The present invention is in the field of medicine. Particularly, the present invention relates to antibodies directed to T-cell immunoglobulin- and mucin-domain-containing protein-3 (Tim-3), compositions comprising such anti-Tim-3 antibodies, and methods of using such anti-Tim-3 antibodies for the treatment of solid and hematological tumors alone or in combination with chemotherapy and other cancer therapeutics.

Tumor cells escape detection and elimination by the immune system through a variety of mechanisms. One such mechanism is by the manipulation of immune checkpoint regulatory pathways that are normally used in the maintenance of self-tolerance and control of T cell activation. Cancer cells can commandeer these immune checkpoint regulatory pathways to suppress the anti-tumor response and prevent their destruction.

Although T cells recognizing tumor antigens can be isolated from patients and mouse models, such cells can exhibit an exhausted phenotype characterized by an impairment in cytotoxic functions, effector cytokine production, and proliferation.

Moreover, such tumor-infiltrating T cells can express high levels of the checkpoint regulator Tim-3. In this regard, it has been shown that anti-Tim-3 antibodies can restore anti-tumor immunity in some murine cancer models.

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 also currently being tested in human clinical trials. However, no antibody targeting

Tim-3 has been approved for therapeutic use in humans.

Tim-3 has been shown to interact with galectin-9 (SEQ ID NO:40),

phosphaditylserine (C13H24NO10P), high-mobility group Box 1 (HMGB1), and carcinoembryonic antigen cell adhesion molecule l(CEACAMl) (SEQ ID NO:39).

CEACAMl expression in the primary tumors of melanoma patients has been shown to be associated with the subsequent development of metastatic disease (Thies et al., J. Clin.

Oncol. 20, (2002), pp. 2530-2536). Additionally, CEACAMl expression has been shown to be a prognosticator for unfavorable non-small cell lung cancer (NSCLC) related survival, an independent risk factor for lymph node metastasis of colon carcinomas, associated with urinary bladder cancer and muscle invasiveness, present on thyroid carcinoma cell lines derived from tumors showing aggressive behavior, and associated with a more malignant transformation in gastric carcinomas (Fiori et al., Ann. 1st. Super Sanita 48 (2012), pp. 161-171). With regards to galectin-9, tumor-derived galectin-9 has been shown to induce the apoptosis of tumor-infiltrating Tim-3+ CD8+ T cells in a CT26 mouse colon tumor model (Kang, C.W. et al., Sci. Rep. 5:15659 (2015).

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 other checkpoint inhibitors, providing alternatives that may display improved efficacy and toxicity profiles when combined with other therapeutics. Thus, there 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.

There also remain a need for alternative anti-human Tim-3 antibodies that may be clinically beneficial. In particular, there remains a need for alternative anti-Tim-3 antibodies that specifically bind human Tim-3 and alleviate immune exhaustion such as the failure of the T cell to produce cytokines. There also remains a need for alternative anti-Tim-3 antibodies that specifically bind human Tim-3 and enhance the anti-tumor immune response. There also remains a need for anti-human Tim-3 antibodies that display sufficient potency as a cancer monotherapy.

Anti-Tim-3 antibodies of the present invention can block human Tim-3 's binding with human galectin-9 and phosphatidylserine while simultaneously not blocking the binding of human Tim-3 and human CEACAMl. Surprisingly, the anti-Tim-3 antibodies of the present invention enhance T cell responses to tumors as measured by tumor size in established tumor models by blocking the interaction of human Tim-3 with human phosphatidylserine and human galectin-9 while not blocking the interaction of human CEACAMl with human Tim-3. Surprisingly, certain anti-Tim-3 antibodies of the present invention mediate enhanced T cell responses to a tumor as measured by CD8-positive

CD3-positive T cell infiltration or persistence by blocking the interaction of human Tim-3 with human phosphatidylserine and human galectin-9 while not blocking the interaction of human CEACAM1 with human Tim-3.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively.

The present invention provides an antibody that binds human Tim-3, (SEQ ID NO:l), the antibody comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 wherein:

a) HCDR1 has the amino acid sequence of SEQ ID: 2, HCDR2 has the amino acid sequence of SEQ ID NO: 3, HCDR3 has the amino acid sequence of SEQ ID NO: 4, LCDR1 has the amino acid sequence of SEQ ID NO:5, LCDR2 has the amino acid sequence of SEQ ID NO:6, and LCDR3 has the amino acid sequence of SEQ ID NO:7;

b) HCDR1 has the amino acid sequence of SEQ ID NO: 14, HCDR2 has the amino acid sequence of SEQ ID NO: 15, HCDR3 has the amino acid sequence of SEQ ID NO: 16, LCDR1 has the amino acid sequence of SEQ ID NO: 17, LCDR2 has the amino acid sequence of SEQ ID NO: 18, and LCDR3 has the amino acid sequence of SEQ ID NO: 19; or

c) HCDR1 has the amino acid sequence of SEQ ID NO:26, HCDR2 has the amino acid sequence of SEQ ID NO:27, HCDR3 has the amino acid sequence of SEQ ID NO:28, LCDR1 has the amino acid sequence of SEQ ID NO:29, LCDR2 has the amino acid sequence of SEQ ID NO:30, and LCDR3 has the amino acid sequence of SEQ ID NO:31.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a HCDR1 of SEQ ID NO:2, HCDR2 of SEQ ID NO:3, HCDR3 of SEQ ID NO:4, LCDR1 of SEQ ID NO:5, LCDR2 of SEQ ID NO:6, and LCDR3 of SEQ ID NO:7.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a HCDR1 of SEQ ID NO: 14, HCDR2 of SEQ ID NO: 15,

LCDR3 of SEQ ID NO: 19.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a HCDR1 of SEQ ID NO:26, HCDR2 of SEQ ID NO:27, HCDR3 of SEQ ID NO:28, LCDR1 of SEQ ID NO:29, LCDR2 of SEQ ID NO:30, and LCDR3 of SEQ ID NO:31.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence given in SEQ ID NO: 8, and the LCVR has the amino acid sequence given in SEQ ID NO: 9; the HCVR has the amino acid sequence given in SEQ ID NO: 20, and the LCVR has the amino acid sequence given in SEQ ID NO: 21; or the HCVR has the amino acid sequence given in SEQ ID NO: 32, and the LCVR has the amino acid sequence given in SEQ ID NO: 33.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO:

1), the antibody comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence given in SEQ ID NO: 8, and the LCVR has the amino acid sequence given in SEQ ID NO: 9.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence given in SEQ ID NO: 20, and the LCVR has the amino acid sequence given in SEQ ID NO: 21.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence given in SEQ ID NO: 32, and the LCVR has the amino acid sequence given in SEQ ID NO: 33.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences given in SEQ ID NOs: 10 and 11,

respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain (HC) having the amino acid sequence of SEQ ID NO: 10,and a light chain (LC) having the amino acid of SEQ ID NO: 11.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain (HC) having the amino acid sequence of SEQ ID NO: 22 and a light chain (LC) having the amino acid sequence of SEQ ID NO: 23.

The present invention provides an antibody that binds human Tim-3 (SEQ ID NO: 1), the antibody comprising a heavy chain (HC) having the amino acid sequence of SEQ ID NO: 34 and a light chain (LC) having the amino acid sequence of SEQ ID NO: 35.

The present invention provides an anti-human Tim-3 antibody, comprising two heavy chains and two light chains, wherein each heavy chain (HC) has the amino acid sequence of SEQ ID NO: 10 and each light chain (LC) has the amino acid sequence of SEQ ID NO: 11.

The present invention provides an anti-human Tim-3 antibody, comprising two heavy chains and two light chains, wherein each heavy chain (HC) has the amino acid sequence of SEQ ID NO:22 and each light chain (LC) has the amino acid sequence of SEQ ID NO:23.

The present invention provides an anti-human Tim-3 antibody, comprising two heavy chains and two light chains, wherein each heavy chain (HC) has the amino acid sequence of SEQ ID NO: 34 and each light chain (LC) has the amino acid sequence of SEQ ID NO: 35.

The present invention provides an antibody that binds the same epitope on human Tim-3 (SEQ ID NO: 1), as an antibody comprising a HCDR1 of SEQ ID NO:2, HCDR2 of SEQ ID NO:3, HCDR3 of SEQ ID NO:4, LCDR1 of SEQ ID NO:5, LCDR2 of SEQ ID NO:6, and LCDR3 of SEQ ID NO:7. The present invention provides an antibody that binds the same epitope on human Tim-3 (SEQ ID NO: 1), as antibody comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence given in SEQ ID NO: 8, and the LCVR has the amino acid sequence given in SEQ ID NO: 9. The present invention provides an antibody that binds the same epitope on human Tim-3 (SEQ ID NO: 1), as an antibody comprising a heavy chain (HC) having the amino acid sequence of SEQ ID NO: 10, and a light chain (LC) having the amino acid of SEQ ID NO: 11.

The present invention provides a monoclonal antibody that binds human Tim-3 (SEQ ID NO:l), wherein said antibody blocks binding of human Tim-3 to human phosphatidylserine, but does not block binding of human Tim-3 to human CEACAM1 (SEQ ID: 39). The present invention provides a monoclonal antibody that binds human Tim-3 (SEQ ID NO:l), wherein said antibody blocks binding of human Tim-3 to human phosphatidylserine and human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 to human CEACAM1 (SEQ ID: 39).

The present invention also provides an antibody that binds a human Tim-3 (SEQ

ID NO:l) epitope, wherein the antibody contacts residues 50, 55-65, 72, 107, 111, 113-120, and 122 of human Tim-3 (SEQ ID NO: l). The present invention also provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts residues 50, 55-65, 72, 107, 111, 113-120, and 122 of human Tim-3 (SEQ ID NO: 1); wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody. The present invention also provides an antibody that binds a human Tim-3 (SEQ ID NO: 1) epitope, wherein the antibody contacts residues 50, 55-65, 72, 107, 111, 113-120, and 122 of human Tim-3 (SEQ ID NO: 1); wherein the epitope is determined by X-ray

crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody; wherein said antibody blocks binding of human Human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40) (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO:l) to human CEACAM1 (SEQ ID: 39).

The present invention provides an antibody that binds an epitope on human Tim-3

(SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive). The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody. The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody; wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: l) to human CEACAM1 (SEQ ID: 39).

The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive), wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues.

The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive), wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody; wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40),

but does not block binding of human Tim-3 (SEQ ID NO: 1) to human CEACAMl (SEQ ID: 39).

The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); and wherein the antibody further contacts at least one residue of the following: 56-61 (inclusive), 107, 119-120 (inclusive) , and 122. The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO: l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); and wherein the antibody further contacts at least one residue of the following: 56-61 (inclusive), 107, 119-120 (inclusive), and 122; wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody; wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: 1) to human CEACAMl (SEQ ID: 39).

The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive), wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; and wherein the antibody further contacts at least one residue of the following: 56-61 (inclusive), 107, 119-120 (inclusive), and 122.

The present invention provides an antibody that binds an epitope on human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive), wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; wherein the antibody further contacts at least one residue of the following: 56-61 (inclusive), 107, 119-120 (inclusive), and 122; wherein the epitope is determined by X-ray crystallography and wherein the residues in contact are within six (6) angstroms or less of the antibody; and wherein said antibody blocks binding of human Tim-3 (SEQ ID NO: 1) to human phosphatidylserine and human Tim-3 (SEQ ID NO: 1) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO:l) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive). An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65

(inclusive), 72, 111, and 113-118 (inclusive); optionally, wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: 1) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the residues in contact are within six (6) angstroms or less of the antibody, as determined by X-ray crystallography; optionally, wherein said antibody blocks binding of human Tim-3 (SEQ ID NO: 1) to human phosphatidylserine and human Tim-3 (SEQ ID NO: 1) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO:l) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the residues in contact are within six (6) angstroms or less of the antibody, as determined by X-ray crystallography; wherein the antibody further

contacts at least one residue of the following: 56-61 (inclusive), 107, 119-120 (inclusive) , and 122; optionally, wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO:l) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts amino acid residues 50, 55-65, 72, 107, 111, 113-120, and 122. An antibody that binds human Tim-3 (SEQ ID NO: l), wherein the antibody contacts amino acid residues 50, 55-65, 72, 107, 111, 113-120, and 122, as determined by X-ray crystallography. An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts amino acid residues 50, 55-65, 72, 107, 111, 113-120, and 122, as determined by X-ray crystallography; optionally, wherein said antibody blocks binding of human Tim-3 (SEQ ID NO: l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: 1) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues.

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: l) to human CEACAM1 (SEQ ID: 39).

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; wherein the residues in contact are within six (6) angstroms or less of the antibody, as determined by X-ray crystallography.

An antibody that binds human Tim-3 (SEQ ID NO:l), wherein the antibody contacts at least one amino acid residue of the following: 50, 55, 62-65 (inclusive), 72, 111, and 113-118 (inclusive); wherein the antibody contacts: at least two of the residues; preferably at least three of the residues; more preferably at least four of the residues; more preferably at least five of the residues; more preferably at least six of the residues; more preferably at least seven of the residues; more preferably at least eight of the residues; more preferably at least nine of the residues; more preferably at least ten of the residues; more preferably at least eleven of the residues; more preferably at least twelve of the residues; more preferably at least thirteen of the residues; or more preferably all of the residues; wherein the residues in contact are within six (6) angstroms or less of the antibody, as determined by X-ray crystallography; optionally, wherein said antibody blocks binding of human Tim-3 (SEQ ID NO:l) to human phosphatidylserine and human

Tim-3 (SEQ ID NO:l) to human galectin-9 (SEQ ID: 40), but does not block binding of human Tim-3 (SEQ ID NO: l) to human CEACAM1 (SEQ ID: 39).

The present invention provides an anti-human Tim-3 antibody, wherein the antibody is glycosylated.

The present invention provides a DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO.10, 22, or 34. The present invention provides a DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO. 11, 23, or 35. The present invention provides a DNA molecule comprising a pair of

polynucleotide sequences encoding two distinct polypeptides having the amino acid sequence of SEQ ID NO. 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides a DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO. 10, 22, or 34, wherein the polynucleotide sequence comprises SEQ ID NO. 12, 24, or 36, respectively. The present invention provides a DNA molecule comprising a

polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO. 11, 23, or 35, wherein the polynucleotide sequence comprises SEQ ID N0.13, 25, or 37, respectively.

The present invention provides a mammalian cell capable of expressing an antibody comprising a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences given in SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides a mammalian cell capable of expressing an antibody comprising a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11.

The present invention provides a mammalian cell capable of expressing an antibody comprising a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23.

The present invention provides a mammalian cell capable of expressing an antibody comprising a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

The present invention provides a process for producing an antibody comprising cultivating a mammalian cell capable of expressing the antibody and recovering the antibody; wherein the antibody comprises a heavy chain and a light chain having the amino acid sequences given in SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides a process for producing an antibody comprising cultivating a mammalian cell capable of expressing the antibody and recovering the antibody; wherein the 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.

The present invention provides a process for producing an antibody comprising cultivating a mammalian cell capable of expressing the antibody and recovering the antibody; wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 22 and a light chain having the amino acid sequences of SEQ ID NO: 23.

The present invention provides a process for producing an antibody comprising cultivating a mammalian cell capable of expressing the antibody and recovering the antibody; wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 34 and a light chain having the amino acid sequence of SEQ ID NO: 35.

The present invention provides an anti-human Tim-3 antibody disclosed herein produced by a process of the present invention.

The present invention provides a pharmaceutical composition, comprising an anti-human Tim-3 antibody of the present invention, and an acceptable carrier, diluent, or excipient.

The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention.

In some embodiments, the present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti- human Tim-3 antibody, wherein the cancer is melanoma, lung cancer, non-small cell 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.

In some embodiments, the present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the the antibody comprises a HCDR1,

HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences shown in SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively.

In some embodiments, the present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the the antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

In some embodiments, the present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the the antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is melanoma. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is lung cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the lung cancer is non-small cell lung cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is head and neck cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is colorectal cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is pancreatic cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is gastric cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is kidney cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is bladder cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is prostate cancer.

The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is breast cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is ovarian cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is esophageal cancer. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is soft tissue sarcoma. The present invention provides a method of treating cancer, comprising administering to a patient in need, thereof an effective amount of an anti-human Tim-3 antibody of the present invention, wherein the cancer is liver cancer.

In some embodiments, the methods comprise the administration of an effective amount of an anti-human Tim-3 antibody of the present invention in simultaneous, separate, or sequential combination with one or more chemotherapeutic agents. Non-limiting examples of chemotherapeutic agents include 5-fluorouracil, hydroxyurea, gemcitabine, methotrexate, pemetrexed, doxorubicin, etoposide, cetuximab, carboplatin, cisplatin, cyclophosphamide, melphalan, dacarbazine, taxol, camptothecin, FOLFIRI, docetaxel, daunorubicin, paclitaxel, oxaliplatin, and combinations thereof. In some embodiments, the methods comprise the administration of an effective amount of an anti-human Tim-3 antibody of the present invention in simultaneous, separate, or sequential combination with ionizing radiation.

The present invention provides an anti-human Tim-3 antibody, for use in therapy.

The present invention provides an anti-human Tim-3 antibody, for use in therapy;

wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences shown in SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti- human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises HCDR1 having the amino acid sequence of SEQ ID NO: 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. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 and comprises HCDR1 having the amino acid sequence of SEQ ID NO: 14, HCDR2 having the amino acid sequence of SEQ ID NO: 15, HCDR3 having the amino acid sequence of SEQ ID NO: 16, LCDRl having the amino acid sequence of SEQ ID NO: 17, LCDR2 having the amino acid sequence of SEQ ID NO: 18, and LCDR3 having the amino acid sequence of SEQ ID NO: 19. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a HCDR1 having the amino acid sequence of SEQ ID NO: 26, HCDR2 having the amino acid sequence of SEQ ID NO: 27, HCDR3 having the amino acid sequence of SEQ ID NO: 28, LCDRl having the amino acid sequence of SEQ ID NO: 29, LCDR2 having the amino acid sequence of SEQ ID NO: 30, and LCDR3 having the amino acid sequence of SEQ ID NO: 31.

The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti -human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23. The present invention provides an anti-human Tim-3 antibody, for use in therapy; wherein the anti-human Tim-3 antibody binds human Tim-3 (SEQ ID NO: 1) and comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences shown in SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID NO: 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. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID NO: 14, HCDR2 having the amino acid sequence of SEQ ID NO: 15, HCDR3 having the amino acid sequence of SEQ ID NO: 16, LCDRl having the amino acid sequence of SEQ ID NO: 17, LCDR2 having the amino acid sequence of SEQ ID NO: 18, and LCDR3 having the amino acid sequence of SEQ ID NO: 19. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDR1 having the amino acid sequence of SEQ ID NO: 26, HCDR2 having the amino acid sequence of SEQ ID NO: 27, HCDR3 having the amino acid sequence of SEQ ID NO: 28, LCDRl having the amino acid sequence of SEQ ID NO: 29, LCDR2 having the amino acid sequence of SEQ ID NO: 30, and LCDR3 having the amino acid sequence of SEQ ID NO: 31.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti -human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region

(HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33. The present invention provides an anti-human Tim-3 antibody, for use

in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti -human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences given in SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO:35.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-human Tim-3 antibody comprises a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is lung cancer. The present invention provides an anti-human Tim-3 antibody for use in the treatment of lung cancer, wherein the lung cancer is non-small cell lung cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is head and neck cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is colorectal cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is pancreatic cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is gastric cancer. The present invention provides an anti-human Tim-3, for use in the treatment of cancer, wherein the cancer is kidney cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is bladder cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is prostate cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is breast cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is ovarian cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is esophageal cancer. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is soft tissue sarcoma. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is liver cancer.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma; wherein the anti-human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is lung cancer; wherein the anti-human Tim-3 antibody comprises 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti -human Tim-3 antibody for use in the treatment of lung cancer, wherein the lung cancer is non-small cell lung cancer; wherein the anti-human Tim-3 antibody comprises 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is head and neck cancer; wherein the anti-human Tim-3 antibody comprises 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is colorectal cancer; wherein the anti-human Tim-3 antibody comprises 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti -human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is pancreatic cancer; wherein the anti-human Tim-3 antibody comprises a 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is gastric cancer; wherein the anti-human Tim-3 antibody comprises a 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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3, for use in the treatment of cancer, wherein the cancer is kidney cancer; wherein the anti-human Tim-3 antibody comprises a

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; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is bladder cancer; wherein the anti-human Tim-3 antibody comprises a HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is prostate cancer;

wherein the anti-human Tim-3 antibody comprises a HCDRl , HCDR2, HCDR3, LCDRl , LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is breast cancer; wherein the anti-human Tim-3 antibody comprises a HCDRl , HCDR2, HCDR3, LCDRl , LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is ovarian cancer; wherein the anti-human Tim-3 antibody comprises a HCDRl , HCDR2, HCDR3, LCDRl , LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is esophageal cancer; wherein the anti-human Tim-3 antibody comprises a HCDRl , HCDR2, HCDR3, LCDRl , LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is soft tissue sarcoma; wherein the anti-human Tim-3 antibody comprises a HCDRl , HCDR2, HCDR3, LCDRl , LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is liver cancer; wherein the anti-human Tim-3 antibody comprises a HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively.

The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is melanoma; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is lung cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody for use in the treatment of lung cancer, wherein the lung cancer is non-small cell lung cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is head and neck cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is colorectal cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is pancreatic cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is gastric cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3, for use in the treatment of cancer, wherein the cancer is kidney cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is bladder cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is prostate cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is breast cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is ovarian cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti -human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is esophageal cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is soft tissue sarcoma; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides an anti-human Tim-3 antibody, for use in the treatment of cancer, wherein the cancer is liver cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the an anti -human Tim-3 antibody for use in simultaneous, separate, or sequential combination with one or more chemotherapeutic agents.

The present invention provides an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with with one or more

chemotherapeutic agents in the treatment of cancer. The present invention provides an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with with one or more chemotherapeutic agents in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with with one or more

chemotherapeutic agents in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides an effective amount of an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with ionizing radiation. The present invention provides an effective amount of an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with ionizing radiation in the treatment of cancer. The present invention provides an effective amount of an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with ionizing radiation in the treatment of cancer; wherein the anti -human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences shown in SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides an effective amount of an anti-human Tim-3 antibody for use in simultaneous, separate, or sequential combination with ionizing radiation in the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer.

The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 14, 15, 16, 17, 18, and 19, respectively. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody

comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 26, 27, 28, 29, 30, and 31, respectively.

The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti -human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region

(HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences given in SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO:23. The present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer; wherein the anti -human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

In a further embodiment, the present invention provides the use of an anti-human

Tim-3 antibody for the manufacture of a medicament for the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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. In a further embodiment, the present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-Tim-3 antibody comprises HCDR1, HCDR2, HCDR3,

LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. In a further embodiment, the present invention provides the use of an anti-human Tim-3 antibody for the manufacture of a medicament for the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC comprises a heavy chain variable region (HCVR) and the LC comprises a light chain variable region (LCVR), wherein: the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9; the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33. In a further embodiment, the present invention provides the use of an anti-human Tim- 3 antibody for the manufacture of a medicament for the treatment of cancer, wherein the cancer is melanoma, lung cancer, non-small cell 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; wherein the anti-Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences given in SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of melanoma; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of melanoma; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of lung cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1,

LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of lung cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of non-small cell lung cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2,

HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of non-small cell lung cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of head and neck cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti -human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of head and neck cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of colorectal

cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti -human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of colorectal cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of pancreatic cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29,

30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of pancreatic cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of gastric cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and

31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of gastric cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of kidney cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1,

LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of kidney cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of bladder cancer; wherein the anti-human Tim-3 antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consisting of the amino acid sequences of SEQ ID NOs: 2, 3, 4, 5, 6, and 7, respectively; 14, 15, 16, 17, 18, and 19, respectively; or 26, 27, 28, 29, 30, and 31, respectively. The present invention provides the use of an anti-human Tim-3 antibody of the present invention in the manufacture of a medicament for the treatment of bladder cancer; wherein the anti-human Tim-3 antibody comprises a heavy chain (HC) and a light chain (LC), wherein the HC and the LC have the amino acid sequences of SEQ ID NOs: 10 and 11, respectively; 22 and 23, respectively; or 34 and 35, respectively.

WE CLAIM:

1. An antibody that binds human Tim-3, (SEQ ID NO:l), the antibody comprising

HCDRl, HCDR2, HCDR3, LCDRl, LCDR2, and LCDR3 wherein:

a) HCDRl has the amino acid sequence of SEQ ID: 2, HCDR2 has the amino acid sequence of SEQ ID NO: 3, HCDR3 has the amino acid sequence of SEQ ID NO: 4, LCDRl has the amino acid sequence of SEQ ID NO:5, LCDR2 has the amino acid sequence of SEQ ID NO:6, and LCDR3 has the amino acid sequence of SEQ ID NO:7;

b) HCDRl has the amino acid sequence of SEQ ID NO: 14, HCDR2 has the amino acid sequence of SEQ ID NO: 15, HCDR3 has the amino acid sequence of SEQ ID NO: 16, LCDRl has the amino acid sequence of SEQ ID NO: 17, LCDR2 has the amino acid sequence of SEQ ID NO: 18, and LCDR3 has the amino acid sequence of SEQ ID NO: 19; or

c) HCDRl has the amino acid sequence of SEQ ID NO:26, HCDR2 has the amino acid sequence of SEQ ID NO:27, HCDR3 has the amino acid sequence of SEQ ID NO:28, LCDRl has the amino acid sequence of SEQ ID NO:29, LCDR2 has the amino acid sequence of SEQ ID NO:30, and LCDR3 has the amino acid sequence of SEQ ID NO:31.

2. The antibody of claim 1, wherein HCDRl has the amino acid sequence of SEQ ID: 2, HCDR2 has the amino acid sequence of SEQ ID NO: 3, HCDR3 has the amino acid sequence of SEQ ID NO: 4, LCDRl has the amino acid sequence of SEQ ID NO:5, LCDR2 has the amino acid sequence of SEQ ID NO: 6, and LCDR3 has the amino acid sequence of SEQ ID NO:7.

3. The antibody of claim 1, wherein HCDRl has the amino acid sequence of SEQ ID NO: 14, HCDR2 has the amino acid sequence of SEQ ID NO: 15, HCDR3 has the amino acid sequence of SEQ ID NO: 16, LCDRl has the amino acid sequence of SEQ ID NO: 17, LCDR2 has the amino acid sequence of SEQ ID NO: 18, and LCDR3 has the amino acid sequence of SEQ ID NO: 19.

4. The antibody of claim 1, wherein HCDRl has the amino acid sequence of SEQ ID NO:26, HCDR2 has the amino acid sequence of SEQ ID NO:27, HCDR3 has the amino acid sequence of SEQ ID NO:28, LCDRl has the amino acid sequence of SEQ ID NO:29, LCDR2 has the amino acid sequence of SEQ ID NO:30, and LCDR3 has the amino acid sequence of SEQ ID NO:31.

5. An antibody, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein:

a) the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9;

b) the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21; or

c) the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

6. The antibody of claim 5, wherein the HCVR has the amino acid sequence of SEQ ID NO: 8, and the LCVR has the amino acid sequence of SEQ ID NO: 9.

7. The antibody of claim 5, wherein the HCVR has the amino acid sequence of SEQ ID NO: 20, and the LCVR has the amino acid sequence of SEQ ID NO: 21.

8. The antibody of claim 5, wherein the HCVR has the amino acid sequence of SEQ ID NO: 32, and the LCVR has the amino acid sequence of SEQ ID NO: 33.

9. An antibody, comprising a heavy chain (HC) and a light chain (LC), wherein:

a. the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11 ;

b. the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23; or

c. the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

10. The antibody of claim 9, wherein the HC has the amino acid sequence of SEQ ID NO:

10 and the LC has the amino acid sequence of SEQ ID NO: 11.

11. The antibody of claim 9, wherein the HC has the amino acid sequence of SEQ ID NO:

22 and the LC has the amino acid sequence of SEQ ID NO: 23.

12. The antibody of claim 9, wherein the HC has the amino acid sequence of SEQ ID NO:

34 and the LC has the amino acid sequence of SEQ ID NO: 35.

13. The antibody of any one of claims 9-12, wherein the antibody has two of the heavy chains and two of the light chains.

14. The antibody of claim 13, wherein one of the heavy chains forms an inter-chain disulfide bond with one of the light chains, and the other heavy chain forms an interchain disulfide bond with the other light chain, and one of the heavy chains forms two inter-chain disulfide bonds with the other heavy chain.

15. The antibody of any one of claims 1-14, wherein the antibody is glycosylated.

16. A mammalian cell capable of expressing an antibody comprising a heavy chain (HC) and a light chain (LC), wherein:

a. the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11 ;

b. the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23; or

c. the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

17. The mammalian cell of claim 16, wherein the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11.

18. The mammalian cell of claim 16, wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23.

19. The mammalian cell of claim 16, wherein the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

20. A process for producing an antibody comprising cultivating a mammalian cell capable of expressing the antibody and recovering the antibody; wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein:

a. the HC has the amino acid sequence of SEQ ID NO: 10 and the LC has the amino acid sequence of SEQ ID NO: 11 ;

b. the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23; or

c. the HC has the amino acid sequence of SEQ ID NO: 34 and the LC has the amino acid sequence of SEQ ID NO: 35.

21. The process of claim 20, wherein the HC has the amino acid sequence of SEQ ID NO:

10 and the LC has the amino acid sequence of SEQ ID NO: 11.

22. The process of claim 20, wherein the HC has the amino acid sequence of SEQ ID NO: 22 and the LC has the amino acid sequence of SEQ ID NO: 23.

23. The process of claim 20, wherein the HC has the amino acid sequence of SEQ ID NO:

34 and the LC has the amino acid sequence of SEQ ID NO: 35.

24. The antibody produced by the process of any one of claims 20-23.

25. A pharmaceutical composition, comprising the antibody of any one of claims 1-15 and an acceptable carrier, diluent, or excipient.

26. A method of treating cancer, comprising administering to a patient in need, thereof an effective amount of the antibody of any one of claims 1-15.

27. The method of claim 26, 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.

28. The method of claim 27, wherein the lung cancer is non-small cell lung cancer.

29. The method of any one of claims 26-28, wherein the antibody is administered in

simultaneous, separate, or sequential combination with ionizing radiation.

30. The method of any one of claims 26-29, wherein the antibody is administered in

simultaneous, separate, or sequential combination with one or more chemotherapeutic agents.

31. The antibody of any one of claims 1-15, for use in therapy.

32. The antibody of any one of claims 1-15, for use in the treatment of cancer.

33. The antibody for use of claim 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 antibody for use of claim 33, wherein the lung cancer is non-small cell lung

cancer.

35. The antibody for use of any one of claims 32-34, wherein the antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation.

36. The antibody for use of any one of claims 32-35, wherein the antibody is administered in simultaneous, separate, or sequential combination with one or more

chemotherapeutic agents.

37. The use of the antibody of claims 1-15 for the manufacture of a medicament for the treatment of cancer.

38. The antibody for use of claim 37, 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.

39. The antibody for use of claim 38, wherein the lung cancer is non-small cell lung cancer.

40. The antibody for use of any one of claims 37-39, wherein the antibody is administered in simultaneous, separate, or sequential combination with ionizing radiation.

41. The antibody for use of any one of claims 37-40, wherein the antibody is administered in simultaneous, separate, or sequential combination with one or more

chemotherapeutic agents.