IL-17 Antagonistic Antibodies

Abstract

An IL-17 binding molecule, in particular an antibody to human IL-17, more preferably a human antibody to human IL-17 is provided, wherein the hypervariable regions of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-17 mediated disease or disorder, e.g. rheumatoid arthritis.

1 . An IL-17 binding molecule which is capable of inhibiting the activity of 1 nM human IL-17 at a concentration of less than 5 nM by 50%, said inhibitory activity being measured on IL-6 production induced by human IL-17 on human dermal fibroblasts. 
     
     
         2 . The IL-17 binding molecule according to  claim 1 , comprising a heavy chain variable domain (V H ) and a light chain variable domain (V L ), wherein the V H  and V L  together form an antigen binding site, wherein said antigen binding site comprises:
 a) in sequence, CDR1, CDR2 and CDR3 in the V H , said CDR1 having the amino acid sequence SEQ ID NO: 1, said CDR2 having the amino acid sequence SEQ ID NO:2, and said CDR3 having the amino acid sequence SEQ ID NO:3 or direct CDR equivalents thereof; and   b) in sequence, CDR1′, CDR2′ and CDR3′ in the V L , said CDR1′ having the amino acid sequence SEQ ID NO:4, said CDR2′ having the amino acid sequence SEQ ID NO:5, and said CDR3′ having the amino acid sequence SEQ ID NO:6 or direct CDR′ equivalents thereof.   
     
     
         3 . The IL-17 binding molecule according to  claim 1 , comprising a heavy chain variable domain (V H ) and a light chain variable domain (V L ), wherein the V H  and V L  together form an antigen binding site, wherein said antigen binding site comprises:
 a) in sequence, CDR1-x, CDR2-x and CDR3-x in the V H , said CDR1-x having the amino acid sequence SEQ ID NO:11, said CDR2-x having the amino acid sequence SEQ ID NO: 12, and said CDR3-x having the amino acid sequence SEQ ID NO: 13 or direct CDR-x equivalents thereof; and   b) in sequence, CDR1′, CDR2′ and CDR3′ in the V L , said CDR1′ having the amino acid sequence SEQ ID NO:4, said CDR2′ having the amino acid sequence SEQ ID NO:5, and said CDR3′ having the amino acid sequence SEQ ID NO:6 or direct CDR′ equivalents thereof.   
     
     
         4 . The IL-17 binding molecule according to  claim 1 , which is a human antibody. 
     
     
         5 . A DNA construct encoding the IL-17 binding molecule according to  claim 4 . 
     
     
         6 . An expression vector able to replicate in a eukaryotic cell line comprising at least one DNA construct according to  claims 5 . 
     
     
         7 . A host cell comprising the expression vector according to  claim 6 . 
     
     
         8 . A process for the product of an IL-17 binding molecule, comprising:
 (i) culturing the host cell according to  claim 7  under conditions sufficient to express the IL-17 binding molecule therefrom; and   (ii) recovering the IL-17 binding molecule from the host cell culture.   
     
     
         9 . A method of treating an IL-17-mediated disease or disorder, comprising administering a therapeutically effective amount of the IL-17 binding molecule according to  claim 1  to a patient in need thereof. 
     
     
         10 . The method according to  claim 9 , wherein the disease or disorder is psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, uveitis, juvenile diabetes, asthma or multiple sclerosis. 
     
     
         11 . A pharmaceutical composition comprising the antibody to IL-17 according to  claim 1  in combination with a pharmaceutically acceptable excipient, diluent or carrier.