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 antibody that binds to IL31, wherein the antibody comprises:
a) a heavy chain comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO: 1; a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 62, SEQ ID NO: 87, or SEQ ID NO: 89; and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO: 3, and a light chain comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO: 9; and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO: 10; or
b) (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain sequence comprising 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 (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence comprising 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); or (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 32; (ii) a variable heavy chain sequence comprising 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),
wherein one or more of SEQ ID NO: 1, 2, 3, 8, 9, 10, 15, 16, 24, 25, 32, 33, 62, 63, 87, and 89 optionally comprise an amino acid substitution.
2 . The antibody of claim 1 , wherein the antibody binds to an epitope comprising or within the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 28, or SEQ ID NO: 29.
3 . The antibody of claim 2 , wherein the epitope is within amino acids 34-50 of SEQ ID NO: 22.
4 . The antibody of claim 2 , wherein the epitope comprises amino acids 34-50 of SEQ ID NO: 22.
5 . The antibody of claim 2 , wherein the epitope consists of the amino acid sequence of SEQ ID NO: 23.
6 . A method for diagnosing an IL-31-induced condition in a companion animal species comprising administering to the companion animal species an antibody that binds to IL31, and detecting whether a complex is formed between the antibody and IL31 in the companion animal species, wherein the antibody comprises:
a) a heavy chain comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO: 1; a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 62, SEQ ID NO: 87, or SEQ ID NO: 89; and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO: 3, and a light chain comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO: 9; and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO: 10; or
b) (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain sequence comprising 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 (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence comprising 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); or (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 32; (ii) a variable heavy chain sequence comprising 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);
wherein one or more of SEQ ID NO: 1, 2, 3, 8, 9, 10, 15, 16, 24, 25, 32, 33, 62, 63, 87, and 89 optionally comprise an amino acid substitution.
7 . A method for detecting IL31 in a sample from a companion animal species comprising contacting the sample with an antibody that binds to IL31, and detecting whether a complex is formed between the antibody and IL31 in the sample, wherein the antibody comprises:
a) a heavy chain comprising a CDR-H1 sequence comprising the amino acid sequence of SEQ ID NO: 1; a CDR-H2 sequence comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 62, SEQ ID NO: 87, or SEQ ID NO: 89; and a CDR-H3 sequence comprising the amino acid sequence of SEQ ID NO: 3, and a light chain comprising a CDR-L1 sequence comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 63; a CDR-L2 sequence comprising the amino acid sequence of SEQ ID NO: 9; and a CDR-L3 sequence comprising the amino acid sequence of SEQ ID NO: 10; or
b) (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 24; (ii) a variable heavy chain sequence comprising 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 (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 16; (ii) a variable heavy chain sequence comprising 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); or (i) a variable light chain sequence comprising the amino acid sequence of SEQ ID NO: 32; (ii) a variable heavy chain sequence comprising 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);
wherein one or more of SEQ ID NO: 1, 2, 3, 8, 9, 10, 15, 16, 24, 25, 32, 33, 62, 63, 87, and 89 optionally comprise an amino acid substitution.
8 . The method of claim 7 , wherein the sample is a biological sample obtained from a canine, a feline, or an equine.
9 . The method of claim 8 , wherein the sample is a healthy biological sample.
10 . The method of claim 8 , wherein the sample is a diseased biological sample.
11 . The method of claim 8 , wherein the biological sample is selected from the group consisting of a cell, tissue, blood, plasma, serum, urine, and synovial fluid.
12 . The method of claim 7 , wherein the antibody comprises a label.
13 . The method of claim 12 , wherein the label is a detectable marker that can produce a signal that is detectable by visual or instrumental means, wherein the label is selected from the group consisting of radioisotopes, fluorescent labels, and enzyme-substrate labels.
14 . The method of claim 7 , wherein said detecting is performed using a second labeled antibody which binds to a first anti-IL31 antibody.
15 . The method of claim 7 , further comprising determining whether the level of binding between the antibody differs from that of a comparison sample.
16 . The method of claim 7 , wherein the antibody binds to IL31 with a dissociation constant (Kd) of less than 5×10 −6 M, less than 1×10 −6 M, less than 5×10 −7 M, less than 1×10 −7 M, less than 5×10 −8 M, less than 1×10 −8 M, less than 5×10 −9 M, less than 1×10 −9 M, less than 5×10 −10 M, less than 1×10 −10 M, less than 5×10 −11 M, less than 1×10 −11 M, less than 5×10 −12 M, or less than 1×10 −12 M, as measured by biolayer interferometry.
17 . The method of claim 7 , wherein the antibody reduces IL31 signaling function in a canine, feline or equine companion animal species, as measured by a reduction in STAT-3 phosphorylation.
18 . The method of claim 7 , wherein the antibody competes with monoclonal M14 antibody in binding to canine IL31, feline IL31, or equine IL31.
19 . The method of claim 7 , wherein the antibody is a monoclonal antibody.
20 . The method of claim 7 , wherein the antibody is a canine, a caninized, a feline, a felinized, an equine, an equinized, or a chimeric antibody.