Antagonists of IL17C for the treatment of inflammatory disorders
The present invention provides antagonists of IL17C for use in the treatment of an inflammatory disorder.
1. An isolated antibody or antibody fragment specific for Interleukin 17C (IL-17C), wherein said antibody:
a) is monoclonal
b) is of the IgG isotype;
c) comprises a human light chain variable region and a human heavy chain variable region;
d) has an IC 50 less than 100 pM for blocking the binding of mouse IL-17C to mouse interleukin 17 receptor E (IL-17RE);
e) binds mouse IL-17C with a K D less than 3 nM;
f) has an EC 50 value on mouse IL-17C between 200 and 1200 pM; and
g) has a coefficient of variation ≤20% in a murine serum stability assay.
2. A method for treating an inflammatory disorder, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising an isolated monoclonal IgG antibody or antibody fragment specific for Interleukin 17C (IL-17C), wherein the inflammatory disorder is lung neutrophilia, pulmonary inflammation, bronchitis, emphysema, arthritis, psoriasis or chronic obstructive pulmonary disease (COPD), and wherein said antibody:
a) comprises a human light chain variable region and a human heavy chain variable region;
b) has an IC 50 less than 100 pM for blocking the binding of mouse IL-17C to mouse interleukin 17 receptor E (IL-17RE);
c) binds mouse IL-17C with a K D less than 3 nM;
d) has an EC 50 value on mouse IL-17C between 200 and 1200 pM; and
e) has a coefficient of variation ≤20% in a murine serum stability assay.
3. The method according to claim 2 wherein the inflammatory disorder is lung neutrophilia, pulmonary inflammation, bronchitis, emphysema, or chronic obstructive pulmonary disease (COPD).
4. The method according to claim 3 , wherein the inflammatory disorder is arthritis.
5. The method according to claim 3 , wherein the inflammatory disorder is psoriasis.
6. The method according to claim 2 , wherein said antibody or antibody fragment is of the IgG 2a or of the IgG 1 isotype.
7. The method according to claim 2 , wherein said effective amount of said antibody or antibody fragment is 5 mg/kg-10 mg/kg.
8. The method according to claim 2 , wherein said antibody or antibody fragment is an antibody fragment selected from the group consisting of a Fab, F(ab2)′, F(ab)2′, and scFV.