Anti-IL-25 Antibodies and Uses Thereof

摘要

The present invention provides antibodies that bind to human interleukin-25 (IL-25) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human IL-25 with high affinity. In certain embodiments, the invention includes antibodies that bind human IL-25 and block IL-25-mediated cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies. The antibodies of the invention are useful for the treatment of various disorders associated with IL-25 activity or expression, including asthma, allergy, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, atopic dermatitis (AD), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), also know as Churg-Strauss Syndrome.

主权项

1. An isolated antibody or antigen-binding fragment thereof that specifically binds human interleukin-25 (IL-25), wherein the antibody or antigen-binding fragment thereof exhibits two or more of the following characteristics:
(a) is a fully human monoclonal antibody; (b) binds human IL-25 with a KD of less than about 120 pM as measured by surface plasmon resonance at 25° C.; (c) binds human IL-25 with a dissociative half life (t½) of greater than about 105 minutes as measured by surface plasmon resonance at 25° C.; (d) blocks human IL-25 signaling in cells engineered to express an IL-25 receptor (IL-17RA/IL-17RB) with an 1050 of less than about 2 nM; (e) blocks human IL-25 signaling in human peripheral blood mononuclear cells (PBMCs) with an 1050 of less than about 16 nM; (f) reduces circulating and/or lung IgE levels in a mammal that overexpresses IL-25; (g) reduces goblet cell metaplasia in a mammal that overexpresses IL-25; (h) comprises three heavy chain complementarity determining regions (HCDRs) contained within a heavy chain variable region (HCVR) comprising an amino acid sequence as set forth in Table 1; or (i) comprises three light chain complementarity determining regions (LCDRs) contained within a light chain variable region (LCVR) comprising an amino acid sequence as set forth in Table 1.