IL-17 antagonistic antibodies
An Interleukin-17 (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 monoclonal antibody that binds to human Interleukin-17 (IL-17), or an antigen-binding fragment thereof, produced by a process comprising:
a) culturing a recombinant host cell comprising:
i) a nucleic acid that encodes an antibody heavy chain variable domain (V H ) comprising, in sequence:
a complementarity determining region (CDR) 1 having the amino acid sequence set forth as SEQ ID NO:1, a CDR2 having the amino acid sequence set forth as SEQ ID NO:2, and a CDR3 having the amino acid sequence set forth as SEQ ID NO:3; or
a CDR1-x having the amino acid sequence set forth as SEQ ID NO:11, a CDR2-x having the amino acid sequence set forth as SEQ ID NO:12, and a CDR3-x having the amino acid sequence set forth as SEQ ID NO:13; and
ii) a nucleic acid that encodes an antibody light chain variable domain (V L ) comprising, in sequence, a CDR1′ having the amino acid sequence set forth as SEQ ID NO:4, a CDR2′ having the amino acid sequence set forth as SEQ ID NO:5, and a CDR3′ having the amino acid sequence set forth as SEQ ID NO:6,
under conditions sufficient to express the anti-IL-17 antibody or antigen-binding fragment thereof; and
b) recovering the anti-IL-17 antibody or antigen-binding fragment thereof from the host cell culture.
2. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 1 , wherein the recombinant host cell comprises:
i) a nucleic acid that encodes an antibody V H comprising the amino acid sequence set forth as SEQ ID NO:8; and
ii) a nucleic acid that encodes an antibody V L comprising the amino acid sequence set forth as SEQ ID NO:10.
3. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 1 , which is a human antibody.
4. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 3 , which is of the IgG 1 /κ isotype.
5. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 4 , which has a K D for binding to human IL-17 of about 122 pM±22 pM as determined by surface plasmon resonance.
6. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 4 , which has an IC 50 of about 5 nM or less for inhibition of Interleukin-6 (IL-6) production induced by 1 nM human IL-17 in human dermal fibroblasts.
7. A pharmaceutical composition comprising the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 3 in combination with a pharmaceutically acceptable excipient, diluent or carrier.
8. A pharmaceutical composition comprising the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 4 in combination with a pharmaceutically acceptable excipient, diluent or carrier.
9. A pharmaceutical composition comprising the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 5 in combination with a pharmaceutically acceptable excipient, diluent or carrier.
10. A pharmaceutical composition comprising the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 6 in combination with a pharmaceutically acceptable excipient, diluent or carrier.
11. The pharmaceutical composition according to claim 8 , which is in liquid form.
12. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 4 , wherein the recombinant host cell is a mammalian cell.
13. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 12 , wherein the mammalian cell is derived from a mammalian cell line.
14. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 13 , which is post-translationally modified as a result of the action of the recombinant mammalian host cell.
15. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 14 , wherein the recombinant mammalian host cell comprises a single expression vector, said single expression vector comprising the nucleic acid that encodes the antibody V H and the nucleic acid that encodes the antibody V L .
16. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 15 , wherein the single expression vector comprises a dihydrofolate reductase (dhfr) gene.
17. The monoclonal anti-IL-17 antibody or antigen-binding fragment thereof according to claim 14 , wherein the recombinant mammalian host cell comprises two expression vectors, one of said expression vectors comprising the nucleic acid that encodes the antibody V H and one of said expression vectors comprising the nucleic that encodes the antibody V L .