IL4/IL13 RECEPTOR MOLECULES FOR VETERINARY USE
Provided are various embodiments relating to IL13R/IL4R contiguous polypeptides and IL13R/IL4R heterodimeric proteins from companion animal species and that bind to IL13 and/or IL4, including long-acting contiguous polypeptides and heterodimeric proteins. Such heterodimeric proteins can be used in methods to treat IL13 and/or IL4-induced conditions in companion animals, such as canines, felines, and equines.
1 - 2 . (canceled)
3 . A contiguous polypeptide comprising an extracellular domain of an IL13R polypeptide and an extracellular domain of an IL4R polypeptide, wherein the IL13R and IL4R polypeptides are from a companion animal species, wherein the contiguous polypeptide comprises the formula (III) IL13R-L1-FP-L2-IL4R, formula (IV) IL4R-L1-FP-L2-IL13R, (V) FP-L1-IL13R-L2-IL4R, or formula (VI) FP-L1-IL4R-L2-IL13R, wherein:
a) IL13R is an extracellular domain of an IL13R polypeptide from the companion animal species,
b) IL4R is an extracellular domain of an IL4R polypeptide from the companion animal species,
c) L1 is a first optional linker,
d) L2 is a second optional linker, and
e) FP is a fusion partner, optionally an IgG Fc polypeptide.
4 . The contiguous polypeptide of claim 3 , wherein the contiguous polypeptide 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, such as at a low pH.
5 - 10 . (canceled)
11 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL13R polypeptide is at least 85% identical to the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 32, SEQ ID NO: 34, or SEQ ID NO: 36.
12 - 14 . (canceled)
15 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL13R polypeptide comprises a cysteine at a position corresponding to position 18 of SEQ ID NO: 22, corresponding to position 18 of SEQ ID NO: 24, or corresponding to position 18 of SEQ ID NO: 26.
16 . (canceled)
17 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL13R polypeptide comprises an amino acid sequence selected from SEQ ID NO: 32, SEQ ID NO: 34, and SEQ ID NO: 36.
18 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL13R polypeptide comprises an amino acid sequence selected from SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 26.
19 . (canceled)
20 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL4R polypeptide is at least 85% identical to the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 163, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 35, or SEQ ID NO: 37.
21 - 23 . (canceled)
24 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL4R polypeptide comprises an amino acid sequence selected from SEQ ID NO: 33, SEQ ID NO: 35, and SEQ ID NO: 37.
25 . The contiguous polypeptide of claim 3 , wherein the extracellular domain of the IL4R polypeptide comprises an amino acid sequence selected from SEQ ID NO: 23, SEQ ID NO: 163, SEQ ID NO: 25, and SEQ ID NO: 27.
26 . The contiguous polypeptide of claim 3 , wherein L1 and L2, if present, each independently comprises an amino acid sequence selected from G, GG, GGG, S, SS, SSS, GS, GSGS (SEQ ID NO: 151), GSGSGS (SEQ ID NO: 152), GGS, GGSGGS (SEQ ID NO: 153), GGSGGSGGS (SEQ ID NO: 154), GGGS (SEQ ID NO: 155), GGGSGGGS (SEQ ID NO: 156), GGGSGGGSGGGS (SEQ ID NO: 157), GSS, GSSGSS (SEQ ID NO: 158), GSSGSSGSS (SEQ ID NO: 159), GGSS (SEQ ID NO: 160), GGSSGGSS (SEQ ID NO: 161), and GGSSGGSSGGSS (SEQ ID NO: 162).
27 . The contiguous polypeptide of claim 3 , wherein the contiguous polypeptide comprises the sequence selected from SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31.
28 . A heterodimeric protein comprising:
a) a first contiguous polypeptide comprising at least one IL13R decoy extracellular domain (ECD) and a first Fc polypeptide, and
b) a second contiguous polypeptide comprising at least one IL4R ECD and a second Fc polypeptide,
wherein the IL13R decoy ECD and/or the IL4R ECD are from a companion animal species.
29 . The heterodimeric protein of claim 28 , wherein the first Fc polypeptide and/or the second Fc polypeptide is 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.
30 - 64 . (canceled)
65 . An isolated polypeptide comprising the amino acid sequence of SEQ ID NO: SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, or SEQ ID NO: 183.
66 . (canceled)
67 . An isolated nucleic acid encoding the contiguous polypeptide of claim 3 .
68 . A host cell comprising the nucleic acid of claim 67 .
69 . (canceled)
70 . A method comprising culturing the host cell of claim 68 and isolating the contiguous polypeptide.
71 . (canceled)
72 . A method of treating a companion animal species having an IL13 and/or 1L4-induced condition, the method comprising administering to the companion animal species a therapeutically effective amount of the contiguous polypeptide of claim 3 .
73 - 78 . (canceled)
79 . A method of reducing IL13 and/or 1L4 signaling activity in a cell, the method comprising exposing the cell to the contiguous polypeptide of claim 3 under conditions permissive for binding of the heterodimeric protein to 1L13 and/or 1L4, thereby (a) reducing binding of IL/4 and/or IL-13 to native IL13 receptor and/or native IL-4 receptor and (b) reducing IL13- and/or IL-4-mediated signaling.
80 - 82 . (canceled)
83 . A method for detecting IL13 or IL4 in a sample from a companion animal species comprising contacting the sample with the contiguous polypeptide of claim 3 under conditions permissive for binding of the heterodimeric protein to IL13 and/or I14, and detecting whether a complex is formed between the heterodimeric protein and IL13 and/or I14 in the sample.
84 . (canceled)