Anti-human interleukin-20 antibodies

Abstract

Anti-human IL20 monoclonal antibodies that can reduce IL20 mediated activation of both IL20R1/IL20R2 and IL22R1/IL20R2 receptor complexes in one or more species, including humans, are described, as well as antigen-binding molecules such as, e.g., antigen-binding antibody fragments, antibody derivatives, and multi-specific molecules designed or derived from such antibodies, and methods or producing such antibodies or other antigen-binding molecules. Such antibodies or other antigen-binding molecules can be used for treating various diseases and disorders, including autoimmune or inflammatory diseases or disorders.

1 . An isolated anti-human IL20 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region that is derived from a set of human genes comprising VH1 — 03, D3-10, and JH6 genes. 
     
     
         2 . The antibody or antigen-binding fragment of  claim 1 , wherein the heavy chain variable region comprises the CDR2 and CDR3 sequences, and optionally the CDR1 sequence, of SEQ ID NO:8, respectively corresponding to Kabat residues 50-65, 95-102, and 31-35. 
     
     
         3 . The antibody or antigen-binding fragment of  claim 1 , comprising a light chain variable region that is derived from a set of human genes comprising VKI_L18 and JK4 genes. 
     
     
         4 . The antibody or antigen-binding fragment of  claim 1 , comprising the light chain variable sequence of SEQ ID NO:9 and the heavy-chain variable sequence of SEQ ID NO:6 or SEQ ID NO:7. 
     
     
         5 . A human antibody, or an antigen-binding fragment thereof, which binds to human IL20 and has one or more properties selected from
 (a) reduces IL20-mediated activation of IL20R1/IL20R2 and IL22R1/IL20R2 receptor complexes;   (b) reduces IL20-mediated proliferation of BaF-3 cells recombinantly expressing IL20R1/IL20R2;   (c) does not reduce IL19- or IL24-mediated proliferation of BaF-3 cells recombinantly expressing IL20R1/IL20R2;   (d) binds to human IL20 with a KD of about 1 nM or less; and   (e) has a solubility of at least about 80 mg/ml in an aqueous buffered solution at about pH 7.4.   
     
     
         6 . The antibody or antigen-binding fragment of  claim 5 , which competes in binding to human IL20 with an antibody comprising a light-chain variable region comprising SEQ ID NO:9 and a heavy-chain variable region comprising SEQ ID NO:6 or SEQ ID NO:7. 
     
     
         7 . The antibody or antigen-binding fragment of  claim 6 , which binds to an epitope comprising at least one residue selected from H79-H103 of mature human IL20 (SEQ ID NO:1). 
     
     
         8 . The antibody or antigen-binding fragment of  claim 7 , wherein the epitope comprises at least one residue selected from H79-L93. 
     
     
         9 . The antibody or antigen-binding fragment of  claim 5 , comprising a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising Kabat residues residues 31-35, 50-65, and 95-102, respectively, of SEQ ID NO:6 or SEQ ID NO:7. 
     
     
         10 . The antibody or antigen-binding fragment of  claim 9 , comprising a light chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising Kabat residues 24-34, 50-56 and 89-97, respectively, of SEQ ID NO:9. 
     
     
         11 . The antibody of  claim 1 , which is of the IgG4 isotype. 
     
     
         12 . A pharmaceutical composition comprising at least about 80 mg/ml of the antibody of  claim 1 , and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         13 . The antibody, antigen-binding fragment, or pharmaceutical composition of  claim 1  for use in treating an inflammatory or autoimmune disorder. 
     
     
         14 . The antibody, antigen-binding fragment, or pharmaceutical composition of  claim 13 , for use in treating rheumatoid arthritis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Sjógren's syndrome, multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, lupus nephritis, or a combination thereof. 
     
     
         15 . A method of producing an anti-IL20 antibody or antigen-binding fragment, comprising culturing a host cell producing the antibody or antigen-binding fragment of  claim 1  under suitable conditions, and recovering said antibody or antigen-binding fragment.