Antibodies against human IL17 and uses thereof
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. An antibody binding to human IL-17, comprising a heavy chain and a light chain, characterized in that:
the heavy chain comprises a variable domain comprising a CDR3 region of SEQ ID NO:1, a CDR2 region selected from SEQ ID NO:2 and SEQ ID NO:9, and a CDR1 region of SEQ ID NO:3; and
the light chain variable domain comprises a CDR3 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5, and a CDR1 region of SEQ ID NO:6.
2. The antibody of claim 1 , wherein the heavy chain variable domain comprises SEQ ID NO:7 or SEQ ID NO:10.
3. The antibody of claim 2 , wherein the light chain variable domain comprises SEQ ID NO:8.
4. The antibody of claim 1 , characterized in being a chimeric or humanized antibody of antibody 3C1 (DSM ACC2941).
5. The antibody of claim 1 , having the human IgG1 isotype modified:
in the hinge region at amino acid position 216-240;
in the second inter-domain region at amino acid position 327-331 between C H 2 and C H 3; or
in both the hinge region and the second inter-domain region.
6. A pharmaceutical composition comprising the antibody according to claim 1 , and a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 , wherein said antibody binds to the same IL-17 epitope to which monoclonal antibody 3C1 (DSM ACC2941) binds.
8. An antibody binding to human IL-17, characterized by binding to the same IL-17 epitope to which monoclonal antibody 3C1 (DSM ACC2941) binds, being of human IgG1 isotype modified in the hinge region at amino acid position 216-240, and/or in the second inter-domain region at amino acid position 327-331 between C H 2 and C H 3.
9. The antibody according to claim 8 , characterized by comprising mutations L234A (alanine instead of leucine at amino acid position 234) and L235A.
10. An antibody binding to human IL-17, wherein the antibody is produced by the hybridoma cell line DSM ACC2941.
11. A hybridoma cell line DSM ACC2941.
12. A method for treating multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn's disease, chronic obstructive pulmonary disease (COPD), asthma, or transplant rejection, comprising administering an effective amount of the antibody of claim 1 to a subject diagnosed with multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn's disease, chronic obstructive pulmonary disease (COPD), or asthma, or at risk of transplant rejection.
13. The method of claim 12 , wherein said antibody binds to the same IL-17 epitope to which monoclonal antibody 3C1 (DSM ACC2941).
14. The method of claim 13 , wherein said antibody comprises antibody 3C1 (DSM ACC2941).
15. An isolated nucleic acid encoding an antibody binding to IL-17, characterized in that said antibody comprises a heavy chain CDR3 region of SEQ ID NO: 1, a heavy chain CDR2 region of SEQ ID NO:2 or SEQ ID NO:9, a heavy chain CDR1 region of SEQ ID NO:3, a light chain CDR3 region of SEQ ID NO: 4, a light chain CDR2 region of SEQ ID NO:5 and a light chain CDR1 region of SEQ ID NO:6.
16. An expression vector comprising the nucleic acid of claim 15 .
17. A method for producing an antibody encoded by the nucleic acid of claim 15 , comprising: culturing a host cell transformed with an expression vector comprising said nucleic acid under conditions suitable for the expression of said antibody; and recovering said antibody from the host cell culture.