RU2795591C2 - Il4/il13 receptor molecule for veterinary use - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: new therapeutic peptides used in medicine. The invention discloses a continuous polypeptide capable of binding to IL13 and IL4.

EFFECT: useful as a therapeutic agent in the treatment of IL13 and/or IL4 induced states in pets.

25 cl, 3 dwg, 2 tbl, 5 ex

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority of U.S. Provisional Application No. 62/488509, filed April 21, 2018, the entire contents of which are incorporated herein by reference for all purposes.

FIELD OF TECHNOLOGY

[0002] The present invention relates to continuous polypeptides containing fragments of the interleukin 4 receptor and the interleukin 13 receptor derived from domestic animal species that bind to IL4 and/or IL13 from domestic animal species, for example, canine IL4 and canine IL13. This invention also relates to methods of using continuous polypeptides, for example, to treat IL4 and/or IL13 induced conditions or reduce IL4 and/or IL13 signaling activity in cells, for example, in domestic animals such as canines, felines and equines.

BACKGROUND OF THE INVENTION

[0003] Interleukin 4 (IL4) is a cytokine that stimulates the differentiation of naive T helper cells to Th2 cells. Interleukin 13 (IL13) has similar effects on immunocytes. Both IL4 and IL13 play important roles in T-cell mediated immune responses directly associated with allergies such as atopic dermatitis and asthma. It is well known that IL4 can form a signaling complex with heterodimeric receptors either from the IL4 receptor alpha subunit (IL4R) and γc or from IL4R and the IL13 receptor alpha-1 subunit (IL13R). IL13 can form a signaling complex with heterodimeric IL4Ra and IL13Ra1 receptors. Extracellular domains of IL4Ra or IL13Ra1 can bind to IL4 and/or IL13 and decrease free cytokine concentrations, thus reducing clinical signs and symptoms associated with dermatitis, asthma and other disorders.

[0004] Pet species such as cats, dogs, and horses suffer from a variety of allergic diseases similar to human allergic diseases, including atopic dermatitis and asthma. Thus, there remains a need for methods and compounds that can be used in a specific manner to bind IL4 and/or IL13 in a pet, to treat IL4/IL13-induced conditions, and to reduce IL4/IL13 signaling activity.

SUMMARY OF THE INVENTION

[0005] In some embodiments, the present invention provides a continuous IL13R/IL4R polypeptide comprising an extracellular domain of an IL13R polypeptide and an extracellular domain of an IL4R polypeptide, wherein the IL13R and IL4R polypeptides are derived from a domestic animal species.

[0006] In some embodiments, a continuous IL13R/IL4R polypeptide is of formula (I) IL13R-L1-IL4R-L2-FP or formula (II) IL4R-L1-IL13R-L2-FP, where:

a. IL13R is the extracellular domain of an IL13R polypeptide derived from a domestic animal species,

b. IL4R is the extracellular domain of an IL4R polypeptide derived from a domestic animal species,

c. L1 is the first optional linker,

d. L2 is the second optional linker, and

e. FP is a merger partner.

[0007] In some embodiments, a continuous IL13R/IL4R polypeptide binds to IL13 from a pet species 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.

[0008] In some embodiments, a continuous IL13R/IL4R polypeptide binds to IL4 from a pet species 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.

[0009] In some embodiments, a continuous IL13R/IL4R polypeptide reduces IL13 and/or IL4 signaling in a pet species.

[0010] In some embodiments, the pet species is canine, feline, or equine.

[0011] In some embodiments, the extracellular domain of an 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. In some embodiments, the extracellular domain of the IL13R polypeptide is at least 90% 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. In some embodiments, the extracellular domain of the IL13R polypeptide is at least 95% 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. In some embodiments, the extracellular domain of an IL13R polypeptide is at least 98% 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.

[0012] In some embodiments, the extracellular domain of the IL13R polypeptide contains a cysteine at 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. In some embodiments, implementation the extracellular domain of the IL13R polypeptide contains a cysteine at position 18 of SEQ ID NO: 22, at position 18 of SEQ ID NO: 24, at position 18 of SEQ ID NO: 26, at position 15 of SEQ ID NO: 32, at position 15 of SEQ ID NO: 34 or at position 15 of SEQ ID NO: 36. In some embodiments, 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. In some embodiments, embodiments, 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.

[0013] In some embodiments, the extracellular domain of an IL4R polypeptide is at least 85% identical to the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments, the extracellular domain of the IL4R polypeptide is at least 90% identical to the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33 , SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments, the extracellular domain of the IL4R polypeptide is at least 95% identical to the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 35, or SEQ ID NO: 37. In some embodiments, the extracellular domain of an IL4R polypeptide is at least 98% identical to the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 35, or SEQ ID NO: 37. In some embodiments, 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. In some embodiments, the extracellular domain of the IL4R polypeptide comprises an amino acid sequence selected from SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO: 27.

[0014] In some embodiments, each of L1 and L2, if present, independently comprises an amino acid sequence selected from G, GG, GGG, S, SS, SSS, GS, GSGS (SEQ ID NO: 38), GSGSGS (SEQ ID NO: 39), GGS, GGSGGS (SEQ ID NO: 40), GGSGGSGGS (SEQ ID NO: 41), GGGS (SEQ ID NO: 42), GGGSGGGS (SEQ ID NO: 43), GGGSGGGSGGGS (SEQ ID NO: 44), GSS, GSSGSS (SEQ ID NO: 45), GSSGSSGSS (SEQ ID NO: 46), GGSS (SEQ ID NO: 47), GGSSGGSS (SEQ ID NO: 48), and GGSSGGSSGGSS (SEQ ID NO: 49).

[0015] In some embodiments, the fusion partner is selected from Fc, albumin, and an albumin-binding moiety. In some embodiments, the Fc is (a) a canine heavy chain constant region selected from an IgG-A, IgG-B, IgG-C, and IgG-D constant region; (b) a feline heavy chain constant region selected from an IgG1, IgG2a and IgG2b constant region; or (c) an equine heavy chain constant region selected from an IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 and IgG7 constant region.

[0016] In some embodiments, the implementation of a continuous IL13R/IL4R polypeptide contains a 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.

[0017] In some embodiments, the implementation of the present invention relates to a nucleic acid encoding a continuous polypeptide IL13R/IL4R described in the present description above. In some embodiments, the present invention relates to a host cell containing a nucleic acid encoding a continuous IL13R/IL4R polypeptide described herein above. In some embodiments, the present invention relates to a method for producing a continuous IL13R/IL4R polypeptide, comprising culturing such a host cell containing a nucleic acid encoding a continuous IL13R/IL4R polypeptide described herein above, and isolating the continuous polypeptide. In some embodiments, the present invention relates to a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide described herein and a pharmaceutically acceptable carrier.

[0018] In some embodiments, the present invention provides methods for treating a pet species having an IL13 and/or IL4 induced condition, comprising administering to the pet species a therapeutically effective amount of a continuous IL13R/IL4R polypeptide described herein, or a pharmaceutical composition comprising continuous IL13R/IL4R polypeptide as described herein. In some embodiments, the pet species is canine, feline, or equine. In some embodiments, the IL13 and/or IL4 induced condition is an pruritic or allergic condition such as atopic dermatitis, pruritus, asthma, psoriasis, scleroderma, or eczema.

[0019] In some embodiments, the IL13R/IL4R continuous polypeptide or pharmaceutical composition is administered parenterally. In some embodiments, the continuous IL13R/IL4R polypeptide or pharmaceutical composition is administered by an intramuscular route, an intraperitoneal route, an intraspinal route, a subcutaneous route, an intra-arterial route, an intra-articular route, an intrathecal route, or an inhalation route.

[0020] In some embodiments, the method further comprises administering a Jak inhibitor, a PI3K inhibitor, an AKT inhibitor, or a MAPK inhibitor. In some embodiments, the method further comprises administering one or more antibodies selected from anti-IL17 antibody, anti-IL31 antibody, anti-TNFα antibody, anti-CD20 antibody, anti-CD19 antibody, anti-CD25 antibody, anti-IL4 antibody, anti-IL13 antibody, anti-IL23 antibody , anti-IgE antibodies, anti-CD11α antibodies, anti-IL6R antibodies, anti-α4 integrin antibodies, anti-IL12 antibodies, anti-IL1β antibodies, and anti-BlyS antibodies.

[0021] In some embodiments, the present invention relates to methods for reducing IL13 and/or IL4 signaling activity in a cell, comprising exposing the cell to a continuous IL13R/IL4R polypeptide or pharmaceutical composition described herein under conditions that allow binding of the continuous polypeptide to IL13 and/or IL4, thus (a) reducing the binding of IL/4 and/or IL-13 to native IL13 receptor and/or native IL-4 receptor, and reducing IL13 and/or IL4 mediated signaling. In some embodiments, the cell is exposed to a continuous IL13R/IL4R polypeptide or pharmaceutical composition ex vivo . In some embodiments, the cell is exposed to the continuous polypeptide or pharmaceutical composition in vivo . In some embodiments, the cage is a canine cage, a feline cage, or an equine cage.

[0022] In some embodiments, the present invention relates to methods for detecting IL13 or IL4 in a sample from a pet species, comprising contacting the sample with a continuous IL13R/IL4R polypeptide or a pharmaceutical composition described herein, under conditions that allow binding of the continuous polypeptide with IL13 and/or IL4, and detecting whether a complex is formed between the continuous polypeptide and IL13 and/or IL4 in the sample. In some embodiments, the sample is a biological sample derived from canine, feline, or equine.

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 is a plot of sequential binding of canine IL4R-IL13R-Fc to canine IL4 and canine IL13, or to canine IL13 and canine IL4, using 30 μg/ml concentrations of IL4 and IL13 in PBS.

[0024] FIG. 2 is a plot of the sequential binding of canine IL13R-IL4R-Fc to canine IL4 and canine IL13 or to canine IL13 and canine IL4 using 30 μg/ml concentrations of IL4 and IL13 in PBS.

[0025] FIG. 3 is a graph of neutralization of canine IL4 activity by canine IL4R-IL13R-Fc in a TF1 cell proliferation assay. Canine IL4 (50 ng/ml or 3.85 nM) was used in the assay.

DESCRIPTION OF SEQUENCES

[0026]IN table 1 provides a list of specific sequences referred to in the present description.

Table 1: Description of sequences SEQID NO: SUBSEQUENCE DESCRIPTION 1 MGLTSQLIPTLVCLLALTSTFVHGHNFNITIKEIIKMLNILTARNDSCMELTVDVFTAPKNTSDKEIFCRAATVLRQIYTHNCSNRYLRGLYRNLSSMANKTCSMNEIKKSTLKDFLERLKVIMQKKYYRH Canis lupus, precursor of interleukin-4 2 MDLTSQLIPALVCLLAFTSTFVHGQNFNNTLKEIIKTLNILTARNDSCMELTMDVLAAPKNTSDKEIFCRATTVLRQIYTHHNCSTKFLKGLDRNLSSMANRTCSVNEVKKCTLKDFLERLKAIMQKKYSKH Felis catus, precursor of interleukin-4 3 MGLTYQLIPALVCLLACTSNFIQGCKYDITLQEIIKTLNNLTDGKGKNSCMELTVADAFAGPKNTDGKEICRAAKVLQQLYKRHDRSLIKECLSGLDRNLKGMANGTCCTVNEAKKSTLKDFLERLKTIMKEKYSKC Equus caballus, precursor of interleukin-4 4 MALWLTVVIALTCLGGLASPSPVTPSPTLKELIEELVNITQNQASLCNGSMVWSVNLTAGMYCAALESLINVSDCSAAIQRTQRMLKALCSQKPAAGQISSERSRDTKIEVIQLVKNLLTYVRGVYRHGNFR Canis lupus, precursor of interleukin-13 5 MWFLDSTRQSGDQGGRRHTWPIKATARGQGHKPLSLGQPTCPLLAPPVLALGSMALWLTVVIALTCLGGLASPGPHSRRELKELIEELVNITQNQVSLCNGSMVWSVNLTTGMYCAALESLINVSDCTAIQRTQRMLKALCTQKPSAGQTASERSRDTKIEVIQLVKNLLNHLRRNFRHGNFK Felis catus, precursor of interleukin-13 6 MALWLTAVIALACLGGLASPAPLPSSMALKELIKELVNITQNQAPLCNGSMVWSVNLTADTYCRALESLSNVSTCSAIQNTRKMLTKLCPHQLSAGQVSSERARDTKIEVIVLVKDLLKNLRKIFHGGKHVDA Equus caballus, precursor of interleukin-13 7 MGRLCSGLTFPVSCLVLVWVASSGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRA WAQTYNSTWSDWSPSTTWLNYYEPWEQHLPLGVSISCLVILAICLSCYFSIIKKGWWDQIPNPAHSPLVAIVIQDSQVSLWGKRSRGQEPAKCPHWKTCLTKLLPCLLEHGLGREEESPKTAKNGPLQGPGKPAWCPVEVSKTILWPESISVVQCVELSEAPVDNEEEEEVEEDKRSLCPSLEGSGGSFQEGREGIVARLTESL FLDLLGGENGGFCPQGLEESCLPPPSGSVGAQMPWAQFPRAGPRAAPEGPEQPRRPESALQASPTQSAGSSAFPEPPPVVTDNPAYRSFGSFLGQSSDPGDGDSDPELADRPGEADPGIPSAPQPPEPPAALQPEPESWEQILRQSVLQHRAAPAPGPGPGSGYREFTCAVKQGSAPDAGGPGFGPSGEAGYKAFCSLLPGGATCPGTSG GEAGSGEGGYKPFQSLTPGCPGAPTPVPVPLFTFGLDTEPPGSPQDSLGAGSSSPEHLGVEPAGKEEDSRKTLLAPEQATDPLRDDLASSIVYSALTCHLCGHLKQWHDQEERGKAHIVPSPCCGCCCGDRSSLLLSPLRAPNVLPGGVLLEASLSPASLVPSGVSKEGKSSPFSQPASSSAQSSSQTPKKLAVLSTEPTCMSAS Canis lupus, interleukin-4 receptor alpha subunit 8 MGRLCSGLTFPVSCLILMWAAGSGSVKVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGTQLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVP GSQCAVISCCRWVLIALTSRGGRWRLTPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEPWEQHLPLGVSISCLVILAVCLSCYLSVIKIKKEWWDQIPNPAHSHLVAIVIQDPQVSLWGKRSRGQEPAKCPHWKTCLRKLLPCLLEHGMERKEDPSKIARNGPSQCSGKSAWCPVEVSKTILWPESISVVRCV ELLEAPVESEEEEEEEEDKGSFCPSPVNLEDSFQEGREGIAARLTESLFMDLLGVEKGGFGPQGSLESWFPPPSGSAGAQMPWAEFPGPGPQEASPQGKEQPFDPRSDPLATLPQSPASPTFPETPPVVTDNPAYRSFGTFQGRSSGPGECDSGPELAGRLGEADPGIPAAPQPSEPPSALQPEAETWEQILRQRVLQHRGAPAPAPGSGYRE FVCAVRQGSTQDSGVGDFGPSEEAGYKAFSSLLTSGAVCPESGGEAGSGDGGYKPFQSLTPGCPGAPAPVPVPLFTFGLDAEPPHCPQDSPLPGSSPEPAGKAQDSHKTPPAPEQAADPLRDDLASGIVYSALTCHLCGHLKQCHGQEEGGEAHPVASPCCGCCCGDRSSPLVSPLRAPDPLPGGVPLEASLSPASPAPPLAVSEEGPPSLCFQ PALSHAHSSSQTPKKVAMLSPEPTCTMAS Felis catus, interleukin-4 receptor alpha subunit 9 MGCLCPGLTLPVSCLILVWAAGSGSVKVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVYELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPDFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQ NYNSTWSEWSPSTTWHNYYEQPLEQRLPLGVSISCVVILAICLSCYFSIIKKEWWDQIPNPAHSPLVAIVLQDSQVSLWGKQSRGQEPAKCPRWKTCLTKLLPCLLEHGLQKEEDSSKTVRNGPFQSPGKSAWHTVEVNHTILRPEIISVVPCVELCEAQVESEEEEVEEDRGSFCPSPESSGSGFQEGREGVAARLTESLFLGL LGAENGALGESCLLPPLGSAHMPWARISSAGPQEAASQGEEQPLNPESNPLATLTQSPGSLAFTEAPAVVADNPAYRSFSNSLSQPRGPPGELDSDPQLAEHLGQVDPSIPSAPQPSEPPTALQPEPETWEQMLRQSVLQQGAAPAPASAPTGGYREFAQAVKQGGGAAGSGPSGEAGYKAFSSLLAGSAVCPGQSGVEASSGEGGYRP YESPDPGAPAPVPVPLFTFGLDVEPPHSPQNSLLPGGSPELPGPEPTVKGEDPRKPLLSAQQATDSLRDDLGSGIVYSALTCHLCGHLKQCHGQEEHGEAHTVASPCCGCCCGDRSSPPVSPVRALDPPPGGVPLEAGLSLASLGSLGLSEERKPSLFFQPAPGNAQSSSQTPLTVAMLSTGPTCTSAS Equus caballus, an alpha subunit of the interleukin-4 receptor 10 MERPARLCGLWALLLCAAGGRGGVAAPTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIV VKDNAGKIRPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNNKLCYEDDKLWSNWSQAMSIGENTDPTFYITMLLATPVIVAGAIIVLLLYLKRLKIIIFPPIPDPGKIFKEMFGDQNDDTLHWRKYDI YEKQTKEETDSVVLIENLKKASQ Canis lupus, alpha-1 subunit of the interleukin-13 receptor eleven MMTKCSSDRNVFKRKWFLFPASQYTFRPIHQARPCEVPAVHLEPSPPWEVGLGLLNLESEFRKLGLRGRRLAAAPPDSRAEAASQTQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGR NTSPDTNYTLYYWHSSLGKILQCENIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRVRTNKLCYEDDRLWSNWSQAMSIGENTDPTFYITMLLA TPVIVAGAIIVLLLYLKRLKIIIFPPIPDPGKIFKEMFGDQNDDSLHWKKYDIYEKQTKEETDSVVLIENASQ Felis catus, alpha-1 subunit of the interleukin-13 receptor 12 MYFLCLIWTESQPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFF NIVPLTSHVKPDPPHIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSIGKKADPTFYIAMLLIIPVIVAGAIIVLLLYLKRLKIIMFPPIPDPGKIFKEMFGDQNDDTLHWKKYDIYEKQTKEET DSVVLIENLKRASQ Equus caballus, alpha-1 subunit of the interleukin-13 receptor 13 TETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHI KRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPTGGGSGSGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQ QLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWLNYYEPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQMQTA KTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Canis lupus, IL13R-IL4R-Fc (no signal sequence) 14 SGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWL NYYEPGGGSGTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLT SHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPTFNECRCTDTPPCPVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLDLGREDPEVQISWFVDGKEVHTAKTQS REQQFNGTYRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERTISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKDFYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGSYFLYSKLSVDKSRWQQGDPFTCAVMHETLQNHYTDLSLSHSPGK Canis lupus, IL4R-IL13R-IgGA (no signal sequence) 15 SGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWL NYYEPGGGSGTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLT SHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPTPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQISWFVDGKQM QTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Canis lupus, IL4R-IL13R-IgGB (no signal sequence) 16 SGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWL NYYEPGGGSGTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLT SHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNNKLCYEDDKLWSNWSQAMSIGENTDPTAKECECKCNCNNCPCPGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVVVDLDPENPEVQISWFVDSKQVQTANT QPREEQSNGTYRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEEIISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLVKDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQISLSHSPGK Canis lupus, IL4R-IL13R-IgGC (no signal sequence) 17 SGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWL NYYEPGGGSGTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLT SHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNNKLCYEDDKLWSNWSQAMSIGENTDPTPKESTCKCISPCPVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDLGREDPEVQISWFVDGKEVHTAKTQP REQQFNSTYRVVSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTISKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKDFFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSYFLYSKLSVDKSRWQQGDTFTCAVMHEALQNHYTDLSLSHSPGK Canis lupus, IL4R-IL13R-IgGD (no signal sequence) 18 SGSVKVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGTQLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVPGSQCAVISCCRWVLIALTSRG GRWRLTPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEPGGGSGSQTQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCE NIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRRVRTNKLCYEDDRLWSNWSQAMSIGENTDPT Felis catus, IL4R-IL13R (no signal sequence) 19 SGSVKVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVYELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPTFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQNYNSTWSEWSPSTTWHNYYE QPGGGSGTESQPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFFNIVP LTSHVKPDPPHIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSIGKKADPT Equus caballus, IL4R-IL13R (no signal sequence) 20 MAVLGLLFCLVTFPSCVLSTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKIVSFEQHSVQVKDNAGKI RPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPTGGGSGSGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCSMPI DDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTWLNYYEPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPEVQ ISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Canis lupus, IL13R-IL4R-IgGB (with signal sequence) 21 MAVLGLLFCLVTFPSCVLSSGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWA QTYNSTWSDWSPSTTWLNYYEPGGGSGTETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQ IVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPTPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK Canis lupus, IL4R-IL13R-IgGB (with signal sequence) 22 TETQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHI KRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNKLCYEDDKLWSNWSQAMSIGENTDPT Canis lupus, IL13R extracellular domain (no signal sequence) 23 SGSGSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNSTWSDWSPSTTW LNYYEP Canis lupus, IL4R extracellular domain (no signal sequence) 24 SQTQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCENIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPP HIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRVRTNLCYEDDRLWSNWSQAMSIGENTDPT Felis catus, IL13R extracellular domain (no signal sequence) 25 SGSVKVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGTQLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVPGSQCAVISCCRWVLIALTSRG GRWRLTPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEP Felis catus, IL4R extracellular domain (no signal sequence) 26 TESQPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFFNIVPLTSHVK PDPPHIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSIGKKADPT Equus caballus, IL13R extracellular domain (no signal sequence) 27 SGSVKVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVYELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPTFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQNYNSTWSEWSPSTTWHNYYE QP Equus caballus, IL4R extracellular domain (no signal sequence) 28 SQTQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCENIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPP HIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRVRTNKLCYEDDRLWSNWSQAMSIGENTDPTGGGSGSSGSVKVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGT QLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVPGSQCAVISCCRWVLIALTSRGGRWRLTPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEPSPKTASTIESKTGECPKCPVPEIPGAPSVFIF PPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLT QSPGK IL13R-IL4R-IgG2 feline (no signal sequence) 29 SGSVKVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGTQLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVPGSQCAVISCCRWVLIALTSRG GRWRLTPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEPGGGSGSSQTQPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQ CENIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRLFFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRVRTNKLCYEDDRLWSNWSQAMSIGENTDPTSPKTASTIESKTGECPKCPVPEIPGAPSVFIF PPKPKDTLSISRTPEVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTYRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLT QSPGK IL4R-IL13R-IgG2 feline (no signal sequence) thirty TESQPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFFNIVPLTSHVK PDPPHIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSIGKKADPTGGGSGSSGSVKVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVY ELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPDFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQNYNSTWSEWSPSTTWHNYYEQPDMSKCPKCPAPELLGGPSVFIFPPNPKDTLMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREA QFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHYTKTDISESLGK Equine IL13R-IL4R-IgG2 (no signal sequence) 31 SGSVKVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVYELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPTFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQNYNSTWSEWSPSTTWHNYYE QPGGGSGSTESQPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFFNIVP LTSHVKPDPPHIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSIGKKAADPTDMSKCPKCPAPELLGGPSVFIFPPNPKDTLMISRTPVVTCVVVNLSDQYPDVQFSWYVDNTEVHSAITKQREA QFNSTYRVVSVLPIQHQDWLSGKEFKCSVTNVGVPQPISRAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCLVKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDGDGSYFLYSKLSLETSRWQQVESFTCAVMHEALHNHYTKTDISESLGK Equine IL4R-IL13R-IgG2 (no signal sequence) 32 QPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRL FFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETNDIFYVEEAKCQNSEFEGNLEGTICFMVPGVLPDTLNTVRIRVRTNNKLCYEDDKLWSNWSQAMSI ECD mini IL13R canine 33 KVLHEPSCFSDYISTSVCQWKMDHPTNCSAELRLSYQLDFMGSENHTCVPENREDSVCVCSMPIDDAVEADVYQLDLWAGQQLLWSGSFQPSKHVKPRTPGNLTVHPNISHTWLLMWTNPYPTENHLHSELTYMVNVSNDNDPEDFKVYNVTYMGPTLRLAASTLKSGASYSARVRAWAQTYNS ECD Mini IL4R Canine 34 QPPVTNLSVSVENLCTVIWTWDPPEGASPNCTLRYFSHFDNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCTPPPEGDPESAVTELQCVWHNLSYMKCTWLPGRNTSPDTNYTLYYWHSSLGKILQCENIYREGQHIGCSFALTNLKDSSFEQHSVQIVVKDNAGKIRPSFNIVPLTSHVKPDPPHIKRL FFQNGNLYVQWKNPQNFYSRCLSYQVEVNNSQTETHDIFYVEEAKCQNSEFEGNLEGTICFMVPGILPDTLNTVRIRVRTNNKLCYEDDRLWSNWSQAMSI ECD mini IL13R feline 35 KVLRAPTCFSDYFSTSVCQWNMDAPTNCSAELRLSYQLNFMGSENRTCVPENGEGAACACSMLMDDFVEADVYQLHLWAGTQLLWSGSFKPSSHVKPRAPGNLTVHPNVSHTWLLRWSNPYPPENHLHAELTYMVNISSEDDPTDVSVCASGFLCHLLGLRRVETGAPGARLPPWLCAPRPRRVPGSQCAVISCCRWVLIALTSRGGRWRL TPGLRSQTRYVSVAEGLFGATPRVLCPGTQAGLASAAREQMSPDPSAFHSIDYEP ECD mini IL4R feline 36 QPPVTNLSVSVENLCTVIWTWNPPEGVSPNCSLWYFSHFGNKQDKKIAPETHRSKEVPLNERICLQVGSQCSTNESDNPSILVEKCISPPEGDPESAVTELQCVWHNLSYMKCTWLPGKNASPDTNYTLYYWHSSLGKILQCEDIYREGQHIGCSFALTEVKDSIFEQHSVQIMVKDNAGKIRPFFNIVPLTSHVKPDPP HIKKLFFQNGDLYVQWKNPQNFYSRCLSYQVEVNNSQTETRDIFSVEEAKCQNPEFEGDLEGTICFMVPGVLPDTVNTVRIRVKTNKLCYEDDKLWSNWSQAMSI ECD Mini IL13R Equine 37 KVLHLTACFSDYISASTCEWKMDRPTNCSAQLRLSYQLNDEFSDNLTCIPENREDEVCVCRMLMDNIVSEDVYELDLWAGNQLLWNSSFKPSRHVKPRAPQNLTVHAISHTWLLTWSNPYPLKNHLWSELTYLVNISKEDDPTFKIYNVTYMDPTLRVTASTLKSRATYSARVKARAQNYNSTWSEWSPSTTWHNYYEQP ECD mini IL4R equine

DESCRIPTION OF EMBODIMENTS

[0027] The present invention relates to continuous polypeptides that bind canine IL13 and/or IL4, feline IL13 and/or IL4, and/or equine IL13 and/or IL4. In some embodiments, the continuous polypeptides comprise an extracellular domain of an IL13R polypeptide and an extracellular domain of an IL4R polypeptide. The present invention also relates to methods for producing or purifying continuous polypeptides. The present invention provides methods of treatment using continuous polypeptides to bind IL13 and/or IL4 and inhibit IL13 and/or IL4 mediated signaling. Such methods include, but are not limited to, methods for treating IL13 and/or IL4 induced conditions in a pet species. The present invention also relates to methods for detecting IL13 and/or IL4 in a sample from a pet species.

[0028] For the convenience of the reader, the following definitions of terms are provided within the scope of the invention.

[0029] Within the scope of the invention, numerical terms such as Kd are calculated from scientific measurements and are thus subject to a corresponding measurement error. In some cases, a numeric term may include numeric values rounded to the nearest significant figure.

[0030] For the purposes of the invention, the singular means "at least one" or "one or more" unless otherwise indicated. Within the scope of the invention, the term "or" means "and/or", unless otherwise indicated. In the context of a plurality of dependent claims, the use of "or" when referring to other claims refers to those claims only as an alternative.

Continuous IL13R/IL4R polypeptides

[0031]The present invention relates to novel continuous IL13R/IL4R polypeptides, for example, continuous polypeptides that bind canine IL13 and/or IL4, feline IL13 and/or IL4, and/or equine IL13 and/or IL4.

[0032] "Amino acid sequence" refers to the sequence of amino acid residues in a peptide or protein. The terms "polypeptide" and "protein" are used interchangeably to refer to a polymer of amino acid residues, and are not limited to a minimum length. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers and multimers of amino acid residues. Both full-length proteins and their fragments are included in this definition. The terms also include post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In addition, for the purposes of the present description, "polypeptide" refers to a protein, including modifications, such as deletions, additions and substitutions (generally conservative nature), in the natural sequence, provided that the protein retains the desired activity. These modifications may be intentional, eg, by site-directed mutagenesis, or may be accidental, eg, by mutations in protein-producing hosts or errors due to PCR amplification.

[0033] The term "continuous polypeptide" in the present description is used to refer to an uninterrupted sequence of amino acids. A continuous polypeptide is usually translated from one continuous DNA sequence. It can be obtained through genetic engineering, for example by removing the stop codon from the DNA sequence for the first protein, then adding the second protein's DNA sequence in frame, such that the DNA sequence is expressed as a single protein. Typically, this is done by cloning the cDNA into an expression vector in frame with the existing gene.

[0034] "IL4R", within the scope of the invention, is a polypeptide containing all or a fragment of the alpha subunit of the IL4 receptor that binds to IL-4.

[0035] For example, "IL4R" refers to an IL4R polypeptide from any vertebrate source, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and domestic animals (eg, dogs, cats and horses), unless otherwise noted. In some embodiments, IL4R is an extracellular domain fragment that binds to IL4. In some such embodiments, IL4R may be referred to as IL4R extracellular domain (ECD). In some embodiments, IL4R comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 33 , SEQ ID NO: 35 or SEQ ID NO: 37.

[0036] "IL13R", in the context of the invention, is a polypeptide containing all or a fragment of the alpha-1 subunit of the IL13 receptor that binds to IL-13.

[0037] For example, "IL13R" refers to an IL13R polypeptide from any vertebrate source, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and domestic animals (eg, dogs, cats and horses), unless otherwise noted. In some embodiments, IL13R is an extracellular domain fragment that binds to IL13. In some such embodiments, IL13R may be referred to as IL13R extracellular domain (ECD). In some embodiments, the IL13R polypeptide comprises the amino acid sequence of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, 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.

[0038] The term "kind of pet" refers to an animal suitable as a companion for humans. In some embodiments, the pet species is a small animal such as a canine, feline, dog, cat, horse, rabbit, ferret, guinea pig, rodent, etc. In some embodiments, the pet species is a farm animal such as a horse, cow, pig, etc.

[0039] An "extracellular domain"("ECD") is a fragment of a polypeptide that extends beyond the transmembrane domain into the extracellular space. The term "extracellular domain", within the scope of the invention, may contain a complete extracellular domain or may contain a truncated extracellular domain, devoid of one or more amino acids, which binds to its ligand. The composition of the extracellular domain may depend on the algorithm used to determine which amino acids are in the membrane. Different algorithms can predict and different systems can express different extracellular domains for a given protein.

[0040] The extracellular domain of an IL4R polypeptide may comprise the entire extracellular domain or a truncated extracellular domain of IL4R that binds to IL4. Within the scope of the invention, the terms "IL4R polypeptide extracellular domain", "IL4R ECD" and similar terms refer to an IL4R polypeptide that does not contain a transmembrane domain or a cytoplasmic domain, even if the term is followed by an open transitional word such as "comprising", "comprises " and so on. In some embodiments, the extracellular domain of an IL4R polypeptide is the extracellular domain of an IL4R polypeptide derived from a domestic animal species. For example, in some embodiments, the extracellular domain of an IL4R polypeptide is derived from canine IL4R, feline IL4R, or equine IL4R. In some embodiments, the extracellular domain of an IL4R polypeptide comprises the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, or SEQ ID NO: 27, or any fragment thereof. In some embodiments, the extracellular domain of an IL4R polypeptide comprises the amino acid sequence of SEQ ID NO: 33, SEQ ID NO: 35, or SEQ ID NO: 37, or any fragment thereof.

[0041] The extracellular domain of an IL13R polypeptide may comprise the entire extracellular domain or a truncated extracellular domain of IL13R that binds to IL13. Within the scope of the invention, the terms "IL13R polypeptide extracellular domain", "IL13R ECD", and similar terms refer to an IL13R polypeptide that does not contain a transmembrane domain or a cytoplasmic domain, even if the term is followed by an open transitional word such as "comprising", "contains" and the like. In some embodiments, the extracellular domain of an IL13R polypeptide is the extracellular domain of an IL13R polypeptide derived from a domestic animal species. For example, in some embodiments, the extracellular domain of an IL13R polypeptide is derived from canine IL13R, feline IL13R, or equine IL13R. In some embodiments, the extracellular domain of an IL13R polypeptide comprises the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 24, or SEQ ID NO: 26, or any fragment thereof. In some embodiments, the extracellular domain of an IL13R polypeptide comprises the amino acid sequence of SEQ ID NO: 32, SEQ ID NO: 34, or SEQ ID NO: 36, or any fragment thereof.

[0042] The terms "continuous IL13R/IL4R polypeptide" and "continuous IL4R/IL13R polypeptide" are used interchangeably to refer to a continuous polypeptide comprising an IL13R polypeptide and an IL4R polypeptide, where the terms are not indicative of the order in which the IL13R and IL4R polypeptides occur in a continuous polypeptide, unless the order is otherwise indicated. For example, a continuous IL13R/IL4R polypeptide or a continuous IL4R/IL13R polypeptide may refer to an IL4R polypeptide preceded or followed in sequence by an IL13R polypeptide. In addition, a continuous IL13R/IL4R polypeptide or a continuous IL4R/IL13R polypeptide may refer to an IL13R polypeptide preceded or followed in sequence by an IL4R polypeptide.

[0043] In some embodiments, a continuous IL13R/IL4R polypeptide comprises an IL13R polypeptide linked to an IL4R polypeptide at the C-terminus of the IL13R polypeptide or at the N-terminus of the IL13R polypeptide. In some embodiments, a continuous IL13R/IL4R polypeptide comprises an IL4R polypeptide linked to an IL13R polypeptide at the C-terminus of the IL4R polypeptide or at the N-terminus of the IL4R polypeptide.

[0044] A continuous IL13R/IL4R polypeptide of the invention may comprise an extracellular domain of an IL13R polypeptide and/or an extracellular domain of an IL4R polypeptide, wherein the polypeptides are derived from a domestic animal species. For example, a continuous polypeptide may comprise an extracellular domain of an IL4R polypeptide from a dog, cat, or horse, and/or may comprise an extracellular domain of an IL13R polypeptide from a dog, cat, or horse.

[0045] "Wild type" refers to an unmutated variant of a polypeptide that occurs naturally, or a fragment thereof. The wild-type polypeptide can be produced recombinantly. "ECD IL13R wild type" or "ECD IL4R wild type" refers to a protein having an amino acid sequence identical to the same fragment of the extracellular domain of IL13R or IL4R, occurring in nature.

[0046] A "variant" is a nucleic acid or polypeptide molecule that differs from a reference nucleic acid molecule or polypeptide as a result of substitutions, deletions, and/or additions of one or more amino acids and substantially retains at least one biological activity of the reference nucleic acid molecule or a polypeptide.

[0047] A "biologically active" molecule, or a molecule having "biological activity", is a molecule having any function associated with or associated with a metabolic or physiological process and/or having the structural, regulatory or biochemical functions of a naturally occurring molecule. Biologically active fragments of a polynucleotide are fragments having an activity similar to, but not necessarily identical to, that of a polynucleotide of the present invention. A biologically active polypeptide, or fragment thereof, includes a polypeptide that can participate in a biological reaction, including, but not limited to, ligand-receptor interaction or antigen-antibody binding. Biological activity may include improved desired activity, or reduced undesirable activity. A molecule may exhibit biological activity when it is involved in a molecular interaction with another molecule, such as hybridization, when it has therapeutic value in alleviating a disease state, when it has prophylactic value in inducing an immune response, when it has diagnostic and/or prognostic value in determining the presence of a molecule, for example, a biologically active fragment of a polynucleotide that can be detected as unique to the polynucleotide molecule, and when it can be used as a primer in a polymerase chain reaction (PCR).

[0048] For the purposes of the invention, "percent (%) amino acid sequence identity" and "homology", as applied to the sequence of a nucleic acid molecule or polypeptide, is defined as the percentage of nucleotides or amino acid residues in a reference sequence that are identical to nucleotides or amino acid residues in a specific sequence. sequences of a nucleic acid molecule or polypeptide, after sequence alignment and gaps, if necessary, to achieve maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent sequence identity can be accomplished in a variety of ways within the skill of the art, for example using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALINE™ (DNASTAR) software. Those skilled in the art can determine suitable parameters for measuring alignment, including any algorithms necessary to achieve maximum alignment over the full length of the compared sequences.

[0049] In some embodiments, the variant has at least about 50% sequence identity with a reference nucleic acid or polypeptide molecule after sequence alignment and gaps, if necessary, to achieve maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identities. Such variants include, for example, polypeptides where one or more amino acid residues are added, deleted at the N- or C-terminus of the polypeptide. In some embodiments, the variant has at least about 50% sequence identity, at least about 60% sequence identity, at least about 65% sequence identity, at least about 70% sequence identity, at least about 75% sequence identity , at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 98% sequence identity with a reference nucleic acid sequence or a polypeptide.

[0050] In some embodiments, a continuous IL13R/IL4R polypeptide comprises an extracellular domain of an IL13R polypeptide having at least 85%, at least 90%, at least 95%, at least 98% sequence identity with 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. In some embodiments, the continuous IL13R/IL4R polypeptide comprises an IL4R polypeptide extracellular domain having at least 85%, at least 90%, at least 95%, at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO : 33, SEQ ID NO: 35, or SEQ ID NO: 37.

[0051] In some embodiments, a continuous IL13R/IL4R polypeptide comprises an extracellular domain of an IL13R polypeptide containing a cysteine at position corresponding to position 18 of SEQ ID NO: 22, at position corresponding to position 18 of SEQ ID NO: 24, or at a position corresponding to position 18 of SEQ ID NO: 26. In some embodiments, the continuous IL13R/IL4R polypeptide comprises an extracellular domain of the IL13R polypeptide containing a cysteine at position 18 of SEQ ID NO: 22, at position 18 of SEQ ID NO: 24, at position 18 from SEQ ID NO: 26, at position 15 from SEQ ID NO: 32, at position 15 from SEQ ID NO: 34, or at position 15 from SEQ ID NO: 36.

[0052] A "point mutation" is a mutation affecting a single nucleotide or amino acid residue. A mutation may be the loss of a nucleotide or amino acid, the substitution of one nucleotide or amino acid residue for another, or the insertion of an additional nucleotide or amino acid residue.

[0053] An amino acid substitution may include, but is not limited to, substitution of one amino acid in a polypeptide for another amino acid. Exemplary substitutions are shown in Table 2. Amino acid substitutions can be introduced into a molecule of interest, and products screened for desired activity, such as maintaining/improving antigen binding, reducing immunogenicity, or improving ADCC or CDC, or improving pharmacokinetics.

[0054] Table 2

original balance Illustrative substitutions Ala (A) Val; Leu; ile Arg(R) Lys; gln; Asn Asn(N) gln; His; asp; Lys; Arg Asp(D) Glu; Asn Cys(C) Ser; Ala Gln(Q) asn; Glu Glu(E) asp; Gln Gly (G) His(H) asn; gln; Lys; Arg Ile (I) Leu; Val; met; Ala; Ph; norleucine Leu(L) Norleucine; Ile; Val; met; Ala; Phe Lys (K) Arg; gln; Asn Met(M) Leu; Ph; ile Phe(F) trp; Leu; Val; Ile; Ala; Tyr Pro (P) Ser(S) Thr Thr(T) Val; Ser TRP(W) Tyr; Phe Tyr (Y) trp; Ph; Thr; Ser Val(V) Ile; Leu; met; Ph; Ala; norleucine

[0055] Amino acids can be grouped according to common side chain properties:

(1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile;

(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln;

(3) acidic: Asp, Glu;

(4) main: His, Lys, Arg;

(5) residues affecting chain orientation: Gly, Pro;

(6) aromatic: Trp, Tyr, Phe.

[0056] Non-conservative replacements include replacing a member of one of these classes with another class.

[0057] A "fusion partner", as used herein, refers to an additional component of a continuous IL13R/IL4R polypeptide, such as an additional polypeptide such as albumin, an albumin-binding fragment, or an immunoglobulin molecule fragment. The fusion partner may contain an oligomerization domain, such as an immunoglobulin heavy chain Fc domain.

[0058] A "crystallizable fragment (Fc) polypeptide" is a portion of an antibody molecule that interacts with effector molecules and cells. It contains the C-terminal portions of the heavy chains of immunoglobulins. Within the scope of the invention, an Fc polypeptide comprises an Fc domain fragment with one or more biological activities of the entire Fc polypeptide. An "effector function" of an Fc polypeptide is an action or activity mediated, in whole or in part, by an antibody in response to a stimulus and may include complement fixation or ADCC (antibody dependent cellular cytotoxicity) induction.

[0059] The term "IgX" or "IgX Fc" refers to an Fc region derived from a particular antibody isotype (eg, IgG, IgA, IgD, IgE, IgM, etc.), where "X" denotes an antibody isotype. Thus, "IgG" or "Fc IgG" denotes the Fc region from the γ chain, "IgA" or "Fc IgA" denotes the Fc region from the α chain, "IgD" or "Fc IgD" denotes the Fc region from the δ chain, "IgE ” or “Fc IgE” indicates an Fc region from the ε chain, “IgM” or “Fc IgM” indicates an Fc region from the μ chain, and so on. In some embodiments, the IgG Fc region comprises CH1, hinge, CH2, CH3, and CL1. "IgXN" or "Fc IgXN" means that the Fc region is from a particular subclass of the antibody isotype (such as subclass A, B, C, or D of canine IgG; subclass 1, 2a, or 2b of feline IgG; or subclass of IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 or IgG7 IgG equine, etc.), where "N" indicates the subclass.

[0060] In some embodiments, the IgX or IgXN regions are from a pet, such as a dog, cat, or horse. In some embodiments, the IgG regions are isolated from canine γ heavy chains, such as IgGA, IgGB, IgGC, or IgGD. In some cases, IgG Fc regions are isolated from feline γ heavy chains such as IgG1, IgG2a, or IgG2b. In other cases, IgG regions are isolated from equine γ heavy chains such as IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 or IgG7. Polypeptides containing an Fc region of IgGA, IgGB, IgGC or IgGD can provide higher levels of expression in recombinant production systems.

[0061] "Signal sequence" refers to a sequence of amino acid residues or polynucleotides encoding them that facilitates the secretion of a polypeptide of interest and is typically cleaved upon export of the polypeptide to the space outside the cell surface membrane.

[0062] "Linker" refers to one or more amino acid residues connecting the first polypeptide to the second polypeptide.

[0063] In some embodiments, the linker is a glycine-rich, serine-rich, or GS-rich flexible, non-structural linker. In some embodiments, the implementation of the linker contains two amino acids G (Gly) and/or S (Ser). For example, the linker may contain a G or a G repeat (eg, GG, GGG, etc.); GS or repeat GS (for example, GSGS (SEQ ID NO: 38), GSGSGS (SEQ ID NO: 39), etc.); GGS or repeat GGS (eg, GGSGGS (SEQ ID NO: 40), GGSGGSGGS (SEQ ID NO: 41), etc.); GGGS (SEQ ID NO: 42) or repeat GGGS (SEQ ID NO: 42) (eg, GGGSGGGS (SEQ ID NO: 43), GGGSGGGSGGGS (SEQ ID NO: 44), etc.); GSS or repeat GSS (for example, GSSGSS (SEQ ID NO: 45), GSSGSSGSS (SEQ ID NO: 46), etc.); or GGSS (SEQ ID NO: 47) or repeat GGSS (SEQ ID NO: 47) (eg, GGSSGGSS (SEQ ID NO: 48), GGSSGGSSGGSS (SEQ ID NO: 49), etc.).

[0064] In some embodiments, a continuous IL13R/IL4R polypeptide contains at least one fusion partner and/or at least one linker. In some embodiments, a continuous IL13R/IL4R polypeptide contains an optional signal sequence, an optional fusion partner, and at least one optional linker. In some embodiments, a continuous IL13R/IL4R polypeptide does not contain a signal sequence, fusion partner, or linker. In some embodiments, a continuous IL13/IL4 polypeptide is translated with a signal sequence, but the signal sequence is cleaved from the continuous IL13R/IL4R polypeptide.

[0065] In some embodiments, a continuous IL13R/IL4R polypeptide comprises:

Formula (I): IL13R-L1-IL4R-L2-FP or

Formula (II): IL4R-L1-IL13R-L2-FP,

where IL13R is an IL13R extracellular domain (ECD) polypeptide derived from a pet species, IL4R is an IL4R ECD polypeptide derived from a pet species, L1 is an optional first linker, L2 is an optional second linker, and FP is an optional merger partner.

[0066] In some embodiments, the continuous IL13R/IL4R polypeptide comprises an amino acid 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, SEQ ID NO: 31.

Expression and production of continuous IL13R/IL4R polypeptide

[0067] The present invention relates to polynucleotide sequences encoding all or part (eg, extracellular domain) of a continuous IL13R/IL4R polypeptide in the presence or absence of a signal sequence. If a homologous signal sequence (ie, a native IL-4R or IL13R signal sequence) is not used in the construction of the nucleic acid molecule, then another signal sequence can be used, for example, any of the signal sequences described in PCT US06/02951.

[0068] Typically, a nucleotide sequence encoding a polypeptide of interest, such as a contiguous IL13R/IL4R polypeptide, is inserted into an expression vector suitable for expression in the selected host cell.

[0069] A "vector" is a plasmid that can be used to transfer a DNA sequence from one organism to another or to express a gene of interest. The vector typically includes an origin of replication and regulatory sequences that regulate the expression of a gene of interest and may or may not carry a selectable marker gene, such as an antibiotic resistance gene. The vector is suitable for the host cell in which it is to be expressed. A vector may be referred to as a "recombinant vector" when the gene of interest is present in the vector.

[0070] "Host cell" refers to a cell that can be or is the recipient of a vector or an isolated polynucleotide. The host cells may be prokaryotic cells or eukaryotic cells. Exemplary eukaryotic cells include mammalian cells such as primate or non-primate animal cells; fungal cells such as yeast; plant cells; and insect cells. Non-limiting examples of mammalian cells include, but are not limited to, NS0 cells, PER.C6® cells (Crucell), 293 cells, and CHO cells, and their derivatives such as 293-6E, DG44, CHO-S, and CHO-K cells. Host cells include the progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or genomic DNA complementarity) to the original parent cell due to natural, accidental or intentional mutation. The host cell includes cells transfected in vivo using a polynucleotide(s) encoding the amino acid sequence(s) provided herein.

[0071] The term "isolated", as used herein, refers to a molecule that has been separated from at least a portion of the components with which it is typically found in nature or produced. For example, a polypeptide is referred to as "isolated" when it is separated from at least some of the components of the cell in which it is produced. When a polypeptide is secreted by a cell after expression, the physical separation of the supernatant containing the polypeptide from the producing cell is considered to be the "isolation" of the polypeptide. Similarly, a polynucleotide is referred to as "isolated" when it is not part of a larger polynucleotide (such as genomic DNA or mitochondrial DNA, in the case of a DNA polynucleotide) in which it is normally found in nature, or is separated by at least from some of the components of the cell in which it is produced, for example in the case of an RNA polynucleotide. Thus, a DNA polynucleotide contained in a vector within a host cell may be referred to as "isolated".

[0072] In some embodiments, a continuous IL13R/IL4R polypeptide is isolated using chromatography, such as size exclusion chromatography, ion exchange chromatography, protein A column chromatography, hydrophobic interaction chromatography, and CHT chromatography.

[0073] The terms "label" and "detectable label" refer to a group attached to a continuous IL13R/IL4R polypeptide to render it detectable. In some embodiments, the label is a detectable marker that can provide a visually or instrumentally detectable signal, such as incorporating a radiolabeled amino acid or attaching biotinyl groups to the polypeptide that can be detected by labeled avidin (for example, streptavidin having a fluorescent a marker or enzymatic activity that can be detected by optical or colorimetric methods). Examples of labels for polypeptides include, but ^are not limited to, the following: radioactive isotopes or radionuclides (e.g. ³ H, ¹⁴ C, ³⁵ S, ⁹⁰ Y, ⁹⁹ Tc, ¹¹¹ In, ¹²⁵ I, ¹³¹ I, ¹⁷⁷ Lu, ¹⁶⁶ Ho or Sm); chromogens, fluorescent labels (eg, FITC, rhodamine, phosphorus lanthanides), enzyme labels (eg, horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; predefined polypeptide epitopes recognized by the secondary reporter (eg, leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags); and magnetic agents such as gadolinium chelates. Representative examples of labels commonly used in immunoassays include light-producing groups, such as acridinium compounds, and fluorescence-producing groups, such as fluorescein. For this purpose, the group itself may not be labeled with a detectable label, but may become detectable upon reaction with another group.

Continuous IL13R/IL4R polypeptides as decoy receptor captures

[0074] The continuous IL13R/IL4R polypeptides of the invention can function as decoy receptors to capture IL13 or IL4 and inhibit their interaction with IL13R and IL4R on the cell surface. Decoy receptors, such as the decoy receptors of the invention, recognize their ligands with high affinity and specificity, but are structurally incapable of signaling. They compete with wild-type receptors for ligand binding and participation in ligand/receptor interactions, thus modulating the activity or number of functioning receptors and/or cellular activity downstream of the receptors. Decoy receptors can act as molecular traps for agonist ligands and thus inhibit ligand-induced receptor activation.

[0075] "IL13", as used herein, refers to any natural IL13 resulting from the expression and processing of IL13 in a cell. The term includes IL13 from any vertebrate source, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and domestic animals (eg, dogs, cats, and horses), unless otherwise noted. . The term also includes naturally occurring variants of IL13, such as splicing variants or allelic variants.

[0076] In some embodiments, canine IL13 comprises the amino acid sequence from SEQ ID NO: 4. In some embodiments, feline IL13 comprises the amino acid sequence from SEQ ID NO: 5. In some embodiments, equine IL13 comprises the amino acid sequence from SEQ ID NO: 6 .

[0077] "IL4", as used herein, refers to any natural IL4 resulting from the expression and processing of IL4 in a cell. The term includes IL4 from any vertebrate source, including mammals such as primates (eg, humans and cynomolgus monkeys), rodents (eg, mice and rats), and domestic animals (eg, dogs, cats, and horses), unless otherwise noted. . The term also includes naturally occurring variants of IL4, such as splicing variants or allelic variants.

[0078] In some embodiments, canine IL4 comprises the amino acid sequence from SEQ ID NO: 1. In some embodiments, feline IL4 comprises the amino acid sequence from SEQ ID NO: 2. In some embodiments, equine IL4 comprises the amino acid sequence from SEQ ID NO: 3 .

[0079]The present the invention relates to continuous IL13R/IL4R polypeptides as drugs. The continuous IL13R/IL4R polypeptides of the invention bind to IL13 and/or IL4, described in more detail herein, that have been shown to be associated with allergic diseases. In various embodiments, continuous IL13R/IL4R polypeptides can bind IL13 and IL4 with very high affinity. In various embodiments, continuous IL13R/IL4R polypeptides can interfere with IL13 and IL4 signaling.

[0080] The term "affinity" refers to the strength of the total amount of non-covalent interactions between one binding site of a molecule (eg, receptor) and its binding partner (eg, ligand). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (K _D ). Affinity can be measured by conventional methods known in the art, such as, for example, immunoblotting, ELISA KD, KinEx A, biolayer interferometry (BLI), or surface plasmon resonance devices.

[0081] The terms "K _D ", "K _d ", "Kd" or "Kd value" are used interchangeably to refer to the equilibrium dissociation constant for a fusion receptor-ligand interaction. In some embodiments, the K _d of a fusion molecule for its ligand is measured using biolayer interferometry assays using a biosensor, such as the ^Octet® system (Pall ForteBio LLC, Fremont, CA), according to the supplier's instructions. Briefly, the biotinylated antigen is bound to the sensor tip and the binding of the fusion molecule is monitored for ninety seconds and dissociation is monitored for 600 seconds. The buffer for the dilution and binding steps is 20 mM phosphate, 150 mM NaCl, pH 7.2. The buffer-only null curve is subtracted to correct for any bias. The data were adjusted to a 2:1 binding model using ForteBio data analysis software to determine the binding rate constant (k _on ), dissociation rate constant (k _off ) and K _d . The equilibrium dissociation constant (K _d ) is calculated as the ratio k _off /k _on . The term "kon" refers to the rate constant for the binding of an X molecule to its partner Y, and the term "koff" refers to the rate constant for the dissociation of an X molecule or partner Y from a molecule X/partner Y complex.

[0082] The term "binds" to a substance is a term well known in the art, and methods for determining such binding are also well known in the art. A molecule is said to exhibit "binding" if it reacts with, associates with, or has an affinity for a particular cell or substance, and the reaction, association, or affinity is detectable by one or more methods known in the art, for example, such as immunoblotting, ELISA KD, KinEx A, biolayer interferometry (BLI), by means of surface plasmon resonance devices, or the like.

[0083] “Surface plasmon resonance” refers to an optical phenomenon that allows real-time analysis of biospecific interactions by detecting changes in protein concentrations within a biosensor array, for example, using the BIAcore™ system (BIAcore International AB, GE Healthcare company, Uppsala, Sweden and Piscataway, NJ). For additional descriptions, see Jonsson et al. (1993) Ann. Biol. Clin. 51:19-26.

[0084] "Biolayer interferometry" refers to an optical analytical method that analyzes the interference pattern of light reflected from the immobilized protein layer on the biosensor tip and the internal reference layer. Changes in the number of molecules bound to the biosensor tip cause shifts in the interference pattern that can be measured in real time. A non-limiting example of a biolayer interferometry device is the ^Octet® system (Pall ForteBio LLC). See, for example, Abdiche et al., 2008, Anal. Biochem . 377:209-277.

[0085] In some embodiments, a continuous IL13R/IL4R polypeptide binds to canine IL13 and/or IL4, feline IL13 and/or IL4, or equine IL13 and/or IL4 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. In some embodiments, a continuous IL13R/IL4R polypeptide binds to canine IL13 and/or IL4, feline IL13 and/or IL4, or equine IL13 and/or IL4 with a Kd between 5×10 ^-6 M and 1×10 ^-6 M, between 5×10 ^-6 M and 5×10 ^-7 M, between 5×10 ^-6 M and 1×10 ^-7 M, between 5×10 ^-6 M and 5×10 ^-8 M, 5×10 ^-6 M and 1×10 ^-8 M, between 5×10 ^-6 M and 5×10 ^-9 M, between 5×10 ^-6 M and 1×10 ^-9 M, between 5×10 ^-6 M and 5×10 ^{- 10} M, between 5×10 ^-6 M and 1×10 ^-10 M, between 5×10 ^-6 M and 5×10 ^-11 M, between 5×10 ^-6 M and 1×10 ^-11 M, between 5 ×10 ^-6 M and 5x10 ^-12 M, between 5x10 ^-6 M and 1x10 ^-12 M, between 1x10 ^-6 M and 5x10 ^-7 M, between 1x10 ^-6 M and 1×10 ^-7 M, between 1×10 ^-6 M and 5×10 ^-8 M, 1×10 ^-6 M and 1×10 ^-8 M, between 1×10 ^-6 M and 5×10 ^-9 M, between 1×10 ^-6 M and 1×10 ^-9 M, between 1×10 ^-6 M and 5×10 ^-10 M, between 1×10 ^-6 M and 1×10 ^-10 M, between 1× 10 ^-6 M and 5×10 ^-11 M, between 1×10 ^-6 M and 1×10 ^-11 M, between 1×10 ^-6 M and 5×10 ^-12 M, between 1×10 ^-6 M and 1×10 ^-12 M, between 5×10 ^-7 M and 1×10 ^-7 M, between 5×10 ^-7 M and 5×10 ^-8 M, 5×10 ^-7 M and 1×10 ^-8 M , between 5×10 ^-7 M and 5×10 ^-9 M, between 5×10 ^-7 M and 1×10 ^-9 M, between 5×10 ^-7 M and 5×10 ^-10 M, between 5×10 ^-7 M and 1×10 ^-10 M, between 5×10 ^-7 M and 5×10 ^-11 M, between 5×10 ^-7 M and 1×10 ^-11 M, between 5×10 ^-7 M and 5 ×10 ^-12 M, between 5x10 ^-7 M and 1x10 ^-12 M, between 1x10 ^-7 M and 5x10 ^-8 M, 1x10 ^-7 M and 1x10 ^-8 M, between 1×10 ^-7 M and 5×10 ^-9 M, between 1×10 ^-7 M and 1×10 ^-9 M, between 1×10 ^-7 M and 5×10 ^-10 M, between 1×10 ^{- 7} M and 1×10 ^-10 M, between 1×10 ^-7 M and 5×10 ^-11 M, between 1×10 ^-7 M and 1×10 ^-11 M, between 1×10 ^-7 M and 5× 10 ^-12 M, between 1x10 ^-7 M and 1x10 ^-12 M, between 5x10 ^-8 M and 1x10 ^-8 M, between 5x10 ^-8 M and 5x10 ^-9 M, between 5×10 ^-8 M and 1×10 ^-9 M, between 5×10 ⁸ M and 5×10 ^-10 M, between 5×10 ^-8 M and 1×10 ^-10 M, between 5×10 ^-8 M and 5×10 ^-11 M, between 5×10 ⁸ M and 1×10 ^-11 M, between 5×10 ^-8 M and 5×10 ^-12 M, between 5×10 ^-8 M and 1×10 ^{- 12} M, 1×10 ^-8 M and 5×10 ^-9 M, between 1×10 ^-8 M and 1×10 ^-9 M, between 1×10 ^-8 M and 5×10 ^-10 M, between 1× 10 ^-8 M and 1×10 ^-10 M, between 1×10 ^-8 M and 5×10 ^-11 M, between 1×10 ⁸ M and 1×10 ^-11 M, between 1×10 ^-8 M and 5 ×10 ^-12 M, between 1x10 ^-8 M and 1x10 ^-12 M, between 5x10 ^-9 M and 1x10 ^-9 M, between 5x10 ^-9 M and 5x10 ^-10 M , between 5×10 ^-9 M and 1×10 ^-10 M, between 5×10 ⁹ M and 5×10 ^-11 M, between 5×10 ⁹ M and 1×10 ^-11 M, between 5×10 ^-9 M and 5×10 ^-12 M, between 5×10 ^-9 M and 1×10 ^-12 M, between 1×10 ^-9 M and 5×10 ^-10 M, between 1×10 ^-9 M and 1×10 ^-10 M, between 1×10 ^-9 M and 5×10 ^-11 M, between 1×10 ^-9 M and 1×10 ^-11 M, between 1×10 ^-9 M and 5×10 ^-12 M, between 1×10 ^-9 M and 1×10 ^-12 M, between 5×10 ¹⁰ M and 1×10 ^-10 M, between 5×10 ^-10 M and 5×10 ^-11 M, between, 1×10 ^-10 M and 5×10 ^-11 M, 1×10 ^-10 M and 1×10 ^-11 M, between 1×10 ^-10 M and 5×10 ^-12 M, between 1×10 ^-10 M and 1×10 ¹² M, between 5×10 ^-11 M and 1×10 ^-12 M, between 5×10 ^-11 M and 5×10 ^-12 M, between 5×10 ¹¹ M and 1×10 ^-12 M, between 1×10 ^-11 M and 5×10 ¹² M, or between 1×10 ^-11 M and 1×10 ^-12 M, as measured by biolayer interferometry. In some embodiments, a continuous IL13R/IL4R polypeptide binds to canine IL13 and/or IL4, feline IL13 and/or IL4, and/or equine IL13 and/or IL4.

[0086] "Reduce" or "inhibit" means to reduce, reduce, or arrest an activity, function, or amount compared to a reference. In some embodiments, "reduce" or "inhibit" refers to the ability to cause an overall reduction of 20% or more. In some embodiments, "reduce" or "inhibit" refers to the ability to cause an overall reduction of 50% or more. In some embodiments, "reduce" or "inhibit" refers to the ability to cause an overall reduction of 75%, 85%, 90%, 95%, or more. In some embodiments, the above amount is inhibited or reduced over a period of time, compared to a control dose (such as placebo), over the same period of time. "Reference", within the meaning of the invention, refers to any sample, standard or level that is used for comparison purposes. The reference can be obtained from a healthy or disease-free sample. In some examples, the reference is obtained from an unaffected or untreated sample from a pet. In some examples, the reference is obtained from one or more healthy non-animal animals of a particular species that have been tested or treated.

[0087] The term "significantly reduced", within the meaning of the invention, denotes a significantly high degree of reduction between a numerical value and a reference numerical value, such that a person skilled in the art may consider the difference between the two values to be statistically significant in the context of the biological characteristic measured by said values. . In some embodiments, substantially reduced numerical values are reduced by more than about any of 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90% or 100% compared to the reference value.

[0088] In some embodiments, a continuous IL13R/IL4R polypeptide can reduce IL13 and/or IL4 signaling in a pet species by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70 %, at least 80%, at least 90%, or 100%, as compared to IL13 and/or IL4 signaling in the absence of the fusion molecule. In some embodiments, signaling is measured by a decrease in IL4-dependent proliferation of TF-1 cells. In some embodiments, the reduction in IL13 and/or IL4 signaling, or the reduction in proliferation, is between 10% and 15%, between 10% and 20%, between 10% and 25%, between 10% and 30%, between 10% and 35%. %, between 10% and 40%, between 10% and 45%, between 10% and 50%, between 10% and 60%, between 10% and 70%, between 10% and 80%, between 10% and 90% , between 10% and 100%, between 15% and 20%, between 15% and 25%, between 15% and 30%, between 15% and 35%, between 15% and 40%, between 15% and 45%, between 15% and 50%, between 15% and 60%, between 15% and 70%, between 15% and 80%, between 15% and 90%, between 15% and 100%, between 20% and 25%, between 20% and 30%, between 20% and 35%, between 20% and 40%, between 20% and 45%, between 20% and 50%, between 20% and 60%, between 20% and 70%, between 20 % and 80%, between 20% and 90%, between 20% and 100%, between 25% and 30%, between 25% and 35%, between 25% and 40%, between 25% and 45%, between 25% and 50%, between 25% and 60%, between 25% and 70%, between 25% and 80%, between 25% and 90%, between 25% and 100%, between 30% and 35%, between 30% and 40%, between 30% and 45%, between 30% and 50%, between 30% and 60%, between 30% and 70%, between 30% and 80%, between 30% and 90%, between 30% and 100 %, between 35% and 40%, between 35% and 45%, between 35% and 50%, between 35% and 60%, between 35% and 70%, between 35% and 80%, between 35% and 90% , between 35% and 100%, between 40% and 45%, between 40% and 50%, between 40% and 60%, between 40% and 70%, between 40% and 80%, between 40% and 90%, between 40% and 100%, between 45% and 50%, between 45% and 60%, between 45% and 70%, between 45% and 80%, between 45% and 90%, between 45% and 100%, between 50% and 60%, between 50% and 70%, between 50% and 80%, between 50% and 90%, between 50% and 100%, between 60% and 70%, between 60% and 80%, between 60 % and 90%, between 60% and 100%, between 70% and 80%, between 70% and 90%, between 70% and 100%, between 80% and 90%, between 80% and 100%, or between 90 % and 100%.

Pharmaceutical compositions

[0089] The terms "pharmaceutical formulation" and "pharmaceutical composition" refer to a formulation that is in such a form as to allow the biological activity of the active ingredient(s) to be effective, and that does not contain additional components that are unacceptably toxic to the subject to be treated. enter composition.

[0090] A "pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid, or liquid excipient, diluent, encapsulating material, formulation adjuvant, or carrier generally accepted in the art for use with a drug, which together constitute a "pharmaceutical composition" for administration. subject. The pharmaceutically acceptable carrier is non-toxic to recipients at all doses and concentrations used and is compatible with the other ingredients of the formulation. A pharmaceutically acceptable carrier is suitable for the composition used. Examples of pharmaceutically acceptable carriers include alumina; aluminum stearate; lecithin; serum proteins such as human serum albumin, canine or other animal serum albumin; buffers such as phosphate, citrate, tromethamine or HEPES buffers; glycine; sorbic acid; potassium sorbate; mixtures of partial glycerides of saturated vegetable fatty acids; water; salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon dioxide or magnesium trisilicate; polyvinylpyrrolidone, cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids, including but not limited to arginine.

[0091] The pharmaceutical composition can be stored in lyophilized form. Thus, in some embodiments, the implementation of the method of obtaining includes the stage of lyophilization. The lyophilized composition can then be re-formulated, typically in the form of an aqueous composition suitable for parenteral administration, prior to administration to a dog, cat or horse. In other embodiments, in particular where the fusion molecule is highly resistant to thermal and oxidative denaturation, the pharmaceutical composition can be stored in liquid form, i.e., in the form of an aqueous composition that can be administered directly or in appropriate dilution, to a dog, cat or horses. The lyophilized composition can be reconstituted with sterile water for injection (WFI). Bacteriostatic agents such as benzyl alcohol may be included. Thus, the invention relates to pharmaceutical compositions in solid or liquid form.

[0092] The pH of the pharmaceutical compositions can range from about pH 5 to about pH 8 when administered. The compositions of the invention are sterile if they are to be used for therapeutic purposes. Sterility can be achieved by any of several methods known in the art, including filtration through sterile filtration membranes (eg, 0.2 micron membranes). Sterility can be maintained with or without the use of antibacterial agents.

Applications of Continuous IL13R/IL4R Polypeptides and Pharmaceutical Compositions

[0093] Continuous IL13R/IL4R polypeptides or pharmaceutical compositions containing continuous IL13R/IL4R polypeptides of the invention can be used to treat an IL13 and/or IL4 induced condition. As used herein, "IL13 or IL4 induced condition" means a disease associated with, caused by, or characterized by increased levels or altered distribution of IL13 or IL4. Such IL13 and/or IL4 induced conditions include, but are not limited to, pruritic or allergic disease. In some embodiments, the IL13 and/or IL4 induced condition is atopic dermatitis, pruritus, asthma, psoriasis, scleroderma, or eczema. An IL13 or IL4 induced condition may be present in a pet, including but not limited to canine, feline or equine.

[0094] In the context of the invention, "treatment" is a method of obtaining advantageous or desirable clinical results. "Treatment", within the meaning of the invention, includes any administration or use of a drug for a disease in a mammal, including a pet. For the purposes of this disclosure, advantageous or desirable clinical results include, but are not limited to, any one or more of: alleviation of one or more symptoms, reduction in the extent of a disease, prevention or delay in the spread of a disease, prevention or delay in the recurrence of a disease, delay or retardation in the progression of a disease , alleviating the condition of the disease, inhibiting the disease or the progression of the disease, inhibiting or slowing the disease or its progression, arresting its development and remission (either partial or complete). "Treatment" also encompasses the reduction of the pathological consequences of proliferative diseases. The methods provided herein include any one or more of these aspects of treatment. In accordance with the above, the term treatment does not require one hundred percent removal of all aspects of the disorder.

[0095] In some embodiments, a continuous IL13R/IL4R polypeptide or pharmaceutical compositions containing it can be used according to the methods herein to treat IL13 or IL4 induced conditions. In some embodiments, the continuous IL13R/IL4R polypeptide or pharmaceutical compositions are administered to a pet, eg, canine, feline, or equine, for the treatment of an IL13 and IL4 induced condition.

[0096] A “therapeutically effective amount” of a substance/molecule, agonist, or antagonist may vary depending on such factors as the type of disease being treated, the condition of the disease, the severity and course of the disease, the type of therapeutic target, any prior therapy, clinical history, response prior treatment, the judgment of the treating veterinarian, the age, sex and weight of the animal, and the ability of the substance/molecule, agonist or antagonist to elicit the desired response in the animal. A therapeutically effective amount also includes an amount in which any toxic or adverse effects of the substance/molecule, agonist or antagonist are outweighed by the therapeutically beneficial effects. A therapeutically effective amount can be delivered in one or more administrations. A therapeutically effective amount refers to an amount effective, at the required dosages and for the required periods of time, to achieve the desired therapeutic or prophylactic result.

[0097] In some embodiments, a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide is administered parenterally, by subcutaneous injection, intravenous infusion, or intramuscular injection. In some embodiments, a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide is administered as a bolus injection or by continuous infusion over a period of time. In some embodiments, a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide is administered by intramuscular, intraperitoneal, intraspinal, subcutaneous, intraarterial, intraarticular, intrathecal, or inhalation routes.

[0098] The continuous IL13R/IL4R polypeptide described herein can be administered in an amount ranging from 0.1 mg/kg body weight to 100 mg/kg body weight per dose. In some embodiments, the anti-IL13/IL4 fusion protein may be administered in an amount ranging from 0.5 mg/kg body weight to 50 mg/kg body weight per dose. In some embodiments, the anti-IL13/IL4 fusion protein can be administered in an amount ranging from 1 mg/kg body weight to 10 mg/kg body weight per dose. In some embodiments, the fusion molecule may be administered in an amount in the range of 0.5 mg/kg body weight to 100 mg/kg body weight, in the range of 1 mg/kg body weight to 100 mg/kg body weight, in the range of 5 mg/kg bw to 100 mg/kg bw, ranging from 10 mg/kg bw to 100 mg/kg bw, ranging from 20 mg/kg bw to 100 mg/kg bw, ranging from 50 mg/kg body weight to 100 mg/kg body weight, in the range 1 mg/kg body weight to 10 mg/kg body weight, in the range 5 mg/kg body weight to 10 mg/kg body weight, in the range from 0.5 mg/kg body weight to 10 mg/kg body weight or in the range from 5 mg/kg body weight to 50 mg/kg body weight.

[0099] A continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide can be administered to a pet at one time or over a series of treatment cycles. For example, a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising IL13R and IL4R can be administered at least once, more than once, at least twice, at least three times, at least four times, or at least five times. once.

[00100] In some embodiments, the dose is administered once a week for at least two or three consecutive weeks, and in some embodiments, this treatment cycle is repeated two or more times, optionally alternating with one or more weeks without treatment. In other embodiments, a therapeutically effective dose is administered once a day for five consecutive days, and in some embodiments, this treatment cycle is repeated two or more times, optionally alternating with one or more days or weeks without treatment.

[00101] The introduction "in combination with" one or more additional drugs includes simultaneous (parallel) administration and subsequent one after another or sequential administration in any order. The term "simultaneous", within the scope of the invention, is intended to mean the administration of two or more drugs, where at least part of the administration overlaps in time, or where the administration of one drug falls within a short period of time relative to the administration of another drug. For example, two or more drugs are administered with a time separation of no more than the specified number of minutes. The term "sequentially", within the scope of the invention, is intended to mean the administration of two or more drugs, where the administration of one or more drug(s) continues after the administration of one or more other drug(s) has ceased, or where the administration of one or more drug(s) ) begins prior to the administration of one or more other agent(s). For example, the administration of two or more drugs is carried out with a time separation of more than the specified number of minutes. In the context of the invention, "in combination with" refers to the implementation of one treatment option in addition to another treatment option. Thus, "in conjunction with" refers to the administration of one treatment option before, during, or after the administration of another treatment option to an animal.

[00102] In some embodiments, the method comprises administering, in combination with a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide, a Jak inhibitor, a PI3K inhibitor, an AKT inhibitor, or a MAPK inhibitor. In some embodiments, the method comprises administering, in combination with a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide, anti-IL17 antibodies, anti-TNFα antibodies, anti-CD20 antibodies, anti-CD19 antibodies, anti-CD25 antibodies, anti-IL31 antibodies, anti-IL23 antibodies, anti-IgE antibodies, anti-CD11α antibodies, anti-IL6R antibodies, anti-α4 integrin antibodies, anti-IL12 antibodies, anti-IL1β antibodies, or anti-BlyS antibodies.

[00103] The present invention relates to methods for exposing a cell to a continuous IL13R/IL4R polypeptide or a pharmaceutical composition comprising a continuous IL13R/IL4R polypeptide under conditions that allow binding to IL13 or IL4. In some embodiments, the cell is exposed to a continuous IL13R/IL4R polypeptide or pharmaceutical composition ex vivo . In some embodiments, the cell is exposed to a continuous IL13R/IL4R polypeptide or pharmaceutical composition in vivo . In some embodiments, the cell is exposed to a continuous IL13R/IL4R polypeptide. In some embodiments, the cell is exposed to a continuous IL13R/IL4R polypeptide or pharmaceutical composition under conditions that allow the fusion molecule to bind to extracellular IL13 or IL4. In some embodiments, a cell can be exposed in vivo to a continuous IL13R/IL4R polypeptide or pharmaceutical composition via one or more of the routes of administration described herein, including, but not limited to, intraperitoneal, intramuscular, intravenous injection into a subject. In some embodiments, the cell can be exposed ex vivo to a continuous IL13R/IL4R polypeptide or pharmaceutical composition by exposing the cell to a culture medium containing the fusion molecule or pharmaceutical composition. In some embodiments, cell membrane permeability may be affected using any number of methods known to one of skill in the art (such as electroporation of cells or exposure of cells to a solution containing calcium chloride) prior to exposing the cell to culture medium containing the fusion molecule or pharmaceutical composition. .

[00104] In some embodiments, exposure leads to a decrease in the cell's IL13 or IL4 signaling function. In some embodiments, a continuous IL13R/IL4R polypeptide can reduce IL13 or IL4 signaling in a cell by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80 %, at least 90% or 100%, compared with the signaling function of IL13 or IL4 in the absence of a continuous polypeptide IL13R/IL4R. In some embodiments, the reduction in IL13 or IL4 signaling or the reduction in TF-1 proliferation is between 10% and 15%, between 10% and 20%, between 10% and 25%, between 10% and 30%, between 10% and 35%. %, between 10% and 40%, between 10% and 45%, between 10% and 50%, between 10% and 60%, between 10% and 70%, between 10% and 80%, between 10% and 90% , between 10% and 100%, between 15% and 20%, between 15% and 25%, between 15% and 30%, between 15% and 35%, between 15% and 40%, between 15% and 45%, between 15% and 50%, between 15% and 60%, between 15% and 70%, between 15% and 80%, between 15% and 90%, between 15% and 100%, between 20% and 25%, between 20% and 30%, between 20% and 35%, between 20% and 40%, between 20% and 45%, between 20% and 50%, between 20% and 60%, between 20% and 70%, between 20 % and 80%, between 20% and 90%, between 20% and 100%, between 25% and 30%, between 25% and 35%, between 25% and 40%, between 25% and 45%, between 25% and 50%, between 25% and 60%, between 25% and 70%, between 25% and 80%, between 25% and 90%, between 25% and 100%, between 30% and 35%, between 30% and 40%, between 30% and 45%, between 30% and 50%, between 30% and 60%, between 30% and 70%, between 30% and 80%, between 30% and 90%, between 30% and 100 %, between 35% and 40%, between 35% and 45%, between 35% and 50%, between 35% and 60%, between 35% and 70%, between 35% and 80%, between 35% and 90% , between 35% and 100%, between 40% and 45%, between 40% and 50%, between 40% and 60%, between 40% and 70%, between 40% and 80%, between 40% and 90%, between 40% and 100%, between 45% and 50%, between 45% and 60%, between 45% and 70%, between 45% and 80%, between 45% and 90%, between 45% and 100%, between 50% and 60%, between 50% and 70%, between 50% and 80%, between 50% and 90%, between 50% and 100%, between 60% and 70%, between 60% and 80%, between 60 % and 90%, between 60% and 100%, between 70% and 80%, between 70% and 90%, between 70% and 100%, between 80% and 90%, between 80% and 100% or between 90% and 100%.

[00105] The present invention provides methods for using a continuous IL13R/IL4R polypeptide, polypeptides, and polynucleotides to detect, diagnose, and monitor an IL13 or IL4 induced condition. The present invention relates to methods for determining whether a pet can respond to therapy with a continuous IL13R/IL4R polypeptide. In some embodiments, the method includes detecting whether the animal has cells expressing IL13 or IL4 using a continuous IL13R/IL4R polypeptide. In some embodiments, the detection method includes contacting the sample with an antibody, polypeptide, or polynucleotide and determining if the level of binding differs from the level of binding for a reference or comparative sample (such as a control). In some embodiments, the method can be used to determine whether the continuous IL13R/IL4R polypeptides described herein are a suitable drug for the animal in question.

[00106] In some embodiments, the sample is a biological sample. The term "biological sample" refers to a quantity of matter from a living organism or a previously living organism. In some embodiments, the biological sample is a cell or cell/tissue lysate. In some embodiments, the biological sample includes, but is not limited to, blood (eg, whole blood), plasma, serum, urine, synovial fluid, and epithelial cells.

[00107] In some embodiments, cells or a cell/tissue lysate are contacted with a continuous IL13R/IL4R polypeptide and the binding between the continuous IL13R/IL4R polypeptide and the cell is determined. When a test cell shows binding activity compared to a reference cell from the same cell type, this may indicate that the subject may benefit from treatment with a continuous IL13R/IL4R polypeptide. In some embodiments, the cells to be tested are from the tissue of a domestic animal.

[00108] Various methods known in the art can be used to detect specific antibody-antigen binding. Illustrative immunoassays that can be performed include polarization fluorescence immunoassay (FPIA), fluorescence immunoassay (FIA), enzyme immunoassay (EIA), nephelometric inhibition immunoassay (NIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). An indicator group or a label group can be attached to the antibodies in question and are chosen to meet the requirements for various applications of the method, which are often dictated by the availability of assay equipment and compatible immunoassay methods. Suitable labels include, without limitation, radioactive isotopes (e.g., ¹²⁵ I, ¹³¹ I, ³⁵ S, ³ H, or ³² P), enzymes (e.g., alkaline phosphatase, horseradish peroxidase, luciferase, or β-galactosidase), fluorescent groups, or proteins ( eg, fluorescein, rhodamine, phycoerythrin, GFP, or BFP), or luminescent groups (eg, Qdot™ nanoparticles available from Quantum Dot Corporation, Palo Alto, Calif.). The general methods used in the implementation of the various immunoassays mentioned above are known to the person skilled in the art.

[00109] For diagnostic purposes, a continuous IL13R/IL4R polypeptide can be labeled with a detectable group, including, but not limited to, radioactive isotopes, fluorescent labels, and various enzyme substrate labels known in the art. Methods for conjugating labels to polypeptides are known in the art. In some embodiments, labeling of the continuous IL13R/IL4R polypeptide is not necessary and its presence can be detected, for example, using an antibody that binds to the continuous IL13R/IL4R polypeptide. In some embodiments, a continuous IL13R/IL4R polypeptide can be used in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. Zola, Monoclonal Antibodies: A Manual of Techniques, pp. 147-158 (CRC Press, Inc. 1987). Anti-IL13 and IL4 antibodies and polypeptides can also be used for in vivo diagnostic assays such as in vivo imaging. In general, an antibody or polypeptide is labeled with a radioactive isotope (such as ¹¹¹ In, ⁹⁹ Tc, ¹⁴ C, ¹³¹ I, ¹²⁵ I, ³ H, or any other radioactive isotope label, including those described herein), such that that cells or tissue of interest can be localized using immunoscintigraphy. The continuous IL13R/IL4R polypeptide can also be used as a staining reagent in pathology using methods well known in the art.

[00110] In some embodiments, a continuous IL13R/IL4R polypeptide is used for diagnosis and a continuous IL13R/IL4R polypeptide is used as a drug. In some embodiments, the first and second continuous IL13R/IL4R polypeptides are different.

[00111] The following examples illustrate specific aspects of the description and are not intended to limit the description in any way.

EXAMPLES

Example 1

Expression and purification of canine IL4 and IL13

[00112] The nucleotide sequence encoding the canine IL13 protein (SEQ ID NO: 4) was synthesized with a poly-His tag at the C-terminus and cloned into a mammalian expression vector and transferred into 293 or CHOS cells. The same method was used to clone and express the nucleotide sequence encoding canine IL4 protein (SEQ ID NO: 1) with a poly-His tag at the C-terminus.

[00113] The supernatant containing canine IL13 protein was collected and filtered. Canine IL13 was affinity purified using a Ni-NTA column ( ^CaptivA® protein A affinity resin, Repligen). The same method was used to purify canine IL4.

Example 2

Extracellular domains of IL13R and IL4R

[00114] Canine, feline, and equine IL4R extracellular domains responsible for binding canine, feline, and equine IL4 and/or IL13 have been identified and delimited. The full-length extracellular domains of canine IL4R, feline IL4R, and equine IL4 were identified as SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO: 27, respectively. Fragments of the extracellular domains of canine IL4R, feline IL4R, and equine IL4R, taken to be biologically active, were identified as SEQ ID NO: 33, SEQ ID NO: 35, and SEQ ID NO: 37, respectively.

[00115] Canine, feline, and equine IL13R extracellular domains responsible for binding canine, feline, and equine IL4 and/or IL13 have been identified and delimited. The full-length extracellular domains of canine IL13R, feline IL13R, and equine IL13R were identified as SEQ ID NO: 22, SEQ ID NO: 24, and SEQ ID NO: 26, respectively. Fragments of the extracellular domains of canine IL13R, feline IL13R, and equine IL13R taken to be biologically active were identified as SEQ ID NO: 32, SEQ ID NO: 34, and SEQ ID NO: 36, respectively.

[00116] The unpaired cysteine (Cys) in canine IL13R (at position 18 of SEQ ID NO: 22), feline IL13R (at position 18 of SEQ ID NO: 24) and equine IL13R (at position 18 of SEQ ID NO: 26) was identified informatically method and determined to be immersed (unexposed) based on 3-D modeling. It is unlikely that an unpaired cysteine will form disulfide bonds, and the likelihood of aggregation is low. Thus, site-directed mutagenesis of this Cys residue was not performed.

Example 3

Expression and purification of continuous canine IL13R/IL4R polypeptides from CHO cells

[00117] Nucleotide sequences encoding contiguous canine IL13R/IL4R polypeptides linked to IgGB Fc were constructed with a signal sequence. In the case of the continuous polypeptide "IL13R-IL4R-IgGB" (SEQ ID NO: 20), the extracellular domain of IL13R (SEQ ID NO: 22) precedes the extracellular domain of IL4R (SEQ ID NO: 23). In the case of the continuous IL4R-IL13R-IgGB polypeptide (SEQ ID NO: 21), the IL4R extracellular domain precedes the IL13R extracellular domain.

[00118] Nucleotide sequences were chemically synthesized and inserted into an expression vector suitable for transfection of a CHO host cell. After transfection of CHO cells, the fusion proteins were secreted from the cells. For example, the fusion protein was purified by one-step protein A column chromatography.

[00119] Each of IL13R-IL4R-IgGB and IL4R-IL13R-IgGB can be expressed and purified in one step using a protein A column or other chromatographic methods such as ion exchange column chromatography, hydrophobic interaction column chromatography, a mixed mode column such as CHT, or a multimodal column chromatography such as CaptoMMC. You can use low pH or other methods to inactivate the virus and remove the virus. The purified protein can be mixed with excipients and sterilized by filtration to obtain a pharmaceutical composition of the invention. The pharmaceutical composition may be administered to a dog with atopic dermatitis or asthma in an amount sufficient to bind and/or inhibit IL13 and/or IL4.

[00120] The vectors were then used to pilot-scale transfection into CHO S cells using the FreestyleMax™ transfection reagent (Life Technologies). The supernatant was collected by clarifying the conditioned media. The protein was purified in a single pass of the Protein A chromatography step and used for further analysis.

Example 4

Demonstration of IL13 and IL4 binding activity

[00121] This example shows that both IL13R-IL4R-IgGB (SEQ ID NO:20) and IL4R-IL13R-IgGB (SEQ ID NO:21) bind canine IL4 and IL13 with the kinetics required for therapeutic activity .

[00122] The binding assay was performed using an Octet biosensor as follows. Briefly, canine IL4 (obtained using 293 cells) was biotinylated. Free unreacted biotin was removed from biotinylated IL4 by extensive dialysis. Biotinylated canine IL4 was coupled to the sensor tips with streptavidin. The binding of IL4 with different concentrations (12, 16 and 44 nm) IL13R-IL4R-IgGB (SEQ ID NO:20) was monitored for ninety seconds. Dissociation was monitored for 600 seconds. The buffer-only null curve was subtracted to correct for any bias. Data were matched to a 1:1 binding model using ForteBio™ data analysis software to determine k _on , k _off and Kd. Buffer for dilution and all binding steps was: 20 mM phosphate, 150 mM NaCl, pH 7.2. Kd for IL13R-IL4R-IgGB and IL4 ligand was 8x10 ^-11 .

[00123] Binding of canine IL4 with different concentrations (40.7 and 140 nM) of IL4R-IL13R-IgGB (SEQ ID NO:21) was monitored for ninety seconds. Dissociation was monitored for 600 seconds. The buffer-only null curve was subtracted to correct for any bias. Data were matched to a 1:1 binding model using ForteBio™ data analysis software to determine k _on , k _off and Kd. Buffer for dilution and all binding steps was: 20 mM phosphate, 150 mM NaCl, pH 7.2. Kd for IL4R-IL13R-IgGB and IL4 ligand was 1.1x10 ^-11 .

[00124] Canine IL4 and canine IL13 with a poly-His C-terminal tag were expressed and purified from 293 cells. cat #18-509).

[00125] Sequential binding experiments of IL4 and IL13 with IL13R-IL4R-IgGB (SEQ ID NO:20) were performed. Biotinylated canine IL13R-IL4R-IgGB was bound to streptavidin sensor tips. Canine IL13R-IL4R-IgGB was exposed to either (1) canine IL4 followed by canine IL13 or (2) canine IL13 followed by canine IL4 using concentrations of 30 μg/mL of IL4 and IL13 in PBS (Figure 1) . These experiments showed that once IL13R-IL4R-IgGB bound to IL13, it could not bind to IL4, and once it bound to IL4, its ability to bind to IL13 decreased.

[00126]Conducted serial linking experiments IL4 and IL13 with IL4R-IL13R-IgGB (SEQ ID NO:21). Biotinylated canine IL4R-IL13R-IgGB was bound to streptavidin sensor tips. Canine IL4R-IL13R-IgGB was exposed to either (1) canine IL4 followed by canine IL13 or (2) canine IL13 followed by canine IL4 using concentrations of 30 μg/mL of IL4 and IL13 in PBS (Figure 2) . These experiments showed that once IL4R-IL13R-IgGB bound to IL13, it could not bind to IL4, and once it bound to IL4, its ability to bind to IL13 decreased.

[00127] The tight binding of IL13R-IL4R-IgGB and IL4R-IL13R-IgGB to IL4 or IL13 is believed to be due to contributions from both IL4R and IL13R co-binding.

Example 5

Cellular functional activity of canine IL4R-IL13R-Fc (SINK)

[00128]Cells TF1 (ATCC, Cat# CRL-2003), a human erythroleukemia cell line expressing endogenous interleukin 4 receptors on the cell surface, was used in a proliferation assay. Cells grown in RPMI1640 (Gibco, cat.#11875) supplemented with 10% heat-inactivated fetal bovine serum (Sigma, cat.#2868) and 2 nM/ml human GM-CSF (R&D System, cat.# 215-GM -010) in the exponential growth phase was used for this analysis. Cells were washed with PBS twice and resuspended in the above medium without GM-CSF. 20,000 cells/well were seeded into a 96-well plate (Corning cat#3610). Canine IL4R-IL13R-Fc (SINK) was added in a series of dilutions followed by canine IL4 (Sino Biological Inc, cat# 70021-DNAE-5) at 50 ng/mL. Cells were incubated at 37°C, 5% CO2 for 48 hours in a total volume of 100 μl. At the end of the incubation, the cells were cooled to room temperature and analyzed for proliferation/viability by measuring cell ATP content using a CellTiter-Glo® fluorescent cell viability assay (Promega, Cat# G7570).

[00129] In this assay, 100 μl of pre-mixed reagents A and B were added to each well. After shaking on an orbital shaker for 2 min, the cells were lysed. Mono-oxygenation of luciferin was catalyzed by luciferase in the presence of Mg2+ and ATP present in the cells, resulting in a luminescent signal proportional to the amount of ATP in the cells. The amount of ATP is directly proportional to the number of cells present in the culture. The plate was incubated at room temperature for 10 minutes to stabilize the luminescent signal, and luminescence was detected using a Synergy HT microplate reader (Biotek, Winooski, VT).

[00130] Data were analyzed using 4-parameter logistic fitting and the IC50 was 2.0 nM. See figure 3.

SEQUENCE LIST

--->

<110> Kindred Biosciences, Inc.

<120> IL4/IL13 RECEPTOR MOLECULE FOR VETERINARY USE

<130> 01157-0008-00PCT

<150> US 62/488509

<151> 2017-04-21

<160> 49

<170> PatentIn version 3.5

<210> 1

<211> 131

<212> protein

<213> Canis lupus

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Met Gly Leu Thr Ser Gln Leu Ile Pro Thr Leu Val Cys Leu Leu Ala

1 5 10 15

Leu Thr Ser Thr Phe Val His Gly His Asn Phe Asn Ile Thr Ile Lys

20 25 30

Glu Ile Ile Lys Met Leu Asn Ile Leu Thr Ala Arg Asn Asp Ser Cys

35 40 45

Met Glu Leu Thr Val Asp Val Phe Thr Ala Pro Lys Asn Thr Ser Asp

50 55 60

Lys Glu Ile Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Ile Tyr Thr

65 70 75 80

His Asn Cys Ser Asn Arg Tyr Leu Arg Gly Leu Tyr Arg Asn Leu Ser

85 90 95

Ser Met Ala Asn Lys Thr Cys Ser Met Asn Glu Ile Lys Lys Ser Thr

100 105 110

Leu Lys Asp Phe Leu Glu Arg Leu Lys Val Ile Met Gln Lys Lys Tyr

115 120 125

Tyr Arg His

130

<210> 2

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<212> protein

<213> Felis catus

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Met Asp Leu Thr Ser Gln Leu Ile Pro Ala Leu Val Cys Leu Leu Ala

1 5 10 15

Phe Thr Ser Thr Phe Val His Gly Gln Asn Phe Asn Asn Thr Leu Lys

20 25 30

Glu Ile Ile Lys Thr Leu Asn Ile Leu Thr Ala Arg Asn Asp Ser Cys

35 40 45

Met Glu Leu Thr Met Asp Val Leu Ala Ala Pro Lys Asn Thr Ser Asp

50 55 60

Lys Glu Ile Phe Cys Arg Ala Thr Thr Val Leu Arg Gln Ile Tyr Thr

65 70 75 80

His His Asn Cys Ser Thr Lys Phe Leu Lys Gly Leu Asp Arg Asn Leu

85 90 95

Ser Ser Met Ala Asn Arg Thr Cys Ser Val Asn Glu Val Lys Lys Cys

100 105 110

Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Ala Ile Met Gln Lys Lys

115 120 125

Tyr Ser Lys His

130

<210> 3

<211> 137

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<213> Equus caballus

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Met Gly Leu Thr Tyr Gln Leu Ile Pro Ala Leu Val Cys Leu Leu Ala

1 5 10 15

Cys Thr Ser Asn Phe Ile Gln Gly Cys Lys Tyr Asp Ile Thr Leu Gln

20 25 30

Glu Ile Ile Lys Thr Leu Asn Asn Leu Thr Asp Gly Lys Gly Lys Asn

35 40 45

Ser Cys Met Glu Leu Thr Val Ala Asp Ala Phe Ala Gly Pro Lys Asn

50 55 60

Thr Asp Gly Lys Glu Ile Cys Arg Ala Ala Lys Val Leu Gln Gln Leu

65 70 75 80

Tyr Lys Arg His Asp Arg Ser Leu Ile Lys Glu Cys Leu Ser Gly Leu

85 90 95

Asp Arg Asn Leu Lys Gly Met Ala Asn Gly Thr Cys Cys Thr Val Asn

100 105 110

Glu Ala Lys Lys Ser Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Thr

115 120 125

Ile Met Lys Glu Lys Tyr Ser Lys Cys

130 135

<210> 4

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<213> Canis lupus

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Met Ala Leu Trp Leu Thr Val Val Ile Ala Leu Thr Cys Leu Gly Gly

1 5 10 15

Leu Ala Ser Pro Ser Pro Val Thr Pro Ser Pro Thr Leu Lys Glu Leu

20 25 30

Ile Glu Glu Leu Val Asn Ile Thr Gln Asn Gln Ala Ser Leu Cys Asn

35 40 45

Gly Ser Met Val Trp Ser Val Asn Leu Thr Ala Gly Met Tyr Cys Ala

50 55 60

Ala Leu Glu Ser Leu Ile Asn Val Ser Asp Cys Ser Ala Ile Gln Arg

65 70 75 80

Thr Gln Arg Met Leu Lys Ala Leu Cys Ser Gln Lys Pro Ala Ala Gly

85 90 95

Gln Ile Ser Ser Glu Arg Ser Arg Asp Thr Lys Ile Glu Val Ile Gln

100 105 110

Leu Val Lys Asn Leu Leu Thr Tyr Val Arg Gly Val Tyr Arg His Gly

115 120 125

Asn Phe Arg

130

<210> 5

<211> 183

<212> protein

<213> Felis catus

<400> 5

Met Trp Phe Leu Asp Ser Thr Arg Gln Ser Gly Asp Gln Gly Gly Arg

1 5 10 15

Arg His Thr Trp Pro Ile Lys Ala Thr Ala Arg Gly Gln Gly His Lys

20 25 30

Pro Leu Ser Leu Gly Gln Pro Thr Cys Pro Leu Leu Ala Pro Pro Val

35 40 45

Leu Ala Leu Gly Ser Met Ala Leu Trp Leu Thr Val Val Ile Ala Leu

50 55 60

Thr Cys Leu Gly Gly Leu Ala Ser Pro Gly Pro His Ser Arg Arg Glu

65 70 75 80

Leu Lys Glu Leu Ile Glu Glu Leu Val Asn Ile Thr Gln Asn Gln Val

85 90 95

Ser Leu Cys Asn Gly Ser Met Val Trp Ser Val Asn Leu Thr Thr Gly

100 105 110

Met Tyr Cys Ala Ala Leu Glu Ser Leu Ile Asn Val Ser Asp Cys Thr

115 120 125

Ala Ile Gln Arg Thr Gln Arg Met Leu Lys Ala Leu Cys Thr Gln Lys

130 135 140

Pro Ser Ala Gly Gln Thr Ala Ser Glu Arg Ser Arg Asp Thr Lys Ile

145 150 155 160

Glu Val Ile Gln Leu Val Lys Asn Leu Leu Asn His Leu Arg Arg Asn

165 170 175

Phe Arg His Gly Asn Phe Lys

180

<210> 6

<211> 133

<212> protein

<213> Equus caballus

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Met Ala Leu Trp Leu Thr Ala Val Ile Ala Leu Ala Cys Leu Gly Gly

1 5 10 15

Leu Ala Ser Pro Ala Pro Leu Pro Ser Ser Met Ala Leu Lys Glu Leu

20 25 30

Ile Lys Glu Leu Val Asn Ile Thr Gln Asn Gln Ala Pro Leu Cys Asn

35 40 45

Gly Ser Met Val Trp Ser Val Asn Leu Thr Ala Asp Thr Tyr Cys Arg

50 55 60

Ala Leu Glu Ser Leu Ser Asn Val Ser Thr Cys Ser Ala Ile Gln Asn

65 70 75 80

Thr Arg Lys Met Leu Thr Lys Leu Cys Pro His Gln Leu Ser Ala Gly

85 90 95

Gln Val Ser Ser Glu Arg Ala Arg Asp Thr Lys Ile Glu Val Ile Val

100 105 110

Leu Val Lys Asp Leu Leu Lys Asn Leu Arg Lys Ile Phe His Gly Gly

115 120 125

Lys His Val Asp Ala

130

<210> 7

<211> 823

<212> protein

<213> Canis lupus

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Met Gly Arg Leu Cys Ser Gly Leu Thr Phe Pro Val Ser Cys Leu Val

1 5 10 15

Leu Val Trp Val Ala Ser Ser Gly Ser Val Lys Val Leu His Glu Pro

20 25 30

Ser Cys Phe Ser Asp Tyr Ile Ser Thr Ser Val Cys Gln Trp Lys Met

35 40 45

Asp His Pro Thr Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu

50 55 60

Asp Phe Met Gly Ser Glu Asn His Thr Cys Val Pro Glu Asn Arg Glu

65 70 75 80

Asp Ser Val Cys Val Cys Ser Met Pro Ile Asp Asp Ala Val Glu Ala

85 90 95

Asp Val Tyr Gln Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser

100 105 110

Gly Ser Phe Gln Pro Ser Lys His Val Lys Pro Arg Thr Pro Gly Asn

115 120 125

Leu Thr Val His Pro Asn Ile Ser His Thr Trp Leu Leu Met Trp Thr

130 135 140

Asn Pro Tyr Pro Thr Glu Asn His Leu His Ser Glu Leu Thr Tyr Met

145 150 155 160

Val Asn Val Ser Asn Asp Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn

165 170 175

Val Thr Tyr Met Gly Pro Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys

180 185 190

Ser Gly Ala Ser Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr

195 200 205

Asn Ser Thr Trp Ser Asp Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr

210 215 220

Tyr Glu Pro Trp Glu Gln His Leu Pro Leu Gly Val Ser Ile Ser Cys

225 230 235 240

Leu Val Ile Leu Ala Ile Cys Leu Ser Cys Tyr Phe Ser Ile Ile Lys

245 250 255

Ile Lys Lys Gly Trp Trp Asp Gln Ile Pro Asn Pro Ala His Ser Pro

260 265 270

Leu Val Ala Ile Val Ile Gln Asp Ser Gln Val Ser Leu Trp Gly Lys

275 280 285

Arg Ser Arg Gly Gln Glu Pro Ala Lys Cys Pro His Trp Lys Thr Cys

290 295 300

Leu Thr Lys Leu Leu Pro Cys Leu Leu Glu His Gly Leu Gly Arg Glu

305 310 315 320

Glu Glu Ser Pro Lys Thr Ala Lys Asn Gly Pro Leu Gln Gly Pro Gly

325 330 335

Lys Pro Ala Trp Cys Pro Val Glu Val Ser Lys Thr Ile Leu Trp Pro

340 345 350

Glu Ser Ile Ser Val Val Gln Cys Val Glu Leu Ser Glu Ala Pro Val

355 360 365

Asp Asn Glu Glu Glu Glu Glu Glu Val Glu Glu Asp Lys Arg Ser Leu Cys

370 375 380

Pro Ser Leu Glu Gly Ser Gly Gly Ser Phe Gln Glu Gly Arg Glu Gly

385 390 395 400

Ile Val Ala Arg Leu Thr Glu Ser Leu Phe Leu Asp Leu Leu Gly Gly

405 410 415

Glu Asn Gly Gly Phe Cys Pro Gln Gly Leu Glu Glu Ser Cys Leu Pro

420 425 430

Pro Pro Ser Gly Ser Val Gly Ala Gln Met Pro Trp Ala Gln Phe Pro

435 440 445

Arg Ala Gly Pro Arg Ala Ala Pro Glu Gly Pro Glu Gln Pro Arg Arg

450 455 460

Pro Glu Ser Ala Leu Gln Ala Ser Pro Thr Gln Ser Ala Gly Ser Ser

465 470 475 480

Ala Phe Pro Glu Pro Pro Pro Val Val Thr Asp Asn Pro Ala Tyr Arg

485 490 495

Ser Phe Gly Ser Phe Leu Gly Gln Ser Ser Asp Pro Gly Asp Gly Asp

500 505 510

Ser Asp Pro Glu Leu Ala Asp Arg Pro Gly Glu Ala Asp Pro Gly Ile

515 520 525

Pro Ser Ala Pro Gln Pro Pro Glu Pro Pro Ala Ala Leu Gln Pro Glu

530 535 540

Pro Glu Ser Trp Glu Gln Ile Leu Arg Gln Ser Val Leu Gln His Arg

545 550 555 560

Ala Ala Pro Ala Pro Gly Pro Gly Pro Gly Ser Gly Tyr Arg Glu Phe

565 570 575

Thr Cys Ala Val Lys Gln Gly Ser Ala Pro Asp Ala Gly Gly Pro Gly

580 585 590

Phe Gly Pro Ser Gly Glu Ala Gly Tyr Lys Ala Phe Cys Ser Leu Leu

595 600 605

Pro Gly Gly Ala Thr Cys Pro Gly Thr Ser Gly Gly Glu Ala Gly Ser

610 615 620

Gly Glu Gly Gly Tyr Lys Pro Phe Gln Ser Leu Thr Pro Gly Cys Pro

625 630 635 640

Gly Ala Pro Thr Pro Val Pro Val Pro Leu Phe Thr Phe Gly Leu Asp

645 650 655

Thr Glu Pro Pro Gly Ser Pro Gln Asp Ser Leu Gly Ala Gly Ser Ser

660 665 670

Pro Glu His Leu Gly Val Glu Pro Ala Gly Lys Glu Glu Asp Ser Arg

675 680 685

Lys Thr Leu Leu Ala Pro Glu Gln Ala Thr Asp Pro Leu Arg Asp Asp

690 695 700

Leu Ala Ser Ser Ile Val Tyr Ser Ala Leu Thr Cys His Leu Cys Gly

705 710 715 720

His Leu Lys Gln Trp His Asp Gln Glu Glu Arg Gly Lys Ala His Ile

725 730 735

Val Pro Ser Pro Cys Cys Gly Cys Cys Cys Gly Asp Arg Ser Ser Leu

740 745 750

Leu Leu Ser Pro Leu Arg Ala Pro Asn Val Leu Pro Gly Gly Val Leu

755 760 765

Leu Glu Ala Ser Leu Ser Pro Ala Ser Leu Val Pro Ser Gly Val Ser

770 775 780

Lys Glu Gly Lys Ser Ser Pro Phe Ser Gln Pro Ala Ser Ser Ser Ala

785 790 795 800

Gln Ser Ser Ser Gln Thr Pro Lys Lys Leu Ala Val Leu Ser Thr Glu

805 810 815

Pro Thr Cys Met Ser Ala Ser

820

<210> 8

<211> 881

<212> protein

<213> Felis catus

<400> 8

Met Gly Arg Leu Cys Ser Gly Leu Thr Phe Pro Val Ser Cys Leu Ile

1 5 10 15

Leu Met Trp Ala Ala Gly Ser Gly Ser Val Lys Val Leu Arg Ala Pro

20 25 30

Thr Cys Phe Ser Asp Tyr Phe Ser Thr Ser Val Cys Gln Trp Asn Met

35 40 45

Asp Ala Pro Thr Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu

50 55 60

Asn Phe Met Gly Ser Glu Asn Arg Thr Cys Val Pro Glu Asn Gly Glu

65 70 75 80

Gly Ala Ala Cys Ala Cys Ser Met Leu Met Asp Asp Phe Val Glu Ala

85 90 95

Asp Val Tyr Gln Leu His Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser

100 105 110

Gly Ser Phe Lys Pro Ser Ser His Val Lys Pro Arg Ala Pro Gly Asn

115 120 125

Leu Thr Val His Pro Asn Val Ser His Thr Trp Leu Leu Arg Trp Ser

130 135 140

Asn Pro Tyr Pro Pro Glu Asn His Leu His Ala Glu Leu Thr Tyr Met

145 150 155 160

Val Asn Ile Ser Ser Glu Asp Asp Pro Thr Asp Val Ser Val Cys Ala

165 170 175

Ser Gly Phe Leu Cys His Leu Leu Gly Leu Arg Arg Val Glu Thr Gly

180 185 190

Ala Pro Gly Ala Arg Leu Pro Pro Trp Leu Cys Ala Pro Arg Pro Arg

195 200 205

Arg Val Pro Gly Ser Gln Cys Ala Val Ile Ser Cys Cys Arg Trp Val

210 215 220

Leu Ile Ala Leu Thr Ser Arg Gly Gly Arg Trp Arg Leu Thr Pro Gly

225 230 235 240

Leu Arg Ser Gln Thr Arg Tyr Val Ser Val Ala Glu Gly Leu Phe Gly

245 250 255

Ala Thr Pro Arg Val Leu Cys Pro Gly Thr Gln Ala Gly Leu Ala Ser

260 265 270

Ala Ala Arg Glu Gln Met Ser Pro Asp Pro Ser Ala Phe His Ser Ile

275 280 285

Asp Tyr Glu Pro Trp Glu Gln His Leu Pro Leu Gly Val Ser Ile Ser

290 295 300

Cys Leu Val Ile Leu Ala Val Cys Leu Ser Cys Tyr Leu Ser Val Ile

305 310 315 320

Lys Ile Lys Lys Glu Trp Trp Asp Gln Ile Pro Asn Pro Ala His Ser

325 330 335

His Leu Val Ala Ile Val Ile Gln Asp Pro Gln Val Ser Leu Trp Gly

340 345 350

Lys Arg Ser Arg Gly Gln Glu Pro Ala Lys Cys Pro His Trp Lys Thr

355 360 365

Cys Leu Arg Lys Leu Leu Pro Cys Leu Leu Glu His Gly Met Glu Arg

370 375 380

Lys Glu Asp Pro Ser Lys Ile Ala Arg Asn Gly Pro Ser Gln Cys Ser

385 390 395 400

Gly Lys Ser Ala Trp Cys Pro Val Glu Val Ser Lys Thr Ile Leu Trp

405 410 415

Pro Glu Ser Ile Ser Val Val Arg Cys Val Glu Leu Leu Glu Ala Pro

420 425 430

Val Glu Ser Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Lys Gly Ser Phe

435 440 445

Cys Pro Ser Pro Val Asn Leu Glu Asp Ser Phe Gln Glu Gly Arg Glu

450 455 460

Gly Ile Ala Ala Arg Leu Thr Glu Ser Leu Phe Met Asp Leu Leu Gly

465 470 475 480

Val Glu Lys Gly Gly Phe Gly Pro Gln Gly Ser Leu Glu Ser Trp Phe

485 490 495

Pro Pro Pro Ser Gly Ser Ala Gly Ala Gln Met Pro Trp Ala Glu Phe

500 505 510

Pro Gly Pro Gly Pro Gln Glu Ala Ser Pro Gln Gly Lys Glu Gln Pro

515 520 525

Phe Asp Pro Arg Ser Asp Pro Leu Ala Thr Leu Pro Gln Ser Pro Ala

530 535 540

Ser Pro Thr Phe Pro Glu Thr Pro Pro Val Val Thr Asp Asn Pro Ala

545 550 555 560

Tyr Arg Ser Phe Gly Thr Phe Gln Gly Arg Ser Ser Gly Pro Gly Glu

565 570 575

Cys Asp Ser Gly Pro Glu Leu Ala Gly Arg Leu Gly Glu Ala Asp Pro

580 585 590

Gly Ile Pro Ala Ala Pro Gln Pro Ser Glu Pro Pro Ser Ala Leu Gln

595 600 605

Pro Glu Ala Glu Thr Trp Glu Gln Ile Leu Arg Gln Arg Val Leu Gln

610 615 620

His Arg Gly Ala Pro Ala Pro Ala Pro Gly Ser Gly Tyr Arg Glu Phe

625 630 635 640

Val Cys Ala Val Arg Gln Gly Ser Thr Gln Asp Ser Gly Val Gly Asp

645 650 655

Phe Gly Pro Ser Glu Glu Ala Gly Tyr Lys Ala Phe Ser Ser Leu Leu

660 665 670

Thr Ser Gly Ala Val Cys Pro Glu Ser Gly Gly Glu Ala Gly Ser Gly

675 680 685

Asp Gly Gly Tyr Lys Pro Phe Gln Ser Leu Thr Pro Gly Cys Pro Gly

690 695 700

Ala Pro Ala Pro Val Pro Val Pro Leu Phe Thr Phe Gly Leu Asp Ala

705 710 715 720

Glu Pro Pro His Cys Pro Gln Asp Ser Pro Leu Pro Gly Ser Ser Pro

725 730 735

Glu Pro Ala Gly Lys Ala Gln Asp Ser His Lys Thr Pro Pro Ala Pro

740 745 750

Glu Gln Ala Ala Asp Pro Leu Arg Asp Asp Leu Ala Ser Gly Ile Val

755 760 765

Tyr Ser Ala Leu Thr Cys His Leu Cys Gly His Leu Lys Gln Cys His

770 775 780

Gly Gln Glu Glu Gly Gly Glu Ala His Pro Val Ala Ser Pro Cys Cys

785 790 795 800

Gly Cys Cys Cys Gly Asp Arg Ser Ser Pro Leu Val Ser Pro Leu Arg

805 810 815

Ala Pro Asp Pro Leu Pro Gly Gly Val Pro Leu Glu Ala Ser Leu Ser

820 825 830

Pro Ala Ser Pro Ala Pro Leu Ala Val Ser Glu Glu Gly Pro Pro Ser

835 840 845

Leu Cys Phe Gln Pro Ala Leu Ser His Ala His Ser Ser Ser Gln Thr

850 855 860

Pro Lys Lys Val Ala Met Leu Ser Pro Glu Pro Thr Cys Thr Met Ala

865 870 875 880

Ser

<210> 9

<211> 809

<212> protein

<213> Equus caballus

<400> 9

Met Gly Cys Leu Cys Pro Gly Leu Thr Leu Pro Val Ser Cys Leu Ile

1 5 10 15

Leu Val Trp Ala Ala Gly Ser Gly Ser Val Lys Val Leu His Leu Thr

20 25 30

Ala Cys Phe Ser Asp Tyr Ile Ser Ala Ser Thr Cys Glu Trp Lys Met

35 40 45

Asp Arg Pro Thr Asn Cys Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu

50 55 60

Asn Asp Glu Phe Ser Asp Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu

65 70 75 80

Asp Glu Val Cys Val Cys Arg Met Leu Met Asp Asn Ile Val Ser Glu

85 90 95

Asp Val Tyr Glu Leu Asp Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn

100 105 110

Ser Ser Phe Lys Pro Ser Arg His Val Lys Pro Arg Ala Pro Gln Asn

115 120 125

Leu Thr Val His Ala Ile Ser His Thr Trp Leu Leu Thr Trp Ser Asn

130 135 140

Pro Tyr Pro Leu Lys Asn His Leu Trp Ser Glu Leu Thr Tyr Leu Val

145 150 155 160

Asn Ile Ser Lys Glu Asp Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val

165 170 175

Thr Tyr Met Asp Pro Thr Leu Arg Val Thr Ala Ser Thr Leu Lys Ser

180 185 190

Arg Ala Thr Tyr Ser Ala Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn

195 200 205

Ser Thr Trp Ser Glu Trp Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr

210 215 220

Glu Gln Pro Leu Glu Gln Arg Leu Pro Leu Gly Val Ser Ile Ser Cys

225 230 235 240

Val Val Ile Leu Ala Ile Cys Leu Ser Cys Tyr Phe Ser Ile Ile Lys

245 250 255

Ile Lys Lys Glu Trp Trp Asp Gln Ile Pro Asn Pro Ala His Ser Pro

260 265 270

Leu Val Ala Ile Val Leu Gln Asp Ser Gln Val Ser Leu Trp Gly Lys

275 280 285

Gln Ser Arg Gly Gln Glu Pro Ala Lys Cys Pro Arg Trp Lys Thr Cys

290 295 300

Leu Thr Lys Leu Leu Pro Cys Leu Leu Glu His Gly Leu Gln Lys Glu

305 310 315 320

Glu Asp Ser Ser Lys Thr Val Arg Asn Gly Pro Phe Gln Ser Pro Gly

325 330 335

Lys Ser Ala Trp His Thr Val Glu Val Asn His Thr Ile Leu Arg Pro

340 345 350

Glu Ile Ile Ser Val Pro Cys Val Glu Leu Cys Glu Ala Gln Val

355 360 365

Glu Ser Glu Glu Glu Glu Val Glu Glu Asp Arg Gly Ser Phe Cys Pro

370 375 380

Ser Pro Glu Ser Ser Gly Ser Gly Phe Gln Glu Gly Arg Glu Gly Val

385 390 395 400

Ala Ala Arg Leu Thr Glu Ser Leu Phe Leu Gly Leu Leu Gly Ala Glu

405 410 415

Asn Gly Ala Leu Gly Glu Ser Cys Leu Leu Pro Pro Leu Gly Ser Ala

420 425 430

His Met Pro Trp Ala Arg Ile Ser Ser Ala Gly Pro Gln Glu Ala Ala

435 440 445

Ser Gln Gly Glu Glu Gln Pro Leu Asn Pro Glu Ser Asn Pro Leu Ala

450 455 460

Thr Leu Thr Gln Ser Pro Gly Ser Leu Ala Phe Thr Glu Ala Pro Ala

465 470 475 480

Val Val Ala Asp Asn Pro Ala Tyr Arg Ser Phe Ser Asn Ser Leu Ser

485 490 495

Gln Pro Arg Gly Pro Gly Glu Leu Asp Ser Asp Pro Gln Leu Ala Glu

500 505 510

His Leu Gly Gln Val Asp Pro Ser Ile Pro Ser Ala Pro Gln Pro Ser

515 520 525

Glu Pro Pro Thr Ala Leu Gln Pro Glu Pro Glu Thr Trp Glu Gln Met

530 535 540

Leu Arg Gln Ser Val Leu Gln Gln Gly Ala Ala Pro Ala Pro Ala Ser

545 550 555 560

Ala Pro Thr Gly Gly Tyr Arg Glu Phe Ala Gln Ala Val Lys Gln Gly

565 570 575

Gly Gly Ala Ala Gly Ser Gly Pro Ser Gly Glu Ala Gly Tyr Lys Ala

580 585 590

Phe Ser Ser Leu Leu Ala Gly Ser Ala Val Cys Pro Gly Gln Ser Gly

595 600 605

Val Glu Ala Ser Ser Gly Glu Gly Gly Tyr Arg Pro Tyr Glu Ser Pro

610 615 620

Asp Pro Gly Ala Pro Ala Pro Val Pro Val Pro Leu Phe Thr Phe Gly

625 630 635 640

Leu Asp Val Glu Pro Pro His Ser Pro Gln Asn Ser Leu Leu Pro Gly

645 650 655

Gly Ser Pro Glu Leu Pro Gly Pro Glu Pro Thr Val Lys Gly Glu Asp

660 665 670

Pro Arg Lys Pro Leu Leu Ser Ala Gln Gln Ala Thr Asp Ser Leu Arg

675 680 685

Asp Asp Leu Gly Ser Gly Ile Val Tyr Ser Ala Leu Thr Cys His Leu

690 695 700

Cys Gly His Leu Lys Gln Cys His Gly Gln Glu Glu His Gly Glu Ala

705 710 715 720

His Thr Val Ala Ser Pro Cys Cys Gly Cys Cys Cys Gly Asp Arg Ser

725 730 735

Ser Pro Pro Val Ser Pro Val Arg Ala Leu Asp Pro Pro Pro Gly Gly

740 745 750

Val Pro Leu Glu Ala Gly Leu Ser Leu Ala Ser Leu Gly Ser Leu Gly

755 760 765

Leu Ser Glu Glu Arg Lys Pro Ser Leu Phe Phe Gln Pro Ala Pro Gly

770 775 780

Asn Ala Gln Ser Ser Ser Gln Thr Pro Leu Thr Val Ala Met Leu Ser

785 790 795 800

Thr Gly Pro Thr Cys Thr Ser Ala Ser

805

<210> 10

<211> 427

<212> protein

<213> Canis lupus

<400> 10

Met Glu Arg Pro Ala Arg Leu Cys Gly Leu Trp Ala Leu Leu Leu Cys

1 5 10 15

Ala Ala Gly Gly Arg Gly Gly Gly Val Ala Ala Pro Thr Glu Thr Gln

20 25 30

Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn Leu Cys Thr Val

35 40 45

Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro Asn Cys Thr Leu

50 55 60

Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys Lys Ile Ala Pro

65 70 75 80

Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu Arg Ile Cys Leu

85 90 95

Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp Asn Pro Ser Ile

100 105 110

Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp Pro Glu Ser Ala

115 120 125

Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser Tyr Met Lys Cys

130 135 140

Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr Asn Tyr Thr Leu

145 150 155 160

Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln Cys Glu Asp Ile

165 170 175

Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala Leu Thr Asn Leu

180 185 190

Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile Val Val Lys Asp

195 200 205

Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val Pro Leu Thr Ser

210 215 220

His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu Phe Phe Gln Asn

225 230 235 240

Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn Phe Tyr Ser Arg

245 250 255

Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln Thr Glu Thr Asn

260 265 270

Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn Ser Glu Phe Glu

275 280 285

Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro Gly Val Leu Pro

290 295 300

Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr Asn Lys Leu Cys

305 310 315 320

Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln Ala Met Ser Ile

325 330 335

Gly Glu Asn Thr Asp Pro Thr Phe Tyr Ile Thr Met Leu Leu Ala Thr

340 345 350

Pro Val Ile Val Ala Gly Ala Ile Ile Val Leu Leu Leu Tyr Leu Lys

355 360 365

Arg Leu Lys Ile Ile Ile Phe Pro Pro Ile Pro Asp Pro Gly Lys Ile

370 375 380

Phe Lys Glu Met Phe Gly Asp Gln Asn Asp Asp Thr Leu His Trp Arg

385 390 395 400

Lys Tyr Asp Ile Tyr Glu Lys Gln Thr Lys Glu Glu Thr Asp Ser Val

405 410 415

Val Leu Ile Glu Asn Leu Lys Lys Ala Ser Gln

420 425

<210> 11

<211> 479

<212> protein

<213> Felis catus

<400> 11

Met Met Thr Lys Cys Ser Ser Asp Arg Asn Val Phe Lys Arg Lys Trp

1 5 10 15

Phe Leu Phe Pro Ala Ser Gln Tyr Thr Phe Arg Pro Ile His Gln Ala

20 25 30

Arg Pro Cys Glu Val Pro Ala Val His Leu Glu Pro Ser Pro Pro Trp

35 40 45

Glu Val Gly Leu Gly Leu Leu Asn Leu Glu Ser Glu Phe Arg Lys Leu

50 55 60

Gly Leu Arg Gly Arg Arg Leu Ala Ala Ala Pro Pro Asp Ser Arg Ala

65 70 75 80

Glu Ala Ala Ser Gln Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser

85 90 95

Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly

100 105 110

Ala Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys

115 120 125

Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro

130 135 140

Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn

145 150 155 160

Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro

165 170 175

Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His

180 185 190

Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser

195 200 205

Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys

210 215 220

Ile Leu Gln Cys Glu Asn Ile Tyr Arg Glu Gly Gln His Ile Gly Cys

225 230 235 240

Ser Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser

245 250 255

Val Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe

260 265 270

Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile

275 280 285

Lys Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn

290 295 300

Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn

305 310 315 320

Asn Ser Gln Thr Glu Thr His Asp Ile Phe Tyr Val Glu Glu Ala Lys

325 330 335

Cys Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe

340 345 350

Met Val Pro Gly Ile Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg

355 360 365

Val Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Arg Leu Trp Ser Asn

370 375 380

Trp Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Phe Tyr

385 390 395 400

Ile Thr Met Leu Leu Ala Thr Pro Val Ile Val Ala Gly Ala Ile Ile

405 410 415

Val Leu Leu Leu Tyr Leu Lys Arg Leu Lys Ile Ile Ile Phe Pro Pro

420 425 430

Ile Pro Asp Pro Gly Lys Ile Phe Lys Glu Met Phe Gly Asp Gln Asn

435 440 445

Asp Asp Ser Leu His Trp Lys Lys Tyr Asp Ile Tyr Glu Lys Gln Thr

450 455 460

Lys Glu Glu Thr Asp Ser Val Val Leu Ile Glu Asn Ala Ser Gln

465 470 475

<210> 12

<211> 407

<212> protein

<213> Equus caballus

<400> 12

Met Tyr Phe Leu Cys Leu Ile Trp Thr Glu Ser Gln Pro Pro Val Thr

1 5 10 15

Asn Leu Ser Val Ser Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp

20 25 30

Asn Pro Pro Glu Gly Val Ser Pro Asn Cys Ser Leu Trp Tyr Phe Ser

35 40 45

His Phe Gly Asn Lys Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg

50 55 60

Ser Lys Glu Val Pro Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser

65 70 75 80

Gln Cys Ser Thr Asn Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys

85 90 95

Cys Ile Ser Pro Pro Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu

100 105 110

Gln Cys Val Trp His Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro

115 120 125

Gly Lys Asn Ala Ser Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His

130 135 140

Ser Ser Leu Gly Lys Ile Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly

145 150 155 160

Gln His Ile Gly Cys Ser Phe Ala Leu Thr Glu Val Lys Asp Ser Ile

165 170 175

Phe Glu Gln His Ser Val Gln Ile Met Val Lys Asp Asn Ala Gly Lys

180 185 190

Ile Arg Pro Phe Phe Asn Ile Val Pro Leu Thr Ser His Val Lys Pro

195 200 205

Asp Pro Pro His Ile Lys Lys Leu Phe Phe Gln Asn Gly Asp Leu Tyr

210 215 220

Val Gln Trp Lys Asn Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr

225 230 235 240

Gln Val Glu Val Asn Asn Ser Gln Thr Glu Thr Arg Asp Ile Phe Ser

245 250 255

Val Glu Glu Ala Lys Cys Gln Asn Pro Glu Phe Glu Gly Asp Leu Glu

260 265 270

Gly Thr Ile Cys Phe Met Val Pro Gly Val Leu Pro Asp Thr Val Asn

275 280 285

Thr Val Arg Ile Arg Val Lys Thr Asn Lys Leu Cys Tyr Glu Asp Asp

290 295 300

Lys Leu Trp Ser Asn Trp Ser Gln Ala Met Ser Ile Gly Lys Lys Ala

305 310 315 320

Asp Pro Thr Phe Tyr Ile Ala Met Leu Leu Ile Ile Pro Val Ile Val

325 330 335

Ala Gly Ala Ile Ile Val Leu Leu Leu Tyr Leu Lys Arg Leu Lys Ile

340 345 350

Ile Met Phe Pro Pro Ile Pro Asp Pro Gly Lys Ile Phe Lys Glu Met

355 360 365

Phe Gly Asp Gln Asn Asp Asp Thr Leu His Trp Lys Lys Tyr Asp Ile

370 375 380

Tyr Glu Lys Gln Thr Lys Glu Glu Thr Asp Ser Val Val Leu Ile Glu

385 390 395 400

Asn Leu Lys Arg Ala Ser Gln

405

<210> 13

<211> 761

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL13R-IL4R-Fc (no signal sequence)

<400> 13

Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro

20 25 30

Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile

165 170 175

Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu

195 200 205

Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Gly Gly Gly Ser Gly

305 310 315 320

Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr

325 330 335

Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys

340 345 350

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu

355 360 365

Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys

370 375 380

Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp

385 390 395 400

Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser

405 410 415

Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn

420 425 430

Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu

435 440 445

Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp

450 455 460

Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro

465 470 475 480

Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser

485 490 495

Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp

500 505 510

Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Lys Arg Glu

515 520 525

Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro

530 535 540

Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys

545 550 555 560

Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val

565 570 575

Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp

580 585 590

Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe

595 600 605

Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp

610 615 620

Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu

625 630 635 640

Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His

645 650 655

Gln Pro Ser Val Tyr Val Leu Pro Ser Arg Glu Glu Leu Ser Lys

660 665 670

Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp

675 680 685

Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys

690 695 700

Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu

705 710 715 720

Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr

725 730 735

Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

740 745 750

Glu Ser Leu Ser His Ser Pro Gly Lys

755 760

<210> 14

<211> 758

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R-IL13R-IgGA (no signal sequence)

<400> 14

Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu

35 40 45

Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys

50 55 60

Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp

65 70 75 80

Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser

85 90 95

Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu

115 120 125

Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp

130 135 140

Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro

145 150 155 160

Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser

165 170 175

Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp

180 185 190

Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Gly Gly

195 200 205

Ser Gly Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val

210 215 220

Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala

225 230 235 240

Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln

245 250 255

Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu

260 265 270

Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu

275 280 285

Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu

290 295 300

Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn

305 310 315 320

Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro

325 330 335

Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile

340 345 350

Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser

355 360 365

Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val

370 375 380

Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn

385 390 395 400

Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys

405 410 415

Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro

420 425 430

Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn

435 440 445

Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Glu Ala Lys Cys

450 455 460

Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met

465 470 475 480

Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val

485 490 495

Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp

500 505 510

Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Phe Asn Glu

515 520 525

Cys Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu Gly

530 535 540

Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg

545 550 555 560

Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg

565 570 575

Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val

580 585 590

His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr

595 600 605

Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly

610 615 620

Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile

625 630 635 640

Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val

645 650 655

Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val

660 665 670

Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val

675 680 685

Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met

690 695 700

Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

705 710 715 720

Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys

725 730 735

Ala Val Met His Glu Thr Leu Gln Asn His Tyr Thr Asp Leu Ser Leu

740 745 750

Ser His Ser Pro Gly Lys

755

<210> 15

<211> 762

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R-IL13R-IgGB (no signal sequence)

<400> 15

Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu

35 40 45

Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys

50 55 60

Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp

65 70 75 80

Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser

85 90 95

Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu

115 120 125

Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp

130 135 140

Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro

145 150 155 160

Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser

165 170 175

Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp

180 185 190

Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Gly Gly

195 200 205

Ser Gly Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val

210 215 220

Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala

225 230 235 240

Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln

245 250 255

Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu

260 265 270

Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu

275 280 285

Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu

290 295 300

Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn

305 310 315 320

Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro

325 330 335

Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile

340 345 350

Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser

355 360 365

Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val

370 375 380

Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn

385 390 395 400

Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys

405 410 415

Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro

420 425 430

Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn

435 440 445

Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Glu Ala Lys Cys

450 455 460

Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met

465 470 475 480

Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val

485 490 495

Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp

500 505 510

Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Pro Lys Arg

515 520 525

Glu Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala

530 535 540

Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro

545 550 555 560

Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val

565 570 575

Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val

580 585 590

Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln

595 600 605

Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln

610 615 620

Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala

625 630 635 640

Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala

645 650 655

His Gln Pro Ser Val Tyr Val Leu Pro Ser Arg Glu Glu Leu Ser

660 665 670

Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro

675 680 685

Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser

690 695 700

Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe

705 710 715 720

Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp

725 730 735

Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr

740 745 750

Gln Glu Ser Leu Ser His Ser Pro Gly Lys

755 760

<210> 16

<211> 760

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R-IL13R-IgGC (no signal sequence)

<400> 16

Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu

35 40 45

Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys

50 55 60

Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp

65 70 75 80

Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser

85 90 95

Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu

115 120 125

Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp

130 135 140

Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro

145 150 155 160

Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser

165 170 175

Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp

180 185 190

Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Gly Gly

195 200 205

Ser Gly Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val

210 215 220

Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala

225 230 235 240

Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln

245 250 255

Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu

260 265 270

Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu

275 280 285

Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu

290 295 300

Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn

305 310 315 320

Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro

325 330 335

Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile

340 345 350

Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser

355 360 365

Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val

370 375 380

Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn

385 390 395 400

Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys

405 410 415

Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro

420 425 430

Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn

435 440 445

Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Glu Ala Lys Cys

450 455 460

Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met

465 470 475 480

Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val

485 490 495

Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp

500 505 510

Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Ala Lys Glu

515 520 525

Cys Glu Cys Lys Cys Asn Cys Asn Asn Cys Pro Cys Pro Gly Cys Gly

530 535 540

Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp

545 550 555 560

Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys Val Val Val Asp

565 570 575

Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp Phe Val Asp Ser

580 585 590

Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu Glu Glu Gln Ser Asn

595 600 605

Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp

610 615 620

Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro

625 630 635 640

Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly Gln Ala His Gln

645 650 655

Pro Asn Val Tyr Val Leu Pro Ser Arg Asp Glu Met Ser Lys Asn

660 665 670

Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe Pro Pro Glu Ile

675 680 685

Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr

690 695 700

Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr

705 710 715 720

Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe

725 730 735

Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Ile

740 745 750

Ser Leu Ser His Ser Pro Gly Lys

755 760

<210> 17

<211> 758

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R-IL13R-IgGD (no signal sequence)

<400> 17

Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu

35 40 45

Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys

50 55 60

Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp

65 70 75 80

Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser

85 90 95

Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu

115 120 125

Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp

130 135 140

Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro

145 150 155 160

Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser

165 170 175

Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp

180 185 190

Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Gly Gly

195 200 205

Ser Gly Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val

210 215 220

Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala

225 230 235 240

Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln

245 250 255

Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu

260 265 270

Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu

275 280 285

Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu

290 295 300

Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn

305 310 315 320

Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro

325 330 335

Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile

340 345 350

Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser

355 360 365

Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val

370 375 380

Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn

385 390 395 400

Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys

405 410 415

Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro

420 425 430

Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn

435 440 445

Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Glu Ala Lys Cys

450 455 460

Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met

465 470 475 480

Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val

485 490 495

Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp

500 505 510

Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Pro Lys Glu

515 520 525

Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu Gly

530 535 540

Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg

545 550 555 560

Ile Thr Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp Leu Gly Arg

565 570 575

Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val

580 585 590

His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn Ser Thr Tyr

595 600 605

Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly

610 615 620

Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro Ile

625 630 635 640

Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val

645 650 655

Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val

660 665 670

Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp Val

675 680 685

Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys Tyr His Thr

690 695 700

Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys

705 710 715 720

Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys

725 730 735

Ala Val Met His Glu Ala Leu Gln Asn His Tyr Thr Asp Leu Ser Leu

740 745 750

Ser His Ser Pro Gly Lys

755

<210> 18

<211> 590

<212> protein

<213> Artificial sequence

<220>

<223> Felis catus, IL4R-IL13R (no signal sequence)

<400> 18

Ser Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr

1 5 10 15

Phe Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu

35 40 45

Asn Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys

50 55 60

Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His

65 70 75 80

Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser

85 90 95

Ser His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Val Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu

115 120 125

Asn His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu

130 135 140

Asp Asp Pro Thr Asp Val Ser Val Cys Ala Ser Gly Phe Leu Cys His

145 150 155 160

Leu Leu Gly Leu Arg Arg Val Glu Thr Gly Ala Pro Gly Ala Arg Leu

165 170 175

Pro Pro Trp Leu Cys Ala Pro Arg Pro Arg Arg Val Pro Gly Ser Gln

180 185 190

Cys Ala Val Ile Ser Cys Cys Arg Trp Val Leu Ile Ala Leu Thr Ser

195 200 205

Arg Gly Gly Arg Trp Arg Leu Thr Pro Gly Leu Arg Ser Gln Thr Arg

210 215 220

Tyr Val Ser Val Ala Glu Gly Leu Phe Gly Ala Thr Pro Arg Val Leu

225 230 235 240

Cys Pro Gly Thr Gln Ala Gly Leu Ala Ser Ala Ala Arg Glu Gln Met

245 250 255

Ser Pro Asp Pro Ser Ala Phe His Ser Ile Asp Tyr Glu Pro Gly Gly

260 265 270

Gly Ser Gly Ser Gln Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser

275 280 285

Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly

290 295 300

Ala Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys

305 310 315 320

Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro

325 330 335

Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn

340 345 350

Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro

355 360 365

Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His

370 375 380

Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser

385 390 395 400

Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys

405 410 415

Ile Leu Gln Cys Glu Asn Ile Tyr Arg Glu Gly Gln His Ile Gly Cys

420 425 430

Ser Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser

435 440 445

Val Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe

450 455 460

Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile

465 470 475 480

Lys Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn

485 490 495

Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn

500 505 510

Asn Ser Gln Thr Glu Thr His Asp Ile Phe Tyr Val Glu Glu Ala Lys

515 520 525

Cys Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe

530 535 540

Met Val Pro Gly Ile Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg

545 550 555 560

Val Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Arg Leu Trp Ser Asn

565 570 575

Trp Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr

580 585 590

<210> 19

<211> 525

<212> protein

<213> Artificial sequence

<220>

<223> Equus caballus, IL4R-IL13R (no signal sequence)

<400> 19

Ser Gly Ser Val Lys Val Leu His Leu Thr Ala Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Ala Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys

20 25 30

Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp

35 40 45

Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys

50 55 60

Arg Met Leu Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp

65 70 75 80

Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser

85 90 95

Arg His Val Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile

100 105 110

Ser His Thr Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn

115 120 125

His Leu Trp Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp

130 135 140

Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr

145 150 155 160

Leu Arg Val Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala

165 170 175

Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp

180 185 190

Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro Gly Gly Gly

195 200 205

Ser Gly Thr Glu Ser Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val

210 215 220

Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asn Pro Pro Glu Gly Val

225 230 235 240

Ser Pro Asn Cys Ser Leu Trp Tyr Phe Ser His Phe Gly Asn Lys Gln

245 250 255

Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu

260 265 270

Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu

275 280 285

Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Ile Ser Pro Pro Glu

290 295 300

Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn

305 310 315 320

Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Lys Asn Ala Ser Pro

325 330 335

Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile

340 345 350

Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser

355 360 365

Phe Ala Leu Thr Glu Val Lys Asp Ser Ile Phe Glu Gln His Ser Val

370 375 380

Gln Ile Met Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Phe Phe Asn

385 390 395 400

Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys

405 410 415

Lys Leu Phe Phe Gln Asn Gly Asp Leu Tyr Val Gln Trp Lys Asn Pro

420 425 430

Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn

435 440 445

Ser Gln Thr Glu Thr Arg Asp Ile Phe Ser Val Glu Glu Ala Lys Cys

450 455 460

Gln Asn Pro Glu Phe Glu Gly Asp Leu Glu Gly Thr Ile Cys Phe Met

465 470 475 480

Val Pro Gly Val Leu Pro Asp Thr Val Asn Thr Val Arg Ile Arg Val

485 490 495

Lys Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp

500 505 510

Ser Gln Ala Met Ser Ile Gly Lys Lys Ala Asp Pro Thr

515 520 525

<210> 20

<211> 780

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL13R-IL4R-IgGB (with signal sequence)

<400> 20

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser

20 25 30

Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly

35 40 45

Ala Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys

50 55 60

Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro

65 70 75 80

Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn

85 90 95

Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro

100 105 110

Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His

115 120 125

Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser

130 135 140

Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys

145 150 155 160

Ile Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys

165 170 175

Ser Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser

180 185 190

Val Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe

195 200 205

Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile

210 215 220

Lys Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn

225 230 235 240

Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn

245 250 255

Asn Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Glu Ala Lys

260 265 270

Cys Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe

275 280 285

Met Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg

290 295 300

Val Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn

305 310 315 320

Trp Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Gly Gly

325 330 335

Gly Ser Gly Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe

340 345 350

Ser Asp Tyr Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro

355 360 365

Thr Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met

370 375 380

Gly Ser Glu Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val

385 390 395 400

Cys Val Cys Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr

405 410 415

Gln Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe

420 425 430

Gln Pro Ser Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val

435 440 445

His Pro Asn Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr

450 455 460

Pro Thr Glu Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val

465 470 475 480

Ser Asn Asp Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr

485 490 495

Met Gly Pro Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala

500 505 510

Ser Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr

515 520 525

Trp Ser Asp Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro

530 535 540

Lys Arg Glu Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys

545 550 555 560

Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro

565 570 575

Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys

580 585 590

Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp

595 600 605

Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu

610 615 620

Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly

625 630 635 640

His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn

645 650 655

Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly

660 665 670

Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Ser Arg Glu Glu

675 680 685

Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe

690 695 700

Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro

705 710 715 720

Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser

725 730 735

Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg

740 745 750

Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His

755 760 765

Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

770 775 780

<210> 21

<211> 781

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R-IL13R-IgGB (with signal sequence)

<400> 21

Met Ala Val Leu Gly Leu Leu Phe Cys Leu Val Thr Phe Pro Ser Cys

1 5 10 15

Val Leu Ser Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe

20 25 30

Ser Asp Tyr Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro

35 40 45

Thr Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met

50 55 60

Gly Ser Glu Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val

65 70 75 80

Cys Val Cys Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr

85 90 95

Gln Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe

100 105 110

Gln Pro Ser Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val

115 120 125

His Pro Asn Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr

130 135 140

Pro Thr Glu Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val

145 150 155 160

Ser Asn Asp Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr

165 170 175

Met Gly Pro Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala

180 185 190

Ser Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr

195 200 205

Trp Ser Asp Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro

210 215 220

Gly Gly Gly Ser Gly Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser

225 230 235 240

Val Ser Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro

245 250 255

Glu Gly Ala Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp

260 265 270

Asn Lys Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu

275 280 285

Val Pro Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser

290 295 300

Thr Asn Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro

305 310 315 320

Pro Pro Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val

325 330 335

Trp His Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn

340 345 350

Thr Ser Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu

355 360 365

Gly Lys Ile Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile

370 375 380

Gly Cys Ser Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln

385 390 395 400

His Ser Val Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro

405 410 415

Ser Phe Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro

420 425 430

His Ile Lys Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp

435 440 445

Lys Asn Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu

450 455 460

Val Asn Asn Ser Gln Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu

465 470 475 480

Ala Lys Cys Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile

485 490 495

Cys Phe Met Val Pro Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg

500 505 510

Ile Arg Val Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp

515 520 525

Ser Asn Trp Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr

530 535 540

Pro Lys Arg Glu Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys

545 550 555 560

Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro

565 570 575

Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr

580 585 590

Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser

595 600 605

Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg

610 615 620

Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile

625 630 635 640

Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn

645 650 655

Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg

660 665 670

Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu

675 680 685

Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe

690 695 700

Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu

705 710 715 720

Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly

725 730 735

Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln

740 745 750

Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn

755 760 765

His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys

770 775 780

<210> 22

<211> 315

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL13R extracellular domain (no signal sequence)

<400> 22

Thr Glu Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro

20 25 30

Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile

165 170 175

Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu

195 200 205

Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr Asn Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Val Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr

305 310 315

<210> 23

<211> 207

<212> protein

<213> Artificial sequence

<220>

<223> Canis lupus, IL4R extracellular domain (no signal sequence)

<400> 23

Ser Gly Ser Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser

1 5 10 15

Asp Tyr Ile Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr

20 25 30

Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly

35 40 45

Ser Glu Asn His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys

50 55 60

Val Cys Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln

65 70 75 80

Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln

85 90 95

Pro Ser Lys His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His

100 105 110

Pro Asn Ile Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro

115 120 125

Thr Glu Asn His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser

130 135 140

Asn Asp Asn Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met

145 150 155 160

Gly Pro Thr Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser

165 170 175

Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp

180 185 190

Ser Asp Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro

195 200 205

<210> 24

<211> 315

<212> protein

<213> Artificial sequence

<220>

<223> Felis catus, IL13R extracellular domain (no signal sequence)

<400> 24

Ser Gln Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro

20 25 30

Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asn Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile

165 170 175

Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu

195 200 205

Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr His Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Ile Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Arg Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr

305 310 315

<210> 25

<211> 270

<212> protein

<213> Artificial sequence

<220>

<223> Felis catus, IL4R extracellular domain (no signal sequence)

<400> 25

Ser Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr

1 5 10 15

Phe Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu

35 40 45

Asn Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys

50 55 60

Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His

65 70 75 80

Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser

85 90 95

Ser His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Val Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu

115 120 125

Asn His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu

130 135 140

Asp Asp Pro Thr Asp Val Ser Val Cys Ala Ser Gly Phe Leu Cys His

145 150 155 160

Leu Leu Gly Leu Arg Arg Val Glu Thr Gly Ala Pro Gly Ala Arg Leu

165 170 175

Pro Pro Trp Leu Cys Ala Pro Arg Pro Arg Arg Val Pro Gly Ser Gln

180 185 190

Cys Ala Val Ile Ser Cys Cys Arg Trp Val Leu Ile Ala Leu Thr Ser

195 200 205

Arg Gly Gly Arg Trp Arg Leu Thr Pro Gly Leu Arg Ser Gln Thr Arg

210 215 220

Tyr Val Ser Val Ala Glu Gly Leu Phe Gly Ala Thr Pro Arg Val Leu

225 230 235 240

Cys Pro Gly Thr Gln Ala Gly Leu Ala Ser Ala Ala Arg Glu Gln Met

245 250 255

Ser Pro Asp Pro Ser Ala Phe His Ser Ile Asp Tyr Glu Pro

260 265 270

<210> 26

<211> 315

<212> protein

<213> Artificial sequence

<220>

<223> Equus caballus, IL13R extracellular domain (no signal sequence)

<400> 26

Thr Glu Ser Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asn Pro Pro Glu Gly Val Ser Pro

20 25 30

Asn Cys Ser Leu Trp Tyr Phe Ser His Phe Gly Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Ile Ser Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Lys Asn Ala Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Glu Val Lys Asp Ser Ile Phe Glu Gln His Ser Val Gln Ile

165 170 175

Met Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Phe Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Lys Leu

195 200 205

Phe Phe Gln Asn Gly Asp Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr Arg Asp Ile Phe Ser Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Pro Glu Phe Glu Gly Asp Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Val Leu Pro Asp Thr Val Asn Thr Val Arg Ile Arg Val Lys Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Lys Lys Ala Asp Pro Thr

305 310 315

<210> 27

<211> 205

<212> protein

<213> Artificial sequence

<220>

<223> Equus caballus, IL4R extracellular domain (no signal sequence)

<400> 27

Ser Gly Ser Val Lys Val Leu His Leu Thr Ala Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Ala Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys

20 25 30

Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp

35 40 45

Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys

50 55 60

Arg Met Leu Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp

65 70 75 80

Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser

85 90 95

Arg His Val Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile

100 105 110

Ser His Thr Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn

115 120 125

His Leu Trp Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp

130 135 140

Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr

145 150 155 160

Leu Arg Val Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala

165 170 175

Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp

180 185 190

Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro

195 200 205

<210> 28

<211> 829

<212> protein

<213> Artificial sequence

<220>

<223> IL13R-IL4R-IgG2 feline (no signal sequence)

<400> 28

Ser Gln Thr Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro

20 25 30

Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asn Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile

165 170 175

Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu

195 200 205

Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr His Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Ile Leu Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Arg Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Gly Gly Gly Ser Gly

305 310 315 320

Ser Ser Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp

325 330 335

Tyr Phe Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn

340 345 350

Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser

355 360 365

Glu Asn Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala

370 375 380

Cys Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu

385 390 395 400

His Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro

405 410 415

Ser Ser His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro

420 425 430

Asn Val Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro

435 440 445

Glu Asn His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser

450 455 460

Glu Asp Asp Pro Thr Asp Val Ser Val Cys Ala Ser Gly Phe Leu Cys

465 470 475 480

His Leu Leu Gly Leu Arg Arg Val Glu Thr Gly Ala Pro Gly Ala Arg

485 490 495

Leu Pro Pro Trp Leu Cys Ala Pro Arg Pro Arg Arg Val Pro Gly Ser

500 505 510

Gln Cys Ala Val Ile Ser Cys Cys Arg Trp Val Leu Ile Ala Leu Thr

515 520 525

Ser Arg Gly Gly Arg Trp Arg Leu Thr Pro Gly Leu Arg Ser Gln Thr

530 535 540

Arg Tyr Val Ser Val Ala Glu Gly Leu Phe Gly Ala Thr Pro Arg Val

545 550 555 560

Leu Cys Pro Gly Thr Gln Ala Gly Leu Ala Ser Ala Ala Arg Glu Gln

565 570 575

Met Ser Pro Asp Pro Ser Ala Phe His Ser Ile Asp Tyr Glu Pro Ser

580 585 590

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys

595 600 605

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

610 615 620

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

625 630 635 640

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

645 650 655

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

660 665 670

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

675 680 685

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

690 695 700

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

705 710 715 720

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

725 730 735

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

740 745 750

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

755 760 765

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

770 775 780

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

785 790 795 800

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

805 810 815

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

820 825

<210> 29

<211> 829

<212> protein

<213> Artificial sequence

<220>

<223> IL4R-IL13R-IgG2 feline (no signal sequence)

<400> 29

Ser Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr

1 5 10 15

Phe Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys

20 25 30

Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu

35 40 45

Asn Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys

50 55 60

Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His

65 70 75 80

Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser

85 90 95

Ser His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn

100 105 110

Val Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu

115 120 125

Asn His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu

130 135 140

Asp Asp Pro Thr Asp Val Ser Val Cys Ala Ser Gly Phe Leu Cys His

145 150 155 160

Leu Leu Gly Leu Arg Arg Val Glu Thr Gly Ala Pro Gly Ala Arg Leu

165 170 175

Pro Pro Trp Leu Cys Ala Pro Arg Pro Arg Arg Val Pro Gly Ser Gln

180 185 190

Cys Ala Val Ile Ser Cys Cys Arg Trp Val Leu Ile Ala Leu Thr Ser

195 200 205

Arg Gly Gly Arg Trp Arg Leu Thr Pro Gly Leu Arg Ser Gln Thr Arg

210 215 220

Tyr Val Ser Val Ala Glu Gly Leu Phe Gly Ala Thr Pro Arg Val Leu

225 230 235 240

Cys Pro Gly Thr Gln Ala Gly Leu Ala Ser Ala Ala Arg Glu Gln Met

245 250 255

Ser Pro Asp Pro Ser Ala Phe His Ser Ile Asp Tyr Glu Pro Gly Gly

260 265 270

Gly Ser Gly Ser Ser Gln Thr Gln Pro Pro Val Thr Asn Leu Ser Val

275 280 285

Ser Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asp Pro Pro Glu

290 295 300

Gly Ala Ser Pro Asn Cys Thr Leu Arg Tyr Phe Ser His Phe Asp Asn

305 310 315 320

Lys Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val

325 330 335

Pro Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr

340 345 350

Asn Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Thr Pro Pro

355 360 365

Pro Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp

370 375 380

His Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Arg Asn Thr

385 390 395 400

Ser Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly

405 410 415

Lys Ile Leu Gln Cys Glu Asn Ile Tyr Arg Glu Gly Gln His Ile Gly

420 425 430

Cys Ser Phe Ala Leu Thr Asn Leu Lys Asp Ser Ser Phe Glu Gln His

435 440 445

Ser Val Gln Ile Val Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Ser

450 455 460

Phe Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His

465 470 475 480

Ile Lys Arg Leu Phe Phe Gln Asn Gly Asn Leu Tyr Val Gln Trp Lys

485 490 495

Asn Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val

500 505 510

Asn Asn Ser Gln Thr Glu Thr His Asp Ile Phe Tyr Val Glu Glu Ala

515 520 525

Lys Cys Gln Asn Ser Glu Phe Glu Gly Asn Leu Glu Gly Thr Ile Cys

530 535 540

Phe Met Val Pro Gly Ile Leu Pro Asp Thr Leu Asn Thr Val Arg Ile

545 550 555 560

Arg Val Arg Thr Asn Lys Leu Cys Tyr Glu Asp Asp Arg Leu Trp Ser

565 570 575

Asn Trp Ser Gln Ala Met Ser Ile Gly Glu Asn Thr Asp Pro Thr Ser

580 585 590

Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys

595 600 605

Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro

610 615 620

Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr

625 630 635 640

Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr

645 650 655

Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg

660 665 670

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile

675 680 685

Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn

690 695 700

Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys

705 710 715 720

Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu

725 730 735

Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe

740 745 750

His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu

755 760 765

Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly

770 775 780

Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln

785 790 795 800

Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser

805 810 815

His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys

820 825

<210> 30

<211> 754

<212> protein

<213> Artificial sequence

<220>

<223> IL13R-IL4R-IgG2 equine (no signal sequence)

<400> 30

Thr Glu Ser Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn

1 5 10 15

Leu Cys Thr Val Ile Trp Thr Trp Asn Pro Pro Glu Gly Val Ser Pro

20 25 30

Asn Cys Ser Leu Trp Tyr Phe Ser His Phe Gly Asn Lys Gln Asp Lys

35 40 45

Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu

50 55 60

Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp

65 70 75 80

Asn Pro Ser Ile Leu Val Glu Lys Cys Ile Ser Pro Pro Glu Gly Asp

85 90 95

Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser

100 105 110

Tyr Met Lys Cys Thr Trp Leu Pro Gly Lys Asn Ala Ser Pro Asp Thr

115 120 125

Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln

130 135 140

Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala

145 150 155 160

Leu Thr Glu Val Lys Asp Ser Ile Phe Glu Gln His Ser Val Gln Ile

165 170 175

Met Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Phe Phe Asn Ile Val

180 185 190

Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile Lys Lys Leu

195 200 205

Phe Phe Gln Asn Gly Asp Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn

210 215 220

Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln

225 230 235 240

Thr Glu Thr Arg Asp Ile Phe Ser Val Glu Glu Ala Lys Cys Gln Asn

245 250 255

Pro Glu Phe Glu Gly Asp Leu Glu Gly Thr Ile Cys Phe Met Val Pro

260 265 270

Gly Val Leu Pro Asp Thr Val Asn Thr Val Arg Ile Arg Val Lys Thr

275 280 285

Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln

290 295 300

Ala Met Ser Ile Gly Lys Lys Ala Asp Pro Thr Gly Gly Gly Ser Gly

305 310 315 320

Ser Ser Gly Ser Val Lys Val Leu His Leu Thr Ala Cys Phe Ser Asp

325 330 335

Tyr Ile Ser Ala Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn

340 345 350

Cys Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser

355 360 365

Asp Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val

370 375 380

Cys Arg Met Leu Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu

385 390 395 400

Asp Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro

405 410 415

Ser Arg His Val Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala

420 425 430

Ile Ser His Thr Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys

435 440 445

Asn His Leu Trp Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu

450 455 460

Asp Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro

465 470 475 480

Thr Leu Arg Val Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser

485 490 495

Ala Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu

500 505 510

Trp Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro Asp Met

515 520 525

Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

530 535 540

Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg

545 550 555 560

Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro

565 570 575

Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala

580 585 590

Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val

595 600 605

Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe

610 615 620

Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala

625 630 635 640

Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu

645 650 655

Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys

660 665 670

Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser

675 680 685

Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln

690 695 700

Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu

705 710 715 720

Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val Met His

725 730 735

Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu

740 745 750

Gly Lys

<210> 31

<211> 754

<212> protein

<213> Artificial sequence

<220>

<223> IL4R-IL13R-IgG2 equine (no signal sequence)

<400> 31

Ser Gly Ser Val Lys Val Leu His Leu Thr Ala Cys Phe Ser Asp Tyr

1 5 10 15

Ile Ser Ala Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys

20 25 30

Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp

35 40 45

Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys

50 55 60

Arg Met Leu Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp

65 70 75 80

Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser

85 90 95

Arg His Val Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile

100 105 110

Ser His Thr Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn

115 120 125

His Leu Trp Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp

130 135 140

Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr

145 150 155 160

Leu Arg Val Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala

165 170 175

Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp

180 185 190

Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro Gly Gly Gly

195 200 205

Ser Gly Ser Thr Glu Ser Gln Pro Pro Val Thr Asn Leu Ser Val Ser

210 215 220

Val Glu Asn Leu Cys Thr Val Ile Trp Thr Trp Asn Pro Pro Glu Gly

225 230 235 240

Val Ser Pro Asn Cys Ser Leu Trp Tyr Phe Ser His Phe Gly Asn Lys

245 250 255

Gln Asp Lys Lys Ile Ala Pro Glu Thr His Arg Ser Lys Glu Val Pro

260 265 270

Leu Asn Glu Arg Ile Cys Leu Gln Val Gly Ser Gln Cys Ser Thr Asn

275 280 285

Glu Ser Asp Asn Pro Ser Ile Leu Val Glu Lys Cys Ile Ser Pro Pro

290 295 300

Glu Gly Asp Pro Glu Ser Ala Val Thr Glu Leu Gln Cys Val Trp His

305 310 315 320

Asn Leu Ser Tyr Met Lys Cys Thr Trp Leu Pro Gly Lys Asn Ala Ser

325 330 335

Pro Asp Thr Asn Tyr Thr Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys

340 345 350

Ile Leu Gln Cys Glu Asp Ile Tyr Arg Glu Gly Gln His Ile Gly Cys

355 360 365

Ser Phe Ala Leu Thr Glu Val Lys Asp Ser Ile Phe Glu Gln His Ser

370 375 380

Val Gln Ile Met Val Lys Asp Asn Ala Gly Lys Ile Arg Pro Phe Phe

385 390 395 400

Asn Ile Val Pro Leu Thr Ser His Val Lys Pro Asp Pro Pro His Ile

405 410 415

Lys Lys Leu Phe Phe Gln Asn Gly Asp Leu Tyr Val Gln Trp Lys Asn

420 425 430

Pro Gln Asn Phe Tyr Ser Arg Cys Leu Ser Tyr Gln Val Glu Val Asn

435 440 445

Asn Ser Gln Thr Glu Thr Arg Asp Ile Phe Ser Val Glu Glu Ala Lys

450 455 460

Cys Gln Asn Pro Glu Phe Glu Gly Asp Leu Glu Gly Thr Ile Cys Phe

465 470 475 480

Met Val Pro Gly Val Leu Pro Asp Thr Val Asn Thr Val Arg Ile Arg

485 490 495

Val Lys Thr Asn Lys Leu Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn

500 505 510

Trp Ser Gln Ala Met Ser Ile Gly Lys Lys Ala Asp Pro Thr Asp Met

515 520 525

Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

530 535 540

Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg

545 550 555 560

Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro

565 570 575

Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala

580 585 590

Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val

595 600 605

Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe

610 615 620

Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala

625 630 635 640

Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu

645 650 655

Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys

660 665 670

Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser

675 680 685

Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln

690 695 700

Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu

705 710 715 720

Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val Met His

725 730 735

Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu

740 745 750

Gly Lys

<210> 32

<211> 305

<212> protein

<213> Artificial sequence

<220>

<223> ECD mini IL13R canine

<400> 32

Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn Leu Cys Thr

1 5 10 15

Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro Asn Cys Thr

20 25 30

Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys Lys Ile Ala

35 40 45

Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu Arg Ile Cys

50 55 60

Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp Asn Pro Ser

65 70 75 80

Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp Pro Glu Ser

85 90 95

Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser Tyr Met Lys

100 105 110

Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr Asn Tyr Thr

115 120 125

Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln Cys Glu Asp

130 135 140

Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala Leu Thr Asn

145 150 155 160

Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile Val Val Lys

165 170 175

Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val Pro Leu Thr

180 185 190

Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu Phe Phe Gln

195 200 205

Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn Phe Tyr Ser

210 215 220

Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln Thr Glu Thr

225 230 235 240

Asn Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn Ser Glu Phe

245 250 255

Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro Gly Val Leu

260 265 270

Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr Asn Lys Leu

275 280 285

Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln Ala Met Ser

290 295 300

ile

305

<210> 33

<211> 184

<212> protein

<213> Artificial sequence

<220>

<223> ECD mini-IL4R canine

<400> 33

Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile Ser Thr Ser

1 5 10 15

Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser Ala Glu Leu

20 25 30

Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn His Thr Cys

35 40 45

Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser Met Pro Ile

50 55 60

Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu Trp Ala Gly

65 70 75 80

Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys His Val Lys

85 90 95

Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile Ser His Thr

100 105 110

Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn His Leu His

115 120 125

Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn Asp Pro Glu

130 135 140

Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr Leu Arg Leu

145 150 155 160

Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala Arg Val Arg

165 170 175

Ala Trp Ala Gln Thr Tyr Asn Ser

180

<210> 34

<211> 305

<212> protein

<213> Artificial sequence

<220>

<223> ECD mini IL13R feline

<400> 34

Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn Leu Cys Thr

1 5 10 15

Val Ile Trp Thr Trp Asp Pro Pro Glu Gly Ala Ser Pro Asn Cys Thr

20 25 30

Leu Arg Tyr Phe Ser His Phe Asp Asn Lys Gln Asp Lys Lys Ile Ala

35 40 45

Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu Arg Ile Cys

50 55 60

Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp Asn Pro Ser

65 70 75 80

Ile Leu Val Glu Lys Cys Thr Pro Pro Pro Glu Gly Asp Pro Glu Ser

85 90 95

Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser Tyr Met Lys

100 105 110

Cys Thr Trp Leu Pro Gly Arg Asn Thr Ser Pro Asp Thr Asn Tyr Thr

115 120 125

Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln Cys Glu Asn

130 135 140

Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala Leu Thr Asn

145 150 155 160

Leu Lys Asp Ser Ser Phe Glu Gln His Ser Val Gln Ile Val Val Lys

165 170 175

Asp Asn Ala Gly Lys Ile Arg Pro Ser Phe Asn Ile Val Pro Leu Thr

180 185 190

Ser His Val Lys Pro Asp Pro Pro His Ile Lys Arg Leu Phe Phe Gln

195 200 205

Asn Gly Asn Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn Phe Tyr Ser

210 215 220

Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln Thr Glu Thr

225 230 235 240

His Asp Ile Phe Tyr Val Glu Glu Ala Lys Cys Gln Asn Ser Glu Phe

245 250 255

Glu Gly Asn Leu Glu Gly Thr Ile Cys Phe Met Val Pro Gly Ile Leu

260 265 270

Pro Asp Thr Leu Asn Thr Val Arg Ile Arg Val Arg Thr Asn Lys Leu

275 280 285

Cys Tyr Glu Asp Asp Arg Leu Trp Ser Asn Trp Ser Gln Ala Met Ser

290 295 300

ile

305

<210> 35

<211> 266

<212> protein

<213> Artificial sequence

<220>

<223> ECD mini IL4R feline

<400> 35

Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr Phe Ser Thr Ser

1 5 10 15

Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys Ser Ala Glu Leu

20 25 30

Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu Asn Arg Thr Cys

35 40 45

Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys Ser Met Leu Met

50 55 60

Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His Leu Trp Ala Gly

65 70 75 80

Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser Ser His Val Lys

85 90 95

Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Val Ser His Thr

100 105 110

Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu Asn His Leu His

115 120 125

Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu Asp Asp Pro Thr

130 135 140

Asp Val Ser Val Cys Ala Ser Gly Phe Leu Cys His Leu Leu Gly Leu

145 150 155 160

Arg Arg Val Glu Thr Gly Ala Pro Gly Ala Arg Leu Pro Pro Trp Leu

165 170 175

Cys Ala Pro Arg Pro Arg Arg Val Pro Gly Ser Gln Cys Ala Val Ile

180 185 190

Ser Cys Cys Arg Trp Val Leu Ile Ala Leu Thr Ser Arg Gly Gly Arg

195 200 205

Trp Arg Leu Thr Pro Gly Leu Arg Ser Gln Thr Arg Tyr Val Ser Val

210 215 220

Ala Glu Gly Leu Phe Gly Ala Thr Pro Arg Val Leu Cys Pro Gly Thr

225 230 235 240

Gln Ala Gly Leu Ala Ser Ala Ala Arg Glu Gln Met Ser Pro Asp Pro

245 250 255

Ser Ala Phe His Ser Ile Asp Tyr Glu Pro

260 265

<210> 36

<211> 305

<212> protein

<213> Artificial sequence

<220>

<223> ECD Mini IL13R Equine

<400> 36

Gln Pro Pro Val Thr Asn Leu Ser Val Ser Val Glu Asn Leu Cys Thr

1 5 10 15

Val Ile Trp Thr Trp Asn Pro Glu Gly Val Ser Pro Asn Cys Ser

20 25 30

Leu Trp Tyr Phe Ser His Phe Gly Asn Lys Gln Asp Lys Lys Ile Ala

35 40 45

Pro Glu Thr His Arg Ser Lys Glu Val Pro Leu Asn Glu Arg Ile Cys

50 55 60

Leu Gln Val Gly Ser Gln Cys Ser Thr Asn Glu Ser Asp Asn Pro Ser

65 70 75 80

Ile Leu Val Glu Lys Cys Ile Ser Pro Pro Glu Gly Asp Pro Glu Ser

85 90 95

Ala Val Thr Glu Leu Gln Cys Val Trp His Asn Leu Ser Tyr Met Lys

100 105 110

Cys Thr Trp Leu Pro Gly Lys Asn Ala Ser Pro Asp Thr Asn Tyr Thr

115 120 125

Leu Tyr Tyr Trp His Ser Ser Leu Gly Lys Ile Leu Gln Cys Glu Asp

130 135 140

Ile Tyr Arg Glu Gly Gln His Ile Gly Cys Ser Phe Ala Leu Thr Glu

145 150 155 160

Val Lys Asp Ser Ile Phe Glu Gln His Ser Val Gln Ile Met Val Lys

165 170 175

Asp Asn Ala Gly Lys Ile Arg Pro Phe Phe Asn Ile Val Pro Leu Thr

180 185 190

Ser His Val Lys Pro Asp Pro Pro His Ile Lys Lys Leu Phe Phe Gln

195 200 205

Asn Gly Asp Leu Tyr Val Gln Trp Lys Asn Pro Gln Asn Phe Tyr Ser

210 215 220

Arg Cys Leu Ser Tyr Gln Val Glu Val Asn Asn Ser Gln Thr Glu Thr

225 230 235 240

Arg Asp Ile Phe Ser Val Glu Glu Ala Lys Cys Gln Asn Pro Glu Phe

245 250 255

Glu Gly Asp Leu Glu Gly Thr Ile Cys Phe Met Val Pro Gly Val Leu

260 265 270

Pro Asp Thr Val Asn Thr Val Arg Ile Arg Val Lys Thr Asn Lys Leu

275 280 285

Cys Tyr Glu Asp Asp Lys Leu Trp Ser Asn Trp Ser Gln Ala Met Ser

290 295 300

ile

305

<210> 37

<211> 201

<212> protein

<213> Artificial sequence

<220>

<223> ECD Mini IL4R Equine

<400> 37

Lys Val Leu His Leu Thr Ala Cys Phe Ser Asp Tyr Ile Ser Ala Ser

1 5 10 15

Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys Ser Ala Gln Leu

20 25 30

Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp Asn Leu Thr Cys

35 40 45

Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys Arg Met Leu Met

50 55 60

Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp Leu Trp Ala Gly

65 70 75 80

Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser Arg His Val Lys

85 90 95

Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile Ser His Thr Trp

100 105 110

Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn His Leu Trp Ser

115 120 125

Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp Asp Pro Thr Asp

130 135 140

Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr Leu Arg Val Thr

145 150 155 160

Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala Arg Val Lys Ala

165 170 175

Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp Ser Pro Ser Thr

180 185 190

Thr Trp His Asn Tyr Tyr Glu Gln Pro

195 200

<210> 38

<211> 4

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 38

Gly Ser Gly Ser

1

<210> 39

<211> 6

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 39

Gly Ser Gly Ser Gly Ser

15

<210> 40

<211> 6

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 40

Gly Gly Ser Gly Gly Ser

15

<210> 41

<211> 9

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 41

Gly Gly Ser Gly Gly Ser Gly Gly Ser

15

<210> 42

<211> 4

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 42

Gly Gly Gly Ser

1

<210> 43

<211> 8

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 43

Gly Gly Gly Ser Gly Gly Gly Ser

15

<210> 44

<211> 12

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 44

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

1 5 10

<210> 45

<211> 6

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 45

Gly Ser Ser Gly Ser Ser

15

<210> 46

<211> 9

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 46

Gly Ser Ser Gly Ser Ser Gly Ser Ser

15

<210> 47

<211> 4

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 47

Gly Gly Ser Ser

1

<210> 48

<211> 8

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 48

Gly Gly Ser Ser Gly Gly Ser Ser

15

<210> 49

<211> 12

<212> protein

<213> Artificial sequence

<220>

<223> GS linker

<400> 49

Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser

1 5 10

<---

Claims (34)

1. Continuous polypeptide that binds to IL13 and binds to IL4, containing the extracellular domain of the IL13R polypeptide and extracellular domain of the IL4R polypeptide, wherein the extracellular domain of the IL13R polypeptide is at least 98% identical to the amino acid sequence of SEQ ID NO: 22, and the extracellular domain of the IL4R polypeptide is at least 98% identical to the amino acid sequence of SEQ ID NO: 23. 2. Continuous polypeptide according to claim 1, having formula (I) IL13R-L1-IL4R-L2-FP or formula (II) IL4R-L1-IL13R-L2-FP, where: a) IL13R is the extracellular domain of the IL13R polypeptide, b) IL4R is the extracellular domain of the IL4R polypeptide, c) L1 is the first optional peptide linker, d) L2 is the second optional peptide linker, and e) FP is a merger partner. 3. A continuous polypeptide according to claim 1 or 2 that binds to IL13 from a domestic animal species with a dissociation constant (Kd) 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 at measurement by biolayer interferometry. 4. Continuous polypeptide according to any one of paragraphs. 1-3 binding to IL4 from a domestic animal species with a dissociation constant (Kd) 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. 5. Continuous polypeptide according to any one of paragraphs. 1-4 that reduces IL13 and/or IL4 signaling in a pet species. 6. Continuous polypeptide according to any one of paragraphs. 3-5, where the pet species is a member of the canine, feline, or equine family. 7. Continuous polypeptide according to any one of paragraphs. 2-6, where each of L1 and L2, if present, independently contains an amino acid sequence selected from G, GG, GGG, S, SS, SSS, GS, GSGS (SEQ ID NO: 38), GSGSGS (SEQ ID NO : 39), GGS, GGSGGS (SEQ ID NO: 40), GGSGGSGGS (SEQ ID NO: 41), GGGS (SEQ ID NO: 42), GGGSGGGS (SEQ ID NO: 43), GGGSGGGSGGGS (SEQ ID NO: 44) , GSS, GSSGSS (SEQ ID NO: 45), GSSGSSGSS (SEQ ID NO: 46), GGSS (SEQ ID NO: 47), GGSSGGSS (SEQ ID NO: 48), and GGSSGGSSGGSS (SEQ ID NO: 49). 8. Continuous polypeptide according to any one of paragraphs. 2-7 wherein the fusion partner is selected from Fc, albumin and an albumin binding moiety. 9. The continuous polypeptide of claim 8, wherein Fc is (a) a heavy chain constant region of a canine family member selected from the constant region of IgG-A, IgG-B, IgG-C, and IgG-D; (b) a feline heavy chain constant region selected from an IgG1, IgG2a, and IgG2b constant region; or (c) an equine heavy chain constant region selected from an IgG1, IgG2, IgG3, IgG4, IgG5, IgG6 and IgG7 constant region. 10. Continuous polypeptide according to any one of paragraphs. 1-9 containing a 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: 20 and SEQ ID NO: 21 . 11. Selected nucleic acid encoding a continuous polypeptide according to any one of paragraphs. 1-10. 12. A host cell for obtaining a continuous polypeptide containing a nucleic acid according to claim 11. 13. A method for producing a continuous polypeptide, comprising culturing the host cell according to claim 12 and isolating the continuous polypeptide. 14. Pharmaceutical composition for the treatment of a member of the canine, feline or equine family having an pruritic or allergic condition such as atopic dermatitis, pruritus, asthma, psoriasis, scleroderma or eczema, comprising a therapeutically effective amount of a continuous polypeptide according to any one of paragraphs. 1-10 and a pharmaceutically acceptable carrier. 15. A method of treating a canine family member having an pruritic or allergic condition, such as atopic dermatitis, pruritus, asthma, psoriasis, scleroderma, or eczema, comprising administering to the canine a therapeutically effective amount of a continuous polypeptide according to any one of claims. 1-10 or a pharmaceutical composition according to claim 14. 16. The method of claim 15 wherein the continuous polypeptide or pharmaceutical composition is administered parenterally. 17. The method of claim 15 or 16, wherein the continuous polypeptide or pharmaceutical composition is administered by an intramuscular route, an intraperitoneal route, an intraspinal route, a subcutaneous route, an intra-arterial route, an intra-articular route, an intrathecal route, or an inhalation route. 18. The method according to any one of paragraphs. 15-17, wherein the method further comprises administering a Jak inhibitor, a PI3K inhibitor, an AKT inhibitor, or a MAPK inhibitor. 19. The method according to any one of paragraphs. 15-18, wherein the method further comprises administering one or more antibodies selected from anti-IL17 antibody, anti-IL31 antibody, anti-TNFα antibody, anti-CD20 antibody, anti-CD19 antibody, anti-CD25 antibody, anti-IL4 antibody, anti-IL13 antibody, anti- IL23, anti-IgE, anti-CD11α, anti-IL6R, anti-α4-integrin, anti-IL12, anti-IL1β, and anti-BlyS. 20. A method for reducing IL4 signaling activity in a cell, comprising exposing the cell to a continuous polypeptide according to any one of paragraphs. 1-10 or a pharmaceutical composition according to claim 14, under conditions allowing the binding of a continuous polypeptide to IL4, thereby (a) reducing the binding of IL/4 to the native IL13 receptor and/or the native IL-4 receptor and reducing IL4-mediated transmission signals. 21. The method of claim 20, wherein the cell is exposed to the continuous polypeptide or pharmaceutical composition ex vivo . 22. The method of claim 20, wherein the cell is exposed to the continuous polypeptide or pharmaceutical composition in vivo . 23. The method according to any one of paragraphs. 20-22, wherein the cell is a canine cell, a feline cell, or an equine cell. 24. A method for detecting IL13 in a biological sample obtained from a member of the canine family, comprising bringing the sample into contact with a continuous polypeptide according to any one of paragraphs. 1-10 or the pharmaceutical composition of claim 14 under conditions that allow the contiguous polypeptide to bind to IL13 and detect whether a complex is formed between the contiguous polypeptide and IL13 in the sample. 25. A method for detecting IL4 in a biological sample obtained from a member of the canine family, comprising bringing the sample into contact with a continuous polypeptide according to any one of paragraphs. 1-10 or the pharmaceutical composition of claim 14 under conditions that allow the contiguous polypeptide to bind to IL4 and detect whether a complex is formed between the contiguous polypeptide and IL4 in the sample.

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