Antigen binding proteins

Abstract

Antigen binding proteins that bind Lymphocyte Activation Gene 3 (LAG-3), and more particularly to antigen binding proteins that cause depletion of LAG-3+ activated T cells.

1 . A method of treatment, e.g., of a disease associated with the involvement of pathogenic T cells, of a human or animal subject comprising administering a therapeutically effective amount of an antigen binding protein which is capable of binding Lymphocyte Activation Gene 3 (LAG-3) and which comprises CDRL1, CDRL2 and CDRL3 from SEQ ID NO:5 and CDRH1, CDRH2 and CDRH3 from SEQ ID NO:10. 
     
     
         2 . The method of  claim 1 , wherein the disease is an autoimmune disease, infectious disease, allergic disease or cancer. 
     
     
         3 . The method of  claim 2 , wherein the disease is an autoimmune disease and the autoimmune disease is selected from the group consisting of psoriasis, Crohn's disease, rheumatoid arthritis, primary biliary cirrhosis, systemic lupus erythematosus (SLE), Sjögren's syndrome, multiple sclerosis, ulcerative colitis and autoimmune hepatitis. 
     
     
         4 . The method of  claim 1 , wherein the antigen binding protein comprises the following CDRs:
 CDRL1: SEQ ID NO:1   CDRL2: SEQ ID NO:2   CDRL3: SEQ ID NO:3   CDRH1: SEQ ID NO:6   CDRH2: SEQ ID NO:7   CDRH3: SEQ ID NO:8.   
     
     
         5 . The method of  claim 1 , wherein the antigen binding protein comprises a) the variable light chain (VL) of SEQ ID NO:4 and b) the variable heavy chain (VH) of SEQ ID NO:9. 
     
     
         6 . The method of  claim 1 , wherein the antigen binding protein is capable of binding LAG-3 expressed on activated T-cells. 
     
     
         7 . The method of  claim 1 , wherein the antigen binding protein is capable of depleting LAG-3+ activated human T cells. 
     
     
         8 . The method of  claim 1 , wherein the antigen binding protein is a humanised antibody. 
     
     
         9 . The method of  claim 8 , wherein the humanised antibody comprises a human IgG1 constant region. 
     
     
         10 . The method of  claim 8 , wherein the antigen binding protein comprises a) a light chain sequence with at least 97% identity to SEQ ID NO:5, and b) a heavy chain sequence with at least 97% identity to SEQ ID NO:10. 
     
     
         11 . The method of  claim 8 , wherein the humanised antibody comprises a) a light chain sequence of SEQ ID NO:5, and b) a heavy chain sequence of SEQ ID NO:10. 
     
     
         12 . The method of  claim 8 , wherein the humanised antibody is non-fucosylated. 
     
     
         13 . A method of treatment, e.g., of a disease associated with the involvement of pathogenic T cells, of a human or animal subject comprising administering a therapeutically effective amount of a humanised antibody that comprises the variable light chain (VL) of SEQ ID NO:4 and the variable heavy chain (VH) of SEQ ID NO:9, wherein the antibody does not comprise fucose on the core carbohydrate structure attached to Asn297. 
     
     
         14 . An isolated nucleic acid molecule which encodes an antigen binding protein which is capable of binding Lymphocyte Activation Gene 3 (LAG-3) and which comprises CDRL1, CDRL2 and CDRL3 from SEQ ID NO:5 and CDRH1, CDRH2 and CDRH3 from SEQ ID NO:10. 
     
     
         15 . An expression vector comprising the nucleic acid molecule according to  claim 14 . 
     
     
         16 . A host cell comprising the expression vector according to  claim 15 . 
     
     
         17 . An antigen binding protein as produced by the host cell of  claim 16 . 
     
     
         18 . A method of producing an antigen binding protein, comprising a) culturing a host cell according to  claim 16  under conditions suitable to express the antigen binding protein and b) isolating the antigen binding protein. 
     
     
         19 . A host cell comprising the expression vector according to  claim 15 , wherein the FUT8 gene encoding alpha-1,6-fucosyltransferase has been inactivated in the host cell.