IL4/IL13 RECEPTOR MOLECULE FOR VETERINARY USE
Provided are various embodiments relating to IL13R/IL4R contiguous polypeptides derived from companion animal species and that bind to IL13 and/or IL4. Such contiguous polypeptides can be used in methods to treat IL13 and/or IL4-induced conditions in companion animals, such as canines, felines, and equines.
1 . A method of treating a companion animal species having an IL13-induced condition and/or an IL4-induced condition, the method comprising administering to the companion animal species a therapeutically effective amount of a polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of 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.
2 . The method of claim 1 , wherein the companion animal species is canine, feline, or equine.
3 . The method of claim 1 , wherein the IL13-induced condition and/or the IL4-induced condition is a pruritic or allergic condition.
4 . The method of claim 3 , wherein the pruritic or allergic condition is selected from the group consisting of atopic dermatitis, pruritus, asthma, psoriasis, scleroderma, and eczema.
5 . The method of claim 1 , wherein the method further comprises administering:
a) one or more inhibitors selected from a Jak inhibitor, a PI3K inhibitor, and AKT inhibitor, and a MAPK inhibitor; and/or
b) one or more antibodies selected from an anti-IL17 antibody, an anti-IL31 antibody, an anti-TNFα antibody, an anti-CD20 antibody, an anti-CD19 antibody, and anti-CD25 antibody, an anti-IL4 antibody, an anti-IL13 antibody, an anti-IL23 antibody, an anti-IgE antibody, an anti-CD11a antibody, an anti-IL6R antibody, an anti-α4-Integrin antibody, an anti-IL12 antibody, an anti-IL1β antibody, and an anti-BlyS antibody.
6 . The method of claim 1 , wherein the polypeptide comprises a post-expression modification.
7 . The method of claim 6 , wherein the modification comprises glycosylation, sialyation, acetylation, and/or phosphorylation.
8 . The method of claim 1 , wherein the polypeptide comprises an amino acid sequence selected from SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, and SEQ ID NO: 17.
9 . The method of claim 8 , wherein the polypeptide binds to IL13 of a companion animal species with a dissociation constant (Kd) of less than 5×10-6 M, as measured by biolayer interferometry.
10 . The method of claim 8 , wherein the polypeptide binds to IL4 of a companion animal species with a dissociation constant (Kd) of less than 5×10-6 M, as measured by biolayer interferometry.
11 . The method of claim 1 , wherein the polypeptide comprises SEQ ID NO: 15.
12 . The method of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 98% identical to a sequence selected from the group consisting of 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.
13 . The method of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 99% identical to a sequence selected from the group consisting of 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.
14 . The method of claim 1 , wherein the polypeptide optionally comprises an amino acid substitution.
15 . The method of claim 14 , wherein the amino acid substitution is a conservative amino acid substitution.