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 . 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.