Anti-IL31 antibodies for veterinary use
Provided are various embodiments relating to anti-IL31 antibodies binding to canine IL31. Such antibodies can be used in methods to treat IL31-induced conditions in companion animals, such as canines, felines, and equines.
1. A method of treating a companion animal species having an IL31-induced condition, wherein the IL31-induced condition is selected from atopic dermatitis, pruritus, psoriasis, and eczema, the method comprising administering to the companion animal species a therapeutically effective amount of an antibody that binds to canine IL31, wherein the antibody comprises (a) CDR-H1 comprising the amino acid sequence of SEQ ID NO:1; (b) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; (c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; (d) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8; (e) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9; and (f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10.
2. The method of claim 1 , wherein the companion animal species is canine or feline.
3. The method of claim 1 , wherein the antibody is administered parenterally.
4. The method of claim 1 , wherein the antibody or the pharmaceutical composition is administered by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, or an inhalation route.
5. The method of claim 1 , wherein the method comprises administering in combination with the antibody a Jak inhibitor, a PI3K inhibitor, an AKT inhibitor, or a MAPK inhibitor.
6. The method of claim 1 , wherein the method comprises administering in combination with the antibody one or more antibodies selected from an anti-IL17 antibody, an anti-TNFα antibody, an anti-CD20 antibody, an anti-CD19 antibody, an anti-CD25 antibody, an anti-IL4 antibody, an anti-IL13 antibody, an anti-IL23 antibody, an anti-IgE antibody, an anti-CD11α antibody, anti-IL6R antibody, anti-α4-Intergrin antibody, an anti-IL12 antibody, an anti-IL1β antibody, and an anti-BlyS antibody.
7. The method of claim 1 , wherein the antibody binds to canine IL31 with a dissociation constant (Kd) of less than 5×10 −11 M, as measured by biolayer interferometry.
8. The method of claim 1 , wherein the antibody is an antibody fragment selected from Fv, scFv, Fab, Fab′, F(ab′) 2 , and Fab′-SH.
9. The method of claim 1 , wherein the antibody is a caninized, a felinized, or a chimeric antibody.
10. The method of claim 1 , wherein the antibody further comprises one or more of (a) a variable region heavy chain framework 1 (HC-FR1) sequence of SEQ ID NO: 4; (b) a HC-FR2 sequence of SEQ ID NO: 5; (c) a HC-FR3 sequence of SEQ ID NO: 6; (d) a HC-FR4 sequence of SEQ ID NO: 7; (e) a variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO: 11; (f) an LC-FR2 sequence of SEQ ID NO: 12; (g) an LC-FR3 sequence of SEQ ID NO: 13; or (h) an LC-FR4 sequence of SEQ ID NO: 14.
11. The method 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) (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).
12. The method of claim 1 , wherein the antibody comprises:
a) (i) a variable light chain amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain 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) (i) a variable light chain amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain 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).
13. The method 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; or
(b) a feline heavy chain constant region selected from an IgG1, IgG2a, and IgG2b constant region.
14. The method of claim 1 , wherein the antibody comprises:
a) (i) a light chain amino acid sequence of SEQ ID NO: 26; (ii) a heavy chain amino acid sequence of SEQ ID NO: 27; or (iii) a light chain sequence as in (i) and a heavy chain sequence as in (ii); or
b) (i) a light chain amino acid sequence of SEQ ID NO: 30; (ii) a heavy chain amino acid sequence of SEQ ID NO: 31; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii).
15. The method of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21.
16. The method of claim 15 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 17; SEQ ID NO: 18; SEQ ID NO: 19; or SEQ ID NO: 20.
17. The method 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.
18. The method of claim 17 , wherein the antibody comprises a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region.
19. The method of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 and a heavy chain amino acid sequence of SEQ ID NO: 17.
20. The method of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 and a heavy chain amino acid sequence of SEQ ID NO: 18.
21. The method of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 and a heavy chain amino acid sequence of SEQ ID NO: 19.
22. The method of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 and a heavy chain amino acid sequence of SEQ ID NO: 20.
23. A method of treating a canine having an IL31-induced condition, wherein the IL31-induced condition is selected from atopic dermatitis, pruritus, psoriasis, and eczema, comprising administering to the canine a therapeutically effective amount of an antibody that binds to canine IL31, wherein the antibody comprises a variable light chain amino acid sequence of SEQ ID NO: 16 and a variable heavy chain amino acid sequence of SEQ ID NO: 15.
24. A method of treating a canine having an IL31-induced condition, wherein the IL31-induced condition is selected from atopic dermatitis, pruritus, psoriasis, and eczema, comprising administering to the canine a therapeutically effective amount of an antibody that binds to canine IL31, wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21 and a heavy chain amino acid sequence of SEQ ID NO: 17; SEQ ID NO: 18; SEQ ID NO: 19; or SEQ ID NO: 20.
25. The method of claim 24 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 17.
26. The method of claim 24 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 18.
27. The method of claim 24 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 19.
28. The method of claim 24 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 20.