IL17A antibodies and antagonists for veterinary use
Provided are various embodiments relating to anti-IL17A antibodies and IL17Ra ECD polypeptides that bind to IL17A. In various embodiments, such anti-IL17A antibodies or IL17Ra ECD polypeptides can be used in methods to treat IL17-induced conditions in subjects, such as humans or companion animals, such as canines, felines, and equines. Also provided are various embodiments relating to IgG Fc variant polypeptides having one or more amino acid substitutions for reducing binding to C1q and/or CD16. In some embodiments, the IgG Fc variants and/or polypeptides comprising the IgG Fc variants (e.g., fusion polypeptides comprising the IgG Fc variants and the anti-IL17A antibodies and/or IL17Ra ECD polypeptides described herein) may have reduced complement-mediated immune responses and/or antibody-dependent cell-mediated cytotoxicity.
1 . A monoclonal antibody that binds to canine IL17A, wherein the antibody comprises:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and
(ii) a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO: 8, a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO: 9, and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO: 10.
2 . The monoclonal antibody of claim 1 , wherein the antibody binds to canine IL17A with a dissociation constant (K d ) of less than 1×10 −8 M, as measured by biolayer interferometry.
3 . The monoclonal antibody of claim 1 , wherein the antibody is a caninized, a felinized, an equinized, or a chimeric antibody.
4 . The monoclonal antibody of claim 1 , wherein the antibody comprises:
(i) a variable light chain sequence comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 24; and
(ii) a variable heavy chain sequence comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 25.
5 . The monoclonal antibody of claim 1 , wherein the antibody comprises:
a variable light chain sequence comprising an amino acid sequence having 100% sequence identity to SEQ ID NO: 24 and a variable heavy chain sequence comprising an amino acid sequence having 100% sequence identity to SEQ ID NO: 25.
6 . The monoclonal antibody of claim 1 , wherein the antibody comprises (a) a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region; (b) a feline heavy chain constant region selected from an IgG-1a, IgG-1b, and IgG-2 constant region; or (c) an equine heavy chain constant region selected from an IgG-1, IgG-2, IgG-3, IgG-4, IgG-5, IgG-6, and IgG-7 constant region.
7 . The monoclonal antibody of claim 1 , wherein the antibody is an antibody fragment chosen from an Fv, scFv, Fab, Fab′, F(ab′)2, and Fab′-SH fragment.
8 . A nucleic acid encoding the monoclonal antibody of claim 1 .
9 . A host cell comprising the nucleic acid of claim 8 .
10 . A method of producing a monoclonal antibody comprising culturing the host cell of claim 9 and isolating the monoclonal antibody.
11 . A pharmaceutical composition comprising the monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.
12 . A method of treating a companion animal species having an IL17A-induced condition, the method comprising administering to the companion animal species a therapeutically effective amount of the monoclonal antibody of claim 1 .
13 . A method of reducing IL17A signaling function in a cell, the method comprising exposing to the cell the monoclonal antibody of claim 1 under conditions permissive for binding of the antibody to extracellular IL17A, thereby reducing binding to IL17A receptor and/or reducing IL17A signaling function by the cell.
14 . A method for detecting IL17A in a sample from a companion animal species comprising contacting the sample with the monoclonal antibody of claim 1 under conditions permissive for binding of the antibody to IL17A, and detecting whether a complex is formed between the monoclonal antibody and IL17A in the sample.
15 . The monoclonal antibody of claim 1 , further comprising one or more of:
(i) the variable region heavy chain framework 1 (HC-FR1) sequence of SEQ ID NO: 4;
(ii) the variable region heavy chain framework 2 (HC-FR2) sequence of SEQ ID NO: 5;
(iii) the variable region heavy chain framework 3 (HC-FR3) sequence of SEQ ID NO: 6;
(iv) the variable region heavy chain framework 4 (HC-FR4) sequence of SEQ ID NO: 7;
(v) the variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO:11;
(vi) the variable region light chain framework 2 (LC-FR2) sequence of SEQ ID NO:12;
(vii) the variable region light chain framework 3 (LC-FR3) sequence of SEQ ID NO: 13; and
(viii) the variable region light chain framework 4 (LC-FR4) sequence of SEQ ID NO: 14.
16 . The monoclonal antibody of claim 1 , wherein the monoclonal antibody binds to SEQ ID NO: 22.