ANTI-IL4 RECEPTOR ANTIBODIES FOR VETERINARY USE

1 .- 15 . (canceled)

16 . An isolated antibody that binds to canine IL4R or feline IL4R, wherein the antibody comprises a heavy chain comprising:

a) a CDR-H1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of GYTFTSYVMX 1 (SEQ ID NO: 1), wherein X 1 is H or N;

b) a CDR-H2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of YINPX 2 NDGTFYX 3 GX 4 X 5 X 6 G (SEQ ID NO: 2), wherein X 2 is K, A, or N, X 3 is N or A, X 4 is K or A, X 5 is F or V, and X 6 is K or Q, or YINPX 2 NDGT (SEQ ID NO: 268), wherein X 2 is K, A, or N; and

c) a CDR-H3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of FX 7 YGX 8 AY (SEQ ID NO: 3), wherein X 7 is N or Y, and X 8 s I or F; and

wherein the antibody comprises a variant canine or feline IgG Fc polypeptide capable of binding to neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type Fc polypeptide.

17 . The isolated antibody of claim 16 , comprising a heavy chain comprising:

a) a CDR-H1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of GYTFTSYVMX 1 (SEQ ID NO: 1), wherein X 1 is H or N;

b) a CDR-H2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of YINPX 2 NDGTFYX 3 GX 4 X 5 X 6 G (SEQ ID NO: 2), wherein X 2 is K, A, or N, X 3 is N or A, X 4 is K or A, X 5 is F or V, and X 6 is K or Q, or YINPX 2 NDGT (SEQ ID NO: 268), wherein X 2 is K, A, or N; and

c) a CDR-H3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of FX 7 YGX 8 AY (SEQ ID NO: 3), wherein X 7 is N or Y, and X 8 s I or F.

18 . The isolated antibody of claim 16 , comprising a heavy chain comprising:

a) a CDR-H1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 29, or SEQ ID NO: 358;

b) a CDR-H2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 269, SEQ ID NO: 30, SEQ ID NO: 271, SEQ ID NO: 359, or SEQ ID NO: 272; and

c) a CDR-H3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 31.

19 . The isolated antibody of claim 16 , comprising a heavy chain comprising:

a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:7, SEQ ID NO: 29, or SEQ ID NO: 358;

b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 269, SEQ ID NO: 30, SEQ ID NO: 271, SEQ ID NO: 359, or SEQ ID NO: 272; and

c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 31.

20 . (canceled)

21 . The isolated antibody of claim 16 , comprising a light chain comprising:

a) a CDR-L1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of RASQEISGYLX 9 (SEQ ID NO: 4) wherein X 9 is S or A;

b) a CDR-L2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of AASX 10 X 11 DX 12 (SEQ ID NO: 5), wherein X 10 is T or N, X 11 is R or L, and X 12 is S or T; and

c) a CDR-L3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of X 13 QYASYPWT (SEQ ID NO: 6), wherein X 13 is V or L.

22 . An isolated antibody that binds to canine IL4R or feline IL4R, wherein the antibody comprises:

a) a CDR-H1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of GYTFTSYVMX 1 (SEQ ID NO: 1), wherein X 1 is H or N;

b) a CDR-H2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of YINPX 2 NDGTFYX 3 GX 4 X 5 X 6 G (SEQ ID NO: 2), wherein X 2 is K, A, or N, X 3 is N or A, X 4 is K or A, X 5 is F or V, and X 6 is K or Q, or YINPX 2 NDGT (SEQ ID NO: 268), wherein X 2 is K, A, or N; and

c) a CDR-H3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of FX 7 YGX 9 AY (SEQ ID NO: 3), wherein X 7 is N or Y, and X 8 s I or F;

d) a CDR-L1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of RASQEISGYLX 9 (SEQ ID NO: 4) wherein X 9 is S or A;

e) a CDR-L2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of AASX 10 X 11 DX 12 (SEQ ID NO: 5), wherein X 10 is T or N, X 11 is R or L, and X 12 is S or T; and

f) a CDR-L3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of X 13 QYASYPWT (SEQ ID NO: 6), wherein X 13 is V or L; and

wherein the antibody comprises a variant canine or feline IgG Fc polypeptide capable of binding to neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type Fc polypeptide.

23 . The isolated antibody of claim 16 , comprising a light chain comprising:

a) a CDR-L1 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 36, or SEQ ID NO: 360;

b) a CDR-L2 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 37, SEQ ID NO: 361, or SEQ ID NO: 362; and

c) a CDR-L3 sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 38.

24 . The isolated antibody of claim 16 , comprising a light chain comprising:

a) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 36, or SEQ ID NO: 360;

b) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 15, SEQ ID NO: 37, SEQ ID NO: 361, or SEQ ID NO: 362; and

c) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:16 or SEQ ID NO: 38.

25 . 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: 10 or SEQ ID NO: 32; (b) a HC-FR2 sequence of SEQ ID NO: 11 or SEQ ID NO: 33; (c) a HC-FR3 sequence of SEQ ID NO: 12, SEQ ID NO: 270, SEQ ID NO: 34, SEQ ID NO: 273; (d) a HC-FR4 sequence of SEQ ID NO: 13 or SEQ ID NO: 35; (e) a variable region light chain framework 1 (LC-FR1) sequence of SEQ ID NO: 17 or SEQ ID NO: 39; (f) an LC-FR2 sequence of SEQ ID NO: 18 or SEQ ID NO: 40; (g) an LC-FR3 sequence of SEQ ID NO: 19 or SEQ ID NO: 41; or (h) an LC-FR4 sequence of SEQ ID NO: 20 or SEQ ID NO: 42.

26 . The antibody of claim 16 , wherein the antibody comprises:

a. (i) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 43; (ii) a variable light chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 44; or (iii) a variable heavy chain sequence as in (i) and a variable light chain sequence as in (ii); or

b. (i) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 274, or SEQ ID NO: 363; (ii) a variable light chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 275, or SEQ ID NO: 364; or (iii) a variable heavy chain sequence as in (i) and a variable light chain sequence as in (ii); or

c. (i) a variable heavy chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 67 or SEQ ID NO: 69; (ii) a variable light chain sequence having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 68 or SEQ ID NO: 70; or (iii) a variable heavy chain sequence as in (i) and a variable light chain sequence as in (ii).

27 .- 29 . (canceled)

30 . An isolated antibody, wherein the antibody comprises:

a) a variable heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 43, and a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 44;

b) a variable heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 274, or SEQ ID NO: 363, and a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 275, or SEQ ID NO: 364; or

c) a variable heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 365, or SEQ ID NO: 366, and a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 367, SEQ ID NO: 368, or SEQ ID NO: 369, and

wherein the antibody comprises a variant canine or feline IgG Fc polypeptide capable of binding to neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type Fc polypeptide.

31 .- 129 . (canceled)

130 . The antibody of claim 16 , wherein the antibody is a bispecific antibody that binds to IL4R and one or more antigens selected from IL17, IL31, TNFα, CD20, CD19, CD25, IL4, IL13, IL23, IgE, CD11α, IL6R, α4-Intergrin, IL12, IL1β, or BlyS.

131 . (canceled)

132 . The antibody of claim 16 , wherein the antibody is an antibody fragment, optionally such as an Fv, scFv, Fab, Fab′, F(ab′) 2 , or Fab′-SH fragment.

133 . An isolated nucleic acid encoding the antibody of claim 16 .

134 . A host cell comprising the nucleic acid of claim 133 .

135 . (canceled)

136 . A method of producing an antibody comprising culturing the host cell of claim 134 and isolating the antibody.

137 . A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier.

138 . A method of treating a companion animal species having an IL4/1L13-induced condition, the method comprising administering to the companion animal species a therapeutically effective amount of the antibody of claim 16 or a composition thereof.

139 .- 145 . (canceled)

146 . A method of reducing IL4 and/or IL13 signaling function in a cell, the method comprising exposing to the cell the antibody of claim 16 or a composition thereof under conditions permissive for binding of the antibody to extracellular IL4 and/or IL13, thereby reducing binding of IL4 and/or IL13 to IL4R and/or reducing IL4 and/or IL13 signaling function by the cell.

147 .- 151 . (canceled)

152 . A method for detecting IL4R in a sample from a companion animal species comprising contacting the sample with the antibody of claim 16 or a composition thereof under conditions permissive for binding of the antibody to IL4R.

153 . (canceled)