Methods of treating a companion animal species comprising administering anti-IL31 antibodies
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, pruritis, asthma, psoriasis, scleroderma, allergic dermatitis, and eczema, the method comprising administering to the companion animal species a therapeutically effective amount of an isolated antibody that binds to canine IL31, wherein the antibody comprises:
a) (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 1; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 62, SEQ ID NO: 89, or SEQ ID NO: 87 or a variant thereof having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 62, SEQ ID NO: 89, or SEQ ID NO: 87; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3 or a variant thereof having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 3, and
b) (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63 or a variant thereof having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9 or a variant thereof having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 9; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10 or a variant thereof having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 10.
2. The method of claim 1 , wherein the antibody comprises a heavy chain and a light chain, wherein:
a) the heavy chain comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, 62, 89, or 87; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and
b) the light chain comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10.
3. The method of claim 2 , wherein the heavy chain comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 89; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
4. The method of claim 2 , wherein the heavy chain comprises (i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1; (ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 62 or SEQ ID NO: 87; and (iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3.
5. The method of claim 2 , wherein the light chain comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 8; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10.
6. The method of claim 2 , wherein the light chain comprises (i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63; (ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 9; and (iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10.
7. 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);
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);
c) (i) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 32; (ii) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 33; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii);
d) (i) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 64; (ii) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 67; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii); or
e) (i) a variable light chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65; (ii) a variable heavy chain sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 68; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii).
8. 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;
b) a variable light chain sequence of SEQ ID NO: 16 and a variable heavy chain sequence of SEQ ID NO: 15;
c) a variable light chain sequence of SEQ ID NO: 32 and a variable heavy chain sequence of SEQ ID NO: 33;
d) a variable light chain sequence of SEQ ID NO: 64 and a variable heavy chain sequence of SEQ ID NO: 67; or
e) a variable light chain sequence of SEQ ID NO: 65 and a variable heavy chain sequence of SEQ ID NO: 68.
9. The method of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 32 and a variable heavy chain sequence of SEQ ID NO: 33.
10. The method of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 64 and a variable heavy chain sequence of SEQ ID NO: 67.
11. The method of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 65 and a variable heavy chain sequence of SEQ ID NO: 68.
12. 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; (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.
13. The method of claim 1 , wherein the antibody comprises: (i) a light chain amino acid sequence of SEQ ID NO: 34; (ii) a heavy chain amino acid sequence of SEQ ID NO: 35; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii).
14. The method of claim 1 , wherein the antibody binds to canine IL31 with a dissociation constant (Kd) of between 5×10 −11 M and 1×10 −12 M, as measured by biolayer interferometry.
15. The method of claim 1 , wherein the antibody is a monoclonal antibody.
16. The method of claim 1 , wherein the antibody is a caninized, a felinized, an equinized, or a chimeric antibody.
17. The method of claim 1 , wherein the antibody is an antibody fragment selected from Fv, scFv, Fab, Fab′, F(ab′)2, and Fab′-SH.
18. The method of claim 1 , wherein the companion animal species is canine, feline, or equine.
19. The method of claim 1 , wherein the antibody is administered parenterally 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.
20. The method of claim 1 , wherein the method comprises administering in combination with the antibody:
a) a Jak inhibitor, a PI3K inhibitor, an AKT inhibitor, or a MAPK inhibitor; or
b) 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.