LONG-ACTING ANTI-IL31 ANTIBODIES FOR VETERINARY USE
Provided are various embodiments relating to long-acting anti-IL31 antibodies binding to canine IL31 and/or feline 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 binds to an epitope comprising the amino acid sequence of SEQ ID NO: 23, and wherein the antibody comprises a variant IgG Fc polypeptide from a companion animal species capable of binding to neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type Fc polypeptide, optionally at a low pH.
2 . An isolated antibody that binds to canine IL31, wherein the antibody binds to an epitope comprising the amino acid sequence of PSDX 1 X 2 KI (SEQ ID NO: 45), wherein X is any amino acid residue.
3 - 15 . (canceled)
16 . The antibody of claim 1 , comprising a heavy chain and a light chain, wherein:
a) the heavy chain comprises a CDR-H1 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1; a CDR-H2 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2, 62, 89, or 87; and a CDR-H3 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 3, and
b) the light chain comprises a CDR-L1 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; a CDR-L2 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 9; and a CDR-L3 sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 10.
17 - 18 . (canceled)
19 . The antibody of claim 16 , further comprising one or more of (a) a variable region heavy chain framework 1 (HC-FR1) sequence of SEQ ID NO: 4, 70, or 79; (b) a HC-FR2 sequence of SEQ ID NO: 5, 71, or 80; (c) a HC-FR3 sequence of SEQ ID NO: 6, 72, 73, or 81; (d) a HC-FR4 sequence of SEQ ID NO: 7, 74, 124, or 82; (e) a variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO: 11, 75, or 83; (f) an LC-FR2 sequence of SEQ ID NO: 12, 76, or 84; (g) an LC-FR3 sequence of SEQ ID NO: 13, 77, or 85; or (h) an LC-FR4 sequence of SEQ ID NO: 14, 78, or 86.
20 . The antibody of claim 1 , wherein the antibody comprises:
a) (i) a variable light chain sequence having at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, or at least 98% 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 85%, at least 90%, at least 95%, or at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 123; or (iii) a variable light chain sequence as in (i) and a variable heavy chain sequence as in (ii); or
c) (i) a variable light chain sequence having at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 32; (ii) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, or at least 98% 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).
21 . The antibody of claim 1 , wherein the antibody comprises a variable light chain sequence of SEQ ID NO: 24; SEQ ID NO: 16; or SEQ ID NO: 32.
22 . The antibody of claim 1 , wherein the antibody comprises a variable heavy chain sequence of SEQ ID NO: 25; SEQ ID NO: 15; SEQ ID NO: 123; or SEQ ID NO: 33.
23 - 27 . (canceled)
28 . The antibody of claim 1 , wherein the variant IgG Fc polypeptide comprises an amino acid sequence of SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, or SEQ ID NO: 107.
29 . The antibody of claim 1 , wherein the variant IgG Fc polypeptide comprises:
a) a tyrosine or a phenylalanine at a position corresponding to position 23 of SEQ ID NO: 90;
b) a tyrosine at a position corresponding to position 82 of SEQ ID NO: 90;
c) a tyrosine at a position corresponding to position 82 and a histidine at a position corresponding to position 207 of SEQ ID NO: 90;
d) a tyrosine at a position corresponding to position 82 and a tyrosine at a position corresponding to position 207 of SEQ ID NO: 90;
e) a tyrosine at a position corresponding to position 207 of SEQ ID NO: 90;
f) a tyrosine at a position corresponding to position 82 and a histidine at a position corresponding to position 207 of SEQ ID NO: 90;
g) a tyrosine at a position corresponding to position 82 and a tyrosine at a position corresponding to position 207 of SEQ ID NO: 90; or
h) a tyrosine at a position corresponding to position 207 of SEQ ID NO: 90.
30 . (canceled)
31 . The antibody of claim 1 , wherein the antibody comprises:
a) a heavy chain amino acid sequence of SEQ ID NO: 108, SEQ ID NO: 109, or SEQ ID NO: 110;
b) a heavy chain amino acid sequence of SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 125, SEQ ID NO: 126, or SEQ ID NO: 127;
c) a heavy chain amino acid sequence of SEQ ID NO: 114, SEQ ID NO: 115, or SEQ ID NO: 116;
d) a heavy chain amino acid sequence of SEQ ID NO: 117, SEQ ID NO: 118, or SEQ ID NO: 119; or
e) a heavy chain amino acid sequence of SEQ ID NO: 120, SEQ ID NO: 121, or SEQ ID NO: 122.
32 . 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: 108, SEQ ID NO: 109, or SEQ ID NO: 110; 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: 21; (ii) a heavy chain amino acid sequence of SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 125, SEQ ID NO: 126, or SEQ ID NO: 127; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii);
c) (i) a light chain amino acid sequence of SEQ ID NO: 37; (ii) a heavy chain amino acid sequence of SEQ ID NO: 114, SEQ ID NO: 115, or SEQ ID NO: 116; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii);
d) (i) a light chain amino acid sequence of SEQ ID NO: 38; (ii) a heavy chain amino acid sequence of SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii); or
e) (i) a light chain amino acid sequence of SEQ ID NO: 39; (ii) a heavy chain amino acid sequence of SEQ ID NO: 120, SEQ ID NO: 121, or SEQ ID NO: 122; or (iii) a light chain amino acid sequence as in (i) and a heavy chain amino acid sequence as in (ii).
33 . The antibody of claim 1 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 21.
34 . The antibody of claim 1 , wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 125, SEQ ID NO: 126, or SEQ ID NO: 127.
35 . (canceled)
36 . The antibody of claim 1 , wherein the antibody is bi-specific, wherein the antibody binds to IL31 and one or more antigens selected from IL4R, IL17, TNFα, CD20, CD19, CD25, IL4, IL13, IL23, IgE, CD11α, IL6R, α4-Intergrin, IL12, IL1β, IL5, IL5R, IL22, IL22R, IL33, IL33R, TSLP, TSLPR, or BlyS.
37 . An isolated nucleic acid encoding the antibody of claim 1 .
38 . A host cell comprising the nucleic acid of claim 37 .
39 . A method of producing an antibody comprising culturing the host cell of claim 38 and isolating the antibody.
40 - 51 . (canceled)
52 . A method of treating a companion animal species having an IL31-induced condition, the method comprising administering to the companion animal species a therapeutically effective amount of the antibody of claim 1 .
53 - 62 . (canceled)
63 . A method of reducing IL31 signaling function in a cell, the method comprising exposing to the cell the antibody of claim 1 under conditions permissive for binding of the antibody to extracellular IL31, thereby reducing binding to IL31 receptor and/or reducing IL31 signaling function by the cell.
64 - 66 . (canceled)
67 . A method for detecting IL31 in a sample from a companion animal species comprising contacting the sample with the antibody of claim 1 under conditions permissive for binding of the antibody to IL31, and detecting whether a complex is formed between the antibody and IL31 in the sample.
68 . (canceled)