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. An isolated 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 comprising the amino acid sequence of SEQ ID NO: 8, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 108, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10.
2. The 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 antibody of claim 1 , wherein the antibody is a monoclonal antibody.
4. The antibody of claim 1 , wherein the antibody is a caninized, a felinized, an equinized, or a chimeric antibody.
5. The antibody of claim 1 , wherein the antibody comprises:
(a) (i) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 25; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii); or
(b) (iv) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16; (11 v) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 15; or (vi) a variable light chain sequence as in (14 iv) and a variable heavy chain sequence as in (V).
6. The antibody of claim 1 , wherein the antibody comprises:
(a) a variable light chain sequence of SEQ ID NO: 24 and a variable heavy chain sequence of SEQ ID NO: 25; or
(b) a variable light chain sequence of SEQ ID NO: 16 and a variable heavy chain sequence of SEQ ID NO: 15.
7. The 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.
8. The antibody of claim 1 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 27.
9. The antibody of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 26.
10. The antibody of claim 1 , wherein the antibody is an antibody fragment, selected from an Fv, scFv, Fab, Fab′, F(ab′)2, and Fab′-SH fragment.
11. An isolated nucleic acid encoding the antibody of claim 1 .
12. A host cell comprising the nucleic acid of claim 11 .
13. A method of producing an antibody comprising culturing the host cell of claim 12 and isolating the antibody.
14. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
15. 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 antibody of claim 1 , wherein the IL17A-induced condition is plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, airway inflammation, asthma, osteoarthritis, inflammatory bowel disorder, Crohn's disease, ankylosing spondylitis, atopic dermatitis, degenerative myelopathy, multiple sclerosis, or uveitis.
16. The antibody of claim 1 , comprising (i) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 15; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii).
17. The antibody of claim 1 , comprising a variable light chain sequence having the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence having the amino acid sequence of SEQ ID NO: 15; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii).
18. An isolated antibody that binds to canine IL17A, comprising a variable light chain sequence having the amino acid sequence of SEQ ID NO: 16 and a variable heavy chain sequence having the amino acid sequence of SEQ ID NO: 15.
19. The antibody of claim 18 , wherein the antibody comprises a constant heavy chain region or constant light chain region derived from a companion animal.
20. The antibody of claim 18 , 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.
21. The antibody of claim 18 , wherein the antibody is an antibody fragment, selected from an Fv, scFv, Fab, Fab′, F(ab′)2, and Fab′-SH fragment.
22. An isolated nucleic acid encoding the antibody of claim 18 .
23. A host cell comprising the nucleic acid of claim 22 .
24. A method of producing an antibody comprising culturing the host cell of claim 23 and isolating the antibody.
25. A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier.
26. 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 antibody of claim 18 , wherein the IL17A-induced condition is plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, airway inflammation, asthma, osteoarthritis, inflammatory bowel disorder, Crohn's disease, ankylosing spondylitis, atopic dermatitis, degenerative myelopathy, multiple sclerosis, or uveitis.
27. An isolated antibody that binds to canine IL17A, comprising
(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 comprising the amino acid sequence of SEQ ID NO: 8, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 108, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10;
and comprising a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16 and a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 15.
28. The antibody of claim 27 , wherein the antibody comprises a constant heavy chain region or constant light chain region derived from a companion animal.
29. The antibody of claim 27 , 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.
30. The antibody of claim 27 , wherein the antibody is an antibody fragment, selected from an Fv, scFv, Fab, Fab′, F(ab′)2, and Fab′-SH fragment.
31. An isolated nucleic acid encoding the antibody of claim 27 .
32. A host cell comprising the nucleic acid of claim 31 .
33. A method of producing an antibody comprising culturing the host cell of claim 32 and isolating the antibody.
34. A pharmaceutical composition comprising the antibody of claim 27 and a pharmaceutically acceptable carrier.
35. 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 antibody of claim 27 , wherein the IL17A-induced condition is plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, airway inflammation, asthma, osteoarthritis, inflammatory bowel disorder, Crohn's disease, ankylosing spondylitis, atopic dermatitis, degenerative myelopathy, multiple sclerosis, or uveitis.