RASQSVSSAVA (SEQ ID NO: 328), a light chain complementary determining region 2 (CDR2) comprising SASSLYS (SEQ ID NO: 329), and a light chain complementary determining region 3 (CDR3) comprising QQSSTDPIT (SEQ ID NO: 352).
2 . The isolated antibody of claim 1 , which is a full-length antibody or an antigen-binding fragment thereof.
3 . The isolated antibody of claim 1 , which is a single chain antibody.
4 . The isolated antibody of claim 1 , which is a human antibody.
5 . The isolated antibody of claim 1 , which is an IgG molecule.
6 . The isolated antibody of claim 5 , wherein the antibody is an IgG1 or IgG4 molecule.
7 . The isolated antibody of claim 6 , wherein the antibody is an IgG4 molecule.
8 . The isolated antibody of claim 7 , wherein the IgG molecule has a S228P mutation.
9 . The isolated antibody of claim 1 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 316 and a light chain comprising the amino acid sequence of SEQ ID NO: 108.
10 . The isolated antibody of claim 9 , wherein the heavy chain consists of the amino acid sequence of SEQ ID NO: 316 and the light chain consists of the amino acid sequence of SEQ ID NO: 108.
11 . A pharmaceutical composition, comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
12 . The pharmaceutical composition of claim 11 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 316 and a light chain comprising the amino acid sequence of SEQ ID NO: 108.
13 . The pharmaceutical composition of claim 12 , wherein the heavy chain consists of the amino acid sequence of SEQ ID NO: 316 and the light chain consists of the amino acid sequence of SEQ ID NO: 108.
14 . The pharmaceutical composition of claim 13 , wherein the pharmaceutically acceptable carrier comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
15 . The pharmaceutical composition of claim 12 , wherein the pharmaceutically acceptable carrier comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
16 . The pharmaceutical composition of claim 11 , wherein the pharmaceutically acceptable carrier comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
17 . A method for inhibiting the activity of galectin-9 or treating a solid tumor in a subject, the method comprising administering to the subject in need thereof an effective amount of the pharmaceutical composition of claim 11 .
18 . The method of claim 17 , wherein the pharmaceutical composition comprises an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 316 and a light chain comprising the amino acid sequence of SEQ ID NO: 108.
19 . The method of claim 18 , wherein the heavy chain consists of the amino acid sequence of SEQ ID NO: 316 and the light chain consists of the amino acid sequence of SEQ ID NO: 108.
20 . The method of claim 19 , wherein the pharmaceutical composition comprises a pharmaceutical acceptable carrier, which comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
21 . The method of claim 18 , wherein the pharmaceutical composition comprises a pharmaceutical acceptable carrier, which comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
22 . The method of claim 18 , wherein the subject is a human patient having or suspected of having a solid tumor.
23 . The method of claim 22 , wherein the solid tumor is selected from the group consisting of pancreatic cancer, head and neck cancer, bladder cancer, renal cancer, breast cancer, cervical cancer, melanoma, lung cancer, endometrial cancer, ovarian cancer, gastric cancer, esophageal cancer, sarcomas, cholangiocarcinoma, mesothelioma, colorectal cancer, prostate cancer, penile cancer and glioblastoma.
24 . The method of claim 22 , wherein the solid tumor is pancreatic cancer, melanoma, colorectal or cholangiocarcinoma.
25 . The method of claim 22 , wherein the solid tumor is metastatic.
26 . The method of claim 22 , further comprising subjecting the human patient to a radiation therapy, an immunotherapy, or a chemotherapy.
27 . The method of claim 26 , wherein the human patient is treated with an immunotherapy, which comprises a checkpoint inhibitor.
28 . The method of claim 27 , wherein the checkpoint inhibitor is an anti-PD-1 antibody.
29 . The method of claim 26 , wherein the human patient is treated with a chemotherapy.
30 . The method of claim 17 , wherein the pharmaceutical composition comprises a pharmaceutical acceptable carrier, which comprises a buffer, a preservative, an amino acid, a chelating agent, a non-ionic surfactant, or a combination thereof.
31 . The method of claim 17 , wherein the subject is a human patient having or suspected of having a solid tumor.
32 . The method of claim 31 , wherein the solid tumor is selected from the group consisting of pancreatic cancer, head and neck cancer, bladder cancer, renal cancer, breast cancer, cervical cancer, melanoma, lung cancer, endometrial cancer, ovarian cancer, gastric cancer, esophageal cancer, sarcomas, cholangiocarcinoma, mesothelioma, colorectal cancer, prostate cancer, penile cancer and glioblastoma.
33 . The method of claim 31 , wherein the solid tumor is metastatic.
34 . The method of claim 33 , wherein the solid tumor is pancreatic cancer, melanoma, colorectal or cholangiocarcinoma.
35 . The method of claim 31 , further comprising subjecting the human patient to a radiation therapy, an immunotherapy, or a chemotherapy.
36 . The method of claim 35 , wherein the human patient is treated with an immunotherapy, which comprises a checkpoint inhibitor.
37 . The method of claim 36 , wherein the checkpoint inhibitor is an anti-PD-1 antibody.
38 . The method of claim 35 , wherein the human patient is treated with a chemotherapy.
39 . The method of claim 38 , wherein the chemotherapy comprises gemcitabine, paclitaxel, or a combination thereof.