Antibodies Directed Against Lymphocyte Activation Gene 3 (LAG-3)

Abstract

The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to a protein encoded by the Lymphocyte Activation Gene-3 (LAG-3). The invention provides a LAG-3-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using, the LAG-3-binding, agent to treat a disorder or disease that is responsive to LAG-3 inhibition, such as cancer or an infectious disease.

1 - 42 . (canceled) 
     
     
         43 . A method of treating cancer in a human, said method comprising:
 administering to said human an effective amount of a Lymphocyte Activation Gene-3 (LAG-3) binding antibody comprising:
 (i) an immunoglobulin light chain variable (VL) region comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3 of SEQ ID NO:88; and, 
 (ii) an immunoglobulin heavy chain variable (VH) region comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 of SEQ ID NO: 182. 
   
     
     
         44 . The method according to  claim 43 , wherein the cancer is melanoma, renal cell carcinoma, lung cancer, bladder cancer, breast cancer, cervical cancer, colon cancer, gall bladder cancer, laryngeal cancer, liver cancer, thyroid cancer, stomach cancer, salivary gland cancer, prostate cancer, pancreatic cancer, or Merkel cell carcinoma. 
     
     
         45 . The method according to  claim 43 , further comprising administering an anti-PD-1 antibody to the human subject. 
     
     
         46 . The method according to  claim 43 , further comprising administering an anti-TIM-3 antibody to the human subject. 
     
     
         47 . The method according to  claim 43 , wherein the LAG-3 binding antibody is an IgG4 antibody. 
     
     
         48 . A method of treating cancer in a human, said method comprising:
 administering to said human an effective amount of a Lymphocyte Activation Gene-3 (LAG-3) binding antibody comprising:
 (i) an immunoglobulin light chain variable (VL) region comprising SEQ ID NO:88; and, 
 (ii) an immunoglobulin heavy chain variable (VH) region comprising SEQ ID NO: 182. 
   
     
     
         49 . The method according to  claim 48 , wherein the cancer is melanoma, renal cell carcinoma, lung cancer, bladder cancer, breast cancer, cervical cancer, colon cancer, gall bladder cancer, laryngeal cancer, liver cancer, thyroid cancer, stomach cancer, salivary gland cancer, prostate cancer, pancreatic cancer, or Merkel cell carcinoma. 
     
     
         50 . The method according to  claim 48 , further comprising administering an anti-PD-1 antibody to the human. 
     
     
         51 . The method according to  claim 48 , further comprising administering an anti-TIM-3 antibody to the human. 
     
     
         52 . The method according to  claim 48 , wherein the LAG-3 binding antibody is an IgG4 antibody. 
     
     
         53 . A method of treating lung cancer, colon cancer, or melanoma in a human, said method comprising:
 administering to said human an effective amount of a Lymphocyte Activation Gene-3 (LAG-3) binding antibody comprising:
 (i) an immunoglobulin light chain variable (VL) region comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3 of SEQ ID NO:88; and, 
 (ii) an immunoglobulin heavy chain variable (VH) region comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 of SEQ ID NO: 182. 
   
     
     
         54 . The method according to  claim 53 , further comprising administering an anti-PD-1 antibody to the human. 
     
     
         55 . The method according to  claim 53 , further comprising administering an anti-TIM-3 antibody to the human. 
     
     
         56 . The method according to  claim 53 , wherein the LAG-3 binding antibody is an IgG4 antibody. 
     
     
         57 . A method of treating lung cancer, colon cancer, or melanoma in a human, said method comprising:
 administering to said human an effective amount of an IgG4 Lymphocyte Activation Gene-3 (LAG-3) binding antibody comprising:
 (i) an immunoglobulin light chain variable (VL) region comprising SEQ ID NO:88; and, 
 (ii) an immunoglobulin heavy chain variable (VH) region comprising SEQ ID NO: 182. 
   
     
     
         58 . The method according to  claim 57 , further comprising administering an anti-PD-1 antibody to the human. 
     
     
         59 . The method according to  claim 57 , further comprising administering an anti-TIM-3 antibody to the human.