Antibodies Directed Against T Cell Immunoglobulin and Mucin Protein 3 (TIM-3)

Abstract

Provided herein are anti-T Cell Immunoglobulin and Mucin Protein-3 (TIM-3) antibodies having particular immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide sequences and methods of using the anti-TIM-3 antibodies to treat a disorder or disease that is responsive to TIM-3 inhibition, such as cancer, an infectious disease, or an autoimmune disease.

1 - 14 . (canceled) 
     
     
         15 . An antibody agent comprising a heavy chain polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1, and a light chain polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 2. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The antibody agent of  claim 15 , wherein the antibody agent binds to TEVI-3 with a K D  between about 1 picomolar (pM) and about 100 micromolar (μM). 
     
     
         19 . A composition comprising the antibody agent of  claim 15  and a pharmaceutically acceptable carrier. 
     
     
         20 . (canceled) 
     
     
         21 . A method of treating a disorder in a mammal that is responsive to TIM-3 inhibition, which method comprises administering an effective amount of the antibody agent of  claim 15  to a mammal having a disorder that is responsive to TIM-3 inhibition, whereupon the disorder is treated in the mammal. 
     
     
         22 - 26 . (canceled) 
     
     
         27 . The method of  claim 21 , wherein the disorder is cancer. 
     
     
         28 . The method of  claim 27 , wherein the cancer is
 adenocarcinoma, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, testicular cancer, primary peritoneal cancer, colon cancer, colorectal cancer, stomach cancer, small intestine cancer, squamous cell carcinoma of the anogenital region, melanoma, renal cell carcinoma, lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous cell carcinoma of the lung, stomach cancer, bladder cancer, gall bladder cancer, liver cancer, thyroid cancer, laryngeal cancer, salivary gland cancer, esophageal cancer, head and neck cancer, squamous cell carcinoma of the head and neck, prostate cancer, pancreatic cancer, mesothelioma, Merkel cell carcinoma, sarcoma, glioblastoma, a hematological cancer, multiple myeloma, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma/primary mediastinal B-cell lymphoma, or chronic myelogenous leukemia.   
     
     
         29 - 34 . (canceled) 
     
     
         35 . The method of  claim 21 , wherein the method further comprises administering to the mammal an agent that inhibits Programmed Cell Death 1 (PD-1), and wherein the agent that inhibits PD-1 is a PD-1-binding agent. 
     
     
         36 . The method of  claim 35 , wherein the PD-1-binding agent is an antibody, an antibody conjugate, or an antigen-binding fragment thereof. 
     
     
         37 . The method of  claim 36 , wherein the agent that inhibits PD-1 is nivolumab, pembrolizumab or TSR-042. 
     
     
         38 - 54 . (canceled) 
     
     
         55 . The method of  claim 21 , wherein the mammal is human. 
     
     
         56 . The method of  claim 21 , wherein the mammal has previously been treated with one or more different cancer treatment modalities. 
     
     
         57 . The method of  claim 56 , wherein the mammal has previously been treated with one or more of surgery, radiotherapy, chemotherapy, or immunotherapy. 
     
     
         58 . The method of  claim 56 , wherein the mammal has previously been treated with a cytotoxic therapy. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 21 , wherein the method further comprises administering one or more of surgery, a radiotherapy, a chemotherapy, an immunotherapy, an anti-angiogenic agent, or an anti-inflammatory. 
     
     
         61 . (canceled) 
     
     
         62 . A method of manufacturing the antibody agent of  claim 15  by expressing a nucleic acid encoding the antibody agent in a host cell culture. 
     
     
         63 - 65 . (canceled) 
     
     
         66 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2. 
     
     
         67 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2. 
     
     
         68 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2. 
     
     
         69 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 96% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 96% sequence identity to SEQ ID NO: 2. 
     
     
         70 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 97% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 97% sequence identity to SEQ ID NO: 2. 
     
     
         71 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 2. 
     
     
         72 . The antibody agent of  claim 15 , wherein the heavy chain polypeptide comprising an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 1, and/or wherein the light chain polypeptide comprising an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 2. 
     
     
         73 . The method of  claim 27 , wherein the cancer is a lung cancer. 
     
     
         74 . The method of  claim 27 , wherein the cancer is a non-small cell lung cancer. 
     
     
         75 . The method of  claim 27 , wherein the cancer is a lung adenocarcinoma. 
     
     
         76 . The method of  claim 27 , wherein the cancer is melanoma. 
     
     
         77 . The method of  claim 27 , wherein the administration is by intravenous injection. 
     
     
         78 . The method of  claim 35 , wherein the agent that inhibits PD-1 is nivolumab. 
     
     
         79 . The method of  claim 35 , wherein the agent that inhibits PD-1 is pembrolizumab. 
     
     
         80 . The method of  claim 35 , wherein the agent that inhibits PD-1 is TSR-042.