IL-17 antagonistic antibodies
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. A purified IL-17 antibody or antigen binding fragment thereof comprising a heavy chain variable domain (V H ) and a light chain variable domain (V L ):
a) wherein said V H comprises the three Complementarity Determining Regions (CDRs) of the amino acid sequence set forth as SEQ ID NO:8 and wherein said V L comprises the three CDRs of the amino acid sequence set forth as SEQ ID NO:10;
b) wherein said V H comprises the amino acid sequence set forth as SEQ ID NO:8;
c) wherein said V L comprises the amino acid sequence set forth as SEQ ID NO:10; or
d) wherein said V H comprises the amino acid sequence set forth as SEQ ID NO:8 and wherein said V L comprises the amino acid sequence set forth as SEQ ID NO:10.
2. The IL-17 antibody or antigen binding fragment thereof according to claim 1 , wherein said V H comprises the three CDRs of the amino acid sequence set forth as SEQ ID NO:8 and wherein said V L comprises the three CDRs of the amino acid sequence set forth as SEQ ID NO:10, and further wherein:
a) the three CDRs of the amino acid sequence set forth as SEQ ID NO:8 are the amino acid sequences set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3; or
b) the three CDRs of the amino acid sequence set forth as SEQ ID NO:8 are the amino acid sequences set forth as SEQ ID NO:11, SEQ ID NO:12, and SEQ ID NO:13.
3. The IL-17 antibody or antigen binding fragment thereof according to claim 1 , wherein said V H comprises the three CDRs of the amino acid sequence set forth as SEQ ID NO:8 and wherein said V L comprises the three CDRs of the amino acid sequence set forth as SEQ ID NO:10, and further wherein the three CDRs of the amino acid sequence set forth as SEQ ID NO:10 are the amino acid sequences set forth as SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6.
4. The IL-17 antibody or antigen binding fragment thereof according to claim 1 , wherein said V H comprises the amino acid sequence set forth as SEQ ID NO:8 and wherein said V L comprises the amino acid sequence set forth as SEQ ID NO:10.
5. The IL-17 antibody or antigen binding fragment thereof according to any one of claims 1 or 2 - 4 , wherein the IL-17 antibody or antigen binding fragment thereof is an antibody, and wherein said antibody is selected from the group consisting of a human antibody, a chimeric antibody and a CDR-grafted antibody.
6. A pharmaceutical composition comprising the purified IL-17 antibody or antigen binding fragment thereof according to any one of claims 1 or 2 - 4 and a pharmaceutically acceptable diluent, excipient, carrier or mixture thereof.
7. A pharmaceutical composition comprising the purified IL-17 antibody according to claim 5 and a pharmaceutically acceptable diluent, excipient, carrier or mixture thereof.
8. A method for inhibiting the binding of IL-17 to an IL-17 receptor in a subject, comprising administering to the subject the purified IL-17 antibody or antigen binding fragment thereof of claim 1 in an amount effective to inhibit the binding of IL-17 to the IL-17 receptor in the subject.
9. A method for binding IL-17 in a subject, comprising administering to the subject the purified IL-17 antibody or antigen binding fragment thereof of claim 1 in an amount effective to bind IL-17 in the subject.
10. A method for treating an IL-17 mediated inflammatory condition or an IL-17 mediated autoimmune disease, comprising administering to a subject in need thereof an effective amount of the purified IL-17 antibody or antigen binding fragment thereof of claim 1 .
11. A method for inhibiting the binding of IL-17 to an IL-17 receptor in a subject, comprising administering to the subject the purified IL-17 antibody of claim 5 in an amount effective to inhibit the binding of IL-17 to the IL-17 receptor in the subject.
12. A method for binding IL-17 in a subject, comprising administering to the subject the purified IL-17 antibody of claim 5 in an amount effective to bind IL-17 in the subject.
13. A method for treating an IL-17 mediated inflammatory condition or an IL-17 mediated autoimmune disease, comprising administering to a subject in need thereof an effective amount of the purified IL-17 antibody of claim 5 .
14. The method according to claim 10 or 13 , wherein said IL-17 mediated inflammatory condition or IL-17 mediated autoimmune disease is psoriasis, rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
15. The method according to claim 10 or 13 , wherein said IL-17 mediated inflammatory condition or IL-17 mediated autoimmune disease is uveitis.
16. The method according to claim 10 or 13 , wherein said IL-17 mediated inflammatory condition or IL-17 mediated autoimmune disease is multiple sclerosis or keratoconjunctivitis sicca.
17. The IL-17 antibody or fragment thereof according to claim 2 , wherein the three CDRs of the amino acid sequence set forth as SEQ ID NO:10 are the amino acid sequences set forth as SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6.
18. The IL-17 antibody according to claim 5 , wherein the IL-17 antibody is a human antibody.
19. The IL-17 antibody or antigen binding fragment thereof according to any one of claims 1 or 2 - 4 , wherein the IL-17 antibody or fragment thereof inhibits the activity of 1 nM of human IL-17 at a concentration of less than 5 nM by 50%, and wherein inhibition of the activity of 1 nM of human IL-17 is measured on IL-6 production induced by human IL-17 on human dermal fibroblasts.
20. The IL-17 antibody or antigen binding fragment thereof according to any one of claims 1 or 2 - 4 , wherein the IL-17 antibody or antigen binding fragment thereof is an antigen binding fragment, and wherein said an antigen binding fragment is selected from the group consisting of a F(ab′)2 fragment, a Fab fragment, and a single chain antibody.
21. A purified IL-17 antibody or antigen binding fragment thereof comprising:
a) a V H comprising, in sequence, the three CDRs set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 or the three CDRs set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and a V L comprising, in sequence, the three CDRs set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6;
b) a V H comprising the amino acid sequence set forth as SEQ ID NO:8;
c) a V L comprising the amino acid sequence set forth as SEQ ID NO:10; or
d) a V H comprising the amino acid sequence set forth as SEQ ID NO:8 and a V L comprising the amino acid sequence set forth as SEQ ID NO:10.
22. The IL-17 antibody or antigen binding fragment thereof according to claim 21 , wherein the IL-17 antibody or antigen binding fragment thereof is an antibody, and wherein said antibody is selected from the group consisting of a human antibody, a chimeric antibody and a CDR-grafted antibody.
23. The IL-17 antibody or antigen binding fragment thereof according to claim 21 , wherein the IL-17 antibody or antigen binding fragment thereof is an antigen binding fragment, and wherein said an antigen binding fragment is selected from the group consisting of a F(ab′)2 fragment, a Fab fragment, a single chain antibody and a single domain antibody.