Antibodies against human il17 and uses thereof

Abstract

An antibody binding to IL-17 characterized by binding to the same IL-17 epitope to which monoclonal antibody 3C1 binds, and being of human IgG1 isotype modified in the hinge region at amino acid position 216-240, preferably at amino acid position 220-240, between C H 1 and C H 2 and/or in the second inter-domain region at amino acid position 327-331 between C H 2 and C H 3 has advantageous properties for the treatment of inflammatory diseases.

1 - 17 . (canceled) 
     
     
         18 . An antibody binding to human IL-17, wherein said antibody binds to the same IL-17 epitope to which monoclonal antibody 3C1 (DSM ACC2941) binds. 
     
     
         19 . The antibody of  claim 18 , having the human IgG1 isotype modified in the hinge region at amino acid position 216-240. 
     
     
         20 . The antibody of  claim 18 , having the human IgG1 isotype modified in the second inter-domain region at amino acid position 327-331 between C H 2 and C H 3. 
     
     
         21 . The antibody of  claim 18 , having the human IgG1 isotype modified in both the hinge region at amino acid position 216-240 and in the second inter-domain region at amino acid position 327-331 between C H 2 and C H 3. 
     
     
         22 . The antibody of  claim 18 , having the human IgG1 isotype modified in the hinge region at amino acid position 220-240. 
     
     
         23 . The antibody of  claim 18 , wherein the antibody comprises mutations L234A and L235A. 
     
     
         24 . The antibody of  claim 18 , wherein the antibody binds to IL-17 with an affinity of at least 10 −8  M −1  to 10 −12  M −1 . 
     
     
         24 . The antibody of  claim 18 , wherein the antibody is a humanized or human antibody. 
     
     
         25 . A pharmaceutical composition comprising the antibody of  claim 18 , and a pharmaceutically acceptable excipient. 
     
     
         26 . An antibody binding to human IL-17, wherein said antibody contains an Fc part of human origin. 
     
     
         27 . The antibody of  claim 26 , wherein said antibody does not bind human complement factor C1q. 
     
     
         28 . The antibody of  claim 27  wherein said antibody is an antibody of human subclass IgG1 or IG2, and contains at least one mutation in L234, L235, and D265 and/or contains the PVA236 mutation. 
     
     
         29 . The antibody of  claim 27  wherein said antibody is an antibody of human subclass IgG1 or IG2, and contains at least one mutation selected from L234A, L235A, L235E and PVA236. 
     
     
         30 . The antibody of  claim 26  wherein said antibody is an antibody of human subclass IgG1 and contains at least one mutation in L234, L235, D270, N297, E318, K320, K322, and P331. 
     
     
         31 . The antibody of  claim 30  wherein said antibody binds to IL-17 with a K D  value of less than 10 −8  M in a BIAcore assay. 
     
     
         32 . A method for producing the antibody of  claim 27 , the method comprising:
 modifying the sequence of a nucleic acid encoding the heavy chain of a human IgG1 type antibody binding to IL-17 to include at least one mutation selected from L234A, L235A, L235E and PVA236;   inserting the modified nucleic acid and the nucleic acid encoding the light chain of said antibody into an expression vector;   inserting the expression vector in a eukaryotic host cell;   expressing the antibody in the eukaryotic host cell; and   recovering the antibody from the eukaryotic host cell or the supernatant.   
     
     
         33 . A method for inhibiting release of IL-8 from cells, the method comprising treating the cells with an antibody of  claim 18 . 
     
     
         34 . The method of  claim 33 , wherein the cells express IL-17 receptor. 
     
     
         35 . The method of  claim 33 , wherein the cells are stimulated with TNF-alpha.