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. An isolated 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 antibody 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.
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 , further comprising 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.
6. 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. (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).
7. The antibody of claim 6 , wherein the antibody comprises: a variable light chain sequence of SEQ ID NO: 24 and a variable heavy chain sequence of SEQ ID NO: 25; or a variable light chain sequence of SEQ ID NO: 16 and a variable heavy chain sequence of SEQ ID NO: 15.
8. The antibody of claim 7 , wherein the antibody comprises a constant heavy chain region derived from a companion animal.
9. The antibody of claim 8 , 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 IgG1, IgG2a, and IgG2b constant region; or (c) an equine heavy chain constant region selected from an IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 and IgG7 constant region.
10. The antibody 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 amino acid sequence as in (i) and a heavy chain amino acid 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).
11. The antibody of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21.
12. The antibody of claim 11 , 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.
13. The antibody of claim 1 , wherein the antibody is an antibody fragment selected from Fv, scFv, Fab, Fab′, F(ab′) 2 , and Fab′-SH.
14. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
15. The antibody of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 24 and a variable heavy chain sequence of SEQ ID NO: 25.
16. The antibody of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 16 and a variable heavy chain sequence of SEQ ID NO: 15.
17. The antibody of claim 16 , wherein the antibody comprises a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region.
18. The antibody of claim 16 , wherein the antibody comprises a canine IgG-B heavy chain constant region.
19. The antibody of claim 1 , wherein the antibody comprises a feline heavy chain constant region selected from an IgG1, IgG2a, and IgG2b constant region.
20. The antibody 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.
21. The antibody 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.
22. The antibody 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.
23. The antibody 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.