Anti il-36r antibodies

Abstract

The present invention relates to anti-IL-36R binding compounds, in particular new anti-IL-36R antibodies and therapeutic and diagnostic methods and compositions for using the same.

1 . An anti-IL-36R antibody or antigen-binding fragment thereof, which binds to human IL-36R at a K D  equal to or <0.1 nM. 
     
     
         2 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the said antibody or antigen-binding fragment is a monoclonal antibody or antigen-binding fragment thereof. 
     
     
         3 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the said antibody or antigen-binding fragment is a humanized antibody or antigen-binding fragment thereof. 
     
     
         4 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 3 , which binds to human IL-36R at a K D  equal to or <50 pM. 
     
     
         5 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , which does not bind to human IL-1R1. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
 a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36 (L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36 (L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 (H-CDR1); the amino acid sequence of SEQ ID NO: 64 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36 (L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 54 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 or 64 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3).   
     
     
         17 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment fragment thereof comprises a light chain variable region comprising the amino acid sequence of any one of SEQ ID NO: 84, 85 or 86; and a heavy chain variable region comprising the amino acid sequence of any one of SEQ ID NO: 96, 97, 98, 99, 100 or 101. 
     
     
         18 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 17 , wherein the antibody or antigen-binding fragment fragment thereof comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 85; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 100; or
 a light chain variable region comprising the amino acid sequence of SEQ ID NO: 85;   and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:101.   
     
     
         19 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 17 , wherein the antibody or antigen-binding fragment fragment thereof comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86; and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 100; or
 a light chain variable region comprising the amino acid sequence of SEQ ID NO: 86;   and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:101.   
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . An anti-IL-36R antibody according to  claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of any one of SEQ ID NO: 122, 123 or 124; and a heavy chain comprising the amino acid sequence of any one of SEQ ID NO: 134, 135, 136, 137, 138 or 139. 
     
     
         28 . An anti-IL-36R antibody according to  claim 27 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         29 . An anti-IL-36R antibody according to  claim 27 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 123; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 139. 
     
     
         30 . An anti-IL-36R antibody according to  claim 27 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 124; and a heavy chain comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment fragment thereof comprises:
 a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36(L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and   b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3).   
     
     
         34 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment fragment thereof comprises:
 a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36(L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and   b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 (H-CDR1); the amino acid sequence of SEQ ID NO: 64 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3).   
     
     
         35 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment fragment thereof comprises:
 a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21 (L-CDR1); the amino acid sequence of SEQ ID NO: 30 (L-CDR2); the amino acid sequence of SEQ ID NO: 39 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 48 (H-CDR1); the amino acid sequence of SEQ ID NO: 57 (H-CDR2); the amino acid sequence of SEQ ID NO: 67 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); the amino acid sequence of SEQ ID NO: 40 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 49 (H-CDR1); the amino acid sequence of SEQ ID NO: 58 (H-CDR2); the amino acid sequence of SEQ ID NO: 68 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 23 (L-CDR1); the amino acid sequence of SEQ ID NO: 32 (L-CDR2); the amino acid sequence of SEQ ID NO: 41 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 50 (H-CDR1); the amino acid sequence of SEQ ID NO: 59 (H-CDR2); the amino acid sequence of SEQ ID NO: 69 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 24 (L-CDR1); the amino acid sequence of SEQ ID NO: 33 (L-CDR2); the amino acid sequence of SEQ ID NO: 42 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 51 (H-CDR1); the amino acid sequence of SEQ ID NO: 60 (H-CDR2); the amino acid sequence of SEQ ID NO: 70 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25 (L-CDR1); the amino acid sequence of SEQ ID NO: 34 (L-CDR2); the amino acid sequence of SEQ ID NO: 43 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 52 (H-CDR1); the amino acid sequence of SEQ ID NO: 61 (H-CDR2); the amino acid sequence of SEQ ID NO: 71 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 26 (L-CDR1); the amino acid sequence of SEQ ID NO: 35 (L-CDR2); the amino acid sequence of SEQ ID NO: 44 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 53 (H-CDR1); the amino acid sequence of SEQ ID NO: 62 (H-CDR2); the amino acid sequence of SEQ ID NO: 72 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36 (L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 54 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 27 (L-CDR1); the amino acid sequence of SEQ ID NO: 36 (L-CDR2); the amino acid sequence of SEQ ID NO: 45 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 54 (H-CDR1); the amino acid sequence of SEQ ID NO: 64 (H-CDR2); the amino acid sequence of SEQ ID NO: 73 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28 (L-CDR1); the amino acid sequence of SEQ ID NO: 37 (L-CDR2); the amino acid sequence of SEQ ID NO: 46 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 55 (H-CDR1); the amino acid sequence of SEQ ID NO: 65 (H-CDR2); the amino acid sequence of SEQ ID NO: 74 (H-CDR3); or   a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29 (L-CDR1); the amino acid sequence of SEQ ID NO: 38 (L-CDR2); the amino acid sequence of SEQ ID NO: 47 (L-CDR3); and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 56 (H-CDR1); the amino acid sequence of SEQ ID NO: 66 (H-CDR2); the amino acid sequence of SEQ ID NO: 75 (H-CDR3).   
     
     
         36 . An anti-IL-36R antibody or antigen-binding fragment thereof according to  claim 1 , wherein the antibody or antigen-binding fragment fragment thereof comprises a light chain protein comprising the amino acid sequence of SEQ ID NO: 1;
 and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 11; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 2; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 12; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 3; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 13; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 4; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 14; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 5; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 15; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 6; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 16; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 7; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 17; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 8; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 18; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 9; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 19; or   a light chain protein comprising the amino acid sequence of SEQ ID NO: 10; and a heavy chain protein comprising the amino acid sequence of SEQ ID NO: 20.   
     
     
         37 . A pharmaceutical composition comprising an antibody or antigen-binding fragment according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         38 . A method of treating a disease comprising administering the antibody or antigen-binding fragment according to  claim 1  or a pharmaceutical composition thereof, to a patient in need thereof, wherein the disease is selected from an inflammatory disease, an autoimmune disease, a respiratory disease, a metabolic disorder, an epithelial mediated inflammatory disorder, fibrosis and cancer. 
     
     
         39 . A method according to  claim 38 , wherein the disease is selected from psoriasis, inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, COPD, chronic asthma and ankylosing spondylitis. 
     
     
         40 . A method according to  claim 38 , wherein the disease is Crohn's disease. 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . Diagnostic kit or diagnostic method comprising an anti-IL-36R antibody or antigen-binding fragment according to  claim 1 , or the use thereof. 
     
     
         46 . Diagnostic kit or diagnostic method according to  claim 45 , for the diagnosis of an inflammatory disease, an autoimmune disease, a respiratory disease, a metabolic disorder, an epithelial mediated inflammatory disorder, fibrosis, cancer, psoriasis, inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, COPD, chronic asthma, ankylosing spondylitis, or Crohn's disease.