The present invention is in the field of medicine. Particularly, the present invention relates to antibodies directed to human T-cell immunoglobulin- and mucin-domain-containing protein-3 (Tim-3) (SEQ ID NO: 1) that can be combined with antibodies directed to human PD-1 (SEQ ID NO: 34), compositions comprising such anti-human Tim-3 antibodies or anti-human PD-1 antibodies, and methods of using such anti-human Tim-3 antibodies in combination with anti -human PD-1 antibodies for the treatment of solid and hematological tumors alone or in further combination with chemotherapy, ionizing radiation, and other cancer therapeutics.

Tumor cells escape detection and elimination by the immune system through multiple mechanisms some of which include the manipulation of immune checkpoint pathways. Immune checkpoint pathways are used in self-tolerance maintenance and in the regulation of T cell activation, but cancer cells can manipulate these pathways to prolong tumor survival. The PD-l/human programmed cell death 1 ligand 1 (PD-L1) pathway is one such immune checkpoint. Human PD-1 (SEQ ID NO: 34) is expressed on T cells, and the binding of PD-L1 or PD-L2 to PD-1 has been shown to inhibit T cell proliferation and cytokine production. Morever, some tumors are known to express PD-Ll and PD-L2 and such expression can contribute to the inhibition of the intratumoral immune response.

In addition to the PD-1/PD-L1 pathway, T cells recognizing tumor antigens can also express other checkpoint receptors, such as Tim-3. In particular, T cells expressing Tim-3 can exhibit an exhausted phenotype characterized by an impairment in cytotoxic functions, effector cytokine production, and proliferation. In this regard, it has been shown that anti-Tim-3 antibodies can restore anti-tumor immunity in some murine cancer models. Morever, it has also been shown that some patients who develop adaptive resistance to anti -PD-1 treatment display an upregulation of Tim-3 on their T cells.

Antibodies directed to human Tim-3 are known. Humanized antibodies against human Tim-3 are described in W015117002. MBG453, an anti-human Tim-3 antibody, is currently being tested in human clinical trials as a single agent and in combination with an anti-human PD-1 antibody. However, no antibody targeting Tim-3 has been approved

for therapeutic use in humans nor has any anti-human Tim-3 antibody been shown to display efficacy against human tumors when combined with an anti-human PD-1 antibody. Thus, there remains a need for anti-human Tim-3 antibodies that can be combined with anti-human PD-1 antibodies as well as other therapies for treating human cancers.

Tim-3 (SEQ ID NO: 1) has been shown to interact with galectin-9 (SEQ ID NO: 15), phosphaditylserine (C13H24NO10P), high-mobility group Box 1 (HMGB1), and carcinoembryonic antigen cell adhesion molecule l(CEACAMl) (SEQ ID NO: 14).

Because all of the aforementioned Tim-3 ligands are not exclusive ligands of Tim-3, it is desirable to provide therapeutic anti-Tim-3 antibodies that differentially block the activity of said ligands as these ligands can regulate the immune system independently of Tim-3. Such a strategy can provide alternative ways to more specifically modulate Tim-3 activity, allowing for tailored immuno-oncology based therapies for patients.

Furthermore, such anti-Tim-3 antibodies can provide options for combinatorial therapies with anti -human PD-1 antibodies. Thus, there also remains a need to provide antibodies that bind human Tim-3 and inhibit Tim-3 's interactions with some of Tim-3 's ligands, but not others, and that can be combined with anti-human PD-1 antibodies.

The anti-human Tim-3 antibodies described herein can block human Tim-3 (SEQ ID NO: 1) from binding to human galectin-9 (SEQ ID NO: 15) and phosphatidylserine while simultaneously not blocking the binding of human Tim-3 and human CEACAM1 (SEQ ID NO: 14). Surprisingly,the anti-Tim-3 antibodies of the present invention can be combined with an anti -human PD-1 antibody to enhance tumor clearance. Surprisingly, the anti-Tim-3 antibodies described herein block human Tim-3 interactions with phosphatidylserine (C13H24NO10P) and galectin-9 (SEQ ID NO: 15), but not human Tim-3 ' s interactions with CEACAM1 (SEQ ID NO: 14) and can be combined with an anti-human PD-1 antibody to treat cancer.

While antibodies targeting PD-1 (SEQ ID NO:34) for cancer immunotherapy have proven effective for some cancers, some cancers become less sensitive to PD-1 therapy over time or do not respond at all. In some embodiments, the present invention provides an anti-human Tim-3 antibody that can be administered to patients who have progressed or are progressing under anti-human PD-1 antibody therapy. In some embodiments, the

present invention provides an anti-human Tim-3 antibody that can be administered in combination with an anti-human PD-1 antibody to patients who have no previously received anti -human PD-1 antibody therapy.

The present invention includes anti -human Tim-3 (SEQ ID NO: 1) antibodies comprising HCDR1, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; and/or a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 for simultaneous, separate, or sequential combination with an anti-human PD-1 antibody.

Non-limiting examples of known anti -human PD-1 antibodies include PDR001 (described in US20150210769; CAS registry number 1859072-53-9), MEDI0680, REGN2810, BGB-A317, nivolumab (CAS registry number 946414-94-4; wherein nivolumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 30 and a light chain having the amino acid sequence of SEQ ID NO: 31), and

pembrolizumab (CAS registry number 137-4853-91-4; wherein pembrolizumab comprises a heavy chain having the amino acid sequence of SEQ ID NO: 32 and a light chain having the amino acid sequence of SEQ ID NO: 33). Furthermore, said known anti-human PD-1 antibodies can be expressed in a variety of cell lines and produced via various manufacturing processes and may exhibit some difference(s) as a result.

Non-limiting examples of other anti-human PD-1 (SEQ ID NO: 34) antibodies include anti-human PD-1 antibodies comprising at least one of the following: (a) HCDR1 having the amino acid sequence of SEQ ID: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the

amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti -human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1

(SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 1 1.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO:

7; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 1 1; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or

pembrolizumab.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody comprises: (a) HCDRl having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of

SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1

(SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; wherein the anti-human PD-1 antibody comprises: (a) HCDRl having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19,

LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 1 1; wherein the anti-human PD-1 antibody comprises: a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is melanoma. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is lung cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is melanoma. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the lung cancer is non-small cell lung cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is head and neck cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is colorectal cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti -human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is pancreatic cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is gastric cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is kidney cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an

effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is bladder cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is prostate cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is breast cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is ovarian cancer. A method of treating cancer comprising

administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is esophageal cancer. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous,

separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is soft tissue sarcoma. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is liver cancer.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti -human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation and/or one or more chemotherapeutic agents.

A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises: (a) HCDRl having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26; wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation and/or one or more chemotherapeutic agents.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ

ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or

pembrolizumab.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody is PDR001, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the

amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti -human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti -human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is melanoma. An effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present

invention for use in simultaneous, separate, or sequential combination with an effective amount of an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is lung cancer. An an anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is melanoma. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the lung cancer is non-small cell lung cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is head and neck cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is colorectal cancer. An anti -human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is pancreatic cancer. An anti -human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is gastric cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is kidney cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is bladder cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is prostate cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is breast cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11; and wherein the cancer is ovarian cancer. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody

comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is esophageal cancer. An anti -human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is soft tissue sarcoma. An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is liver cancer.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti -human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation and/or one or more chemotherapeutic agents.

An anti-human Tim-3 (SEQ ID NO: 1) antibody of the present invention for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody; optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26; wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in

simultaneous, separate, or sequential combination with ionizing radiation and/or one or more chemotherapeutic agents.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7; wherein the anti-human PD-1 antibody is PDROOl, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody is PDROOl, REGN2810, MEDI0680, BGB-A317, nivolumab, or

pembrolizumab .

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody is PDROOl, REGN2810, MEDI0680, BGB-A317, nivolumab, or pembrolizumab.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of

SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9; wherein the anti-human PD-1 antibody comprises: (a) HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises: (a)

HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21 ; (b) a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23; (c) a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26; or (d) a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a medicament for the treatment of cancer, wherein the medicament is to be administered simultaneously, separately, or sequentially with and an anti -human PD-1 (SEQ ID NO: 34) antibody, optionally, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11 ; and wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

WE CLAIM:

1. A method of treating cancer comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 (SEQ ID NO: 1) antibody in simultaneous, separate, or sequential combination with an effective amount of an anti -human PD-1

(SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDRl having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7.

2. The method of Claim 1, wherein the anti -human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9.

3. The method of Claim 2, wherein the anti -human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11.

4. The method of any one of Claims 1-3, wherein the anti-human PD-1 antibody is

nivolumab, or pembrolizumab.

5. The method of any one of Claims 1-3, wherein the anti -human PD-1 antibody

comprises HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDRl having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21.

6. The method of Claim 5, wherein the anti -human PD-1 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23.

7. The method of Claim 6, wherein the anti -human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

8. The method of Claim 6, wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

9. The method of any one of Claims 1-8, wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

10. The method of Claim 9, wherein the lung cancer is non-small cell lung cancer.

11. The method of any one of Claims 1-10, wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation.

12. The method of any one of Claims 1-11, wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with one or more chemotherapeutic agents.

13. An anti-human Tim-3 (SEQ ID NO: 1) antibody for use in simultaneous, separate, or sequential combination with an anti-human PD-1 (SEQ ID NO: 34) antibody, in the treatment of cancer, wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO: 5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO: 7.

14. The anti-human Tim-3 antibody for use of claim 13, wherein the anti-human Tim-3 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of

SEQ ID NO: 9.

15. The anti-human Tim-3 antibody for use of claim 14, wherein the anti-human Tim-3 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11.

16. The anti-human Tim-3 antibody for use of any one of Claims 13-15, wherein the anti- human PD-1 antibody is nivolumab, or pembrolizumab.

17. The anti-human Tim-3 antibody for use of any one of Claims 13-15, wherein the anti- human PD-1 antibody comprises HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and

LCDR3 having the amino acid sequence of SEQ ID NO: 21.

18. The anti-human Tim-3 antibody for use of Claim 17, wherein the anti-human PD-1 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23.

19. The anti-human Tim-3 antibody for use of Claim 18, wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

20. The anti-human Tim-3 antibody for use of Claim 18, wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

21. The anti-human Tim-3 antibody for use of any one of Claims 13-20, wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

22. The anti-human Tim-3 antibody for use of Claim 21, wherein the lung cancer is non- small cell lung cancer.

23. The anti-human Tim-3 antibody for use of any one of Claims 13-22, wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation.

24. The anti-human Tim-3 antibody for use of any one of Claims 13-23, wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with one or more

chemotherapeutic agents.

25. Use of an anti-human Tim-3 (SEQ ID NO: 1) antibody for the manufacture of a

medicament for the treatment of cancer, wherein the medicament is to be

administered simultaneously, separately, or sequentially with an anti-human PD-1 (SEQ ID NO: 34) antibody; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID: 2, HCDR2 having the amino acid sequence of SEQ ID NO: 3, HCDR3 having the amino acid sequence of SEQ ID NO: 4, LCDR1 having the amino acid sequence of SEQ ID NO:5, LCDR2 having the amino acid sequence of SEQ ID NO: 6, and LCDR3 having the amino acid sequence of SEQ ID NO:7.

26. The use of Claim 25, wherein the anti-human Tim-3 antibody comprises a heavy

chain variable region having the amino acid sequence of SEQ ID NO: 8 and a light chain variable region having the amino acid sequence of SEQ ID NO: 9.

27. The use of Claim 26, wherein the anti-human Tim-3 antibody comprises a heavy

chain having the amino acid sequence of SEQ ID NO: 10 and a light chain having the amino acid sequence of SEQ ID NO: 11.

28. The use of any one of Claims 25-27, wherein the anti-human PD-1 antibody is

nivolumab, or pembrolizumab.

29. The use of any one of Claims 25-27, wherein the anti-human PD-1 antibody

comprises HCDR1 having the amino acid sequence of SEQ ID NO: 16, HCDR2 having the amino acid sequence of SEQ ID NO: 17, HCDR3 having the amino acid sequence of SEQ ID NO: 18, LCDR1 having the amino acid sequence of SEQ ID NO: 19, LCDR2 having the amino acid sequence of SEQ ID NO: 20, and LCDR3 having the amino acid sequence of SEQ ID NO: 21.

30. The use of Claim 29, wherein the anti-human PD-1 antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 22 and a light chain variable region having the amino acid sequence of SEQ ID NO: 23.

31. The use of Claim 30, wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 24 and a light chain having the amino acid sequence of SEQ ID NO: 26.

32. The use of Claim 30, wherein the anti-human PD-1 antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 25 and a light chain having the amino acid sequence of SEQ ID NO: 26.

33. The use of any one of Claims 25-32, wherein the cancer is melanoma, lung cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric cancer, kidney cancer, bladder cancer, prostate cancer, breast cancer, ovarian cancer, esophageal cancer, soft tissue sarcoma, or liver cancer.

34. The use of Claim 33, wherein the lung cancer is non-small cell lung cancer.

35. The use of any one of Claims 25-34, wherein at least one of the anti -human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation.
36. The use of any one of Claims 25-35, wherein at least one of the anti-human Tim-3 antibody and anti-human PD-1 antibody is administered in simultaneous, separate, or sequential combination with one or more chemotherapeutic agents.