CN115515635A - 兽用抗il4受体抗体 - Google Patents
兽用抗il4受体抗体 Download PDFInfo
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- CN115515635A CN115515635A CN202180034148.5A CN202180034148A CN115515635A CN 115515635 A CN115515635 A CN 115515635A CN 202180034148 A CN202180034148 A CN 202180034148A CN 115515635 A CN115515635 A CN 115515635A
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Abstract
提供了涉及与犬类IL4R结合的抗IL4R抗体的各种实施方案。在各种实施方案中，此类抗IL4R抗体可以用于治疗伴生动物如犬类和猫类的IIL4/IL13诱导的病症如特应性皮炎、过敏性皮炎、瘙痒、哮喘、银屑病、硬皮病和湿疹的方法中。还提供了涉及用于制备抗体或双特异性抗体的伴生动物物种的变体IgG Fc多肽和变体轻链恒定区的各种实施方案。
Description
本申请要求2020年3月18日提交的美国临时申请号62/991,568的权益，将所述临时申请出于任何目的通过引用以其整体并入本文。
序列表
本申请是连同电子格式的序列表一起提交的。序列表以2021年3月17日创建的、大小为774KB的名为01157-0032-00PCT_ST25.txt”的文件提供。将在电子格式的序列表中的信息通过引用以其整体并入本文。
技术领域
本公开文本涉及分离的抗IL4受体(IL4R)抗体，其例如与犬类或猫类IL4R结合并且减少与IL4或IL13结合；以及使用所述抗体例如治疗例如伴生动物(如犬类和猫类)的IL4诱导和/或IL13诱导的病症或降低细胞的IL4或IL13信号传导功能的方法。
背景技术
白细胞介素4(IL4)是一种细胞因子，其诱导幼稚T辅助细胞分化为Th2细胞。IL4还可以刺激激活的B细胞和T细胞增殖，并且诱导B细胞类别转换为IgE。IL13对免疫细胞的作用与IL4相似。这两种细胞因子都与过敏相关。
IL4受体也称为IL4Rα或IL4R。IL4R可以与普通γ链受体配对，并且特异性结合IL4。IL4R也可以与IL13Ra1配对，并且它们可以一起结合IL4或IL13。因此，阻断IL4R上的结合位点可以潜在地减少IL4和/或IL13的结合，并且降低这两种细胞因子的信号传导作用。
伴生动物(如猫、狗和马)患有许多类似于人类皮肤病的皮肤病，包括特应性皮炎和过敏性病症。因此，仍然需要可以特异性地用于阻断伴生动物IL4/IL13以治疗IL4诱导和/或IL13诱导的病症并且降低IL4/IL13信号传导的方法和化合物。
发明内容
实施方案1.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含LX10FMGSENX11T(SEQ ID NO:85)的氨基酸序列的表位结合，其中X10是D或N并且X11是H或R，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案2.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含RLSYQLX10FMGSENX11TCVPEN(SEQ ID NO:86)的氨基酸序列的表位结合，其中X10是D或N并且X11是H或R，其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案3.根据实施方案2所述的分离的抗体，其中所述抗体与包含LX10FMGSENX11T(SEQ ID NO:85)的氨基酸序列的表位结合，其中X10是D或N，并且X11是H或R。
实施方案4.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:88或SEQ ID NO:91的氨基酸序列的表位结合。
实施方案5.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:89或SEQ ID NO:92的氨基酸序列的表位结合。
实施方案6.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体与包含SMX12X13DDX14VEADVYQLX15LWAGX16Q(SEQ ID NO:87)的氨基酸序列的表位结合，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T。
实施方案7.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SMX12X13DDX14VEADVYQLX15LWAGX16Q(SEQ ID NO:87)的氨基酸序列的表位结合，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案8.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:90或SEQ ID NO:93的氨基酸序列的表位结合。
实施方案9.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
实施方案10.根据前述实施方案中任一项所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
实施方案11.根据前述实施方案中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
实施方案12.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体与单克隆克隆B或克隆I抗体竞争结合至犬类IL4R或猫类IL4R。
实施方案13.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
实施方案14.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
实施方案15.根据前述实施方案中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
实施方案16.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含重链，所述重链包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案17.根据前述实施方案中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F。
实施方案18.根据前述实施方案中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:7、SEQ ID NO:29或SEQ ID NO:358的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271、SEQ ID NO:359或SEQ ID NO:272的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:9或SEQ ID NO:31的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案19.根据前述实施方案中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1，其包含SEQ ID NO:7、SEQ ID NO:29或SEQ ID NO:358的氨基酸序列；
b)CDR-H2，其包含SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271、SEQ ID NO:359或SEQ ID NO:272的氨基酸序列；和
c)CDR-H3，其包含SEQ ID NO:9或SEQ ID NO:31的氨基酸序列。
实施方案20.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含轻链，所述轻链包含：
a)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
b)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
c)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案21.根据前述实施方案中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
b)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
c)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L。
实施方案22.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F；
d)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
e)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
f)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案23.根据前述实施方案中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:14、SEQ ID NO:36或SEQ ID NO:360的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:15、SEQ ID NO:37、SEQ ID NO:361或SEQ ID NO:362的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:16或SEQ ID NO:38的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案24.根据前述实施方案中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1，其包含SEQ ID NO:14、SEQ ID NO:36或SEQ ID NO:360的氨基酸序列；
b)CDR-L2，其包含SEQ ID NO:15、SEQ ID NO:37、SEQ ID NO:361或SEQ ID NO:362的氨基酸序列；和
c)CDR-L3，其包含SEQ ID NO:16或SEQ ID NO:38的氨基酸序列。
实施方案25.根据实施方案16至24中任一项所述的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:10或SEQ ID NO:32的可变区重链框架1(HC-FR1)序列；(b)SEQ IDNO:11或SEQ ID NO:33的HC-FR2序列；(c)SEQ ID NO:12、SEQ ID NO:270、SEQ ID NO:34、SEQ ID NO:273的HC-FR3序列；(d)SEQ ID NO:13或SEQ ID NO:35的HC-FR4序列；(e)SEQ IDNO:17或SEQ ID NO:39的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:18或SEQ ID NO:40的LC-FR2序列；(g)SEQ ID NO:19或SEQ ID NO:41的LC-FR3序列；或(h)SEQ ID NO:20或SEQ ID NO:42的LC-FR4序列。
实施方案26.根据前述实施方案中任一项所述的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:21或SEQ ID NO:43的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:22或SEQ ID NO:44的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ IDNO:64、SEQ ID NO:274或SEQ ID NO:363的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:61、SEQ ID NO:62、SEQID NO:65、SEQ ID NO:66、SEQ ID NO:275或SEQ ID NO:364的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
c.(i)可变重链序列，其与SEQ ID NO:67或SEQ ID NO:69的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:68或SEQ ID NO:70的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
实施方案27.根据前述实施方案中任一项所述的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:21、SEQ ID NO:43、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274、SEQ ID NO:363、SEQ ID NO:67或SEQ IDNO:69的氨基酸序列。
实施方案28.根据前述实施方案中任一项所述的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:22、SEQ ID NO:44、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:275、SEQ ID NO:364、SEQ ID NO:68或SEQ IDNO:70的氨基酸序列。
实施方案29.根据前述实施方案中任一项所述的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:21或SEQ ID NO:43的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:22或SEQ ID NO:44的氨基酸序列；
b)可变重链序列，所述可变重链序列包含SEQ ID NO:59、SEQ ID NO:60、SEQ IDNO:63、SEQ ID NO:64、SEQ ID NO:274、SEQ ID NO:363的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ IDNO:275、SEQ ID NO:364的氨基酸序列；或
c)可变重链序列，所述可变重链序列包含SEQ ID NO:67、SEQ ID NO:69、SEQ IDNO:365或SEQ ID NO:366的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ IDNO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ ID NO:369的氨基酸序列。
实施方案30.一种分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:21或SEQ ID NO:43的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:22或SEQ ID NO:44的氨基酸序列；
b)可变重链序列，所述可变重链序列包含SEQ ID NO:59、SEQ ID NO:60、SEQ IDNO:63、SEQ ID NO:64、SEQ ID NO:274或SEQ ID NO:363的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ IDNO:275或SEQ ID NO:364的氨基酸序列；或
c)可变重链序列，所述可变重链序列包含SEQ ID NO:67、SEQ ID NO:69、SEQ IDNO:365或SEQ ID NO:366的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ IDNO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ ID NO:369的氨基酸序列，并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案31.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SEQ ID NO:354的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案32.根据实施方案31所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
实施方案33.根据实施方案31或实施方案32所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
实施方案34.根据实施方案31至33中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
实施方案35.根据实施方案31至34中任一项所述的分离的抗体，其中所述抗体与单克隆M3抗体竞争结合至犬类IL4R或猫类IL4R。
实施方案36.根据实施方案31至35中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
实施方案37.根据实施方案31至36中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
实施方案38.根据实施方案31至37中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
实施方案39.根据实施方案31至38中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:278的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:279的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:280的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案40.根据实施方案31至39中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:285的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:286的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:287的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案41.根据实施方案31至40中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:281的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:282的HC-FR2序列；(c)SEQ ID NO:283的HC-FR3序列；(d)SEQ ID NO:284的HC-FR4序列；(e)SEQID NO:288的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:289的LC-FR2序列；(g)SEQ IDNO:290的LC-FR3序列；或(h)SEQ ID NO:291的LC-FR4序列。
实施方案42.根据实施方案31至41中任一项所述的分离的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:292的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:293的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:342或SEQ ID NO:343的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQID NO:344的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
实施方案43.根据实施方案31至42中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:292、SEQ ID NO:342或SEQ ID NO:343的氨基酸序列。
实施方案44.根据实施方案31至43中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:293或SEQ ID NO:344的氨基酸序列。
实施方案45.根据实施方案31至44中任一项所述的分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:292的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:293的氨基酸序列；和/或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:342或SEQ ID NO:343的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:344的氨基酸序列。
实施方案46.一种分离的抗体，其包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:292的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:293的氨基酸序列；或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:342或SEQ ID NO:343的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:344的氨基酸序列；
并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案47.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SEQ ID NO:355的氨基酸序列的表位和/或包含SEQ ID NO:356的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案48.根据实施方案47所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
实施方案49.根据实施方案47或实施方案48所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
实施方案50.根据实施方案47至49中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
实施方案51.根据实施方案47至50中任一项所述的分离的抗体，其中所述抗体与单克隆M8抗体竞争结合至犬类IL4R或猫类IL4R。
实施方案52.根据实施方案47至51中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
实施方案53.根据实施方案47至52中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
实施方案54.根据实施方案47至53中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
实施方案55.根据实施方案47至54中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:310的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:311的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:312的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案56.根据实施方案47至55中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:317的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:318的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:319的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案57.根据实施方案47至56中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:313的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:314的HC-FR2序列；(c)SEQ ID NO:315的HC-FR3序列；(d)SEQ ID NO:316的HC-FR4序列；(e)SEQID NO:320的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:321的LC-FR2序列；(g)SEQ IDNO:322的LC-FR3序列；或(h)SEQ ID NO:323的LC-FR4序列。
实施方案58.根据实施方案47至57中任一项所述的分离的抗体，其中所述抗体包含：
(a)可变重链序列，其与SEQ ID NO:324的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
(b)可变轻链序列，其与SEQ ID NO:325的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或
(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
实施方案59.根据实施方案47至58中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:324的氨基酸序列。
实施方案60.根据实施方案47至59中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列。
实施方案61.根据实施方案47至60中任一项所述的分离的抗体，其中所述抗体包含：可变重链序列，所述可变重链序列包含SEQ ID NO:324的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列。
实施方案62.一种分离的抗体，其包含：可变重链序列，所述可变重链序列包含SEQID NO:324的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案63.一种与犬类IL4R结合的分离的抗体，其中所述抗体与包含SEQ IDNO:357的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案64.根据实施方案63所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
实施方案65.根据实施方案63或实施方案64所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R结合。
实施方案66.根据实施方案63至65中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类IL4多肽和/或犬类IL13多肽与犬类IL4R的结合。
实施方案67.根据实施方案63至66中任一项所述的分离的抗体，其中所述抗体与单克隆M9抗体竞争结合至犬类IL4R。
实施方案68.根据实施方案63至67中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
实施方案69.根据实施方案63至68中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
实施方案70.根据实施方案63至69中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
实施方案71.根据实施方案63至70中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:326或SEQ ID NO:407的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:327的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:328的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案72.根据实施方案63至71中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:333的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:334的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:335的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案73.根据实施方案63至72中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:329的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:330的HC-FR2序列；(c)SEQ ID NO:331的HC-FR3序列；(d)SEQ ID NO:332的HC-FR4序列；(e)SEQID NO:336的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:337的LC-FR2序列；(g)SEQ IDNO:338的LC-FR3序列；或(h)SEQ ID NO:339的LC-FR4序列。
实施方案74.根据实施方案63至73中任一项所述的分离的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:340的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:341的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:345或SEQ ID NO:346的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQID NO:347或SEQ ID NO:408的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
实施方案75.根据实施方案63至74中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:340、SEQ ID NO:345或SEQ ID NO:346的氨基酸序列。
实施方案76.根据实施方案63至75中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:341、SEQ ID NO:347或SEQ ID NO:408的氨基酸序列。
实施方案77.根据实施方案63至76中任一项所述的分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:340的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:341的氨基酸序列；和/或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:345或SEQ ID NO:346的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:347或SEQ ID NO:408的氨基酸序列。
实施方案78.一种分离的抗体，其包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:340的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:341的氨基酸序列；或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:345或SEQ ID NO:346的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:347或SEQ ID NO:408的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案79.一种与犬类IL4R结合的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:294的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:295的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:296的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案80.一种与犬类IL4R结合的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:301的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:302的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:303的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案81.根据实施方案79所述的分离的抗体，其包含轻链，所述轻链包含：
a)DR-L1序列，其与SEQ ID NO:301的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:302的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:303的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
实施方案82.根据实施方案79至81中任一项所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10- 9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
实施方案83.根据实施方案79至82中任一项所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R结合。
实施方案84.根据实施方案79至83中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类IL4多肽和/或犬类IL13多肽与犬类IL4R的结合。
实施方案85.根据实施方案79至84中任一项所述的分离的抗体，其中所述抗体与单克隆M5抗体竞争结合至犬类IL4R。
实施方案86.根据实施方案79至85中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
实施方案87.根据实施方案79至86中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
实施方案88.根据实施方案79至87中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
实施方案89.根据实施方案79至88中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:297的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:298的HC-FR2序列；(c)SEQ ID NO:299的HC-FR3序列；(d)SEQ ID NO:300的HC-FR4序列；(e)SEQID NO:304的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:305的LC-FR2序列；(g)SEQ IDNO:306的LC-FR3序列；或(h)SEQ ID NO:307的LC-FR4序列。
实施方案90.根据实施方案79至89中任一项所述的分离的抗体，其中所述抗体包含：
(a)可变重链序列，其与SEQ ID NO:308的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
(b)可变轻链序列，其与SEQ ID NO:309的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或
(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
实施方案91.根据实施方案79至90中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:308的氨基酸序列。
实施方案92.根据实施方案79至91中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列。
实施方案93.根据实施方案79至92中任一项所述的分离的抗体，其中所述抗体包含：可变重链序列，所述可变重链序列包含SEQ ID NO:308的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列。
实施方案94.一种分离的抗体，其包含：可变重链序列，所述可变重链序列包含SEQID NO:308的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案95.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽是变体犬类IgG-A Fc多肽；变体犬类IgG-B Fc多肽；变体IgG-C Fc多肽；变体IgG-D Fc多肽；变体猫类IgG1a Fc多肽；变体猫类IgG1b Fc多肽；或变体猫类IgG2 Fc多肽。
实施方案96.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽相对于野生型IgG Fc多肽包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽相对于所述野生型IgG Fc多肽具有增加的对蛋白质A的结合亲和力；相对于所述野生型IgG Fc多肽具有降低的对C1q的结合亲和力；和/或相对于所述野生型IgG Fc多肽具有降低的对CD16的结合亲和力。
实施方案97.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽相对于野生型IgG Fc多肽包含对铰链区的至少一个氨基酸修饰，其中如在还原和/或非还原条件下通过SDS-PAGE分析所确定的，所述变体IgG Fc多肽相对于所述野生型IgG Fc多肽具有增加的重组产生和/或增加的铰链二硫化物形成。
实施方案98.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:162的位置21、23、25、80、205和/或207的位置处的至少一个氨基酸取代；
b)在对应于SEQ ID NO:163的位置5、38、39、94、97和/或98的位置处的至少一个氨基酸取代；
c)在对应于SEQ ID NO:165的位置5、21、23、24、38、39、93、97和/或98的位置处的至少一个氨基酸取代；
d)在对应于SEQ ID NO:167的位置21、23、25、80和/或207的位置处的至少一个氨基酸取代；
e)在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198的位置处的至少一个氨基酸取代；和/或
f)在对应于SEQ ID NO:207的位置14和/或16的位置处的至少一个氨基酸取代。
实施方案99.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:162的位置21、23、25、80、205和/或207处的至少一个氨基酸取代；
b)在SEQ ID NO:163的位置5、38、39、94、97和/或98处的至少一个氨基酸取代；
c)在SEQ ID NO:164的位置5、21、23、24、38、39、93、97和/或98处的至少一个氨基酸取代；
d)在SEQ ID NO:165的位置21、23、25、80和/或207处的至少一个氨基酸取代；
e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198处的至少一个氨基酸取代；和/或
f)在SEQ ID NO:207的位置14和/或16处的至少一个氨基酸取代。
实施方案100.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:162的位置21的位置处的苏氨酸、在对应于SEQ ID NO:162的位置23的位置处的亮氨酸、在对应于SEQ ID NO:162的位置25的位置处的丙氨酸、在对应于SEQ ID NO:162的位置80的位置处的甘氨酸、在对应于SEQ ID NO:162的位置205的位置处的丙氨酸、和/或在对应于SEQ ID NO:162的位置207的位置处的组氨酸；
b)在对应于SEQ ID NO:163的位置5的位置处的脯氨酸、在对应于SEQ ID NO:163的位置38的位置处的甘氨酸、在对应于SEQ ID NO:163的位置39的位置处的精氨酸、在对应于SEQ ID NO:163的位置93的位置处的精氨酸、在对应于SEQ ID NO:163的位置97的位置处的异亮氨酸、和/或在对应于SEQ ID NO:163的位置98的位置处的甘氨酸；
c)在对应于SEQ ID NO:164的位置5的位置处的脯氨酸、在对应于SEQ ID NO:164的位置21的位置处的苏氨酸、在对应于SEQ ID NO:164的位置23的位置处的亮氨酸、在对应于SEQ ID NO:164的位置24的位置处的异亮氨酸、在对应于SEQ ID NO:164的位置38的位置处的甘氨酸、在对应于SEQ ID NO:164的位置39的位置处的精氨酸、在对应于SEQ ID NO:164的位置93的位置处的精氨酸、在对应于SEQ ID NO:164的位置97的位置处的异亮氨酸、和/或在对应于SEQ ID NO:164的位置98的位置处的甘氨酸；
d)在对应于SEQ ID NO:165的位置21的位置处的苏氨酸、在对应于SEQ ID NO:165的位置23的位置处的亮氨酸、在对应于SEQ ID NO:165的位置25的位置处的丙氨酸、在对应于SEQ ID NO:165的位置80的位置处的甘氨酸、和/或在对应于SEQ ID NO:165的位置207的位置处的组氨酸；
e)在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16的位置处的脯氨酸和/或在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置198的位置处的丙氨酸；和/或
f)在对应于SEQ ID NO:207的位置14的位置处的半胱氨酸和/或在对应于SEQ IDNO:207的位置16的位置处的脯氨酸。
实施方案101.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:162的位置21处的苏氨酸、在SEQ ID NO:162的位置23处的亮氨酸、在SEQ ID NO:162的位置25处的丙氨酸、在SEQ ID NO:162的位置80处的甘氨酸、在SEQID NO:162的位置205处的丙氨酸、和/或在SEQ ID NO:162的位置207处的组氨酸；
b)在SEQ ID NO:163的位置5处的脯氨酸、在SEQ ID NO:163的位置38处的甘氨酸、在SEQ ID NO:163的位置39处的精氨酸、在SEQ ID NO:163的位置93处的精氨酸、在SEQ IDNO:163的位置97处的异亮氨酸、和/或在SEQ ID NO:163的位置98处的甘氨酸；
c)在SEQ ID NO:164的位置5处的脯氨酸、在SEQ ID NO:164的位置21处的苏氨酸、在SEQ ID NO:164的位置23处的亮氨酸、在SEQ ID NO:164的位置24处的异亮氨酸、在SEQID NO:164的位置38处的甘氨酸、在SEQ ID NO:164的位置39处的精氨酸、在SEQ ID NO:164的位置93处的精氨酸、在SEQ ID NO:164的位置97处的异亮氨酸、和/或在SEQ ID NO:164的位置98处的甘氨酸；
d)在SEQ ID NO:165的位置21处的苏氨酸、在SEQ ID NO:165的位置23处的亮氨酸、在SEQ ID NO:165的位置25处的丙氨酸、在SEQ ID NO:165的位置80处的甘氨酸、和/或在SEQ ID NO:165的位置207处的组氨酸；
e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16处的脯氨酸和/或在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置198处的丙氨酸；和/或
f)在SEQ ID NO:207的位置14处的半胱氨酸和/或在SEQ ID NO:207的位置16处的脯氨酸。
实施方案102.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24和/或位置30的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:238的位置24和/或位置29的位置处的至少一个氨基酸取代。实施方案103.一种抗体，所述抗体包含变体IgG Fc多肽，所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24和/或位置30的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:238的位置24和/或位置29的位置处的至少一个氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案104.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ IDNO:237的位置24和/或位置30处的至少一个氨基酸取代；或
b)在SEQ ID NO:238的位置24和/或位置29处的至少一个氨基酸取代。
实施方案105.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24的位置处的亮氨酸和/或在对应于位置30的位置处的天冬酰胺；或
b)在对应于SEQ ID NO:238的位置24的位置处的亮氨酸和/或在对应于位置29的位置处的天冬酰胺。
实施方案106.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ IDNO:237的位置24处的亮氨酸和/或位置30处的天冬酰胺；或
b)在SEQ ID NO:238的位置24处的亮氨酸和/或位置29处的天冬酰胺。
实施方案107.根据前述实施方案中任一项所述的抗体，其中所述抗体包含野生型或变体犬类或猫类轻链恒定区。
实施方案108.根据前述实施方案中任一项所述的抗体，其中所述抗体包含野生型或变体犬类或猫类轻链κ恒定区。
实施方案109.根据实施方案107或实施方案108所述的抗体，其中所述变体轻链恒定区相对于野生型犬类或猫类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11和/或位置22的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:241的位置11和/或位置22的位置处的至少一个氨基酸取代。
实施方案110.一种包含变体轻链恒定区的抗体，所述变体轻链恒定区相对于野生型犬类或猫类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11和/或位置22的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:241的位置11和/或位置22的位置处的至少一个氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案111.根据实施方案107至110中任一项所述的抗体，其中所述变体轻链恒定区相对于野生型猫类或犬类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11的位置处的丙氨酸和/或在对应于其位置22的位置处的精氨酸；或
b)在对应于SEQ ID NO:241的位置11的位置处的丙氨酸和/或在对应于其位置22的位置处的精氨酸。
实施方案112.根据实施方案107至111中任一项所述的抗体，其中所述变体轻链恒定区相对于野生型猫类或犬类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在SEQ ID NO:235的位置11处的丙氨酸和/或其位置22处的精氨酸；或
b)在SEQ ID NO:241的位置11处的丙氨酸和/或其位置22处的精氨酸。
实施方案113.根据实施方案107至112中任一项所述的抗体，其中所述轻链恒定区包含SEQ ID NO:235、236、241和/或242的氨基酸序列。
实施方案114.根据前述实施方案中任一项所述的抗体，其中所述抗体是双特异性抗体。
实施方案115.根据前述实施方案中任一项所述的抗体，其中所述抗体是双特异性抗体，其包含：
i)第一变体犬类IgG Fc多肽，其相对于第一野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体犬类IgG Fc多肽，其相对于第二野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ IDNO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的氨基酸取代，和/或
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138和/或位置140、SEQ ID NO:163的位置137和/或位置139、SEQ ID NO:165的位置137和/或位置139或SEQ ID NO:167的位置138和/或位置140的位置处的氨基酸取代；或
ii)第一变体猫类IgG Fc多肽，其相对于第一野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体猫类IgG Fc多肽，其相对于第二野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的氨基酸取代，和/或
b)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156的位置处的氨基酸取代。
实施方案116.一种抗体或双特异性抗体，其包含：
i)第一变体犬类IgG Fc多肽，其相对于第一野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体犬类IgG Fc多肽，其相对于第二野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ IDNO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的氨基酸取代，和/或
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138和/或位置140、SEQ ID NO:163的位置137和/或位置139、SEQ ID NO:165的位置137和/或位置139或SEQ ID NO:167的位置138和/或位置140的位置处的氨基酸取代；
ii)第一变体猫类IgG Fc多肽，其相对于第一野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体猫类IgG Fc多肽，其相对于第二野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的氨基酸取代，和/或
b)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156的位置处的氨基酸取代；或
iii)第一变体马类IgG Fc多肽，其相对于第一野生型马类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体马类IgG Fc多肽，其相对于第二野生型马类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的氨基酸取代，和/或
b)所述第二变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130和/或位置132的位置处的氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
实施方案117.根据实施方案115或实施方案116所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ IDNO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的色氨酸；
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸、在对应于SEQ ID NO:163的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸、在对应于SEQ ID NO:165的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸、或在对应于SEQ IDNO:167的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸；
c)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的色氨酸；
d)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的丝氨酸和/或在对应于位置156的位置处的丙氨酸；
e)所述第一变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的色氨酸；和/或
f)所述第二变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的丝氨酸和/或在对应于位置132的位置处的丙氨酸。
实施方案118.根据实施方案115至117中任一项所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138处的氨基酸取代；
b)所述第二变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138和/或位置140处的氨基酸取代、在SEQ ID NO:163的位置137和/或位置139处的氨基酸取代、在SEQ IDNO:165的位置137和/或位置139处的氨基酸取代，或在SEQ ID NO:167的位置138和/或位置140处的氨基酸取代；
c)所述第一变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ IDNO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的氨基酸取代；
d)所述第二变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ IDNO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156处的氨基酸取代；
e)所述第一变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ IDNO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的氨基酸取代；和/或
f)所述第二变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ IDNO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130和/或位置132处的氨基酸取代。
实施方案119.根据实施方案115至118中任一项所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138处的色氨酸；
b)所述第二变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138处的丝氨酸和/或位置140处的丙氨酸、在SEQ ID NO:163的位置137处的丝氨酸和/或位置139处的丙氨酸、在SEQ ID NO:165的位置137处的丝氨酸和/或位置139处的丙氨酸、或在SEQ ID NO:167的位置138处的丝氨酸和/或位置140处的丙氨酸；
c)所述第一变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ IDNO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的色氨酸；
d)所述第二变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ IDNO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的丝氨酸和/或位置156处的丙氨酸；
e)所述第一变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ IDNO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的色氨酸；和/或
f)所述第二变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ IDNO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的丝氨酸和/或位置132处的丙氨酸。
实施方案120.根据实施方案115至119中任一项所述的抗体，其中所述第一野生型IgG Fc多肽和所述第二野生型IgG Fc多肽来自相同IgG亚型。
实施方案121.根据实施方案115至117中任一项所述的抗体，其中所述第一野生型IgG Fc多肽和所述第二野生型IgG Fc多肽来自不同IgG亚型。
实施方案122.根据前述实施方案中任一项所述的抗体，其中所述变体Fc多肽以比所述野生型IgG Fc多肽更大的亲和力与FcRn结合，所述亲和力是通过生物膜层干涉法、表面等离子体共振或任何蛋白质-蛋白质相互作用工具在约5.0至约6.5范围内的pH下，如在约5.0的pH、约5.2的pH、约5.5的pH、约6.0的pH、约6.2的pH或约6.5的pH下测量的。
实施方案123.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10- 12M或小于1x10-12M的解离常数(Kd)与FcRn结合，所述解离常数是通过生物膜层干涉法、表面等离子体共振或任何蛋白质-蛋白质相互作用工具在约5.0至约6.5范围内的pH下，如在约5.0的pH、约5.5的pH、约6.0的pH或约6.5的pH下测量的。
实施方案124.根据前述实施方案中任一项所述的抗体，其中所述抗体相对于具有野生型IgG Fc多肽的抗体具有增加的血清半衰期。
实施方案125.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:163的位置23的位置处的酪氨酸或苯丙氨酸；
b)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸；
c)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸和在对应于其位置207的位置处的组氨酸；
d)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸和在对应于其位置207的位置处的酪氨酸；或
e)在对应于SEQ ID NO:163的位置207的位置处的酪氨酸。
实施方案126.根据前述实施方案中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:163的位置23处的酪氨酸或苯丙氨酸；
b)在SEQ ID NO:163的位置82处的酪氨酸；
c)在SEQ ID NO:163的位置82处的酪氨酸和位置207处的组氨酸；
d)在SEQ ID NO:163的位置82处的酪氨酸和位置207处的酪氨酸，或
e)在SEQ ID NO:163的位置207处的酪氨酸。
实施方案127.根据前述实施方案中任一项所述的抗体，其中所述抗体包含IgG Fc多肽，所述IgG Fc多肽包含SEQ ID NO:162、163、164、165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、228、229、230、231、232、233、234、237、238、239、240、254、255、256、257、258、259、260、261、262、263、264、265、266、267、381、382、383、384、385、386、387、388、389、390、391、392、393和/或394的氨基酸序列。
实施方案128.根据前述实施方案中任一项所述的抗体，其中所述抗体包含：
a)(i)SEQ ID NO:25或SEQ ID NO:47的重链氨基酸序列；(ii)SEQ ID NO:26或SEQID NO:48的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
b)(i)SEQ ID NO:51或SEQ ID NO:55的重链氨基酸序列；(ii)SEQ ID NO:52或SEQID NO:56的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
c)(i)SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:276、SEQ ID NO:370、SEQ ID NO:395、SEQ ID NO:396、SEQ ID NO:397、SEQ ID NO:398、SEQID NO:399、SEQ ID NO:400、SEQ ID NO:401、SEQ ID NO:402、SEQ ID NO:403、SEQ ID NO:404、SEQ ID NO:405、SEQ ID NO:406、SEQ ID NO:410、SEQ ID NO:411、SEQ ID NO:412、SEQID NO:413、SEQ ID NO:414、SEQ ID NO:415、SEQ ID NO:416、SEQ ID NO:417、SEQ ID NO:418、SEQ ID NO:419、SEQ ID NO:420、或SEQ ID NO:421的重链氨基酸序列；(ii)SEQ IDNO:73、SEQ ID NO:74、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:277、SEQ ID NO:371的轻链氨基酸序列；或者(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
d)(i)SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:82、SEQ ID NO:372、SEQ ID NO:373、SEQ ID NO:83、SEQ ID NO:374、或SEQ ID NO:375的重链氨基酸序列；(ii)SEQ ID NO:81、SEQ ID NO:84、SEQ ID NO:376、SEQ ID NO:377、SEQ ID NO:378的轻链氨基酸序列；或者(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
e)(i)SEQ ID NO:243的重链氨基酸序列；(ii)SEQ ID NO:244的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
f)(i)SEQ ID NO:348或SEQ ID NO:349的重链氨基酸序列；(ii)SEQ ID NO:350的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链；或
g)(i)SEQ ID NO:351或SEQ ID NO:352的重链氨基酸序列；(ii)SEQ ID NO:253的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列。
实施方案129.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含SEQ ID NO:408的可变轻链氨基酸序列和/或SEQ ID NO:409的轻链氨基酸序列。
实施方案130.根据前述实施方案中任一项所述的抗体，其中所述抗体是双特异性抗体，其结合IL4R和选自以下的一种或多种抗原：IL17、IL31、TNFα、CD20、CD19、CD25、IL4、IL13、IL23、IgE、CD11α、IL6R、α4-整合素、IL12、IL1β或BlyS。
实施方案131.根据前述实施方案中任一项所述的抗体，其中所述抗体包含(i)SEQID NO:245的重链氨基酸序列；(ii)SEQ ID NO:246的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列。
实施方案132.根据前述实施方案中任一项所述的抗体，其中所述抗体是抗体片段，如Fv、scFv、Fab、Fab'、F(ab')2或Fab'-SH片段。
实施方案133.一种分离的核酸，其编码根据前述实施方案中任一项所述的抗体。
实施方案134.一种宿主细胞，其包含根据实施方案133所述的核酸。
实施方案135.一种宿主细胞，其表达根据实施方案1至134中任一项所述的抗体。
实施方案136.一种生产抗体的方法，其包括培养根据实施方案134或实施方案135所述的宿主细胞并且分离所述抗体。
实施方案137.一种药物组合物，其包含根据实施方案1至132中任一项所述的抗体和药学上可接受的载体。
实施方案138.一种治疗患有IL4/IL13诱导的病症的伴生动物物种的方法，所述方法包括向所述伴生动物物种施用治疗有效量的根据实施方案1至132中任一项所述的抗体或根据实施方案137所述的药物组合物。
实施方案139.根据实施方案138所述的方法，其中所述伴生动物物种是犬类、猫类或马类。
实施方案140.根据实施方案138或实施方案138所述的方法，其中所述IL4/IL13诱导的病症是瘙痒性病症或过敏性病症。
实施方案141.根据实施方案138至140中任一项所述的方法，其中所述IL4/IL13诱导的病症选自特应性皮炎、过敏性皮炎、瘙痒、哮喘、银屑病、硬皮病和湿疹。
实施方案142.根据实施方案138至141中任一项所述的方法，其中肠胃外施用所述抗体或所述药物组合物。
实施方案143.根据实施方案138至142中任一项所述的方法，其中所述抗体或所述药物组合物是通过肌内途径、腹膜内途径、脑脊髓内途径、皮下途径、动脉内途径、滑膜内途径、鞘内途径或吸入途径施用的。
实施方案144.根据实施方案138至143中任一项所述的方法，其中所述方法包括与所述抗体或所述药物组合物组合施用Jak抑制剂、PI3K抑制剂、ERK抑制剂。
实施方案145.根据实施方案138至144中任一项所述的方法，其中所述方法包括与所述抗体或所述药物组合物组合施用选自以下的一种或多种抗体：抗IL17抗体、抗IL31抗体、抗TNFα抗体、抗CD20抗体、抗CD19抗体、抗CD25抗体、抗IL4抗体、抗IL13抗体、抗IL23抗体、抗IgE抗体、抗CD11α抗体、抗IL6R抗体、抗α4-整合素抗体、抗IL12抗体、抗IL1β抗体和抗BlyS抗体。
实施方案146.一种降低细胞中IL4和/或IL13信号传导功能的方法，所述方法包括在允许根据实施方案1至132中任一项所述的抗体与细胞外IL4和/或IL13结合的条件下向所述细胞暴露所述抗体或根据实施方案137所述的药物组合物，从而降低IL4和/或IL13与IL4R的结合和/或降低所述细胞的IL4和/或IL13信号传导功能。
实施方案147.根据实施方案146所述的方法，其中将所述细胞离体暴露于所述抗体或所述药物组合物。
实施方案148.根据实施方案146所述的方法，其中将所述细胞在体内暴露于所述抗体或所述药物组合物。
实施方案149.根据实施方案146至148中任一项所述的方法，其中所述细胞是犬类细胞或猫类细胞。
实施方案150.根据实施方案146至149中任一项所述的方法，其中如通过STAT6磷酸化的减少所确定的，所述抗体降低所述细胞中的IL4和/或IL13信号传导功能。
实施方案151.根据实施方案146至150中任一项所述的方法，其中所述细胞是犬类DH82细胞。
实施方案152.一种用于检测来自伴生动物物种的样品中的IL4R的方法，所述方法包括在允许根据实施方案1至132中任一项所述的抗体与IL4R结合的条件下，使所述样品与所述抗体或根据实施方案137所述的药物组合物接触。
实施方案153.根据实施方案152所述的方法，其中所述样品是从犬类或猫类获得的生物样品。
附图说明
图1是克隆B和克隆I小鼠单克隆抗体克隆的重链和轻链氨基酸序列的比对。
图2A和图2B是用克隆B随后是克隆I(图2A)和用克隆I随后是克隆B的犬类IL4R竞争性表位结合分析的图。
图3A、3B、3C和3D是用克隆B或克隆I随后是犬类IL4(图3A)；用克隆B或克隆I随后是犬类IL13(图3B)；用犬类IL4随后是克隆B或克隆I(图3C)；以及用犬类IL13随后是克隆B或克隆I(图3D)的犬类IL4R竞争性结合分析的图。
图4A和4B是在非还原(-DTT，左图)和还原(+DTT，右图)条件下，用克隆I(图4A)和作为对照的抗人Fc抗体(图4B)探测的猫类、马类、鼠类、人和犬类IL4R ECD多肽的免疫印迹。
图5A是用于犬类IL4R表位作图分析的犬类/人IL4R ECD杂合多肽的图示。图5B和5C是用克隆I(图5B)和作为对照的抗人Fc抗体(图5C)探测的在5A中展示的犬类IL4R ECD、人IL4R ECD、各种犬类/人IL4R ECD杂合多肽的免疫印迹。
图6A是用于另外的犬类IL4R表位作图分析的犬类/人IL4R ECD杂合多肽的图示。图6B和6C是用克隆I(图6B)和作为对照的抗人Fc抗体(图6C)探测的在6A中展示的犬类IL4RECD、人IL4R ECD和各种犬类/人IL4R ECD杂合多肽的免疫印迹。
图7A鉴定了表1中进一步描述的犬类IL4R ECD丙氨酸突变多肽，其用于另外的犬类IL4R表位作图分析。图7B和7C是用克隆I(图7B)和作为对照的抗人Fc抗体(图7C)探测的人IL4R ECD、犬类IL4R ECD和各种犬类IL4R ECD丙氨酸突变多肽的免疫印迹。
图8是犬类IL4、犬类IL4R ECD和犬类IL13R ECD的复合物的三维模型。第一表位由箭头指示。
图9A是用于犬类IL4R表位作图分析的犬类/人IL4R ECD杂合多肽的图示。图9B总结了用M3、M8和M9抗体探测的犬类IL4R ECD、人IL4R ECD和各种犬类/人IL4R ECD杂合多肽的蛋白质印迹分析。
图10示出了各种浓度(12.5、25、50、100和200nM)的犬类FcRn与野生型犬类IgG-BFc多肽的结合的Biacore传感图。
图11示出了各种浓度(12.5、25、50、100和200nM)的犬类FcRn与变体犬类IgG-B Fc多肽L(23)Y的结合的Biacore传感图。
图12示出了各种浓度(12.5、25、50、100和200nM)的犬类FcRn与变体犬类IgG-B Fc多肽L(23)F的结合的Biacore传感图。
图13示出了各种浓度(12.5、25、50、100和200nM)的犬类FcRn与变体犬类IgG-B Fc多肽L(23)M的结合的Biacore传感图。
图14示出了各种浓度(12.5、25、50、100和200nM)的犬类FcRn与变体犬类IgG-B Fc多肽YTE的结合的Biacore传感图。
图15是与不具有Phe突变的嵌合变体犬类IgG-A Fc(C)和不具有Phe突变的IgG-DFc(D)相比，嵌合变体犬类IgG-A Fc F00抗体(A)和IgG-D Fc F00抗体(B)与犬类FcRn的结合的OctetRed传感图。
图16示出了嵌合变体犬类IgG-A F00抗体(“IgG-A F00”；n＝2)和不具有Phe突变的嵌合变体犬类IgG-A(“IgG-A”；n＝2)在以2mg/kg皮下施用于大鼠后的血清药代动力学特征。
图17是与具有野生型犬类IgG-B的嵌合抗体相比，具有变体犬类IgG-B Fc(0Y0、0YH、0YY或00Y)的嵌合抗体与犬类FcRn的结合的OctetRed传感图。
图18是示出了由如实施例27中所述的狗体内药代动力学研究产生的随时间归一化的抗体百分比的图表。
序列说明
表1提供了本文中提及的某些序列的列表。
具体实施方式
提供了结合犬类IL4R和/或猫类IL4R的抗体。还提供了能够形成结合IL4R的抗体的抗体重链和轻链。另外，提供了包含一个或多个特定互补决定区(CDR)的抗体、重链和轻链。提供了编码针对犬类或猫类IL4R的抗体的多核苷酸。还提供了产生或纯化针对犬类或猫类IL4R的抗体的方法。提供了使用针对犬类和/或猫类IL4/IL13的抗体的治疗方法。此类方法包括但不限于治疗伴生动物物种的IL4诱导的病症和/或IL13-诱导的病症的方法。提供了检测来自伴生动物物种的样品中的可溶性IL4R的方法。还提供了筛选抑制IL4和/或IL13信号传导功能的分子(例如，抗IL4R、抗IL13R、抗IL4和抗IL13抗体以及IL4R、IL13R、IL4和IL13的小分子拮抗剂)的方法。
还提供了来自伴生动物(如犬类和猫类)的变体IgG Fc多肽，其具有增加的与蛋白质A的结合、减少的与C1q的结合、减少的与CD16的结合、增加的与FcRn的结合，增加的稳定性、增加的重组产生和/或增加的铰链二硫化物形成，其可以用于本文提供的犬类或猫类IL4R抗体的上下文中。另外，本文提供了用于制备双特异性抗体(包括抗IL4R抗体)的来自伴生动物(如犬类、猫类和马类)的变体IgG Fc多肽和变体轻链恒定区。在一些实施方案中，抗IL4R抗体或抗体片段包含变体IgG Fc多肽或变体轻链恒定区。提供了用于制备掺入变体IgG Fc多肽的抗IL4R抗体和双特异性抗体的方法。
提供了针对IL4R的新型抗体，例如与犬类IL4R和/或猫类IL4R结合的抗体。本文提供的抗IL4R抗体包括但不限于单克隆抗体、小鼠抗体、嵌合抗体、犬源化抗体、猫源化抗体和双特异性抗体。在一些实施方案中，抗IL4R抗体是分离的小鼠单克隆抗体，如克隆B、克隆I、M3、M5、M8或M9。
在使用标准杂交瘤技术用犬类IL4R免疫小鼠后获得杂交瘤克隆。在酶联免疫吸附测定(ELISA)筛选、结合亲和力测定和体外中和测定后，选择单克隆抗体克隆B、克隆I、M3、M5、M8和M9用于进一步研究。对克隆B和克隆I的重链和轻链进行测序，并且通过序列比对进行分析(图1；SEQ ID NO:27(克隆B HC)、SEQ ID NO:28(克隆B LC)、SEQ ID NO:49(克隆IHC)和SEQ ID NO:50(克隆I LC))。还对M3、M5、M8和M9的可变重(VH)和可变轻(VL)链进行测序(SEQ ID NO:292(M3 VH)、SEQ ID NO:293(M3 VL)、SEQ ID NO:308(M5 VH)、SEQ ID NO:309(M5 VL)、SEQ ID NO:324(M8 VH)、SEQ ID NO:325(M8 VL)、SEQ ID NO:340(M9 VH)和SEQ ID NO:341(M9 VL)。
本文还提供了单克隆抗体克隆B和克隆I的氨基酸序列。示例性共有CDR序列被鉴定为CDR-H1：GYTFTSYVMX1(SEQ ID NO:1)(其中X1是H或N)；CDR-H2：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)(其中X2是K、A或N；X3是N或A；X4是K或A；X5是F或V；并且X6是K或Q)或者YINPX2NDGT(SEQ ID NO:268)(其中X2是K、A或N)；CDR-H3：FX7YGX8AY(SEQ ID NO:3)(其中X7是N或Y；并且X8是I或F)；CDR-L1：RASQEISGYLX9(SEQ ID NO:4)(其中X9是S或A)；CDR-L2：AASX10X11DX12(SEQ ID NO:5)(其中X10是T或N；X11是R或L；并且X12是S或T)；以及CDR-L3：X13QYASYPWT(SEQ ID NO:6)(其中X13是V或L)。
另外，例如，提供了单克隆抗体克隆B的可变重链CDR(SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:269和SEQ ID NO:9)、可变轻链CDR(SEQ ID NO:14、SEQ ID NO:15和SEQ ID NO:16)、可变区重链框架序列(SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:270和SEQ ID NO:13)和可变区轻链框架序列(SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19和SEQID NO:20)。单克隆抗体克隆B的可变重链和可变轻链的氨基酸序列提供有和未提供有前导序列(SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23和SEQ ID NO:24)。克隆B的重链和轻链的氨基酸序列提供有和未提供有前导序列(SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27和SEQ ID NO:28)。
作为另一个例子，提供了单克隆抗体克隆I的可变重链CDR(SEQ ID NO:29、SEQ IDNO:358、SEQ ID NO:30、SEQ ID NO:271、SEQ ID NO:359、SEQ ID NO:272和SEQ ID NO:31)、可变轻链CDR(SEQ ID NO:36、SEQ ID NO:360、SEQ ID NO:37、SEQ ID NO:361、SEQ ID NO:362和SEQ ID NO:38)、可变区重链框架序列(SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:273和SEQ ID NO:35)以及可变区轻链框架序列(SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41和SEQ ID NO:42)。单克隆抗体克隆I的可变重链和可变轻链的氨基酸序列提供有和未提供有前导序列(SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45和SEQ ID NO:46)。克隆I的重链和轻链的氨基酸序列提供有和未提供有前导序列(SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49和SEQ ID NO:50)。
作为另一个例子，提供了M3的可变重链CDR(SEQ ID NO:278、SEQ ID NO:279、SEQID NO:280)、可变轻链CDR(SEQ ID NO:285、SEQ ID NO:286和SEQ ID NO:287)、可变区重链框架序列(SEQ ID NO:281-284)和可变区轻链框架序列(SEQ ID NO:288-291)。
作为另一个例子，提供了M5的可变重链CDR(SEQ ID NO:294、SEQ ID NO:295、SEQID NO:296)、可变轻链CDR(SEQ ID NO:301、SEQ ID NO:302和SEQ ID NO:303)、可变区重链框架序列(SEQ ID NO:297-300)和可变区轻链框架序列(SEQ ID NO:304-307)。
本文进一步例示了M8的可变重链CDR(SEQ ID NO:310、SEQ ID NO:311、SEQ IDNO:312)、可变轻链CDR(SEQ ID NO:317、SEQ ID NO:318和SEQ ID NO:319)、可变区重链框架序列(SEQ ID NO:313-316)和可变区轻链框架序列(SEQ ID NO:320-323)。
本文还例示了M9的可变重链CDR(SEQ ID NO:326、SEQ ID NO:407、SEQ ID NO:327和SEQ ID NO:328)、可变轻链CDR(SEQ ID NO:333、SEQ ID NO:334和SEQ ID NO:335)、可变区重链框架序列(SEQ ID NO:329-332)和可变区轻链框架序列(SEQ ID NO:336-339)。
本文还提供了来源于单克隆抗体克隆B、克隆I、M3、M5、M8和M9的嵌合、犬源化和猫源化抗体。在一些实施方案中，提供了来源于克隆B的嵌合抗体的氨基酸序列，如SEQ IDNO:51、SEQ ID NO:52、SEQ ID NO:53和SEQ ID NO:54，在一些实施方案中，提供了来源于克隆I的嵌合抗体的氨基酸序列，如SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57和SEQ IDNO:58。在一些实施方案中，提供了犬源化克隆B的氨基酸序列，如SEQ ID NO:59、SEQ IDNO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73和SEQID NO:74。在一些实施方案中，提供了犬源化克隆I的氨基酸序列，如SEQ ID NO:63、SEQ IDNO:64、SEQ ID NO:274、SEQ ID NO:363、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:275、SEQID NO:364、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:276、SEQ ID NO:370、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:277、SEQ ID NO:371、SEQ ID NO:395、SEQ ID NO:396、SEQ IDNO:397、SEQ ID NO:398、SEQ ID NO:399、SEQ ID NO:400、SEQ ID NO:401、SEQ ID NO:402、SEQ ID NO:403、SEQ ID NO:404、SEQ ID NO:405、SEQ ID NO:406、SEQ ID NO:410、SEQ IDNO:411、SEQ ID NO:412、SEQ ID NO:413、SEQ ID NO:414、SEQ ID NO:415、SEQ ID NO:416、SEQ ID NO:417、SEQ ID NO:418、SEQ ID NO:419、SEQ ID NO:420和SEQ ID NO:421。在一些实施方案中，提供了来源于克隆B的猫源化抗体的氨基酸序列，如SEQ ID NO:67、SEQ IDNO:68、SEQ ID NO:79、SEQ ID NO:80和SEQ ID NO:81。在一些实施方案中，提供了来源于克隆I的猫源化抗体的氨基酸序列，如SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:82、SEQ IDNO:372、SEQ ID NO:373、SEQ ID NO:83、SEQ ID NO:374、SEQ ID NO:375、SEQ ID NO:84、SEQ ID NO:376、SEQ ID NO:377和SEQ ID NO:378。在一些实施方案中，提供了来源于M3的犬源化抗体的氨基酸序列，如SEQ ID NO:342、SEQ ID NO:343、SEQ ID NO:344、SEQ ID NO:348、SEQ ID NO:349和SEQ ID NO:350。在一些实施方案中，提供了来源于M9的犬源化抗体的氨基酸序列，如SEQ ID NO:345、SEQ ID NO:346、SEQ ID NO:347、SEQ ID NO:408、SEQ IDNO:351、SEQ ID NO:352、SEQ ID NO:353和SEQ ID NO:409。
如本文所用，如Kd的数字术语是基于科学测量计算的，因此受到适当的测量误差的影响。在一些情况下，数字术语可以包括化整到最接近的有效数字的数值。
如本文所用，“一种/个(a或an)”意指“至少一种/个”或“一种/个或多种/个”，除非另外说明。如本文所用，术语“或”意指“和/或”，除非另外说明。在多个从属权利要求的上下文中，当引用其他权利要求时，“或”的使用仅指替代方案中的那些权利要求。
本文的术语“抗体”以最广泛的含义使用并且涵盖各种抗体结构，包括但不限于单克隆抗体、多克隆抗体、多特异性抗体(例如，双特异性抗体(如双特异性T细胞衔接器)和三特异性抗体)和抗体片段(如Fab、F(ab')2、ScFv、微型抗体、双抗体、三抗体和四抗体)，只要它们表现出所需的抗原结合活性即可。犬类、猫类和马类物种具有不同种类(类别)的被许多哺乳动物共有的抗体。
术语抗体包括但不限于能够与抗原结合的片段，如Fv、单链Fv(scFv)、Fab、Fab'、di-scFv、sdAb(单结构域抗体)和F(ab')2(包括化学连接的F(ab')2)。抗体的木瓜蛋白酶消化产生两个相同的抗原结合片段，称为“Fab”片段，每个片段具有单个抗原结合位点；和残留的“Fc”片段，这一名称反映了容易结晶的能力。胃蛋白酶处理产生F(ab')2片段，其具有两个抗原组合位点并且仍然能够交联抗原。术语抗体还包括但不限于嵌合抗体、人源化抗体和各种物种的抗体，如小鼠、人、食蟹猴、犬类、猫类、马类等。此外，对于本文提供的所有抗体构建体，还考虑了具有来自其他生物的序列的变体。因此，如果公开了鼠类形式的抗体，本领域技术人员将会想到如何将基于鼠类序列的抗体转化为猫、狗、马等序列。抗体片段还包括单链scFv、串联二-scFv、双链抗体、串联三-sdcFv、微抗体等的取向。抗体片段还包括纳米抗体(sdAb，具有单个单体结构域的抗体，如一对重链可变结构域，没有轻链)。在一些实施方案中，抗体片段可以被称为特定物种(例如，小鼠scFv或犬类scFv)。这表示至少部分非CDR区的序列，而不是构建体的来源。在一些实施方案中，抗体包含标记或与第二部分缀合。
术语“标记”和“可检测标记”意指与抗体或其分析物附接以使特异性结合对的成员之间的反应(例如，结合)可检测的部分。特异性结合对的经标记的成员被称为“被可检测地标记”。因此，术语“经标记的结合蛋白”是指掺入了标记的蛋白质，所述标记提供结合蛋白的鉴定。在一些实施方案中，标记是可以产生可通过视觉或仪器手段检测的信号的可检测标记物，例如，掺入放射性标记的氨基酸或将生物素基部分附接到多肽，所述生物素基部分可以通过加标记的抗生物素蛋白(例如，含有可以通过光学方法或比色法检测的荧光标记物或酶活性的链霉亲和素)检测。用于多肽的标记的例子包括但不限于以下：放射性同位素或放射性核素(例如，3H、14C、35S、90Y、99Tc、111In、125I、131I、177Lu、166Ho或153Sm)；色原、荧光标记(例如，FITC、罗丹明、镧系元素磷光体)、酶标记(例如，辣根过氧化物酶、萤光素酶、碱性磷酸酶)；化学发光标记物；生物素基团；由第二报吿分子识别的预定多肽表位(例如，亮氨酸拉链对序列、第二抗体的结合位点、金属结合结构域、表位标签)；和诸如钆螯合物等磁性剂。通常用于免疫测定的标记的代表性例子包括产生光的部分，例如吖啶鎓化合物；和产生荧光的部分，例如荧光素。在这方面，所述部分本身可以未被可检测地标记，但在与又另一种部分反应时可能变得可检测。
术语“单克隆抗体”是指基本上同质的抗体群体中的抗体，即构成群体的单独抗体是相同的，除了可以少量存在的可能天然存在的突变之外。单克隆抗体是高度特异性的，针对单个抗原位点。此外，与通常包括针对不同决定簇(表位)的不同抗体的多克隆抗体制剂相反，每种单克隆抗体针对抗原上的单个决定簇。因此，单克隆抗体样品可以与抗原上的相同表位结合。修饰语“单克隆”指示抗体的特征是从基本上同质的抗体群体获得，并且不应解释为需要通过任何特定方法产生抗体。例如，单克隆抗体可以通过Kohler和Milstein,1975,Nature 256:495首次描述的杂交瘤方法制备，或者可以通过重组DNA方法(如美国专利号4,816,567中所述)制备。例如，还可以从使用McCafferty等人,1990,Nature 348:552-554中所述的技术产生的噬菌体文库中分离单克隆抗体。
在一些实施方案中，单克隆抗体是选自克隆B、克隆I、M3、M5、M8和M9的分离的小鼠抗体。
“氨基酸序列”意指肽或蛋白质中的氨基酸残基序列。术语“多肽”和“蛋白质”可互换地使用以指代氨基酸残基的聚合物，并且不限于最小长度。氨基酸残基的此类聚合物可以含有天然或非天然氨基酸残基，并且包括但不限于氨基酸残基的肽、寡肽、二聚体、三聚体和多聚体。所述定义涵盖了全长蛋白质及其片段两者。所述术语还包括多肽的表达后修饰，例如糖基化、唾液酸化、乙酰化、磷酸化等。此外，出于本公开文本的目的，“多肽”是指包括对天然序列的修饰(如缺失、添加和取代，在本质上通常是保守的)的蛋白质，只要蛋白质保持所需活性即可。这些修饰可能是故意的(如通过定点诱变)，或者可能是偶然的(如通过产生蛋白质的宿主的突变或由于PCR扩增引起的错误)。
如本文所用，关于肽、多肽或抗体序列的“氨基酸序列同一性百分比(％)”和“同源性”定义为在用以实现最大百分比序列同一性并且不将任何保守取代视为序列同一性的一部分而比对序列和引入缺口(如果需要)后，候选序列中与特定肽或多肽序列中的氨基酸残基相同的氨基酸残基的百分比。用于确定氨基酸序列同一性百分比的比对可以以本领域熟知的多种方式来实现，例如，使用公众可获得的计算机软件，如BLAST、BLAST-2、ALIGN或MEGALINETM(DNASTAR)软件。本领域技术人员可以确定用于测量比对的适当参数，包括为了在所比较的序列的全长上实现最大比对所需要的任何算法。
在一些实施方案中，在比对序列并引入空位(如果需要)以实现最大序列同一性百分比并且不将任何保守取代视为序列同一性的一部分之后，变体与参考核酸分子或多肽具有至少约50％序列同一性。此类变体包括，例如，其中在多肽的N末端或C末端添加、缺失一个或多个氨基酸残基的多肽。在一些实施方案中，变体与参考核酸或多肽的序列具有至少约50％序列同一性、至少约60％序列同一性、至少约65％序列同一性、至少约70％序列同一性、至少约75％序列同一性、至少约80％序列同一性、至少约85％序列同一性、至少约90％序列同一性、至少约95％序列同一性、至少约97％序列同一性、至少约98％序列同一性或至少约99％序列同一性。
“点突变”是涉及单个氨基酸残基的突变。突变可能是氨基酸丢失、另一个氨基酸残基对一个氨基酸残基的取代或另外的氨基酸残基的插入。
“氨基酸取代”是指用另一种氨基酸替代多肽中的一种氨基酸。在一些实施方案中，氨基酸取代是保守取代。非限制性示例性保守氨基酸取代示于表2中。可以将氨基酸取代引入目的分子中，并且筛选产物以得到所希望的活性，例如，保留/改善的抗原结合、减少的免疫原性、改善的ADCC或CDC、改善的重组产生和/或增强的药代动力学。
表2
可根据常见的侧链特性将氨基酸分组：
(1)疏水性：正亮氨酸、Met、Ala、Val、Leu、Ile；
(2)中性亲水性：Cys、Ser、Thr、Asn、Gln；
(3)酸性：Asp、Glu；
(4)碱性：His、Lys、Arg；
(5)影响链取向的残基：Gly、Pro；
(6)芳香族：Trp、Tyr、Phe。
非保守取代将需要将这些类别之一的成员交换为另一类别。
如本文所用，“氨基酸衍生物”是指任何氨基酸、修饰的氨基酸和/或氨基酸类似物，而不是在人中发现的20种常见的天然氨基酸之一。示例性氨基酸衍生物包括在人中未发现的天然氨基酸(例如，可能在一些微生物中发现的硒代半胱氨酸和吡咯赖氨酸)和非天然氨基酸。示例性氨基酸衍生物包括但不限于通过化学产品制造商可商购的氨基酸衍生物(例如，于2017年5月6日访问的sigmaaldrich.com/chemistry/chemistry-products.html？TablePage＝16274965，将其通过引用并入本文)。可以使用利用宿主细胞、来源于真细菌合成酶的正交氨酰基-tRNA合成酶、正交tRNA和氨基酸衍生物的翻译系统在特定位置处将一种或多种氨基酸衍生物掺入多肽中。有关进一步说明，参见例如，美国专利号9,624,485。
在一些实施方案中，多肽包含用氨基酸衍生物的氨基酸取代。在一些实施方案中，氨基酸衍生物是丙氨酸衍生物、半胱氨酸衍生物、天冬氨酸衍生物、谷氨酸衍生物、苯丙氨酸衍生物、甘氨酸衍生物、组氨酸衍生物、异亮氨酸衍生物、赖氨酸衍生物、亮氨酸衍生物、甲硫氨酸衍生物、天冬酰胺衍生物、脯氨酸衍生物、谷氨酰胺衍生物、精氨酸衍生物、丝氨酸衍生物、苏氨酸衍生物、缬氨酸衍生物、色氨酸衍生物或酪氨酸衍生物。
如本文所用，“IL4R”是包含与IL4结合的IL4受体亚基α的整体或片段的多肽。
例如，除非另有指示，否则“IL4R”是指来自任何脊椎动物来源的IL4R多肽，所述脊椎动物包括哺乳动物如灵长类动物(例如，人和食蟹猴)、啮齿动物(例如，小鼠和大鼠)以及伴生动物(例如，狗、猫和马类)。所述术语还包括IL4R的天然存在的变体，例如剪接变体或等位变体；或IL4R的人造变体，例如标记的IL4R多肽。在一些实施方案中，IL4R是结合IL4的细胞外结构域片段。在一些此类实施方案中，IL4R可以被称为IL4R细胞外结构域(ECD)。在一些实施方案中，IL4R包含SEQ ID NO:94、95、96、97、98、99、100、101、102、103、104、105、106、107、108、109、110、111、112、113、114、115、116或117的氨基酸序列。
如本文所用，“IL4”是包含与IL4R结合的IL4的整体或片段的多肽。
例如，除非另有指示，否则IL4是指来自任何脊椎动物来源的IL4多肽，所述脊椎动物包括哺乳动物如灵长类动物(例如，人和食蟹猴)、啮齿动物(例如，小鼠和大鼠)以及伴生动物(例如，狗、猫和马类)。所述术语还包括IL4的天然存在的变体，例如剪接变体或等位变体；或IL4的人造变体，例如标记的IL4多肽。在一些实施方案中，IL4包含SEQ ID NO:118、119、120、121、122或123的氨基酸序列或其加工形式。在一些实施方案中，IL4包含SEQ IDNO:124、125、126、127、128、129、130或131的氨基酸序列。
如本文所用，“IL13”是包含与IL4R结合的IL13的整体或片段的多肽。
例如，除非另有指示，否则IL13是指来自任何脊椎动物来源的IL13多肽，所述脊椎动物包括哺乳动物如灵长类动物(例如，人和食蟹猴)、啮齿动物(例如，小鼠和大鼠)以及伴生动物(例如，狗、猫和马类)。所述术语还包括IL13的天然存在的变体，例如剪接变体或等位变体；或IL13的人造变体，例如标记的IL13多肽。在一些实施方案中，IL13包含SEQ IDNO:154或155的氨基酸序列或其加工形式。在一些实施方案中，IL31包含SEQ ID NO:156、157、158或159的氨基酸序列。
如本文所用，“IL13R”或“IL13Ra1”是包含IL13R的整体或片段的多肽，所述整体或片段与IL4R配对以结合IL4或IL13。
如本文所用，“γC受体”是包含常见γ链受体的整体或片段的多肽，所述整体或片段与IL4R配对以结合IL4。
术语抗体的“IL4R结合结构域”意指由抗IL4R抗体的轻链和重链形成的结合结构域，所述结合结构域结合IL4R。
在一些实施方案中，IL4R结合结构域以比其结合人IL4R更大的亲和力结合犬类IL4R。在一些实施方案中，IL4R结合结构域结合猫类IL4R。
如本文所用，“IL4/IL13信号传导功能”是指当IL4结合至与IL13R或γC受体配对的IL4R时或当IL13结合至与IL13R配对的IL4R时产生的任何细胞效应。细胞效应可以包括STAT6磷酸化、T辅助细胞分化为Th2细胞、B细胞和/或T细胞增殖的激活、和/或诱导B细胞类别转换为IgE。
如本文所用，术语“表位”是指抗原结合分子(例如，抗体、抗体片段或含有抗体结合区的支架蛋白)结合到靶分子(例如，诸如蛋白质、核酸、碳水化合物或脂质等抗原)上的位点。表位通常包括诸如氨基酸、多肽或糖侧链等分子的化学活性表面分组，并且具有特定的三维结构特征以及特定的电荷特征。表位可以由所述靶分子的连续或并置的非连续残基(例如，氨基酸、核苷酸、糖、脂质部分)形成。由连续残基(例如，氨基酸、核苷酸、糖、脂质部分)形成的表位通常在暴露于变性溶剂时保留，而通过三级折叠形成的表位通常在用变性溶剂处理时丢失。表位可包括但不限于至少3个、至少5个或8-10个残基(例如，氨基酸或核苷酸)。在一些例子中，表位长度为少于20个残基(例如，氨基酸或核苷酸)、少于15个残基或少于12个残基。如果两种抗体显示对一种抗原的竞争性结合，则它们可以结合所述抗原内的相同表位。在一些实施方案中，表位可以通过与抗原结合分子上的CDR残基的一定最小距离来鉴定。在一些实施方案中，表位可以通过上述距离鉴定，并且进一步限于参与抗体残基与抗原残基之间的键(例如，氢键)的那些残基。表位也可以通过各种扫描来鉴定，例如丙氨酸或精氨酸扫描可以指示抗原结合分子可以与之相互作用的一个或多个残基。除非明确指出，否则作为表位的一组残基不排除其他残基为特定抗体的表位的一部分。相反，这样一组的存在表示表位的最小系列(或物种组)。因此，在一些实施方案中，鉴定为表位的一组残基表示与抗原相关的最小表位，而不是抗原上表位的残基的排他列表。
在一些实施方案中，表位在犬类IL4R ECD(SEQ ID NO:99)或猫类IL4R ECD(SEQID NO:100)的L41和T50内，如在R36和N55内。例如，表位可以包含SEQ ID NO:88、SEQ IDNO:89、SEQ ID NO:91或SEQ ID NO:92的氨基酸序列。在一些实施方案中，表位包含氨基酸序列LX10FMGSENX11T，其中X10是D或N并且X11是H或R(SEQ ID NO:85)。在一些实施方案中，表位包含氨基酸序列RLSYQLX10FMGSENX11TCVPEN，其中X10是D或N并且X11是H或R(SEQ ID NO:86)。
在一些实施方案中，表位在犬类IL4R ECD(SEQ ID NO:99)或猫类IL4R ECD(SEQID NO:100)的氨基酸S64和Q85内。例如，表位可以包含SEQ ID NO:90或SEQ ID NO:93的氨基酸序列。在一些实施方案中，表位包含氨基酸序列SMX12X13DDX14VEADVYQLX15LWAGXQ，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T(SEQ ID NO:87)。
在一些实施方案中，表位在犬类IL4R ECD(SEQ ID NO:99)的氨基酸D65和N78内。例如，表位可以包含SEQ ID NO:354的氨基酸序列。
在一些实施方案中，第一表位在犬类IL4R ECD(SEQ ID NO:99)的氨基酸G24和A56内，并且第二表位在犬类IL4R ECD的氨基酸R79和I90内。例如，第一表位可以包含SEQ IDNO:355的氨基酸序列，并且第二表位可以包含SEQ ID NO:356的氨基酸序列。
在一些实施方案中，表位在犬类IL4R ECD(SEQ ID NO:99)的氨基酸R79和V98内。例如，表位可以包含SEQ ID NO:357的氨基酸序列。
术语“CDR”意指如通过本领域技术人员的至少一种鉴定方式定义的互补决定区。在一些实施方案中，CDR可以根据Chothia编号方案、Kabat编号方案、Kabat和Chothia的组合、AbM定义、接触定义或者Kabat、Chothia、AbM或接触定义的组合中的任一种来定义。抗体内的各种CDR可以通过其适当的编号和链类型来表示，包括但不限于CDR-H1、CDR-H2、CDR-HC3、CDR-L1、CDR-L2和CDR-L3。本文使用的术语“CDR”还涵盖“高变区”或HVR，包括高变环。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含(a)包含SEQ ID NO:1、SEQ ID NO:7或SEQ ID NO:29的氨基酸序列的CDR-H1；(b)包含SEQ ID NO:2、SEQ ID NO:268、SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271或SEQ ID NO:272的氨基酸序列的CDR-H2；或(c)包含SEQ ID NO:3、SEQ ID NO:9或SEQ ID NO:31的氨基酸序列的CDR-H3。在一些实施方案中，抗IL4R抗体包含轻链，所述轻链包含(a)包含SEQ ID NO:4、SEQID NO:14或SEQ ID NO:36的氨基酸序列的CDR-L1；(b)包含SEQ ID NO:5、SEQ ID NO:15或SEQ ID NO:37的氨基酸序列的CDR-L2；或(c)包含SEQ ID NO:6、SEQ ID NO:16或SEQ IDNO:38的氨基酸序列的CDR-L3。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含(a)CDR-H1序列，其与SEQID NO:1、SEQ ID NO:7或SEQ ID NO:29的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性；(b)CDR-H2序列，其与SEQ ID NO:2、SEQ ID NO:268、SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271或SEQ ID NO:272的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性；或(c)CDR-H3序列，其与SEQ ID NO:3、SEQ ID NO:9或SEQ ID NO:31的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性。在一些实施方案中，抗IL4R抗体包含轻链，所述轻链包含(a)CDR-L1序列，其与SEQ ID NO:4、SEQ ID NO:14或SEQ ID NO:36的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性；(b)CDR-L2序列，其与SEQ ID NO:5、SEQ ID NO:15或SEQ IDNO:37的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性；或(c)CDR-L3序列，其与SEQ ID NO:6、SEQ ID NO:16或SEQ ID NO:38的氨基酸序列具有至少85％、至少90％、至少95％或至少98％序列同一性。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含：a)CDR-H1序列，其与SEQID NO:278的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-H2序列，其与SEQ ID NO:279的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-H3序列，其与SEQ ID NO:280的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。在一些实施方案中，IL4R抗体包含轻链，所述轻链包含：a)CDR-L1序列，其与SEQ ID NO:285的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-L2序列，其与SEQ ID NO:286的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-L3序列，其与SEQ ID NO:287的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含：a)CDR-H1序列，其与SEQID NO:310的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-H2序列，其与SEQ ID NO:311的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-H3序列，其与SEQ ID NO:312的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。在一些实施方案中，IL4R抗体包含轻链，所述轻链包含：a)CDR-L1序列，其与SEQ ID NO:317的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-L2序列，其与SEQ ID NO:318的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-L3序列，其与SEQ ID NO:319的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含：a)CDR-H1序列，其与SEQID NO:326或SEQ ID NO:407的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-H2序列，其与SEQ ID NO:327的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-H3序列，其与SEQ ID NO:328的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。在一些实施方案中，IL4R抗体包含轻链，所述轻链包含：a)CDR-L1序列，其与SEQ ID NO:333的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-L2序列，其与SEQID NO:334的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-L3序列，其与SEQ ID NO:335的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
在一些实施方案中，抗IL4R抗体包含重链，所述重链包含：a)CDR-H1序列，其与SEQID NO:294的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-H2序列，其与SEQ ID NO:295的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-H3序列，其与SEQ ID NO:296的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。在一些实施方案中，抗IL4R抗体包含轻链，所述轻链包含：a)CDR-L1序列，其与SEQ ID NO:301的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；b)CDR-L2序列，其与SEQ ID NO:302的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和c)CDR-L3序列，其与SEQ ID NO:303的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
如本文所用的术语“可变区”是指包含至少三个CDR的区域。在一些实施方案中，可变区包括三个CDR和至少一个框架区(“FR”)。术语“重链可变区”或“可变重链”可互换地用于指代包含至少三个重链CDR的区域。术语“轻链可变区”或“可变轻链”可互换地用于指代包含至少三个轻链CDR的区域。在一些实施方案中，可变重链或可变轻链包含至少一个框架区。在一些实施方案中，抗体包含选自HC-FR1、HC-FR2、HC-FR3和HC-FR4的至少一个重链框架区。在一些实施方案中，抗体包含选自LC-FR1、LC-FR2、LC-FR3和LC-FR4的至少一个轻链框架区。框架区可以并置在轻链CDR之间或重链CDR之间。例如，抗体可以包含具有以下结构的可变重链：(HC-FR1)-(HC-CDR1)-(HC-FR2)-(HC-CDR2)-(HC-FR3)-(HC-CDR3)-(HC-FR4)。抗体可以包含具有以下结构的可变重链：(HC-CDR1)-(HC-FR2)-(HC-CDR2)-(HC-FR3)-(HC-CDR3)。抗体还可以包含具有以下结构的可变轻链：(LC-FR1)-(LC-CDR1)-(LC-FR2)-(LC-CDR2)-(LC-FR3)-(LC-CDR3)-(LC-FR4)。抗体还可以包含具有以下结构的可变轻链：(LC-CDR1)-(LC-FR2)-(LC-CDR2)-(LC-FR3)-(LC-CDR3)。
在一些实施方案中，抗IL4R抗体包含以下中的一项或多项：(a)SEQ ID NO:10或SEQ ID NO:32的可变区重链框架1(HC-FR1)序列，(b)SEQ ID NO:11或SEQ ID NO:33的HC-FR2序列，(c)SEQ ID NO:12、SEQ ID NO:270、SEQ ID NO:34、SEQ ID NO:273的HC-FR3序列，(d)SEQ ID NO:13或SEQ ID NO:35的HC-FR4序列，(e)SEQ ID NO:17或SEQ ID NO:39的可变区轻链框架1(LC-FR1)序列，(f)SEQ ID NO:18或SEQ ID NO:40的LC-FR2序列，(g)SEQ IDNO:19或SEQ ID NO:41的LC-FR3序列，或(h)SEQ ID NO:20或SEQ ID NO:42的LC-FR4序列。
在一些实施方案中，抗IL4R抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:21或SEQ ID NO:43的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:22或SEQ ID NO:44的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、或SEQ IDNO:64、SEQ ID NO:274或SEQ ID NO:363的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:61、SEQ ID NO:62、SEQID NO:65、或SEQ ID NO:66、SEQ ID NO:275、SEQ ID NO:364的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
c.(i)可变重链序列，其与SEQ ID NO:67或SEQ ID NO:69的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:68或SEQ ID NO:70的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:21、SEQ ID NO:43、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274、SEQ ID NO:363、SEQ IDNO:67、SEQ ID NO:69、SEQ ID NO:365或SEQ ID NO:366的可变重链序列，和/或(a)SEQ IDNO:22、SEQ ID NO:44、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ IDNO:275、SEQ ID NO:364、SEQ ID NO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ ID NO:369的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:25、SEQ ID NO:47、SEQ ID NO:51、SEQ ID NO:53、SEQ ID NO:55、SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ IDNO:74、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:82、SEQ ID NO:372、SEQ ID NO:373、SEQID NO:83、SEQ ID NO:374或SEQ ID NO:375的重链序列，和/或SEQ ID NO:26、SEQ ID NO:48、SEQ ID NO:52、SEQ ID NO:54、SEQ ID NO:56、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:77、SEQ ID NO:78、SEQ ID NO:277、SEQ ID NO:371、SEQ ID NO:81、SEQ ID NO:84、SEQID NO:376、SEQ ID NO:377、SEQ ID NO:378的轻链序列。
在一些实施方案中，抗IL4R抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:292的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:293的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:342或SEQ ID NO:343的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQID NO:344的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:292的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:293的氨基酸序列；或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:342或SEQ ID NO:343的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:344的氨基酸序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:292、SEQ ID NO:342或SEQ IDNO:343的可变重链序列和/或(a)SEQ ID NO:293或SEQ ID NO:344的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:348或SEQ ID NO:349的重链序列和/或SEQ ID NO:350的轻链序列。
在一些实施方案中，抗IL4R抗体包含：(a)可变重链序列，其与SEQ ID NO:324的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(b)可变轻链序列，其与SEQ ID NO:325的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:324的可变重链序列和/或(a)SEQID NO:325的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:348或SEQ ID NO:349的重链序列和/或SEQ ID NO:350的轻链序列。
在一些实施方案中，抗IL4R抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:340的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:341的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:345或SEQ ID NO:346的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQID NO:347或SEQ ID NO:408的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:340、SEQ ID NO:345或SEQ IDNO:346的可变重链序列和/或(a)SEQ ID NO:341、SEQ ID NO:347或SEQ ID NO:408的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:348或SEQ ID NO:349的重链序列和/或SEQ ID NO:350的轻链序列。
在一些实施方案中，抗IL4R抗体包含：根据权利要求75至85中任一项所述的分离的抗体，其中所述抗体包含：(a)可变重链序列，其与SEQ ID NO:308的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(b)可变轻链序列，其与SEQ IDNO:309的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
在一些实施方案中，抗IL4R抗体包含SEQ ID NO:308的可变重链序列和/或(a)SEQID NO:341或SEQ ID NO:309的可变轻链序列。
如本文所用的术语“恒定区”是指包含至少三个恒定结构域的区域。术语“重链恒定区”或“恒定重链”可互换地用于指代包含至少三个重链恒定结构域CH1、CH2和CH3的区域。非限制性示例性重链恒定区包括γ、δ、α、ε和μ。每个重链恒定区对应于一种抗体同种型。例如，包含γ恒定区的抗体是IgG抗体，包含δ恒定区的抗体是IgD抗体，包含α恒定区的抗体是IgA抗体，包含μ恒定区的抗体是IgM抗体，并且包含ε恒定区的抗体是IgE抗体。某些同种型可以进一步细分为子类。例如，IgG抗体包括但不限于IgG1(包含γ1恒定区)、IgG2(包含γ2恒定区)、IgG3(包含γ3恒定区)和IgG4(包含γ4恒定区)抗体；IgA抗体包括但不限于IgA1(包含α1恒定区)和IgA2(包含α2恒定区)抗体；并且IgM抗体包括但不限于IgM1和IgM2。术语“轻链恒定区”或“恒定轻链”可互换地用于指代包含轻链恒定结构域CL的区域。非限制性的示例性轻链恒定区包括λ和κ(例如，SEQ ID NO:235或241)。除非另外表示，否则结构域内的非功能改变性缺失和改变涵盖在术语“恒定区”的范围内。犬类、猫类和马类具有诸如IgG、IgA、IgD、IgE和IgM等抗体类别。在犬类IgG抗体类别中有IgG-A、IgG-B、IgG-C和IgG-D。在猫类IgG抗体类别中有IgG1a、IgG1b和IgG2。在马类IgG抗体类别中有IgG1、IgG2、IgG3、IgG4、IgG5、IgG6和IgG7。
“可结晶片段多肽”或“Fc多肽”是抗体分子中与效应分子和细胞相互作用的部分。其包含免疫球蛋白重链的C末端部分。如本文所用，Fc多肽包括具有完整Fc多肽的一种或多种生物活性的Fc结构域的片段。在一些实施方案中，Fc多肽的生物活性是结合FcRn的能力。在一些实施方案中，Fc多肽的生物活性是结合C1q的能力。在一些实施方案中，Fc多肽的生物活性是结合CD16的能力。在一些实施方案中，Fc多肽的生物活性是结合蛋白A的能力。Fc多肽的“效应子功能”是由任何抗体响应于刺激物整体或部分执行的作用或活性，并且可以包括补体结合和/或ADCC(抗体依赖性细胞毒性)诱导。
术语“IgX Fc”意指Fc区源自特定抗体同种型(例如，IgG、IgA、IgD、IgE、IgM等)，其中“X”表示抗体同种型。因此，“IgG Fc”表示γ链的Fc区，“IgA Fc”表示α链的Fc区，“IgDFc”表示δ链的Fc区，“IgE Fc”表示ε链的Fc区，“IgM Fc”表示μ链的Fc区等。在一些实施方案中，所述IgG Fc区包含CH1、铰链、CH2、CH3和CL1。“IgX-N-Fc”表示Fc区源自抗体同种型的特定子类(诸如犬类IgG子类A、B、C或D；猫类IgG子类1、2a或2b；或马类IgG子类IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7等)，其中“N”表示子类。
在一些实施方案中，IgX Fc多肽或IgX-N-Fc多肽来源于伴生动物，如狗、猫或马。在一些实施方案中，IgG Fc多肽分离自犬类γ重链，诸如IgG-A、IgG-B、IgG-C或IgG-D。在一些情况下，IgG Fc多肽分离自猫类γ重链，如IgG1、IgG2a或IgG2b。在其他情况下，IgG Fc多肽分离自马类γ重链，如IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7。
除非另外说明，否则术语“IgX Fc”和“IgX Fc多肽”包括野生型IgX Fc多肽和变体IgX Fc多肽。
“野生型”是指天然存在的多肽或其片段的未突变形式。可以重组产生野生型多肽。
在一些实施方案中，野生型IgG Fc多肽包含SEQ ID NO:162、SEQ ID NO:163、SEQID NO:164、SEQ ID NO:165、SEQ ID NO:166、SEQ ID NO:167、SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206、SEQ ID NO:207、SEQ ID NO:247、SEQ ID NO:248、SEQID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的氨基酸序列。
“变体”是如下多肽，其与参考多肽的不同之处在于单个或多个非天然氨基酸取代、缺失和/或添加。在一些实施方案中，变体保留参考多肽(例如，野生型多肽)的至少一种生物活性。
如本文所用的“变体IgG Fc多肽”是这样的IgG Fc多肽，其与参考IgG Fc多肽的不同之处在于单个或多个氨基酸取代、缺失和/或添加并且基本上保留了参考IgG Fc多肽的至少一种生物活性。
在一些实施方案中，变体IgG Fc多肽包含伴生动物物种的变体IgG Fc多肽。在一些实施方案中，变体IgG Fc多肽包含变体犬类IgG Fc多肽、变体马类IgG Fc多肽或猫类IgGFc多肽。在一些实施方案中，变体IgG Fc多肽(例如，变体犬类IgG-A Fc多肽、变体犬类IgG-C Fc多肽、变体犬类IgG-D Fc多肽、变体猫类IgG1a Fc多肽、变体猫类IgG1b Fc多肽或变体猫类IgG2 Fc多肽)具有参考(例如野生型)多肽基本上缺乏的活性。例如，在一些实施方案中，变体犬类IgG-A Fc多肽、变体犬类IgG-C Fc多肽或变体犬类IgG-D Fc多肽结合蛋白质A。
在一些实施方案中，变体IgG Fc多肽具有修饰的蛋白A结合亲和力。在一些实施方案中，变体IgG Fc多肽具有增加的与蛋白A的结合亲和力。在一些实施方案中，变体IgG Fc多肽可以使用蛋白A柱色谱来纯化。在一些实施方案中，变体IgG Fc多肽具有修饰的CD16结合亲和力。在一些实施方案中，变体IgG Fc多肽具有降低的对CD16的结合亲和力。在一些实施方案中，变体IgG Fc可以具有降低的ADCC免疫应答。在一些实施方案中，变体IgG Fc多肽具有修饰的C1q结合亲和力。在一些实施方案中，变体IgG Fc多肽具有降低的对C1q的结合亲和力。在一些实施方案中，变体IgG Fc多肽可以具有降低的补体结合。在一些实施方案中，变体IgG Fc可以具有降低的补体介导的免疫应答。在一些实施方案中，变体IgG Fc多肽具有修饰的FcRn结合亲和力。在一些实施方案中，变体IgG Fc多肽具有增加的对FcRn的结合亲和力。
“铰链”是指Fc多肽或变体Fc多肽的富含脯氨酸，包含至少一个半胱氨酸残基并且位于重链恒定区的CH1与CH2之间的任何部分。
在一些实施方案中，铰链能够在同一铰链区内(同一Fc多肽内)与单独Fc多肽的铰链区或与单独Fc多肽形成二硫键。在一些实施方案中，铰链包含至少一个、至少两个、至少三个、至少四个、至少五个、至少六个、至少七个、至少八个、至少九个或至少十个脯氨酸残基。
在一些实施方案中，变体猫类IgG Fc多肽相对于野生型猫类IgG Fc多肽具有至少一个另外的链间二硫键，如在铰链区中。在一些实施方案中，具有至少一个另外的链间二硫键的变体猫类IgG2 Fc多肽相对于野生型猫类IgG Fc多肽具有增加的链间稳定性。在一些实施方案中，变体IgG多肽相对于野生型IgG Fc多肽(如野生型猫类IgG Fc多肽)具有对铰链区的至少一个氨基酸修饰。
在一些实施方案中，变体IgG Fc多肽包含来自不同同种型的IgG Fc多肽的铰链区或铰链区的一部分。在一些实施方案中，变体IgG Fc多肽(如犬类IgG2 Fc多肽)包含来自野生型猫类IgG1a或IgG1b Fc多肽的铰链区。在一些实施方案中，相对于野生型IgG Fc多肽，变体IgG Fc多肽具有增加的重组产生和/或增加的铰链二硫化物形成。在一些实施方案中，增加的重组产生和/或增加的铰链二硫化物形成可以在还原和/或非还原条件下通过SDS-PAGE分析来确定。
在一些实施方案中，变体IgG Fc多肽包含：a)在对应于SEQ ID NO:162的位置21、23、25、80、205和/或207的位置处的至少一个氨基酸取代；b)在对应于SEQ ID NO:163的位置5、38、39、94、97和/或98的位置处的至少一个氨基酸取代；c)在对应于SEQ ID NO:165的位置5、21、23、24、38、39、93、97和/或98的位置处的至少一个氨基酸取代；d)在对应于SEQID NO:167的位置21、23、25、80和/或207的位置处的至少一个氨基酸取代；e)在对应于SEQID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198的位置处的至少一个氨基酸取代；和/或f)在对应于SEQ ID NO:207的位置14和/或16的位置处的至少一个氨基酸取代。
在一些实施方案中，变体IgG Fc多肽包含：a)在SEQ ID NO:162的位置21、23、25、80、205和/或207处的至少一个氨基酸取代；b)在SEQ ID NO:163的位置5、38、39、94、97和/或98处的至少一个氨基酸取代；c)在SEQ ID NO:164的位置5、21、23、24、38、39、93、97和/或98处的至少一个氨基酸取代；d)在SEQ ID NO:165的位置21、23、25、80和/或207处的至少一个氨基酸取代；e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198处的至少一个氨基酸取代；和/或f)在SEQ ID NO:207的位置14和/或16处的至少一个氨基酸取代。
在一些实施方案中，变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:162的位置21的位置处的苏氨酸、在对应于位置23的位置处的亮氨酸、在对应于位置25的位置处的丙氨酸、在对应于位置80的位置处的甘氨酸、在对应于位置205的位置处的丙氨酸和/或在对应于位置207的位置处的组氨酸；
b)在对应于SEQ ID NO:163的位置5的位置处的脯氨酸、在对应于位置38的位置处的甘氨酸、在对应于位置39的位置处的精氨酸、在对应于位置93的位置处的精氨酸、在对应于位置97的位置处的异亮氨酸和/或在对应于位置98的位置处的甘氨酸；
c)在对应于SEQ ID NO:164的位置5的位置处的脯氨酸、在对应于位置21的位置处的苏氨酸、在对应于位置23的位置处的亮氨酸、在对应于位置24的位置处的异亮氨酸、在对应于位置38的位置处的甘氨酸、在对应于位置39的位置处的精氨酸、在对应于位置93的位置处的精氨酸、在对应于位置97的位置处的异亮氨酸和/或在对应于位置98的位置处的甘氨酸；
d)在对应于SEQ ID NO:165的位置21的位置处的苏氨酸、在对应于位置23的位置处的亮氨酸、在对应于位置25的位置处的丙氨酸、在对应于位置80的位置处的甘氨酸和/或在对应于位置207的位置处的组氨酸；
e)在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16的位置处的脯氨酸和/或在对应于位置198的位置处的丙氨酸；和/或
f)在对应于SEQ ID NO:207的位置14的位置处的半胱氨酸和/或在对应于位置16的位置处的脯氨酸。
在一些实施方案中，变体IgG Fc多肽包含：
a)在SEQ ID NO:162的位置21处的苏氨酸、位置23处的亮氨酸、位置25处的丙氨酸、位置80处的甘氨酸、位置205处的丙氨酸和/或位置207处的组氨酸；
b)在SEQ ID NO:163的位置5处的脯氨酸、位置38处的甘氨酸、位置39处的精氨酸、位置93处的精氨酸、位置97处的异亮氨酸和/或位置98处的甘氨酸；
c)在SEQ ID NO:164的位置5处的脯氨酸、位置21处的苏氨酸、位置23处的亮氨酸、位置24处的异亮氨酸、位置38处的甘氨酸、位置39处的精氨酸、位置93处的精氨酸、位置97处的异亮氨酸和/或位置98处的甘氨酸；
d)在SEQ ID NO:165的位置21处的苏氨酸、位置23处的亮氨酸、位置25处的丙氨酸、位置80处的甘氨酸和/或位置207处的组氨酸；
e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16处的脯氨酸和/或位置198处的丙氨酸；和/或
f)在SEQ ID NO:207的位置14处的半胱氨酸和/或位置16处的脯氨酸。
在一些实施方案中，变体IgG Fc多肽包含SEQ ID NO:168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、208、209、210、211、212、213、214、215、216、381、382、383、384、385、386、387、388、389、390、391、392、393或394的氨基酸序列。
双特异性抗体对两种不同的表位或靶分子具有结合特异性。在一些实施方案中，双特异性抗体结合相同靶分子的两个不同表位。双特异性抗体可以是全长抗体或抗体片段。
在一些实施方案中，抗体包含含有“杵”突变的第一变体IgG Fc多肽和含有“臼”突变的第二变体IgG Fc多肽。非限制性示例性杵和臼突变例如描述于Merchant,A.M.等人Anefficient route to human bispecific IgG.Nat Biotechnol,16(7):677-81(1998)中。
在一些实施方案中，变体IgG Fc多肽包含杵突变。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:162的位置138；SEQ ID NO:163的位置137、SEQ ID NO:165的位置137；SEQ ID NO:167的位置138；SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQID NO:206或SEQ ID NO:207的位置154；或者SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:162的位置138；SEQID NO:163的位置137；SEQ ID NO:165的位置137；SEQ ID NO:167的位置138；SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154；或者SEQID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:162的位置138；SEQ ID NO:163的位置137；SEQ ID NO:165的位置137；SEQ ID NO:167的位置138，或者SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ IDNO:206或SEQ ID NO:207的位置154；或者SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130的位置处的色氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:162的位置138；SEQ ID NO:163的位置137；SEQ ID NO:165的位置137；SEQ ID NO:167的位置138；SEQ ID NO:203、SEQID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154；或SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130处的色氨酸。在一些实施方案中，变体IgG Fc多肽包含SEQ IDNO:195、196、197、198、217、218、219、220、221、254、255、256、257、258、259或260的氨基酸序列。
在一些实施方案中，变体IgG Fc多肽包含臼突变。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:162的位置138和/或位置140；SEQ ID NO:163的位置137和/或位置139；SEQ ID NO:165的位置137和/或位置139；SEQ ID NO:167的位置138和/或位置140；SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156；和/或SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130和/或位置132的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:162的位置138和/或位置140；SEQ ID NO:163的位置137和/或位置139；SEQ ID NO:165的位置137和/或位置139；SEQ ID NO:167的位置138和/或位置140；SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156；或者SEQ ID NO:247、SEQ IDNO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130和/或位置132处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:162的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸；在对应于SEQ ID NO:163的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸；在对应于SEQ ID NO:165的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸；在对应于SEQ ID NO:167的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸；在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ IDNO:206或SEQ ID NO:207的位置154的位置处的丝氨酸和/或在对应于位置156的位置处的丙氨酸；或在对应于SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130的位置处的丝氨酸和/或在对应于位置132的位置处的丙氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:162的位置138处的丝氨酸和/或位置140处的丙氨酸；在SEQ ID NO:163的位置137处的丝氨酸和/或位置139处的丙氨酸；在SEQ ID NO:165的位置137处的丝氨酸和/或位置139处的丙氨酸；在SEQ ID NO:167的位置138处的丝氨酸和/或位置140处的丙氨酸；在SEQ ID NO:203、SEQID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的丝氨酸和/或位置156处的丙氨酸；或者在SEQ ID NO:247、SEQ ID NO:248、SEQ ID NO:249、SEQ ID NO:250、SEQ ID NO:251、SEQ ID NO:252或SEQ ID NO:253的位置130处的丝氨酸和/或位置132处的丙氨酸。在一些实施方案中，变体IgG Fc多肽包含SEQ ID NO:199、200、201、202、222、223、224、225、226、261、262、263、264、265、266或267的氨基酸序列。
此外，为了促进重链与其预期的轻链的特异性配对，CH1与轻链之间的界面氨基酸可以突变为在形状和电荷-电荷相互作用方面是互补的。
在一些实施方案中，变体IgG Fc多肽包含CH1区域，其包含在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24和/或位置30的位置处的至少一个氨基酸取代；或在对应于SEQ ID NO:238的位置24和/或位置29的位置处的至少一个氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含CH1区域，其包含在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24和/或位置30处的至少一个氨基酸取代；或在SEQ ID NO:238的位置24和/或位置29处的至少一个氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含CH1区域，其包含在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24的位置处的亮氨酸和/或在对应于位置30的位置处的天冬酰胺；或在对应于SEQ ID NO:238的位置24的位置处的亮氨酸和/或在对应于位置29的位置处的天冬酰胺。在一些实施方案中，变体IgG Fc多肽包含CH1区域，其包含在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24处的亮氨酸和/或位置30处的天冬酰胺；或在SEQ ID NO:238的位置24处的亮氨酸和/或位置29处的天冬酰胺。在一些实施方案中，变体IgG Fc多肽包含CH1区域，其包含SEQ ID NO:231、232、233、234、239或240的氨基酸序列。
在一些实施方案中，互补变体轻链恒定区包含在对应于SEQ ID NO:235或SEQ IDNO:241的位置11和/或位置22的位置处的至少一个氨基酸取代。在一些实施方案中，变体轻链恒定区包含在SEQ ID NO:235或SEQ ID NO:241的位置11和/或位置22处的至少一个氨基酸取代。在一些实施方案中，变体轻链恒定区包含在对应于SEQ ID NO:235或SEQ ID NO:241的位置11的位置处的丙氨酸和/或在对应于位置22的位置处的精氨酸。在一些实施方案中，变体轻链恒定区包含在SEQ ID NO:235或SEQ ID NO:241的位置11处的丙氨酸和/或位置22处的精氨酸。在一些实施方案中，变体轻链恒定区包含SEQ ID NO:236或242的氨基酸序列。
术语“嵌合抗体”或“嵌合”是指这样的抗体，其中重链或轻链的一部分源自特定来源或物种，而重链或轻链的其余部分的至少一部分源自不同的来源或物种。在一些实施方案中，嵌合抗体是指包含来自第一物种(如小鼠、大鼠、食蟹猴等)的至少一个可变区和来自第二物种(如人、狗、猫、马类等)的至少一个恒定区的抗体。在一些实施方案中，嵌合抗体包含至少一个小鼠可变区和至少一个犬类恒定区。在一些实施方案中，嵌合抗体包含至少一个小鼠可变区和至少一个猫类恒定区。在一些实施方案中，嵌合抗体的所有可变区均来自第一物种，并且所述嵌合抗体的所有恒定区均来自第二物种。在一些实施方案中，嵌合抗体包含来自伴生动物的恒定重链区或恒定轻链区。在一些实施方案中，嵌合抗体包含小鼠可变重链和可变轻链以及伴生动物恒定重链和恒定轻链。例如，嵌合抗体可以包含小鼠可变重链和可变轻链以及犬类恒定重链和恒定轻链；嵌合抗体可以包含小鼠可变重链和可变轻链以及猫类恒定重链和恒定轻链；或者嵌合抗体可以包含小鼠可变重链和可变轻链以及马类恒定重链和恒定轻链。
“犬类嵌合”或“犬类嵌合抗体”是指具有源自狗的至少一部分重链或一部分轻链的嵌合抗体。“猫类嵌合”或“猫类嵌合抗体”是指具有源自猫的至少一部分重链或一部分轻链的嵌合抗体。在一些实施方案中，犬类嵌合抗体包含小鼠可变重链和可变轻链以及犬类恒定重链和恒定轻链。在一些实施方案中，猫类嵌合抗体包含小鼠可变重链和可变轻链以及猫类恒定重链和恒定轻链。在一些实施方案中，抗体是嵌合抗体，其包含鼠类可变重链框架区或鼠类可变轻链框架区。
在一些实施方案中，抗IL4R抗体包含嵌合抗体，所述嵌合抗体包含：(i)SEQ IDNO:51或SEQ ID NO:55的重链氨基酸序列；(ii)SEQ ID NO:52或SEQ ID NO:56的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列。
如本文所用，“犬类抗体”包括犬类中产生的抗体；在非犬类动物中产生包含犬类免疫球蛋白基因或包含犬类免疫球蛋白肽的抗体；或者使用诸如噬菌体展示等体外方法选择的抗体，其中所述抗体库基于犬类免疫球蛋白序列。术语“犬类抗体”表示作为犬类序列的序列属别。因此，所述术语不表示抗体产生的过程，而是表示相关序列的属别。
“犬源化抗体”意指这样的抗体，其中非犬类可变区的一部分中的至少一个氨基酸已经被来自犬类可变区的相应氨基酸替代。在一些实施方案中，犬源化抗体包含至少一个犬类恒定区(例如，γ恒定区、α恒定区、δ恒定区、ε恒定区、μ恒定区等)或其片段。在一些实施方案中，犬源化抗体是诸如Fab、scFv、(Fab')2等抗体片段。术语“犬源化”还表示作为嵌合免疫球蛋白、免疫球蛋白链或其含有非犬类免疫球蛋白的最小序列的片段(如Fv、Fab、Fab'、F(ab')2或抗体的其他抗原结合序列)的非犬类(例如鼠类)抗体的形式。犬源化抗体可以包括这样的犬类免疫球蛋白(受体抗体)，其中来自受体的CDR的残基被来自具有所需的特异性、亲和力和能力的诸如小鼠、大鼠或兔等非犬类物种(供体抗体)的CDR的残基取代。在一些情况下，犬类免疫球蛋白的Fv框架区(FR)残基被相应的非犬类残基替代。此外，犬源化抗体可以包含这样的残基，它们既不在受体抗体中也不在导入的CDR或框架序列中被发现，但是被包括在内以进一步改善和优化抗体性能。
在一些实施方案中，小鼠可变重链或小鼠可变轻链的一部分中的至少一个氨基酸残基已被来自犬类可变区的相应氨基酸替代。在一些实施方案中，经修饰的链与犬类恒定重链或犬类恒定轻链融合。在一些实施方案中，抗IL4R抗体是犬源化抗体，其包含SEQ IDNO:59、60、63或64的可变重链氨基酸序列和/或SEQ ID NO:61、62、65或66的可变轻链氨基酸序列。
在一些实施方案中，抗IL4R抗体包含选自IgG-A、IgG-B、IgG-C和IgG-D恒定区的犬类重链恒定区。在一些实施方案中，抗IL4R抗体包括野生型或变体犬类IgG-A、IgG-B、IgG-C或IgG-D Fc多肽，如本文所述。在一些实施方案中，抗IL4R抗体包括包含SEQ ID NO:162的氨基酸序列的犬类IgG-A Fc多肽；包含SEQ ID NO:163或164的氨基酸序列的犬类IgG-B Fc多肽；(c)包含SEQ ID NO:165或166的氨基酸序列的犬类IgG-C Fc多肽；或(d)包含SEQ IDNO:167的氨基酸序列的犬类IgG-D Fc多肽。在一些实施方案中，抗IL4R抗体包括包含SEQID NO:168、169、195、199、383、384的氨基酸序列的变体犬类IgG-A Fc多肽；包含SEQ IDNO:170、171、172、173、174、175、176、177、178、179、196、200、381、382、387、388、389、390、391、392、393或394的氨基酸序列的变体犬类IgG-B Fc多肽；(c)包含SEQ ID NO:180、181、182、183、184、185、186、187、188、189、190、191、192、197或201的氨基酸序列的变体犬类IgG-C Fc多肽；或(d)包含SEQ ID NO:194、198、202、385或386的氨基酸序列的变体犬类IgG-D Fc多肽。
在一些实施方案中，抗IL4R抗体包含犬类轻链恒定区，如犬类κ轻恒定区。在一些实施方案中，抗IL4R抗体包含野生型犬类κ轻恒定区(例如，SEQ ID NO:235)或变体犬类κ轻恒定区(例如，SEQ ID NO:236)。
在一些实施方案中，抗IL4R抗体包含克隆B、克隆I、M3、M5、M8或M9的犬源化可变重链和变体犬类IgG Fc多肽，如SEQ ID NO:71、72、75、76、276、370、348、349、351、352、395、396、397、398、399、400、401、402、403、404、405、406、410、411、412、413、414、415、416、417、418、419、420或421。在一些实施方案中，抗IL4R抗体包含克隆B、克隆I、M3、M5、M8或M9的犬源化可变轻链和野生型犬类κ轻链恒定区，如SEQ ID NO:73、74、77、78、277、371、350或352。
如本文所用，“猫类抗体”包括猫类中产生的抗体；在非猫类动物中产生包含猫类免疫球蛋白基因或包含猫类免疫球蛋白肽的抗体；或者使用诸如噬菌体展示等体外方法选择的抗体，其中所述抗体库基于猫类免疫球蛋白序列。术语“猫类抗体”表示作为猫类序列的序列属别。因此，所述术语不表示抗体产生的过程，而是表示相关序列的属别。
“猫源化抗体”意指这样的抗体，其中非猫类可变区的一部分中的至少一个氨基酸已经被来自猫类可变区的相应氨基酸替代。在一些实施方案中，猫源化抗体包含至少一个猫类恒定区(例如，γ恒定区、α恒定区、δ恒定区、ε恒定区、μ恒定区等)或其片段。在一些实施方案中，猫源化抗体是抗体片段，如Fab、scFv、F(ab')2。术语“猫源化”还表示作为嵌合免疫球蛋白、免疫球蛋白链或其含有非猫类免疫球蛋白的最小序列的片段(如Fv、Fab、Fab'、F(ab')2或抗体的其他抗原结合序列)的非猫类(例如鼠类)抗体的形式。猫源化抗体可以包括这样的猫类免疫球蛋白(受体抗体)，其中来自受体的CDR的残基被来自具有所需的特异性、亲和力和能力的诸如小鼠、大鼠或兔等非猫类物种(供体抗体)的CDR的残基取代。在一些情况下，猫类免疫球蛋白的Fv框架区(FR)残基被相应的非猫类残基替代。此外，猫源化抗体可以包含这样的残基，它们既不在受体抗体中也不在导入的CDR或框架序列中被发现，但是被包括在内以进一步改善和优化抗体性能。
在一些实施方案中，小鼠可变重链或小鼠可变轻链的一部分中的至少一个氨基酸残基已经被来自猫类可变区的相应氨基酸替代。在一些实施方案中，所述被修饰的链与猫类恒定重链或猫类恒定轻链融合。在一些实施方案中，抗IL4R抗体是猫源化抗体，所述猫源化抗体包含SEQ ID NO:67、或SEQ ID NO:69、SEQ ID NO:365或SEQ ID NO:366的可变重链氨基酸序列和/或SEQ ID NO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ IDNO:369的可变轻链氨基酸序列。
在一些实施方案中，抗IL4R抗体包含选自IgG1a、IgG1b和IgG2恒定区的猫类重链恒定区。在一些实施方案中，抗IL4R抗体包含野生型或变体猫类IgG1a、IgG1b或IgG2Fc多肽，如本文所述。在一些实施方案中，抗IL4R抗体包括包含SEQ ID NO:203或204的氨基酸序列的猫类IgG1a Fc多肽；包含SEQ ID NO:205或206的氨基酸序列的猫类IgG1b Fc多肽；I(c)包含SEQ ID NO:207的氨基酸序列的猫类IgG2 Fc多肽。在一些实施方案中，抗IL4R抗体包括包含SEQ ID NO:208、209、210、217、218、222或223的氨基酸序列的变体猫类IgG1a Fc多肽；包含SEQ ID NO:211、212、213、219、220、224或225的氨基酸序列的变体猫类IgG1b Fc多肽；或(c)包含SEQ ID NO:214、215、216、221或226的氨基酸序列的变体猫类IgG2 Fc多肽。
在一些实施方案中，抗IL4R抗体包含猫类轻链恒定区，如猫类κ轻恒定区。在一些实施方案中，抗IL4R抗体包含野生型猫类κ轻恒定区(例如，SEQ ID NO:241)或变体猫类κ轻恒定区(例如，SEQ ID NO:242)。
在一些实施方案中，抗IL4R抗体包含克隆B或克隆I的猫源化可变重链和变体猫类IgG Fc多肽，如SEQ ID NO:79、80、82、372、373、83、374或375。在一些实施方案中，抗IL4R抗体包含克隆B或克隆I的猫源化可变轻链和猫类κ轻链恒定区，如SEQ ID NO:81、84、376、377或378。
在一些实施方案中，抗IL4R抗体是对IL4R和不同靶分子(如IL17、IL31、TNFα、CD20、CD19、CD25、IL4、IL13、IL23、IgE、CD11α、IL6R、α4-整合素、IL12、IL1β或BlyS)具有结合特异性的双特异性抗体。在一些实施方案中，双特异性抗体包含犬源化或猫源化克隆B或克隆I可变重链和可以与变体κ恒定区配对的“杵”变体犬类或猫类IgG Fc多肽(例如，SEQID NO:243)。在一些实施方案中，双特异性抗体包含针对不同靶分子(例如，犬类或猫类IL31)的可变重链和“臼”变体犬类或猫类IgG Fc多肽(例如，SEQ ID NO:245)。在一些实施方案中，双特异性抗体包含犬源化或猫源化克隆B或克隆I可变轻链和可以与杵Fc多肽配对的可变κ恒定区(例如，SEQ ID NO:244)。在一些实施方案中，双特异性抗体包含针对不同靶分子(例如，犬类或猫类IL31)的可变轻链和可以与臼Fc多肽配对的野生型κ恒定区(例如，SEQ ID NO:246)。
可以制备其他双特异性抗体排列。例如，在一些实施方案中，双特异性抗体包含犬源化或猫源化克隆B或克隆I可变重链和可以与变体κ恒定区配对的“臼”变体犬类或猫类IgG Fc多肽。在一些实施方案中，双特异性抗体包含针对不同靶分子(例如，犬类或猫类IL31)的可变重链和“杵”变体犬类或猫类IgG Fc多肽。在一些实施方案中，双特异性抗体包含犬源化或猫源化克隆B或克隆I可变轻链和可以与臼Fc多肽配对的可变κ恒定区。在一些实施方案中，双特异性抗体包含针对不同靶分子(例如，犬类或猫类IL31)的可变轻链和可以与杵Fc多肽配对的野生型κ恒定区。
术语“亲和力”意指在分子(例如抗体)的单个结合位点与其结合配偶体(例如抗原)之间的非共价相互作用的总和的强度。分子X对其配偶体Y的亲和力通常可以由解离常数(KD)表示。亲和力可以通过本领域中已知的常用方法来测量，所述常用方法例如免疫印迹、ELISA KD、KinEx A、生物膜层干涉法(BLI)或表面等离子体共振装置。
术语“KD”、“Kd”、“Kd”或“Kd值”可互换使用，指抗体-抗原相互作用的平衡解离常数。在一些实施方案中，根据供应商说明书，使用诸如
系统(Pall ForteBio LLC,费利蒙,加利福尼亚州)等生物传感器，通过使用生物膜层干涉测定来测量抗体的Kd。简言之，将生物素化的抗原与传感器尖端结合，并监测抗体缔合90秒，监测解离600秒。用于稀释和结合步骤的缓冲液是20mM磷酸盐、150mM NaCl，pH 7.2。减去仅缓冲液的空白曲线以校正任何漂移。使用ForteBio数据分析软件将数据拟合至2:1结合模型以确定缔合速率常数(kon)、解离速率常数(koff)和Kd。平衡解离常数(Kd)计算为koff/kon的比率。术语“kon”是指抗体与抗原缔合的速率常数，而术语“koff”是指抗体与抗体/抗原复合物解离的速率常数。
术语与抗原或表位“结合”是本领域熟知的术语，并且确定这种结合的方法也是本领域熟知的。如果分子与特定细胞或物质反应，与特定细胞或物质缔合或者具有对特定细胞或物质的亲和力，并且所述反应、缔合或亲和力可通过本领域中已知的一种或多种方法(如免疫印迹、ELISA KD、KinEx A、生物膜层干涉法(BLI)、表面等离子体共振装置等)来检测，则称所述分子展现“结合”。
“表面等离子体共振”表示光学现象，其允许通过检测生物传感器基质内蛋白质浓度的变化来分析实时生物特异性相互作用，例如使用BIAcoreTM系统(BIAcoreInternational AB,a GE Healthcare公司,乌普萨拉,瑞典以及皮斯卡塔韦,新泽西州)。有关进一步说明，请参见Jonsson等人(1993)Ann.Biol.Clin.51:19-26。
“生物膜层干涉法”是指光学分析技术，其分析在生物传感器尖端和内部参考层上从固定化蛋白质层反射的光的干涉图案。与生物传感器尖端结合的分子数量的变化引起可以实时测量的干涉图案的偏移。用于生物膜层干涉法的非限制性示例性装置是
系统(Pall ForteBio LLC)。参见例如Abdiche等人,2008,Anal.Biochem.377:209-277。
在一些实施方案中，抗IL4R抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。在一些实施方案中，抗IL4R抗体以如下的Kd与犬类IL4R或猫类IL4R结合：在5x10-6M与1x10-6M之间、在5x10-6M与5x10-7M之间、在5x10-6M与1x10-7M之间、在5x10-6M与5x10-8M之间、在5x10-6M与1x10-8M之间、在5x10-6M与5x10-9M之间、在5x10-6M与1x10-9M之间、在5x10-6M与5x10-10M之间、在5x10-6M与1x10-10M之间、在5x10-6M与5x10-11M之间、在5x10-6M与1x10-11M之间、在5x10-6M与5x10-12M之间、在5x10- 6M与1x10-12M之间、在1x10-6M与5x10-7M之间、在1x10-6M与1x10-7M之间、在1x10-6M与5x10-8M之间、在1x10-6M与1x10-8M之间、在1x10-6M与5x10-9M之间、在1x10-6M与1x10-9M之间、在1x10- 6M与5x10-10M之间、在1x10-6M与1x10-10M之间、在1x10-6M与5x10-11M之间、在1x10-6M与1x10- 11M之间、在1x10-6M与5x10-12M之间、在1x10-6M与1x10-12M之间、在5x10-7M与1x10-7M之间、在5x10-7M与5x10-8M之间、在5x10-7M与1x10-8M之间、在5x10-7M与5x10-9M之间、在5x10-7M与1x10-9M之间、在5x10-7M与5x10-10M之间、在5x10-7M与1x10-10M之间、在5x10-7M与5x10-11M之间、在5x10-7M与1x10-11M之间、在5x10-7M与5x10-12M之间、在5x10-7M与1x10-12M之间、在1x10- 7M与5x10-8M之间、在1x10-7M与1x10-8M之间、在1x10-7M与5x10-9M之间、在1x10-7M与1x10-9M之间、在1x10-7M与5x10-10M之间、在1x10-7M与1x10-10M之间、在1x10-7M与5x10-11M之间、在1x10- 7M与1x10-11M之间、在1x10-7M与5x10-12M之间、在1x10-7M与1x10-12M之间、在5x10-8M与1x10-8M之间、在5x10-8M与5x10-9M之间、在5x10-8M与1x10-9M之间、在5x10-8M与5x10-10M之间、在5x10-8M与1x10-10M之间、在5x10-8M与5x10-11M之间、在5x10-8M与1x10-11M之间、在5x10-8M与5x10- 12M之间、在5x10-8M与1x10-12M之间、在1x10-8M与5x10-9M之间、在1x10-8M与1x10-9M之间、在1x10-8M与5x10-10M之间、在1x10-8M与1x10-10M之间、在1x10-8M与5x10-11M之间、在1x10-8M与1x10-11M之间、在1x10-8M与5x10-12M之间、在1x10-8M与1x10-12M之间、在5x10-9M与1x10-9M之间、在5x10-9M与5x10-10M之间、在5x10-9M与1x10-10M之间、在5x10-9M与5x10-11M之间、在5x10- 9M与1x10-11M之间、在5x10-9M与5x10-12M之间、在5x10-9M与1x10-12M之间、在1x10-9M与5x10- 10M之间、在1x10-9M与1x10-10M之间、在1x10-9M与5x10-11M之间、在1x10-9M与1x10-11M之间、在1x10-9M与5x10-12M之间、在1x10-9M与1x10-12M之间、在5x10-10M与1x10-10M之间、在5x10-10M与5x10-11M之间、在1x10-10M与5x10-11M之间、在1x10-10M与1x10-11M之间、在1x10-10M与5x10-12M之间、在1x10-10M与1x10-12M之间、在5x10-11M与1x10-12M之间、在5x10-11M与5x10-12M之间、在5x10-11M与1x10-12M之间、在1x10-11M与5x10-12M之间或在1x10-11M与1x10-12M之间，所述Kd是通过生物膜层干涉法测量的。在一些实施方案中，如通过免疫印迹分析所测定的，抗IL4R抗体与犬类IL4R或猫类IL4R结合。
在一些实施方案中，提供了抗IL4R抗体，其与本文所述的抗IL4R抗体(如克隆B或克隆I)竞争结合至IL4R。在一些实施方案中，可以制备或使用与本文提供的任何抗体竞争结合的抗体。在一些实施方案中，提供了抗IL4R抗体，其与单克隆克隆B或克隆I抗体竞争结合至犬类IL4R或猫类IL4R。
术语“载体”用于描述可以被工程化为含有一种或多种克隆的多核苷酸的可以在宿主细胞中繁殖的多核苷酸。载体可以包括一种或多种以下元件：复制起点、调节目的多肽表达的一种或多种调节序列(例如，启动子或增强子)、或一种或多种选择性标记基因(例如，抗生素抗性基因和可以用于比色测定的基因，例如β-半乳糖苷酶)。术语“表达载体”是指用于在宿主细胞中表达目的多肽的载体。
“宿主细胞”是指可以是或已经是载体或分离的多核苷酸的受体的细胞。宿主细胞可以是原核细胞或真核细胞。示例性真核细胞包括哺乳动物细胞，如灵长类动物或非灵长类动物细胞；真菌细胞，如酵母；植物细胞；和昆虫细胞。非限制性示例性哺乳动物细胞包括但不限于NS0细胞、PER.
细胞(Crucell)、293细胞和CHO细胞，及其衍生物，如293-6E、DG44、CHO-S和CHO-K细胞。宿主细胞包括单个宿主细胞的后代，并且由于天然的、偶然的或故意的突变，所述后代可能不一定与原始亲本细胞完全相同(在形态方面或基因组DNA互补序列方面)。宿主细胞包括在体内用编码本文提供的一个或多个氨基酸序列的一个或多个多核苷酸转染的细胞。
如本文所用，术语“分离的”是指已经与通常在自然界中发现或产生的至少一些组分分离的分子。例如，当多肽与产生它的细胞的至少一些组分分离时，称其为“分离的”。当多肽在表达后由细胞分泌时，将含有所述多肽的上清液与产生它的细胞物理分离，认为是“分离”所述多肽。类似地，当多核苷酸不是通常在自然界中发现的较大的多核苷酸(如在DNA多核苷酸的情况下的基因组DNA或线粒体DNA)的一部分时，或例如在RNA多核苷酸的情况下与产生它的细胞的至少一些组分分离时，称多核苷酸为“分离的”。因此，包含在宿主细胞内的载体中的DNA多核苷酸可称为“分离的”。在一些实施方案中，使用色谱法(如尺寸排阻色谱法、离子交换色谱法、蛋白质A柱色谱法、疏水相互作用色谱法和CHT色谱法)纯化抗IL4R抗体。
术语“伴生动物物种”是指适合作为人同伴的动物。在一些实施方案中，伴生动物物种是诸如犬类、猫类、狗、猫、马、兔、雪貂、豚鼠、啮齿动物等小型哺乳动物。在一些实施方案中，伴生动物物种是诸如马、牛、猪等农场动物。
“降低”或“抑制”意指与参考相比使活性、功能或量减少、降低或停滞。在一些实施方案中，“降低”或“抑制”意指引起总体减少20％或更多的能力。在一些实施方案中，“降低”或“抑制”意指引起总体减少50％或更多的能力。在一些实施方案中，“降低”或“抑制”意指引起总体减少75％、85％、90％、95％或更多的能力。在一些实施方案中，在相同的时间段内，相对于对照剂量(如安慰剂)，上述量在一段时间内被抑制或减少。如本文所用，“参考”是指用于比较目的的任何样品、标准或水平。可以从健康或非患病样品中获得参考。在一些例子中，从伴生动物的未患病或未处理样品中获得参考。在一些例子中，从特定物种的一种或多种健康动物而不是被测试或治疗的动物获得参考。
如本文所用，术语“显著降低”表示在数值与参考数值之间的足够高的降低程度，使得本领域技术人员将认为在由所述值测量的生物学特征的背景下这两个值之间的差异具有统计学显著性。在一些实施方案中，与参考值相比，显著降低的数值降低大于约10％、15％、20％、25％、30％、35％、40％、45％、50％、60％、70％、80％、90％或100％中的任何一个。
术语“药物配制品”和“药物组合物”是指呈使得一种或多种活性成分的生物活性有效的形式，并且不含对所述配制品所施用的受试者具有不可接受的毒性的其他组分的制剂。
“药学上可接受的载体”是指本领域常规的无毒固体、半固体或液体填充剂、稀释剂、包封材料、配制辅助剂或载体，其与共同构成用于施用于受试者的“药物组合物”的治疗剂一起使用。药学上可接受的载体在使用的剂量和浓度下对接受者无毒，并且与配制品的其他成分相容。药学上可接受的载体适用于所用配制品。药学上可接受的载体的例子包括氧化铝；硬脂酸铝；卵磷脂；诸如人血清白蛋白、犬类或其他动物白蛋白等血清蛋白；诸如磷酸盐、柠檬酸盐、氨丁三醇或HEPES缓冲液等缓冲液；甘氨酸；山梨酸；山梨酸钾；饱和植物脂肪酸的偏甘油酯混合物；水；盐或诸如硫酸鱼精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、胶体二氧化硅或三硅酸镁等电解质；聚乙烯吡咯烷酮，纤维素基物质；聚乙二醇；蔗糖；甘露糖醇；或包括但不限于精氨酸的氨基酸。
所述药物组合物可以以冻干形式储存。因此，在一些实施方案中，所述制备方法包括冻干步骤。然后可以在施用于狗、猫或马之前，将冻干的组合物重新配制，通常作为适用于肠胃外施用的水性组合物。在其他实施方案中，特别是在抗体对热变性和氧化变性而言高度稳定的情况下，药物组合物可以作为液体储存，即作为水性组合物储存，其可以直接或在适当稀释的情况下施用于狗、猫或马。可以用无菌注射用水(WFI)重构冻干的组合物。可以包括抑菌试剂，如苯甲醇。因此，本发明提供了固体或液体形式的药物组合物。
当施用时，所述药物组合物的pH可以在约pH 5至约pH 8的范围内。如果本发明的组合物用于治疗目的，则它们是无菌的。无菌可以通过本领域已知的几种方法中的任何一种来实现，包括通过无菌过滤膜(例如0.2微米膜)过滤。可以使用或不使用抗细菌剂来维持无菌。
本发明的抗体或包含所述抗体的药物组合物可以用于治疗IL4/IL13诱导的病症。如本文所用，“IL4/IL13诱导的病症”意指与IL4/IL13浓度升高的水平或改变的梯度相关、由其引起或表征的疾病。此类IL4/IL13诱导的病症包括但不限于瘙痒性疾病或过敏性疾病。在一些实施方案中，IL4/IL13诱导的病症是特应性皮炎、过敏性皮炎、瘙痒、哮喘、银屑病、硬皮病或湿疹。IL4/IL13诱导的病症可以表现在伴生动物中，所述伴生动物包括但不限于犬类或猫类。
如本文所用，“治疗”是用于获得有益或期望的临床结果的途径。如本文所用，“治疗”包括哺乳动物(包括伴生动物)中疾病治疗剂的任何施用或应用。出于本公开文本的目的，有益或期望的临床结果包括但不限于以下中的任何一个或多个：减轻一种或多种症状，降低疾病程度，预防或延迟疾病的传播，预防或延迟疾病的复发，延迟或减缓疾病的进展，改善疾病状态，抑制疾病或疾病进展，抑制或减缓疾病或疾病进展，停滞疾病发展和缓解(无论是部分还是全部)。“治疗”还涵盖降低增殖性疾病的病理后果。本文提供的方法考虑了这些治疗方面中的任何一个或多个。与上述一致，术语治疗不需要百分之百地去除所述障碍的所有方面。
在一些实施方案中，可以根据本文的方法使用抗IL4R抗体或包含抗IL4R抗体的药物组合物来治疗IL4/IL13诱导的病症。在一些实施方案中，将抗IL4R抗体或包含抗IL4R抗体的药物组合物施用于伴生动物(如犬类或猫类)，以治疗IL4/IL13诱导的病症。
物质/分子、激动剂或拮抗剂的“治疗有效量”可根据诸如待治疗的疾病类型，疾病状态，疾病的严重程度和病程，治疗目的的类型，任何既往治疗，临床病史，对先前治疗的反应，主治兽医的判断，动物的年龄、性别和体重，以及物质/分子、激动剂或拮抗剂在动物中引起期望反应的能力等因素而变化。治疗有效量也是治疗有益效果超过物质/分子、激动剂或拮抗剂的任何毒性或有害作用的量。治疗有效量可以按一次或多次施用来递送。“治疗有效量”是指在必要的剂量和持续必要的时间段的情况下能有效实现所需治疗或预防结果的量。
在一些实施方案中，抗IL4R抗体或包含抗IL4R抗体的药物组合物是肠胃外施用的，通过皮下施用、静脉输注或肌内注射进行。在一些实施方案中，抗IL4R抗体或包含抗IL4R抗体的药物组合物按团注或连续输注施用一段时间。在一些实施方案中，抗IL4R抗体或包含抗IL4R抗体的药物组合物是通过肌内、腹膜内、脑脊髓内、皮下、动脉内、滑膜内、鞘内或吸入途径施用的。
本文所述的抗IL4R抗体可以以每剂0.01mg/kg体重至100mg/kg体重范围内的量施用。在一些实施方案中，抗IL4R抗体可以以每剂0.5mg/kg体重至50mg/kg体重范围内的量施用。在一些实施方案中，抗IL4R抗体可以以每剂0.1mg/kg体重至10mg/kg体重范围内的量施用。在一些实施方案中，抗IL4R抗体可以以每剂0.1mg/kg体重至100mg/kg体重范围内的量施用。在一些实施方案中，抗IL4R抗体可以以每剂1mg/kg体重至10mg/kg体重范围内的量施用。在一些实施方案中，抗IL4R抗体可以以0.5mg/kg体重至100mg/kg体重范围内、1mg/kg体重至100mg/kg体重范围内、5mg/kg体重至100mg/kg体重范围内、10mg/kg体重至100mg/kg体重范围内、20mg/kg体重至100mg/kg体重范围内、50mg/kg体重至100mg/kg体重范围内、1mg/kg体重至10mg/kg体重范围内、5mg/kg体重至10mg/kg体重范围内、0.5mg/kg体重至10mg/kg体重范围内、0.01mg/kg体重至0.5mg/kg体重范围内、0.01mg/kg体重至0.1mg/kg体重范围内或在5mg/kg体重至50mg/kg体重范围内的量施用。
可以一次或在一系列治疗中将抗IL4R抗体或包含抗IL4R抗体的药物组合物施用于伴生动物。例如，抗IL4R抗体或包含抗IL4R抗体的药物组合物可以施用至少一次、多于一次、至少两次、至少三次、至少四次或至少五次。
在一些实施方案中，将所述剂量每周施用一次，持续至少连续两周或三周，并且在一些实施方案中，该治疗周期重复两次或更多次，任选地穿插有一周或多周未治疗。在其他实施方案中，将所述治疗有效剂量每天施用一次，持续连续二至五天，并且在一些实施方案中，该治疗周期重复两次或更多次，任选地穿插有一天或多天未治疗。
与一种或多种其他治疗剂“组合”施用包括以任何顺序同时(并行)和连续或依序施用。术语“并行”在本文中用于指两种或更多种治疗剂的施用，其中至少部分施用在时间上重叠或者一种治疗剂的施用相对于另一种治疗剂的施用在很短的时间内发生。例如，以不超过约指定分钟数的时间间隔施用所述两种或更多种治疗剂。术语“依序”在本文中用于指两种或更多种治疗剂的施用，其中在中断施用一种或多种药剂后继续施用一种或多种其他药剂，或者其中在施用一种或多种药剂之前施用一种或多种其他药剂。例如，以超过约指定分钟数的时间间隔施用所述两种或更多种治疗剂。如本文所用，术语“与……结合”是指除了一种治疗模式之外还施用另一种治疗模式。因此，“与……结合”是指在向动物施用一种治疗模式之前、期间或之后施用另一种治疗模式。
在一些实施方案中，所述方法包括与抗IL4R抗体或包含抗IL4R抗体、Jak抑制剂、Tyk2抑制剂、PI3K抑制剂、ERK抑制剂的药物组合物组合施用。在一些实施方案中，所述方法包括与抗IL4R抗体或包含抗IL4R抗体、抗IL31抗体、抗IL17抗体、抗TNFα抗体、抗CD20抗体、抗CD19抗体、抗CD25抗体、抗IL4抗体、抗IL13抗体、抗IL23抗体、抗IgE抗体、抗CD11α抗体、抗IL6R抗体、抗α4-整合素抗体、抗IL12抗体、抗IL1β抗体和抗BlyS抗体的药物组合物组合施用。
本文提供了在允许抗体与IL4R结合的条件下向细胞暴露抗IL4R抗体或包含抗IL4R抗体的药物组合物的方法。在一些实施方案中，所述细胞是犬类细胞、猫类细胞、或马类细胞。在一些实施方案中，所述细胞是犬类DH82细胞。在一些实施方案中，所述细胞离体暴露于所述抗体或药物组合物。在一些实施方案中，将所述细胞在体内暴露于所述抗体或药物组合物。在一些实施方案中，将细胞暴露于抗IL4R抗体。在一些实施方案中，在允许抗体与细胞外IL4R结合的条件下，将细胞暴露于所述抗IL4R抗体或所述药物组合物。在一些实施方案中，细胞可以通过本文所述的任何一种或多种施用方法体内暴露于所述抗IL4R抗体或所述药物组合物，包括但不限于腹膜内、肌内、静脉注射到所述受试者体内。在一些实施方案中，通过将细胞暴露于包含所述抗体或所述药物组合物的培养基，可以将细胞离体暴露于所述抗IL4R抗体或所述药物组合物。在一些实施方案中，在将细胞暴露于包含所述抗体或所述药物组合物的培养基之前，可以使用本领域技术人员理解的任何数量的方法(如电穿孔细胞或将细胞暴露于含有氯化钙的溶液)影响细胞膜的渗透性。
本文提供了使用所述抗IL4R抗体、多肽和多核苷酸用于检测、诊断和监测IL4R诱导的病症的方法。本文提供了确定伴生动物是否将对抗IL4R抗体疗法有反应的方法。在一些实施方案中，所述方法包括使用抗IL4R抗体检测动物是否具有表达IL4R的细胞。在一些实施方案中，所述检测方法包括使样品与抗体、多肽或多核苷酸接触，并且确定结合水平是否不同于参考或对照样品(如对照)的结合水平。在一些实施方案中，所述方法可用于确定本文所述的抗体或多肽是否是对所述受试动物而言合适的治疗。
在一些实施方案中，样品是生物样品。术语“生物样品”意指来自活物或以前的活物的一定量的物质。在一些实施方案中，生物样品是细胞或细胞/组织裂解物。在一些实施方案中，生物样品包括但不限于血液(例如，全血)、血浆、血清、尿液、滑液和上皮细胞。
在一些实施方案中，使细胞或细胞/组织裂解物与抗IL4R抗体接触，并且确定抗体与细胞之间的结合。当测试细胞与相同组织类型的参考细胞相比显示出结合活性时，它可以指示受试者将受益于用抗IL4R抗体的治疗。在一些实施方案中，测试细胞来自伴生动物的组织。
可以使用本领域已知的用于检测特异性抗体-抗原结合的各种方法。可以进行的示例性免疫测定包括荧光偏振免疫测定(FPIA)、荧光免疫测定(FIA)、酶免疫测定(EIA)、比浊法抑制免疫测定(NIA)、酶联免疫吸附测定(ELISA)和放射免疫测定(RIA)。可以将指示剂部分或标记基团与主题抗体附接并且进行选择以便满足所述方法的通常由测定设备的可用性和相容的免疫测定程序决定的各种应用的需要。适当的标记包括但不限于放射性核素(例如125I、131I、35S、3H或32P)、酶(例如，碱性磷酸酶、辣根过氧化物酶、萤光素酶或β-半乳糖苷酶)、荧光部分或蛋白质(例如，荧光素、罗丹明、藻红蛋白、GFP或BFP)或发光部分(例如，由Quantum Dot Corporation,Palo Alto，加利福尼亚州，提供的QdotTM纳米颗粒)。用于进行上述各种免疫测定的一般技术是本领域普通技术人员已知的。
出于诊断目的，可以用可检测部分标记多肽(包括抗体)，所述可检测部分包括但不限于放射性同位素、荧光标记和本领域已知的各种酶-底物标记。将标记与抗体缀合的方法是本领域已知的。在一些实施方案中，不需要标记抗IL4R抗体，并且可以使用与第一抗IL4R抗体结合的第二标记抗体检测其存在。在一些实施方案中，抗IL4R抗体可以用于任何已知的测定方法，如竞争性结合测定、直接和间接夹心测定和免疫沉淀测定。Zola,Monoclonal Antibodies:A Manual of Techniques,第147-158页(CRC Press,Inc.1987)。抗IL4R抗体和多肽也可以用于体内诊断测定，如体内成像。通常，用放射性核素(如111In、99Tc、14C、131I、125I、3H或任何其他放射性核素标记(包括本文概述的那些))标记抗体或多肽，使得可以用免疫闪烁成像术定位目的细胞或组织。使用本领域熟知的技术，抗体还可以用作病理学中的染色试剂。
在一些实施方案中，第一抗体用于诊断，并且第二抗体用作治疗剂。在一些实施方案中，第一抗体与第二抗体是不同的。在一些实施方案中，第一抗体和第二抗体均可以通过与单独的表位结合而同时与抗原结合。
本文提供了筛选抑制IL4和/或IL13信号传导功能的分子的方法，所述方法包括将所述分子暴露于犬类DH82细胞，并且检测STAT6磷酸化是否降低。在一些实施方案中，所述分子包含抗IL4R抗体或IL4R的小分子拮抗剂。在一些实施方案中，所述分子包含抗IL4R抗体或IL13R的小分子拮抗剂。在一些实施方案中，所述分子包含抗IL4R抗体或IL4的小分子拮抗剂。在一些实施方案中，所述分子包含抗IL4R抗体或IL13的小分子拮抗剂。
以下实施例说明了本公开文本的具体方面，并不旨在以任何方式限制本公开文本。
实施例
实施例1
IL4和IL4R ECD试剂的制备
合成编码融合蛋白的核苷酸序列，并且将其克隆到单独的哺乳动物表达质粒中，所述融合蛋白包含：(1)全长犬类IL4R(SEQ ID NO:94)、犬类、猫类、马类、鼠类或人IL4RECD(SEQ ID NO:99、100、101、102或103)，或犬类、猫类或马类IL4(SEQ ID NO:121、122或123)，(2)一个或多个His6、人Fc和/或FLAG标签，(3)一个或多个接头序列，和(4)前导序列。将质粒单独地转染到293细胞中，培养，并且单独地收集和过滤含有分泌的IL4R ECD或IL4融合多肽的上清液。使用Ni-NTA柱(GE Healthcare Life Sciences)亲和纯化多-His融合蛋白，并且使用
蛋白质A亲和树脂(Repligen)亲和纯化人Fc融合蛋白。纯化的融合蛋白通过SDS-PAGE分析证实(数据未示出)。融合蛋白(在加工之前和之后)总结在下表3中。
表3.
实施例2
与犬类IL4R结合的小鼠单克隆抗体的鉴定
在用纯化的犬类IL4R-ECD_C-His6(SEQ ID NO:107)作为免疫原进行标准免疫后，鉴定小鼠单克隆抗体。在免疫期间使用不同的佐剂(Akesobio,Inc，中国)，并且通过标准杂交瘤技术获得单克隆抗体。
显影酶联免疫吸附测定(ELISA)以筛选产生IL4R结合抗体的克隆。首先，将生物素化的IL4R-ECD_C-His6(SEQ ID NO:107)引入链霉亲和素包被的孔中。然后将免疫的血清添加到孔中，随后用HRP缀合的抗小鼠抗体洗涤和检测。犬类IL4R结合抗体的存在显露了阳性信号。鉴定超过121种ELISA阳性的顶部克隆。
通过ELISA筛选所述121种抗体克隆阻断犬类IL4与犬类IL4R ECD之间的相互作用的能力。将犬类IL4R-ECD_C-HuFc_His6(SEQ ID NO:109)固定到包被有抗人Fc的孔中。添加杂交瘤上清液，随后添加生物素化的犬类IL4_C-His6(SEQ ID NO:127)，并且然后添加链霉亲和素-HRP。信号减弱表明犬类IL4R ECD与犬类IL4之间的相互作用降低。鉴定出11种克隆，并且将其指定为克隆A、B、C、D、E、F、G、H、I、J和K。进一步培养每种克隆，并且使用标准蛋白质A亲和色谱法纯化所产生的IgG抗体。
通过生物传感器测定(Forte Bio Octet)证实每种克隆与犬类IL4R ECD的结合。首先，将生物素化的犬类IL4R-ECD_C-His6(SEQ ID NO:107)与链霉亲和素传感器尖端结合。然后，评估11种抗体克隆中的每种与结合犬类IL4R-ECD的传感器尖端的结合。
实施例3
克隆B和克隆I抗体阻断IL4与犬类IL4R的结合
通过生物传感器测定(Forte Bio Octet)评估这11种抗体的抗体-IL4R ECD复合物降低配体犬类IL4结合的能力。在链霉亲和素传感器尖端上捕获生物素化的犬类IL4R-ECD_C-His6(SEQ ID NO:107)。将结合IL4R ECD的尖端分别暴露于20μg/mL的11种鼠类抗体(克隆A、B、C、D、E、F、G、H、I、J和K)中的每种，以形成IL4R ECD-抗体二元复合物。然后将复合物结合尖端暴露于高浓度(240μg/mL)的犬类IL4_C-His6(SEQ ID NO:127)。克隆B和克隆I的犬类IL4R ECD-抗体复合物未能与犬类IL4结合，表明克隆B和克隆I两者均是中和抗体。
实施例4
编码单克隆抗体的VH和VL的DNA序列的鉴定
使杂交瘤克隆B和I沉淀，并且提取总RNA。使用标准技术，使用用于扩增小鼠免疫球蛋白(Ig)可变结构域的寡核苷酸引物来获得cDNA。对每种克隆的重链和轻链进行测序，并且通过序列比对进行分析(分别为图1A和图1B)。克隆B的示例性CDR序列被鉴定为SEQ IDNO 7-9和14-16，并且克隆I的示例性CDR序列被鉴定为SEQ ID NO29-31和36-38。示例性共有CDR序列被鉴定为CDR-H1：GYTFTSYVMH(SEQ ID NO:1)、CDR-H2：YINPX1NDGTFYNGX2X3X4G(SEQ ID NO:2)，其中X1是K或A，X2是K或A，X3是F或V，并且X4是K或Q，或YINPX1NDGT，其中X1是K或A(SEQ ID NO:268)；CDR-H3：FX5YGX6AY(SEQ ID NO:3)，其中X5是N或Y，并且X6是I或F，CDR-L1：RASQEISGYLS(SEQ ID NO:4)；CDR-L2：AASX7X8DX9(SEQ ID NO:5)，其中X7是T或N，X8是R或L，并且X9是S或T；和CDR-L3：VQYASYPWT(SEQ ID NO:6)。
实施例5
抗IL4R-mAb克隆B和I的表达和纯化
化学合成编码具有前导序列的全长克隆B和I重链和轻链多肽(SEQ ID NO 27、28、49和50)的核苷酸序列，并且将其克隆到适用于转染到CHO宿主细胞中的单独的表达载体中。将克隆B和克隆I载体转染到单独的CHO宿主细胞中并且培养。通过单步蛋白质A柱色谱法从培养基中纯化克隆B和克隆I抗体。
通过差示扫描荧光测定法(DSF)测量克隆B和I抗体的热稳定性随pH的变化。在不同pH下每种抗体的熔解温度(Tm)列出于下表4中。将缓冲液和12μg抗体与1X蛋白热转移染料(Applied Biosystem，目录号4461146)混合在一起。用StepOne实时PCR系统(AppliedBiosystem，目录号4376357)进行熔解曲线分析。根据制造商的说明，以1％的斜坡速率使温度从25℃升高至99℃。通过蛋白质热ShiftTM软件v1.0(Applied Biosystem，目录号4466038)分析数据以确定Tm，其被计算为从取蛋白质解链曲线的一阶导数得出的最高值。
表4.
| 测试的pH | 测定缓冲液 | 克隆B Tm(℃) | 克隆I Tm(℃) |
| 4.5 | 0.1M NaAc | 58.5 | 59.2 |
| 6 | 0.1M NaPO<sub>4</sub> | 65.1 | 65.6 |
| 7.5 | 0.1M NaPO<sub>4</sub> | 66.5 | 67.8 |
| 9 | 0.1M TrisHCl | 66.7 | 67.1 |
实施例6
犬类IL4R结合活性的证明
克隆B和I抗体各自表现出对犬类IL4R的亲和力，其动力学对于治疗活性潜在地是足够的。如下使用Octet生物传感器进行结合分析。简言之，通过胺化学对犬类IL4R-ECD_C-His6(SEQ ID NO:107)进行生物素化。通过广泛的透析去除游离的未反应的生物素。在链霉亲和素传感器尖端上捕获生物素化的犬类IL4R-ECD_C-His6。监测克隆B或I抗体与犬类IL4R-ECD_C-His6(25μg/mL)的缔合，持续600秒。监测解离持续600秒。减去仅缓冲液空白曲线以校正任何漂移。使用ForteBioTM数据分析软件将数据拟合至1:1结合模型以确定kon、koff和Kd。用于稀释和所有结合步骤的缓冲液是：20mM磷酸盐、150mM NaCl，pH 7.2。克隆B抗体与犬类IL4R-ECD_C-His6的Kd是2.03x10-9M，并且克隆I抗体与犬类IL4R-ECD_C-His6的Kd是1.79x10-9M。
还使用Octet生物传感器进行替代结合测定。在抗人Fc结合的传感器尖端上捕获犬类IL4R-ECD_C-HuFc_His6(SEQ ID NO:109)。监测克隆B或I抗体与犬类IL4R-ECD_C-HuFc_His6的缔合，持续600秒。监测解离持续600秒。用于稀释和所有结合步骤的缓冲液是：20mM磷酸盐、150mM NaCl，pH 7.2。克隆B抗体与犬类IL4R-ECD_C-HuFc_His6的Kd是约10- 10M，并且克隆I抗体与犬类IL4R-ECD_C-HuFc_His6的Kd是2.75x10-10M。第二测定观察到的增加的亲和力可能是由于克隆B和I抗体对犬类IL4R-ECD_C-HuFc_His6相对于对犬类IL4R-ECD_C-His6而言增加的亲合力所致。另外，胺缀合可能影响犬类IL4R-ECD_C-His6与克隆B和I抗体相互作用的亲和力。
实施例7
克隆B和I抗体竞争相同的IL4R表位组
使用Octet生物传感器进行表位结合分析。在抗人Fc结合的传感器尖端上捕获犬类IL4R-ECD_C-HuFc_His6(SEQ ID NO:109)。监测克隆B抗体(50μg/mL)与犬类IL4R-ECD_C-HuFc_His6的缔合，持续600秒。短暂洗涤复合物结合的尖端，并且然后将其暴露于克隆I抗体(50μg/mL)。在洗涤步骤和暴露于克隆I抗体之后，没有观察到对犬类IL4R-ECD_C-HuFc_His6的进一步缔合(图2A)，这表明克隆B和I抗体与相同的表位组结合。还进行相反的结合测定。监测克隆I抗体(50μg/mL)与在抗人Fc结合的传感器尖端上捕获的犬类IL4R-ECD_C-HuFc_His6之间的缔合，持续600秒。短暂洗涤复合物结合的尖端，并且然后将其暴露于克隆B抗体(50μg/mL)。在洗涤步骤和暴露于克隆B抗体之后，没有观察到对犬类IL4R-ECD_C-HuFc_His6的进一步缔合(图2B)，这再次表明克隆B和克隆I抗体与相同的表位组结合。
实施例8
克隆B和克隆I抗体阻断IL4和IL13与IL4R的结合
使用Octet生物传感器进行克隆B、克隆I、犬类IL4和犬类IL13配体与犬类IL4R的各种结合分析。在抗人Fc结合的传感器尖端上捕获犬类IL4R-ECD_C-HuFc_His6(SEQ IDNO:109)。监测克隆B或克隆I抗体(25μg/mL)与犬类IL4R-ECD_C-HuFc_His6的缔合，持续600秒。短暂洗涤复合物结合的尖端，并且然后将其暴露于犬类IL4_C-His6(SEQ ID NO:127；50μg/mL)或犬类IL13_C-His6(SEQ ID NO:157；50μg/mL)并且监测600秒。观察到犬类IL4(图3A)或犬类IL13(图3B)几乎没有结合，这表明克隆B和I抗体阻断了犬类IL4和犬类IL13与犬类IL4R的结合。
还进行相反的结合测定。监测犬类IL4_C-His6(SEQ ID NO:127；50μg/mL)或犬类IL13_C-His6(SEQ ID NO:157；50μg/mL)与在抗人Fc结合传感器尖端上捕获的犬类IL4R-ECD_C-HuFc_His6之间的缔合，持续600秒。短暂洗涤复合物结合的尖端，并且然后将其暴露于克隆B抗体(50μg/mL)或克隆I抗体(50μg/mL)，并且监测600秒。在IL4和IL13与IL4R结合之后(分别为图3C和图3D)，观察到与克隆B或克隆I的进一步缔合。这些结果表明，克隆B和克隆I各自具有比犬类IL4或犬类IL13更高的对IL4R的亲和力。
实施例9
通过Western分析克隆B和I抗体对IL4R的免疫反应性
通过蛋白质印迹(Western blot)研究克隆B和I抗体识别犬类IL4R-ECD_C-HuFc_His6(SEQ ID NO:109)的能力。在还原条件(存在DTT)或非还原条件(不存在DTT)下，通过SDS-PAGE分离纯化的犬类IL4R-ECD_C-HuFc_His6。将蛋白质转移至PVDF膜，并且使用克隆B或I抗体，随后使用山羊抗小鼠IgG-HRP进行探测。仅在非还原条件下在样品中观察到克隆B和I抗体的免疫反应阳性信号，这表明二硫化物结合对于维持表位构象可能是重要的，并且克隆B和I抗体的表位可能是不连续的或构象的。
还研究克隆I抗体与猫类、马类、鼠类和人IL4R的交叉反应性。在还原(+DTT)或非还原(-DTT)条件下，通过SDS-PAGE分别分离犬类IL4R-ECD_C-HuFc_His6(SEQ ID NO:109)、猫类IL4R-ECD_C-HuFc_His6(SEQ ID NO:111)、马类IL4R-ECD_C-HuFc_His6(SEQ ID NO:113)、鼠类IL4R-ECD_C-HuFc_His6(SEQ ID NO:115)和人IL4R-ECD_C-HuFc_His6(SEQ IDNO:117)(0.1μg/泳道)。将蛋白质转移至PVDF膜，并且用克隆I抗体(0.3μg/mL)探测印迹，并且通过山羊抗小鼠IgG-HRP进行可视化(图4A)。作为对照，将印迹剥离并且用山羊抗人IgGFc-HRP探测，以可视化IL4R-ECD蛋白的存在(图4B)。在非还原条件下，使克隆I抗体与犬类IL4R-ECD_C-HuFc_His6免疫反应，并且在较小程度上与猫类IL4R-ECD_C-HuFc_His6免疫反应(图4A，分别为泳道5和1)。用马类、鼠类和人IL4R-ECD_C-HuFc_His6融合多肽观察到低背景反应性(图4A，分别为泳道2、3和4)。
实施例10
猫类IL4R结合亲和力
免疫印迹测定检测到，与克隆I与犬类IL4R-ECD_C-HuFc_His6之间的结合相比，克隆I与猫类IL4R-ECD_C-HuFc_His6之间的结合略有降低。此发现与通过Octet生物传感器测量的体外结合亲和力一致。在链霉亲和素传感器尖端上捕获生物素化的猫类IL4R-ECD_C-HuFc_His6(SEQ ID NO:111)。监测克隆I抗体(25μg/mL)与猫类IL4R-ECD_C-HuFc_His6的缔合，持续600秒。监测解离持续600秒。减去仅缓冲液空白曲线以校正任何漂移。使用ForteBioTM数据分析软件将数据拟合至1:1结合模型以确定kon、koff和Kd。用于稀释和所有结合步骤的缓冲液是：20mM磷酸盐、150mM NaCl，pH 7.2。克隆I抗体与猫类IL4R-ECD_C-HuFc_His6的Kd是1.1x10-9M。
实施例11
对于克隆I抗体的犬类IL4R结合表位的鉴定
研究被克隆I抗体(并且推测也被克隆B抗体)识别的犬类IL4R表位。由于克隆I抗体表现出与人IL4R-ECD的低背景交叉反应性，因此将犬类IL4R ECD(SEQ ID NO:99)和人IL4R ECD(SEQ ID NO:103)序列的许多杂合蛋白设计为具有前导序列(SEQ ID NO:132)和C-末端人Fc-His6标签，以便于犬类IL4R表位作图。将犬类和人ECD序列分成三个区段(A、B和C)，并且基于这些区段以A至C的顺序制备六种不同的杂合多肽构建体(参见下图5A和表5)。
表5.
将含有编码杂合体1-6多肽中的每种的核苷酸序列的质粒构建体瞬时转染到293细胞中，并且将上清液浓缩3倍。在非还原(-DTT)条件下，通过SDS-PAGE分离每种融合多肽，并且将蛋白质转移至PVDF膜。使用克隆I抗体(图5B)或作为对照的抗人Fc抗体(图5C)探测印迹。犬类IL4R ECD区段A和B两者的存在给出了最强的信号(杂合体4，图5B，泳道6)。犬类IL4R ECD区段A单独(杂合体1，图5B，泳道3)或与区段C一起(杂合体6，图5B，泳道8)给出了明显的信号，这表明区段A可能含有主要表位。而区段B单独(杂合体2，图5B，泳道4)或与区段C一起(杂合体5，图5B，泳道7)给出了较弱的信号，这表明区段B可能含有辅助(或次要)表位。
基于此信息，将犬类IL4R ECD(SEQ ID NO:99)和人IL4R ECD(SEQ ID NO:103)序列的另外的杂合蛋白设计为具有前导序列(SEQ ID NO:132)和C-末端人Fc-His6标签，以进一步定位一个或多个犬类IL4R表位。进一步划分犬类和人ECD序列的区段A和B，并且基于增加犬类或人序列的氨基酸残基数目制备另外的八种杂合多肽构建体(杂合体7-14)(参见下图6A和表6)。
表6.
将含有编码杂合体7-14多肽中的每种的核苷酸序列的质粒构建体瞬时转染到293细胞中，并且将上清液浓缩3倍。在非还原(-DTT)条件下，通过SDS-PAGE分离每种杂合多肽，并且将蛋白质转移至PVDF膜。使用克隆I抗体(图6B)或作为对照的抗人Fc抗体(图6C)探测印迹。区段A的C-末端半部分和区段B的中央部分两者的存在给出了最强的信号(图6B；杂合体7、11和13；分别为泳道3、7和9)。
为了进一步鉴定由克隆I识别的犬类IL4R表位的氨基酸残基，将基于SEQ ID NO:99的携带丙氨酸突变的多个突变体犬类IL4 ECD序列设计为具有前导序列(SEQ ID NO:132)和C-末端人Fc-His6标签，并且在293细胞中表达。将细胞上清液浓缩3倍，在非还原(-DTT)条件下通过SDS-PAGE分离，并且转移至PVDF膜。使用克隆I抗体(图7B)或作为对照的抗人Fc抗体(图7C)探测印迹。精细表位作图的结果总结在下表7中。结果表明，犬类IL4R ECD(SEQ ID NO:95)的氨基酸M44和G45参与表位结合。
表7.
构建犬类IL4(SEQ ID NO:121)、犬类IL4R ECD(SEQ ID NO:99)和犬类IL13R ECD(SEQ ID NO:161)的复合物的三维模型(图8)。在图8中鉴定了犬类IL4R表位1。对上述研究结果的分析和三维蛋白质建模分析表明，克隆B和I与位于犬类IL4R ECD(SEQ ID NO:99)或猫类IL4R ECD(SEQ ID NO:100)的L41和T50内(如在R36和N55内)的第一表位结合。例如，第一表位可以包含SEQ ID NO:88、SEQ ID NO:89、SEQ ID NO:91或SEQ ID NO:92的氨基酸序列。在一些实施方案中，第一表位包含氨基酸序列LX10FMGSENX11T，其中X10是D或N并且X11是H或R(SEQ ID NO:85)。在一些实施方案中，第一表位包含氨基酸序列RLSYQLX10FMGSENX11TCVPEN，其中X10是D或N并且X11是H或R(SEQ ID NO:86)。
对研究结果和三维蛋白质建模的分析还表明，克隆B和I与犬类IL4R ECD(SEQ IDNO:99)或猫类IL4R ECD(SEQ ID NO:100)的氨基酸S64和Q85内的第二表位结合。例如，第二表位可以包含SEQ ID NO:90或SEQ ID NO:93的氨基酸序列。在一些实施方案中，第二表位包含氨基酸序列SMX12X13DDX14VEADVYQLX15LWAGXQ，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T(SEQ ID NO:87)。
实施例12
嵌合、犬源化和猫源化抗体的表达和纯化
克隆B或I可变重链多肽可以与不同动物物种的重链恒定区融合，所述重链恒定区如野生型犬IgG-A、IgG-B、IgG-C或IgG-D或者野生型猫IgG-1a、IgG-1b或IgG-2Fc多肽(例如，包含SEQ ID NO:162、163、164、165、166、167、203、204、205、206、207、227、228、229、230、237、238、239或240的IgG Fc多肽)，或此类IgG Fc多肽的变体(例如，包含SEQ ID NO:168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、231、232、233、234、239、240、381、382、383、384、385、386、387、388、389、390、391、392、393或394的变体IgG Fc多肽)。嵌合重链的示例性氨基酸序列包括SEQ ID NO:51(克隆B可变HC和犬类IgG-B)和SEQID NO:55(克隆I可变HC和犬类IgG-B)。另外，克隆B或I可变轻链多肽可以与伴生动物物种的轻链恒定区融合，所述轻链恒定区如野生型犬类或猫类轻链恒定区(例如，SEQ ID NO:235或241)或此类多肽的变体(例如，SEQ ID NO:236或242)。嵌合轻链的示例性氨基酸序列包括SEQ ID NO:52(克隆B可变LC和犬类κ轻链恒定区)和SEQ ID NO:56(克隆I可变LC和犬类κ轻链恒定区)。
通过搜索和选择合适的犬类和猫类种系抗体氨基酸序列作为用于CDR移植的模板，对克隆B和I可变重链和可变轻链进行犬源化和猫源化。使用3维结构建模进一步优化序列。所设计的克隆B和I可变重链和可变轻链多肽的犬源化和猫源化变体的例子包括SEQ IDNO 59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQ IDNO:274、SEQ ID NO:363、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:275、SEQ ID NO:364、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69和SEQ ID NO:70。
犬源化或猫源化重链多肽可以与以下的重链恒定区融合：野生型犬类IgG-A、IgG-B、IgG-C或IgG-D或者野生型猫类IgG-1a、IgG-1b或IgG-2Fc多肽(例如，包含SEQ ID NO:162、163、164、165、166、167、203、204、205、206、207、227、228、229、230、237、238、239或240的IgG Fc多肽)，或此类IgG Fc多肽的变体(例如，包含SEQ ID NO:168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、231、232、233、234、239、240、381、382、383、384、385、386、387、388、389、390、391、392、393或394的变体IgG Fc多肽)。犬源化或猫源化可变重链和变体IgG Fc多肽的示例性氨基酸序列包括SEQ ID NO:71、72、75、76、79、80、82、372、373、83、374和375。
犬源化或猫源化轻链多肽可以与伴生动物物种的轻链恒定区融合，所述轻链恒定区如野生型犬类或猫类轻链恒定区(例如，SEQ ID NO:235或241)或此类多肽的变体(例如，SEQ ID NO:236或242)。犬源化或猫源化可变轻链和κ轻链恒定区的示例性氨基酸序列包括SEQ ID NO:73、74、77、78、81、84、376、377和378。
合成编码与犬类或猫类IgG融合的克隆B和I可变重链以及与犬类或猫类恒定轻链融合的克隆B和I可变轻链的嵌合多肽的核苷酸序列，并且将其克隆到适用于转染到CHO宿主细胞中的表达载体中。还合成编码犬源化和猫源化克隆I多肽的核苷酸序列，并且将其克隆到表达载体中。将每对HC和LC核苷酸序列转染到CHO宿主细胞中。培养细胞并且通过蛋白质A柱色谱法从培养基中纯化克隆B、克隆I、嵌合B和嵌合I抗体。
还可以使用FreestyleMaxTM转染试剂(Life Technologies)，将载体用于在CHO-S细胞中进行中试转染。通过澄清条件培养基收获上清液。可以用单程蛋白质A色谱法步骤纯化抗体，并且用于进一步研究。
可以将纯化的抗体制剂与一种或多种药学上可接受的赋形剂混合，并且通过过滤灭菌以制备本发明的药物组合物。可以以治疗有效量将示例性抗体制剂或药物组合物施用于患有IL4R诱导的病症(如特应性皮炎、过敏性皮炎、瘙痒、哮喘、银屑病、硬皮病或湿疹)的狗或猫。
实施例13
变体犬类IgG Fc多肽，用于增加的蛋白质A结合和/或减少的补体结合和/或减少的CD16结合。
使用蛋白A亲和力纯化抗体是成熟的过程。然而，在犬类IgG的四种亚型中，只有IgG-B Fc(例如，SEQ ID NO:163或SEQ ID NO:164)具有蛋白A结合亲和力。犬类IgG-A Fc(例如，SEQ ID NO:162)、IgG-C Fc(例如，SEQ ID NO:165或SEQ ID NO:166)和IgG-D Fc(例如，SEQ ID NO:167)具有弱的或无可测量的蛋白A结合亲和力。设计了变体犬类IgG-A Fc、IgG-C Fc和IgG-D Fc多肽以用于改变蛋白A结合。
此外，犬类IgG-B Fc和IgG-C Fc具有补体活性并且结合至C1q，而犬类IgG-A Fc和IgG-D Fc具有弱的或无可测量的对C1q的结合亲和力。为了潜在地降低C1q结合和/或潜在地降低补体介导的免疫应答，设计了变体犬类IgG-B Fc和IgG-C Fc多肽。
此外，犬类IgG-B Fc和IgG-C Fc具有CD16结合活性。为了潜在地降低CD16与IgG-BFc和IgG-C Fc的结合，和/或潜在地降低ADCC，设计了变体犬类IgG-B Fc和IgG-C Fc多肽。
下表8汇总了犬类IgG Fc亚型的蛋白A和C1q结合特征。值得注意的是，没有一种野生型犬类IgG Fc亚型缺乏C1q结合并且结合蛋白A。
表8.
| 野生型犬类IgG Fc | 蛋白A结合 | C1q结合 | CD16结合 |
| IgG-A Fc | – | – | – |
| IgG-B Fc | + | + | + |
| IgG-C Fc | – | + | + |
| IgG-D Fc | – | – | – |
(-)表示低的或无可测量的结合活性。
使用两种途径来设计变体犬类IgG-A、IgG-C和IgG-D Fc多肽以用于增加蛋白A结合。对于第一种途径，将变体犬类IgG-A、IgG-C和IgG-D Fc多肽设计为具有与犬类IgG-B Fc相同的蛋白A结合基序序列(例如，分别为SEQ ID NO:163、SEQ ID NO:165和SEQ ID NO:167)。对于第二种途径，将变体犬类IgG-A Fc I(21)T/Q(207)H(SEQ ID NO:169)、变体犬类IgG-C Fc I(21)T(SEQ ID NO:181)和变体犬类IgG-D Fc I(21)T/Q(207)H(SEQ ID NO:194)设计为在蛋白A结合区具有一个或两个氨基酸取代以对应于犬类IgG-B Fc序列。
此外，可以制备具有增加的蛋白A结合的变体犬类IgG-A Fc、IgG-C Fc和IgG-D Fc多肽，其具有表9中列出的一个或多个氨基酸取代。
表9.
*列出的氨基酸位置是相对于所指示的SEQ ID NO.。
为了潜在地降低C1q与犬类IgG-B Fc和IgG-C Fc的结合，和/或潜在地降低补体介导的免疫应答，可以制备变体犬类IgG-B Fc和IgG-C Fc多肽，其分别在对应于SEQ ID NO:163或SEQ ID NO:165的位置93的氨基酸位置处具有用除Lys外的任何氨基酸对Lys的氨基酸取代。与据了解未表现出补体活性的犬类IgG-A Fc和IgG-D Fc相比，分析犬类IgG-B Fc和IgG-C Fc的蛋白质序列和3-D结构建模后，鉴定这些氨基酸取代。例如，可以制备变体犬类IgG-B Fc K(93)R(SEQ ID NO:170)和变体犬类IgG-C Fc K(93)R(SEQ ID NO:182)。与包含野生型犬类IgG-B Fc的融合蛋白相比，观察到人C1q与包含变体犬类IgG-B Fc K(93)R的融合蛋白之间的结合降低。
为了潜在地降低CD16与IgG-B Fc和IgG-C Fc的结合和/或潜在地降低ADCC，可以制备具有表10中列出的一个或多个氨基酸取代的变体犬类IgG-B Fc和IgG-C Fc多肽。与据了解未表现出ADCC活性的IgG-A和IgG-D，分析犬类IgG-B和IgG-C的蛋白质序列和3-D结构建模后，鉴定一个或多个氨基酸取代。
表10.
*列出的氨基酸位置是相对于所指示的SEQ ID NO.。
由于野生型犬类IgG-C Fc缺乏蛋白质A结合并且具有C1q结合，可以通过将表9中列出的一个或多个氨基酸取代与K(93)R取代或K(93)X取代(其中X是除了Lys之外的任何氨基酸)组合来制备结合蛋白质A并且具有降低的与C1q的结合的双变体犬类IgG-C Fc。可以通过将表10中列出的一个或多个氨基酸取代与K(93)R取代或K(93)X取代(其中X是除了Lys之外的任何氨基酸)组合来制备与C1q的结合降低并且与CD16的结合降低的双变体犬类IgG-B Fc或双变体犬类IgG-C Fc。可以通过将表9中列出的一个或多个氨基酸取代和表10中列出的一个或多个氨基酸取代与K(93)R取代或K(93)X取代(其中X是除Lys外的任何氨基酸)组合来制备结合蛋白A并且具有降低的与C1q和CD16的结合的三重变体犬类IgG-C Fc。
可以确定任何变体犬类IgG Fc与蛋白A、CD16和/或C1q的结合，并且将其与另一种IgG Fc(例如，相应的野生型犬类IgG Fc、另一种野生型或变体犬类IgG Fc、或另一种伴生动物的野生型或变体IgG Fc等)与蛋白A、CD16和/或C1q的结合进行比较。
结合分析可以使用Octet生物传感器进行。简言之，可以将靶分子(例如，蛋白A、C1q、CD16等)生物素化并去除游离的未反应的生物素(例如，通过透析)。在链霉亲和素传感器尖端上捕获生物素化的靶分子。监测靶分子与各种浓度(例如，10μg/mL)的IgG Fc多肽的缔合持续指定的时间或直到达到稳定状态。监测解离持续指定的时间或直到达到稳定状态。可以减去仅缓冲液的空白曲线以校正任何漂移。使用ForteBioTM数据分析软件将数据拟合至1:1结合模型以确定kon、koff和Kd。
用于增加的蛋白质A结合(例如，为了易于纯化)、减少的C1q结合(例如，为了降低补体介导的免疫应答)、降低的CD16结合(例如，降低的抗体依赖性细胞介导的细胞毒性)和/或增加的稳定性的示例性变体犬类IgG多肽包括SEQ ID NO:169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193和194。此类变体犬类IgG多肽可以与以上实施例中所述的克隆B或I可变重链序列、犬源化克隆B或I可变重链序列或CDR序列结合。
实施例14
变体猫类IgG Fc多肽，用于减少的补体结合和/或增强的铰链二硫化物形成和/或增强的重组产生
猫类IgG、IgG1a Fc(SEQ ID NO:203或SEQ ID NO:204)、IgG1b Fc(SEQ ID NO:205或SEQ ID NO:206)和IgG2 Fc(SEQ ID NO:207)的三种亚型中的每一种都具有蛋白A结合亲和力。然而，只有猫类IgG2 Fc具有弱的或无可测量的对C1q的结合亲和力，而猫类IgG1aFc、IgG1b Fc结合至C1q。为了潜在地降低C1q结合和/或潜在地降低补体介导的免疫应答，设计了变体猫类IgG1a Fc和IgG1b Fc多肽。
下表11汇总了猫类IgG Fc亚型的蛋白A和C1q结合特征。值得注意的是，没有一种野生型马类IgG Fc亚型缺乏C1q结合并且结合蛋白A。
表11.
| 野生型猫类IgG Fc | 蛋白A结合 | C1q结合 |
| IgG1a Fc | + | + |
| IgG1b Fc | + | + |
| IgG2 Fc | + | – |
(-)表示低的或无可测量的结合活性。
为了潜在地降低C1q与猫类IgG1a Fc和IgG1b Fc的结合和/或潜在地降低补体介导的免疫应答，可以制备变体猫类IgG1a Fc和IgG1b Fc多肽，其在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置198的氨基酸位置处具有Pro被除了Pro之外的任何氨基酸进行的氨基酸取代。这些氨基酸取代在猫类IgG1a Fc和IgG1b Fc与猫类IgG2 Fc(了解其未展现出补体活性)相比的蛋白质序列分析和3-D结构建模之后鉴定出。例如，可以制备变体猫类IgG1 Fc多肽P(198)A(SEQ ID NO:209、210、212和213)。
可以确定任何变体猫类IgG Fc与C1q的结合，并且将其与另一种IgG Fc(例如，相应的野生型猫类IgG Fc、另一种野生型或变体猫类IgG Fc、或另一种伴生动物的野生型或变体IgG Fc等)与C1q的结合进行比较。可以使用实施例13中描述的结合测定。
将若干种直系同源铰链结构的三维蛋白质建模分析用于修饰猫类IgG铰链以增强二硫化物形成。为了增强在猫类IgG铰链处的二硫化物形成，可以通过在对应于猫类IgG1a(SEQ ID NO:203或SEQ ID NO:204)(例如，K16P)、猫类IgG1b(SEQ ID NO:205或SEQ ID NO:206)或猫类IgG2(SEQ ID NO:207)(例如，K(16)P)的位置16的位置处用脯氨酸取代赖氨酸来修饰铰链序列。具有经修饰的铰链的变体猫类IgG多肽的氨基酸序列的例子包括SEQ IDNO:208、SEQ ID NO:211和SEQ ID NO:215。
为了增加猫类IgG2铰链处的二硫化物形成，可以通过用半胱氨酸取代氨基酸来修饰铰链序列。例如，通过在对应于SEQ ID NO:207的位置14的氨基酸位置处用Cys取代Gly来制备具有经修饰的铰链的变体猫类IgG2 Fc(SEQ ID NO:214)。
将三维蛋白质建模用于设计猫类变体IgG Fc多肽，所述多肽包含来自不同IgG同种型的铰链区的序列，以增强重组产生和改善铰链二硫化物形成。可以制备包含来自猫类IgG1a或IgG1b的铰链区的序列的变体猫类IgG2 Fc多肽(例如，SEQ ID NO:216)。可以确定变体IgG Fc多肽的重组产生的水平和/或铰链二硫化物形成的水平，并且通过在还原和非还原条件下的SDS-PAGE分析将其与另一种IgG Fc(例如，相同或不同同种型的相应野生型IgG Fc，或另一种伴生动物的野生型或变体IgG Fc)的所述水平进行比较。
用于减少的C1q结合(例如，用于降低的补体介导的免疫应答)和/或增强的铰链二硫化物形成和/或增强的重组产生的示例性变体猫类IgG多肽包括SEQ ID NO:208、209、210、211、212、213、214、215和216。此类变体猫类IgG多肽可以与以上实施例中所述的克隆B或I可变重链序列、猫源化克隆B或I可变重链序列或CDR序列结合。
实施例15
用于双特异性抗体的变体犬类、猫类和马类IgG Fc多肽
为了能够使用杵臼(knob-in-hole)异源二聚化方法制备双特异性犬类、猫类或马类抗体，研究变体犬类IgG Fc多肽、变体猫类IgG Fc多肽和变体马类IgG Fc多肽的配对。双特异性抗体组合了两种抗体针对两种不同靶标的特异性。首先，通过引入CH3接口突变来设计重链配对，使得一条链包含大体积的氨基酸(杵)，并且另一条链在相同的一般位置(臼)中包含较小的氨基酸。此外，为了促进重链与其预期的轻链的特异性配对，CH1与轻链之间的界面氨基酸可以突变为在形状和电荷-电荷相互作用方面是互补的。
可以作为杵引入在对应于犬类IgG-A(SEQ ID NO:162)的位置138的位置处、在对应于犬类IgG-B Fc(SEQ ID NO:163)的位置137的位置处、在对应于犬类IgG-C Fc(SEQ IDNO:165)的位置137的位置处、或在对应于犬类IgG-D Fc(SEQ ID NO:167)的位置138的位置处色氨酸对酪氨酸的氨基酸取代(T138W或T137W)。第一变体犬类IgG-A Fc、IgG-B Fc、IgG-C Fc和IgG-D Fc的氨基酸序列的例子分别是SEQ ID NO:195、SEQ ID NO:196、SEQ ID NO:197和SEQ ID NO:198。
可以作为臼引入在对应于犬类IgG-A(SEQ ID NO:162)或IgG-D(SEQ ID NO:167)的位置138的位置处苏氨酸对丝氨酸以及在对应于位置140的位置处亮氨酸对丙氨酸的氨基酸取代(T138S、L140A)，或者在对应于犬类IgG-B Fc(SEQ ID NO:163)或IgG-C(SEQ IDNO:165)的位置137的位置处苏氨酸对丝氨酸以及在对应于位置139的位置处亮氨酸对丙氨酸的氨基酸取代(T137S、L139A)。第二变体犬类IgG-A Fc、IgG-B Fc、IgG-C Fc和IgG-D Fc的氨基酸序列的例子是SEQ ID NO:199、SEQ ID NO:200、SEQ ID NO:201和SEQ ID NO:202。
可以引入在对应于犬类IgG-A CH1(SEQ ID NO:227)、犬类IgG-B CH1(SEQ ID NO:228)、犬类IgG-C CH1(SEQ ID NO:229)或犬类IgG-D CH1(SEQ ID NO:230)的位置24的位置处丙氨酸对亮氨酸以及在对应于位置30的位置处丝氨酸对天冬酰胺的氨基酸取代(A24L、S30D)。变体犬类IgG-A CH1、IgG-B CH1、IgG-C CH1和IgG-D CH1的氨基酸序列的例子是SEQID NO:231、SEQ ID NO:232、SEQ ID NO:233和SEQ ID NO:234。
可以引入在对应于犬类κ恒定区(SEQ ID NO:235)的位置11的位置处苯丙氨酸对丙氨酸以及在对应于位置22的位置处丝氨酸对精氨酸的氨基酸取代(F11A、S22R)。变体犬类κ恒定区的氨基酸序列的例子是SEQ ID NO:236。
可以作为杵引入在对应于猫类IgG1a Fc(SEQ ID NO:203或SEQ ID NO:204)、猫类IgG1b Fc(SEQ ID NO:205或SEQ ID NO:206)或猫类IgG2(SEQ ID NO:207)的位置154的位置处苏氨酸对色氨酸的氨基酸取代(T154W)。第一变体猫类IgG2 Fc、IgG1a Fc和IgG1b Fc的氨基酸序列的例子是SEQ ID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220和SEQ ID NO:221。
可以作为臼引入在对应于猫类IgG1a(SEQ ID NO:203或SEQ ID NO:204)、猫类IgG-b Fc(SEQ ID NO:205或SEQ ID NO:206)或猫类IgG2 Fc(SEQ ID NO:207)的位置154的位置处苏氨酸对丝氨酸以及在对应于位置156的位置处亮氨酸对丙氨酸的氨基酸取代(T154S、L156A)。第二变体猫类IgG2 Fc、IgG1a Fc和IgG1b Fc的氨基酸序列的例子是SEQID NO:222、SEQ ID NO:223、SEQ ID NO:224、SEQ ID NO:225和SEQ ID NO:226。
可以引入在对应于猫类IgG1 CH1(SEQ ID NO:237)的位置24的位置处丙氨酸对亮氨酸以及在对应于位置30的位置处丝氨酸对天冬酰胺的氨基酸取代，或者在对应于猫类IgG2 CH1(SEQ ID NO:238)的位置24的位置处丙氨酸对亮氨酸以及在对应于位置29的位置处丝氨酸对天冬酰胺的氨基酸取代。变体猫类IgG1 CH1和IgG2 CH1的氨基酸序列的例子是SEQ ID NO:239和SEQ ID NO:240。
可以引入在对应于猫类κ恒定区(SEQ ID NO:241)的位置11的位置处苯丙氨酸对丙氨酸以及在对应于位置22的位置处丝氨酸对精氨酸的氨基酸取代(F11A、S22R)。变体猫类κ恒定区的氨基酸序列的例子是SEQ ID NO:242。
可以作为杵引入在对应于马类IgG1 Fc(SEQ ID NO:247)、马类IgG2 Fc(SEQ IDNO:248)、马类IgG3 Fc(SEQ ID NO:249)、马类IgG4 Fc(SEQ ID NO:250)、马类IgG5 Fc(SEQID NO:251)、马类IgG6 Fc(SEQ ID NO:252)或马类IgG7 Fc(SEQ ID NO:253)的位置130的位置处苏氨酸对色氨酸的氨基酸取代(T130W)。第一变体马类IgG1 Fc、IgG2 Fc、IgG3 Fc、IgG4 Fc、IgG5 Fc、IgG6 Fc和IgG7 Fc的氨基酸序列的例子分别是SEQ ID NO:254、SEQ IDNO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259和SEQ ID NO:260。
可以作为臼引入在对应于马类IgG1 Fc(SEQ ID NO:247)、马类IgG2 Fc(SEQ IDNO:248)、马类IgG3 Fc(SEQ ID NO:249)、马类IgG4 Fc(SEQ ID NO:250)、马类IgG5 Fc(SEQID NO:251)、马类IgG6 Fc(SEQ ID NO:252)或马类IgG7 Fc(SEQ ID NO:253)的位置130的位置处苏氨酸对丝氨酸以及在对应于位置132的位置处亮氨酸对丙氨酸的氨基酸取代(T130W)。第二变体马类IgG1 Fc、IgG2 Fc、IgG3 Fc、IgG4 Fc、IgG5Fc、IgG6 Fc和IgG7 Fc的氨基酸序列的例子分别是SEQ ID NO:261、SEQ ID NO:262、SEQ ID NO:263、SEQ ID NO:264、SEQ ID NO:265、SEQ ID NO:266和SEQ ID NO:267。
上述方法可以用于制备针对IL4R和其他靶标的双特异性抗体，所述其他靶标如IL17、IL31、TNFα、CD20、CD19、CD25、IL4、IL13、IL23、IgE、CD11α、IL6R、α4-整合素、IL12、IL1β或BlyS。例如，可以制备针对犬类IL4R和犬类IL31的双特异性抗体，其具有氨基酸序列SEQID NO:243(具有双特异性杵的犬源化克隆I可变HC v2和变体IgG-B Fc C1q-、CD16-)、SEQID NO:244(犬源化克隆I可变LC v2和可变犬类κ恒定区)、SEQ ID NO:245(具有双特异性臼的犬源化抗犬类IL31克隆M14可变HC和变体犬类IgG-B Fc C1q-、CD16-)和SEQ ID NO:246(犬源化抗犬类IL31克隆M14可变LC和犬类κ恒定区)。
实施例16
与犬类IL4R结合的另外的小鼠单克隆抗体的鉴定
使用由293细胞产生的犬类IL4R细胞外结构域作为免疫原，使用标准免疫鉴定小鼠单克隆抗体。在免疫期间使用不同的佐剂(Antibody Solutions,桑尼维尔(Sunnyvale),加利福尼亚州)，并且通过标准杂交瘤技术获得单克隆抗体。显影酶联免疫吸附测定(ELISA)以筛选产生犬类IL4R结合抗体的克隆。首先将犬类IL4R生物素化，并且然后将其引入链霉亲和素包被的孔中。然后将免疫的血清添加到孔中，随后用HRP缀合的抗小鼠抗体洗涤和检测。犬类IL4R结合抗体的存在显露了阳性信号。鉴定出具有高结合信号的超过100种ELISA阳性克隆。
此外，进行中和(犬类IL4阻断)ELISA。鉴定出四种克隆，它们与犬类IL4R的结合可以被犬类IL4抑制。犬类IL4与犬类IL4R的结合被四种克隆抑制：M3、M5、M8和M9。
从杂交瘤细胞培养物中纯化所述四种小鼠抗体，并且使用生物传感器(ForteBioOctetRed)测量它们与犬类IL4R的亲和力。生物素化的犬类IL4R与链霉亲和素传感器尖端结合。所述4种候选物的Kd均小于10nM。
实施例17
M3、M5、M8和M9的VH和VL序列的鉴定
沉淀产生M3、M5、M8和M9的杂交瘤细胞。提取RNA，并且使用标准技术，使用用于扩增小鼠免疫球蛋白(Ig)可变结构域的寡核苷酸引物来获得cDNA。确定所述四种克隆中的每一种的可变重链(VH)和可变轻链(VL)(SEQ ID NO:292(M3 VH)、SEQ ID NO:293(M3 VL)、SEQ ID NO:308(M5 VH)、SEQ ID NO:309(M5 VL)、SEQ ID NO:324(M8 VH)、SEQ ID NO:325(M8 VL)、SEQ ID NO:340(M9 VH)、SEQ ID NO:341(M9 VL)。
实施例18
鼠类-犬类嵌合抗体从CHO细胞的表达和纯化
设计编码嵌合抗体的DNA序列以用于将鼠类VH和鼠类VL融合至犬类恒定重链IgG-B和犬类恒定轻链(k)。化学合成核苷酸序列并且插入适用于转染到CHO宿主细胞中的表达载体中。转染到CHO细胞中后，从细胞中分泌轻链蛋白或重链蛋白或两者。通过单步蛋白质A柱色谱法纯化所有四种嵌合犬类IgG-B。使用生物传感器(ForteBio OctetRed)证实它们与犬类IL4R的亲和力<10nM。
实施例19
从CHO细胞的犬源化和表达
通过搜索和选择合适的犬类种系抗体序列作为用于CDR移植的模板，随后进行蛋白质建模，对鼠类(M3、M9)VH和VL进行犬源化。将犬源化可变轻链M3(SEQ ID NO:344)和犬源化可变轻链M9(SEQ ID NO:347)与犬类CLκ融合(分别产生SEQ ID NO:350和353)。将M3的犬源化可变重链(SEQ ID NO:342和SEQ ID NO:343)和M9的犬源化可变重链(SEQ ID NO:344和SEQ ID NO:345)与变体犬类IgG-B融合，从而分别产生SEQ ID NO 348、SEQ ID NO:349、SEQ ID NO:351和SEQ ID NO:352)。所述重链和轻链易于表达，并且用蛋白质A柱在单步中纯化。
犬源化抗体表达良好，并且维持与犬类IL4R的结合亲和力≤1nM。
实施例20
基于犬类IL4R细胞的信号传导测定的开发
从ATCC(CRL10389)购买犬类DH82细胞(一种来源于恶性组织细胞增生症的犬类巨噬细胞样细胞系)，将其以10e5个细胞/孔接种在96孔板中，并且在37℃、5％ CO2下孵育过夜(在如ATCC推荐的15％ FBS D-MEM中)。在5％ CO2、37℃下，用在不含FBS的D-MEM中连续稀释的抗IL4R或杂交瘤上清液制剂替换每个孔中的培养基，进行细胞的血清饥饿和抗体预孵育。然后，将犬类IL4细胞因子(RnD AF754)以1ng/mL(最终浓度)添加至每个孔中，在5％CO2、37℃下保持15min。在每个孔中添加二十微升终止溶液(M-per Thermo Fisher#78501)。通过抗磷酸化STAT6(RnD MAB3717)蛋白质印迹法测定每个孔中的IL4诱导的STAT6磷酸化。
如通过抗磷酸化STAT6蛋白质印迹所评估的，M3、M8和M9小鼠抗体抑制了STAT6磷酸化。
实施例21
M3、M8和M9犬类IL4R结合表位的鉴定
由于基于蛋白质印迹，M3、M8和M9不识别人IL4R，但对犬类IL4R有强烈反应，因此制备并且表达组合嵌合犬类-人IL4R融合分子，以鉴定每种抗体结合的一个或多个最小犬类区段。
图9A展示了用于犬类IL4R表位作图分析的犬类/人IL4R ECD杂合多肽(在以上实施例11的表位作图中使用相同的杂合构建体)。图9B总结了用M3、M8和M9抗体探测犬类IL4RECD、人IL4R ECD和不同犬类/人IL4R ECD杂合多肽的蛋白质印迹分析。表中的NR表示在相应的蛋白质印迹中抗体与杂合IL4R ECD无反应，表明被人IL4R序列替代的犬类IL4R序列对于抗体结合(表位)是重要的。
确定了M3结合具有序列DFMGSENHTCVPEN(SEQ ID NO:354)的表位。确定了M8与具有序列GSVKVLHEPSCFSDYISTSVCQWKMDHPTNCSA(SEQ ID NO:355)的第一表位和具有序列REDSVCVCSMPI(SEQ ID NO:356)的第二表位结合。确定了M9与具有序列REDSVCVCSMPIDDAVEADV(SEQ ID NO:357)的表位结合。
实施例22
筛选具有增强的犬类FcRn/B2M结合的变体犬类IgG-B多肽
将具有聚His标签的犬类FcRn(SEQ ID NO:379)和犬类B2M(SEQ ID NO:380)异源二聚体复合物在HEK细胞中瞬时表达，并且使用Ni-NTA色谱纯化。
对犬类IgG-B Fc噬菌体文库进行了针对表达、生物物理特性和亲和力的快速筛选(FASEBA)。简而言之，将犬类IgG-B Fc多肽的开放阅读框亚克隆至质粒pFASEBA中。基于犬类IgG-B/犬类FcRn/犬类B2M复合物的三维蛋白质建模，犬类IgG-B的十二个氨基酸位置被鉴定为可能参与IgG-B与FcRn/B2M之间的结合。鉴定出的犬类IgG-B的十二个位置是SEQ IDNO:163或SEQ ID NO:164的Thr(21)、Leu(22)、Leu(23)、Ile(24)、Ala(25)、Thr(27)、Gly(80)、His(81)、Gln(82)、Leu(85)、Met(201)和Asn(207)。
制备了犬类IgG-B Fc的十二个单位点NNK突变文库，使得每个文库都应包括变体IgG-B Fc多肽，所述变体IgG-B Fc多肽在十二个位点中的每一个处都具有被取代的20种可能氨基酸中的每一种。在pH 6.0下针对犬类FcRn/B2M复合物淘选每个噬菌体文库。在三轮淘选之后，将总共53个Fc噬菌体克隆鉴定为可能具有增强的FcRn/B2M结合，并且通过测序鉴定了突变。
对表达具有SASA标签的53种变体犬类IgG-B Fc多肽中的每一种的单个大肠杆菌(E.coli)菌落进行培养，并诱导其表达Fc多肽。将含有变体犬类IgG-B Fc多肽的细胞培养基暴露于板或Biacore芯片上的固定化BSA。将结合有变体犬类IgG-B Fc多肽的板或芯片暴露于可溶性犬类FcRn/B2M复合物，以筛选pH 6下的缓慢解离速率(koff)。鉴定了与野生型IgG-B Fc多肽相比，展现出的与犬类FcRn/B2M复合物的koff较慢的每种变体IgG-B Fc多肽。鉴定出四种先导变体犬类IgG-B多肽：L(23)Y(SEQ ID NO:382；“Y00”)；L(23)F(SEQ IDNO:381；“F00”)；L(23)M；以及L(23)S。
进一步研究了每种先导变体犬类IgG-B多肽的koff。将生物素化的犬类FcRn/B2M复合物固定在Biacore芯片上，并且使用Biacore T200在pH 6.0下暴露于作为分析物的每种变体犬类IgG-B多肽。野生型犬类IgG-B Fc多肽的koff(1/s)是1.22x10-1；变体犬类IgG-BFc多肽L(23)Y(“Y00”)的koff(1/s)是1.38x10-2；变体IgG-B Fc多肽L(23)F(“F00”)的koff(1/s)是6.31x10-2和8.47x10-2；变体犬类IgG-B多肽L(23)M的koff(1/s)是1.26x10-1；并且变体犬类IgG-B多肽L(23)S的koff(1/s)是2.41x10-1。
使用Biacore T200进行了结合分析。简而言之，将具有SASA标签的先导变体犬类IgG-B Fc多肽各自固定至S系列传感器芯片CM5上。在25℃下监测每种变体IgG-B Fc多肽与各种浓度的犬类FcRn/B2M复合物(12.5、25、50、100和200nM)的缔合，直到达到稳态。使用10mM HEPES、500mM NaCl、3mM EDTA、0.005％ Tween-20的运行缓冲液(pH 6.0)。使用仅缓冲液空白曲线作为对照。结果呈现于图10-图14中。野生型犬类IgG-B Fc多肽的稳态Kd是1.25x10-6(图10)；变体犬类IgG-B Fc多肽L(23)Y(“Y00”)的稳态Kd是1.13x10-7(图11)；变体犬类IgG-B Fc多肽L(23)F(“F00”)的稳态Kd是3.67x10-7(图12)；并且变体犬类IgG-B Fc多肽L(23)M的稳态Kd是4.06x10-7(图13)；并且变体犬类IgG-B Fc多肽YTE的稳态Kd是8.62x10-8(图14)。
实施例23
犬类IgG中的Phe突变增强犬类FcRn相互作用
在嵌合抗体的背景下评价变体犬类Fc多肽对FcRn的亲和力。表达了与犬类κ轻链融合的抗体可变轻链和与包含SEQ ID NO:383(F00；蛋白A+；C1q-；CD16-)或SEQ ID NO:384(蛋白A+；C1q+；CD16+)的变体犬类IgG-A Fc多肽和与包含SEQ ID NO:385(F00；蛋白A+；C1q-；CD16-)或SEQ ID NO:386(蛋白A+；C1q+；CD16+)的变体犬类IgG-D Fc多肽融合的可变重链。
使用生物传感器OctetRed如下进行了结合分析。简而言之，在链霉抗生物素蛋白传感器尖端上捕获生物素化的TNFα。20μg/mL的抗体的缔合是与TNFα结合。然后将复合物用于在pH 6.0下与犬类FcRn(50μg/mL)结合。在pH 7.2下进行解离。
与不具有Phe突变的嵌合变体犬类IgG-A(图15，C)和不具有Phe突变的IgG-D(图15，D)相比，Phe突变增强了在低pH(pH6.0、20mM柠檬酸钠、140mM NaCl)下的犬类FcRn结合，如通过嵌合变体犬类IgG-A“F00”抗体(图15，A)和IgG-D“F00”抗体(图15，B)的结合概况所示的。具有Phe突变的嵌合变体犬类IgG-A和IgG-D抗体(图15，A和B)在低pH(pH 6.0)下展现出增强的与犬类FcRn的缔合，并且在中性pH(PBS pH 7.2)下展现出快速解离。在嵌合变体犬类IgG-B“F00”抗体的情况下也观察到类似的增强的结合概况。
实施例24
犬类IgG中Phe突变的药代动力学
使用斯普拉-道来大鼠进行了药代动力学分析。向大鼠皮下施用2mg/kg的嵌合变体犬类IgG-A“F00”抗体和不具有Phe突变的嵌合变体犬类IgG-A(每组两只大鼠)。在注射前以及注射后0.5、1、6、24、48、72、168、216和336小时从大鼠收集血清样品。通过ELISA如下测定了血清样品中的犬类嵌合抗体浓度。
将捕获抗体(1μg/mL，在PBS中)包被在96孔Maxisorp板上，每孔具有100μl。将板在4℃下孵育过夜并用PBST(含有0.05％ Tween-20的PBS)洗涤五次。将每个孔用在PBST中的200μl 5％ BSA封闭，并将板在室温下孵育1小时。用PBST洗涤板五次。将对照抗体的稀释液(1,000ng/mL至0.1ng/mL)一式两份添加至板中，并与不含对照抗体的空白孔一起用于产生标准曲线。在5％ BSA-PBST中按10倍、20倍和40倍稀释度制备血清样品并将其添加至板中。将板在室温下孵育1小时并用PBST洗涤5次。将100μl的在5％BSA-PBST中的HRP缀合的抗体(Bio-Rad，目录号HCA204P)以0.25μg/mL添加到每个孔中。将板在室温下孵育1小时并用PBST洗涤5次。将100μl QuantaBlu(Thermo Scientific，目录号15169)添加至每个孔中。孵育10-15分钟后，在325nm/420nm(发射/激发)下测量荧光。根据标准曲线计算血清样品中抗TNFα的滴度。
IgG-A的AUC0-336h是150970，而IgG-A“F00”是848924ng/mL*h(图16)。终末半衰期估计分别为33小时和152小时。因此，单个Phe突变显著改善了抗体在大鼠中的药代动力学特征。
实施例25
犬类、猫类和马类IgG Fc中的Phe突变
使用三维蛋白质结构分析对犬类IgG-A、IgG-B、IgG-C和IgG-D Fc中的Phe突变与FcRn之间的相互作用进行了建模。Phe的芳族侧链显现与犬类FcRn在“WPE”基序的Pro疏水环(π-CH)处具有疏水相互作用。此外，Phe疏水侧链可以与同一“WPE”基序的Pro旁边的Glu侧链直接接触。如果Glu侧链去质子化为带负电荷(如在中性pH下)，则该相互作用可能会产生能量损耗。因此，可能需要一定水平的Glu残基质子化以使芳族化合物与Glu-H的相互作用最小化。这可以解释为什么具有Phe突变的变体IgG与FcRn之间的相互作用在中性pH下降低。基于蛋白质结构分析，相互作用在犬类IgG-A、IgG-B、IgG-C和IgG-D Fc之间显现是保守的。
此外，对在复合时猫类IgG1a和IgG2 Fc中的Phe突变与猫类FcRn之间的相互作用进行建模。在犬类IgG Fc的情况下观察到的相同的相互作用显现对于猫类IgG Fc是保守的。
还对复合时马类IgG1、IgG2、IgG3、IgG4、IgG5、IgG6和IgG7 Fc中的Phe突变与马类FcRn之间的相互作用进行建模。马类IgG Fc显现维持了相同的相互作用。
实施例26
其他示例性变体犬类IgG Fc增强犬类FcRn相互作用
在嵌合抗体的背景下评价另外的变体犬类Fc多肽对FcRn的亲和力。表达了与犬类κ轻链融合的抗体可变轻链和与野生型IgG-B Fc多肽(包含SEQ ID NO:163)、变体犬类IgG-B Fc多肽0Y0(包含SEQ ID NO:387)、变体犬类IgG-B Fc多肽0YH(包含SEQ ID NO:388)、变体犬类IgG-B Fc多肽0YY(包含SEQ ID NO:389)以及变体犬类IgG-B Fc多肽00Y(包含SEQID NO:390)融合的可变重链序列。
使用生物传感器OctetRed如下进行了结合分析。简而言之，在链霉亲和素传感器尖端上捕获生物素化的靶标。20μg/mL的抗体的缔合是与生物素化的靶标结合。然后将复合物用于在pH 6.0下与犬类FcRn(50μg/mL)结合。在pH 7.2下进行解离。
与嵌合野生型犬类IgG-B抗体相比，每种嵌合变体犬类IgG-B抗体在pH 6.0下均展现出增强的与犬类FcRn的结合，并且各自在中性pH下具有相当可观的解离速率(图17)。
实施例27
变体犬类IgG Fc延长抗体在犬类体内的半衰期
在嵌合抗体的背景下评价针对FcRn的变体犬类Fc多肽的体内半衰期。表达了与犬类κ轻链融合的抗体可变轻链和与野生型IgG-B Fc多肽(包含SEQ ID NO:163)、变体犬类IgG-B Fc多肽YTE(包含SEQ ID NO:391)、变体犬类IgG-B Fc多肽0Y0(包含SEQ ID NO:387)、变体犬类IgG-B Fc多肽F00(包含SEQ ID NO:381)、变体犬类IgG-B Fc多肽0YH(包含SEQ ID NO:388)和变体犬类IgG-B Fc多肽Y00(包含SEQ ID NO:382)融合的可变重链，并将其在PBS(pH 7.2)中纯化至40mg/mL。
在Absorption Systems加利福尼亚州公司进行犬类药代动力学。从纽约州NorthRose的Marshall Bioresources获得雄性比格犬(约8-14kg)。共使用12只狗用于研究，每组n＝2只狗。将六种抗体以4mg/Kg皮下施用于狗。在注射前和注射后6、24、48、72、96、120、144、168、216、264、336、504和672小时收集血清样品。如所述通过ELISA确定犬类嵌合抗体浓度。将在144小时和336小时的时间之间的Cp转换为Ln[Cp]，然后拟合至Ln[Cp]t＝-k*t+Ln[Cp]144h形式的线性方程。然后从斜率k计算终末半衰期，如下表12中列出的。犬类IgG-BFc中的0Y0、F00、0YH和Y00突变大大改善了抗体在狗体内的半衰期。
表12：变体犬类IgG Fc对狗体内抗体半衰期的影响
| 狗 | 半衰期(天) |
| WT 1 | 13 |
| WT 2 | 13 |
| YTE 1 | *NR |
| YTE 2 | 15 |
| 0Y0 1 | *NR |
| 0Y0 2 | 28 |
| F00 1 | *NR |
| F00 2 | 23 |
| 0YH 1 | 22 |
| 0YH 2 | 23 |
| Y00 1 | 33 |
| Y00 2 | 39 |
*NR：结果不可靠
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<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B LC-FR2
<400> 18
Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile Tyr
1 5 10 15
<210> 19
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B LC-FR3
<400> 19
Gly Val Pro Lys Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser
1 5 10 15
Leu Thr Ile Ser Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys
20 25 30
<210> 20
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B LC-FR4
<400> 20
Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys
1 5 10
<210> 21
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B可变HC
<400> 21
Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 22
<211> 106
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B可变LC
<400> 22
Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Leu Gly Glu
1 5 10 15
Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu
20 25 30
Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile Tyr
35 40 45
Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly Ser
50 55 60
Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser Glu
65 70 75 80
Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp Thr
85 90 95
Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys
100 105
<210> 23
<211> 135
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆B可变HC
<400> 23
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser
130 135
<210> 24
<211> 126
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆B可变LC
<400> 24
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala
20 25 30
Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile
35 40 45
Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys
50 55 60
Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg
65 70 75 80
Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser
85 90 95
Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser
100 105 110
Tyr Pro Trp Thr Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys
115 120 125
<210> 25
<211> 440
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B HC
<400> 25
Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala
115 120 125
Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu
130 135 140
Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly
145 150 155 160
Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp
165 170 175
Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Pro Arg Pro
180 185 190
Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys
195 200 205
Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile
210 215 220
Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val
245 250 255
Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val
260 265 270
Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala
305 310 315 320
Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro
325 330 335
Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala
340 345 350
Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu
355 360 365
Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr
370 375 380
Lys Asn Thr Gln Pro Ile Met Asn Thr Asn Gly Ser Tyr Phe Val Tyr
385 390 395 400
Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe
405 410 415
Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys
420 425 430
Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 26
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆B LC
<400> 26
Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Leu Gly Glu
1 5 10 15
Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu
20 25 30
Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile Tyr
35 40 45
Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly Ser
50 55 60
Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser Glu
65 70 75 80
Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp Thr
85 90 95
Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys Arg Ala Asp Ala Ala Pro
100 105 110
Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly
115 120 125
Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn
145 150 155 160
Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser
165 170 175
Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr
180 185 190
Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe
195 200 205
Asn Arg Asn Glu Cys
210
<210> 27
<211> 459
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆B HC
<400> 27
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr
130 135 140
Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu
145 150 155 160
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp
165 170 175
Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser
195 200 205
Pro Arg Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser
210 215 220
Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys
225 230 235 240
Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
245 250 255
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
260 265 270
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
275 280 285
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
290 295 300
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
305 310 315 320
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
325 330 335
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
340 345 350
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
355 360 365
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
370 375 380
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
385 390 395 400
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asn Thr Asn Gly Ser Tyr
405 410 415
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
420 425 430
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
435 440 445
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455
<210> 28
<211> 233
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆B LC
<400> 28
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala
20 25 30
Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile
35 40 45
Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys
50 55 60
Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg
65 70 75 80
Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser
85 90 95
Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser
100 105 110
Tyr Pro Trp Thr Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys Arg Ala
115 120 125
Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu
130 135 140
Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro
145 150 155 160
Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn
165 170 175
Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr
180 185 190
Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His
195 200 205
Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile
210 215 220
Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 29
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-H1
<400> 29
Gly Tyr Thr Phe Thr Ser Tyr Val Met His
1 5 10
<210> 30
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-H2
<400> 30
Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe Lys
1 5 10 15
Gly
<210> 31
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-H3
<400> 31
Phe Tyr Tyr Gly Phe Ala Tyr
1 5
<210> 32
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I HC-FR1
<400> 32
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser
20 25
<210> 33
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I HC-FR2
<400> 33
Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly
1 5 10
<210> 34
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I HC-FR3
<400> 34
Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Ala
20 25 30
<210> 35
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I HC-FR4
<400> 35
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
1 5 10
<210> 36
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-L1
<400> 36
Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu Ser
1 5 10
<210> 37
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-L2
<400> 37
Ala Ala Ser Thr Leu Asp Ser
1 5
<210> 38
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I CDR-L3
<400> 38
Leu Gln Tyr Ala Ser Tyr Pro Trp Thr
1 5
<210> 39
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I LC-FR1
<400> 39
Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Ser Leu Thr Cys Arg Ala Ser
20 25
<210> 40
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I LC-FR2
<400> 40
Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile Tyr
1 5 10 15
<210> 41
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I LC-FR3
<400> 41
Gly Val Pro Lys Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser
1 5 10 15
Leu Thr Ile Ser Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys
20 25 30
<210> 42
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I LC-FR4
<400> 42
Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys
1 5 10
<210> 43
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I可变HC
<400> 43
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ala
115
<210> 44
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I可变LC
<400> 44
Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser
65 70 75 80
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys
100 105
<210> 45
<211> 135
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆I可变HC
<400> 45
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ala
130 135
<210> 46
<211> 127
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆I可变LC
<400> 46
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu
35 40 45
Ile Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile
50 55 60
Lys Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys
65 70 75 80
Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser
85 90 95
Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala
100 105 110
Ser Tyr Pro Trp Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys
115 120 125
<210> 47
<211> 440
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I HC
<400> 47
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala
115 120 125
Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu
130 135 140
Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly
145 150 155 160
Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp
165 170 175
Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Pro Arg Pro
180 185 190
Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys
195 200 205
Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile
210 215 220
Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val
245 250 255
Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val
260 265 270
Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala
305 310 315 320
Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro
325 330 335
Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala
340 345 350
Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu
355 360 365
Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr
370 375 380
Lys Asn Thr Gln Pro Ile Met Asn Thr Asn Gly Ser Tyr Phe Val Tyr
385 390 395 400
Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe
405 410 415
Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys
420 425 430
Ser Leu Ser His Ser Pro Gly Lys
435 440
<210> 48
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆I LC
<400> 48
Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser
65 70 75 80
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala
100 105 110
Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly
115 120 125
Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu
145 150 155 160
Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser
165 170 175
Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr
180 185 190
Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser
195 200 205
Phe Asn Arg Asn Glu Cys
210
<210> 49
<211> 459
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆I HC
<400> 49
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser Val Tyr
130 135 140
Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu
145 150 155 160
Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp
165 170 175
Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu
180 185 190
Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser
195 200 205
Pro Arg Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser
210 215 220
Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys
225 230 235 240
Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro
245 250 255
Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr
260 265 270
Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser
275 280 285
Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg
290 295 300
Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile
305 310 315 320
Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn
325 330 335
Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys
340 345 350
Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu
355 360 365
Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe
370 375 380
Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala
385 390 395 400
Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asn Thr Asn Gly Ser Tyr
405 410 415
Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly
420 425 430
Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His
435 440 445
Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys
450 455
<210> 50
<211> 234
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的克隆I LC
<400> 50
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu
35 40 45
Ile Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile
50 55 60
Lys Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys
65 70 75 80
Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser
85 90 95
Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala
100 105 110
Ser Tyr Pro Trp Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg
115 120 125
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln
130 135 140
Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln
165 170 175
Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr
180 185 190
Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg
195 200 205
His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro
210 215 220
Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
225 230
<210> 51
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：嵌合克隆B可变HC和犬类IgG-B
(嵌合B HC)
<400> 51
Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 52
<211> 216
<212> PRT
<213> 人工序列
<220>
<223> 合成的：嵌合克隆B可变LC和犬类κ轻
恒定区(嵌合B LC)
<400> 52
Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Leu Gly Glu
1 5 10 15
Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu
20 25 30
Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile Tyr
35 40 45
Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly Ser
50 55 60
Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser Glu
65 70 75 80
Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp Thr
85 90 95
Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys Arg Asn Asp Ala Gln Pro
100 105 110
Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly Ser
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile Asn
130 135 140
Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr
165 170 175
Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser Cys
180 185 190
Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe Gln
195 200 205
Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 53
<211> 470
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的嵌合克隆B可变HC和犬类IgG-B
<400> 53
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Lys Leu Glu Glu Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu
145 150 155 160
Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser
195 200 205
Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala
210 215 220
Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg
225 230 235 240
Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
245 250 255
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
275 280 285
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
290 295 300
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
325 330 335
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
340 345 350
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
355 360 365
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
370 375 380
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
385 390 395 400
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
405 410 415
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
420 425 430
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
435 440 445
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
450 455 460
Ser His Ser Pro Gly Lys
465 470
<210> 54
<211> 236
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的嵌合克隆B可变LC和犬类κ轻
恒定区
<400> 54
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala
20 25 30
Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile
35 40 45
Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys
50 55 60
Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg
65 70 75 80
Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser
85 90 95
Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Ser
100 105 110
Tyr Pro Trp Thr Phe Gly Gly Gly Ala Arg Leu Glu Ile Lys Arg Asn
115 120 125
Asp Ala Gln Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu
130 135 140
His Thr Gly Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro
145 150 155 160
Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr
165 170 175
Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser
180 185 190
Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu
195 200 205
Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile
210 215 220
Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
225 230 235
<210> 55
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：嵌合克隆I可变HC和犬类IgG-B
(嵌合I HC)
<400> 55
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ala Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 56
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：嵌合克隆I可变LC和犬类κ轻
恒定区(嵌合I LC)
<400> 56
Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser
65 70 75 80
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 57
<211> 470
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的嵌合克隆I可变HC和犬类IgG-B
<400> 57
Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys
1 5 10 15
Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys
20 25 30
Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe
35 40 45
Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn
65 70 75 80
Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser
85 90 95
Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val
100 105 110
Tyr Tyr Cys Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly
115 120 125
Thr Leu Val Thr Val Ser Ala Ala Ser Thr Thr Ala Pro Ser Val Phe
130 135 140
Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu
145 150 155 160
Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
165 170 175
Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu
180 185 190
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser
195 200 205
Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala
210 215 220
Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg
225 230 235 240
Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
245 250 255
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
275 280 285
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
290 295 300
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
325 330 335
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
340 345 350
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
355 360 365
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
370 375 380
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
385 390 395 400
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
405 410 415
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
420 425 430
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
435 440 445
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
450 455 460
Ser His Ser Pro Gly Lys
465 470
<210> 58
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有前导序列的嵌合克隆I可变LC和犬类κ轻
恒定区
<400> 58
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser
20 25 30
Ala Ser Leu Gly Glu Arg Val Ser Leu Thr Cys Arg Ala Ser Gln Glu
35 40 45
Ile Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile
50 55 60
Lys Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Lys
65 70 75 80
Arg Phe Ser Gly Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser
85 90 95
Ser Leu Glu Ser Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Tyr Ala
100 105 110
Ser Tyr Pro Trp Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg
115 120 125
Asn Asp Ala Gln Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln
130 135 140
Leu His Thr Gly Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp
165 170 175
Thr Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr
180 185 190
Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His
195 200 205
Glu Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu
210 215 220
Ile Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
225 230 235
<210> 59
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变HC v1
<400> 59
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 60
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变HC v2
<400> 60
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 61
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变LC v1
<400> 61
Glu Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ser Leu Ser Gln Glu
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Ser Phe Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Val Ala Val Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys
100 105
<210> 62
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变LC v2
<400> 62
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys
100 105
<210> 63
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v1
<400> 63
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 64
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2
<400> 64
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 65
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v1
<400> 65
Glu Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ser Leu Ser Gln Glu
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Ser Phe Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Val Ala Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys
100 105
<210> 66
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v2
<400> 66
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys
100 105
<210> 67
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆B可变HC
<400> 67
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 68
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆B可变LC
<400> 68
Asp Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 69
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v1
<400> 69
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 70
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v1
<400> 70
Asp Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 71
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变HC v1和变体犬类
IgG-B C1q -, CD16 -
<400> 71
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 72
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变HC v2和变体犬类
IgG-B C1q -, CD16 -
<400> 72
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 73
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变LC v1和犬类κ
轻恒定区
<400> 73
Glu Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ser Leu Ser Gln Glu
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Ser Phe Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Val Ala Val Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 74
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆B可变LC v2和犬类κ
轻恒定区
<400> 74
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 75
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v1和变体犬类
IgG-B C1q -, CD16 -
<400> 75
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 76
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2和变体犬类
IgG-B C1q -, CD16 -
<400> 76
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 77
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v1和犬类κ
轻恒定区
<400> 77
Glu Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ser Leu Ser Gln Glu
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Ser Phe Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Val Ala Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Ala Lys Leu Glu Ile Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 78
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v2和犬类κ
轻恒定区
<400> 78
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 79
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆B可变HC和具有铰链Cys修饰的变体猫类IgG2
<400> 79
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys
210 215 220
Thr Gly Glu Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 80
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆B可变HC和具有猫类IgG1铰链的变体猫类IgG2
<400> 80
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Lys Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Asn Tyr Gly Ile Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Arg Lys Thr Asp His Pro Pro Gly Pro Lys
210 215 220
Pro Cys Asp Cys Pro Lys Cys Pro Pro Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 81
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆B可变LC和猫类κ轻
恒定区
<400> 81
Asp Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Val Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ser Asp Ala Gln
100 105 110
Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp Glu Leu His Thr Gly
115 120 125
Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe Tyr Pro Lys Glu Val
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Val Gln Asn Lys Gly Ile Gln
145 150 155 160
Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln Ser His Glu Lys Phe
180 185 190
Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser Thr Leu Val Lys Ser
195 200 205
Phe Asn Arg Ser Glu Cys Gln Arg Glu
210 215
<210> 82
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v1和具有铰链Cys修饰的变体猫类
IgG2
<400> 82
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys
210 215 220
Thr Gly Glu Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 83
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v1和具有猫类IgG1铰链的变体猫类
IgG2
<400> 83
Gln Val Leu Leu Val Gln Ser Gly Ala Glu Val Arg Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Phe Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Leu Arg Gln Ala Pro Ala Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Leu Thr Leu Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Ala Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Arg Lys Thr Asp His Pro Pro Gly Pro Lys
210 215 220
Pro Cys Asp Cys Pro Lys Cys Pro Pro Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 84
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v1和猫类κ
轻恒定区
<400> 84
Asp Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ser Asp Ala Gln
100 105 110
Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp Glu Leu His Thr Gly
115 120 125
Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe Tyr Pro Lys Glu Val
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Val Gln Asn Lys Gly Ile Gln
145 150 155 160
Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln Ser His Glu Lys Phe
180 185 190
Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser Thr Leu Val Lys Ser
195 200 205
Phe Asn Arg Ser Glu Cys Gln Arg Glu
210 215
<210> 85
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：IL4R表位1 (最小序列)
<220>
<221> 尚未归类的特征
<222> (2)..(2)
<223> X是D或N
<220>
<221> 尚未归类的特征
<222> (9)..(9)
<223> X是H或R
<400> 85
Leu Xaa Phe Met Gly Ser Glu Asn Xaa Thr
1 5 10
<210> 86
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成的：IL4R表位1 (扩展序列)
<220>
<221> 尚未归类的特征
<222> (7)..(7)
<223> X是D或N
<220>
<221> 尚未归类的特征
<222> (14)..(14)
<223> X是H或R
<400> 86
Arg Leu Ser Tyr Gln Leu Xaa Phe Met Gly Ser Glu Asn Xaa Thr Cys
1 5 10 15
Val Pro Glu Asn
20
<210> 87
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：IL4R表位2
<220>
<221> 尚未归类的特征
<222> (3)..(3)
<223> X是P或L
<220>
<221> 尚未归类的特征
<222> (4)..(4)
<223> X是I或M
<220>
<221> 尚未归类的特征
<222> (7)..(7)
<223> X是A或F
<220>
<221> 尚未归类的特征
<222> (16)..(16)
<223> X是D或H
<220>
<221> 尚未归类的特征
<222> (21)..(21)
<223> X是Q或T
<400> 87
Ser Met Xaa Xaa Asp Asp Xaa Val Glu Ala Asp Val Tyr Gln Leu Xaa
1 5 10 15
Leu Trp Ala Gly Xaa Gln
20
<210> 88
<211> 10
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(10)
<223> 犬类IL4R表位1 (最小序列)
<400> 88
Leu Asp Phe Met Gly Ser Glu Asn His Thr
1 5 10
<210> 89
<211> 20
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(20)
<223> 犬类IL4R表位1 (扩展序列)
<400> 89
Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn His Thr Cys
1 5 10 15
Val Pro Glu Asn
20
<210> 90
<211> 22
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(22)
<223> 犬类IL4R表位2
<400> 90
Ser Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp
1 5 10 15
Leu Trp Ala Gly Gln Gln
20
<210> 91
<211> 10
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(10)
<223> 猫类IL4R表位1 (最小序列)
<400> 91
Leu Asn Phe Met Gly Ser Glu Asn Arg Thr
1 5 10
<210> 92
<211> 20
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(20)
<223> 猫类IL4R表位1 (扩展序列)
<400> 92
Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu Asn Arg Thr Cys
1 5 10 15
Val Pro Glu Asn
20
<210> 93
<211> 22
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(22)
<223> 猫类IL4R表位2
<400> 93
Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His
1 5 10 15
Leu Trp Ala Gly Thr Gln
20
<210> 94
<211> 823
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(823)
<223> 犬类IL4R NCBI参考序列：XP_0139700003.1
白细胞介素-4受体亚基α同种型X1 [家犬]
<400> 94
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 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> 95
<211> 818
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(818)
<223> 猫类IL4R NCBI参考序列： XP_023102076.1
白细胞介素-4受体亚基α[家猫(Felis catus)]
<400> 95
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 Ser Arg Ile Tyr Asn
165 170 175
Val Thr Tyr Met Gly Pro Thr Leu Arg Val Ala Ala Ser Thr Leu Thr
180 185 190
Ser Gly Ala Ser Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Ser Tyr
195 200 205
Asn Ser Thr Trp Ser Glu Trp Ser Pro Ser Thr Lys Trp Leu Asn His
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 Val Cys Leu Ser Cys Tyr Leu Ser Val Ile Lys
245 250 255
Ile Lys Lys Glu Trp Trp Asp Gln Ile Pro Asn Pro Ala His Ser His
260 265 270
Leu Val Ala Ile Val Ile Gln Asp Pro Gln Val Ser Leu Trp Gly Lys
275 280 285
Arg Ser Arg Gly Gln Glu Pro Ala Lys Cys Ser His Trp Lys Thr Cys
290 295 300
Leu Arg Lys Leu Leu Pro Cys Leu Leu Glu His Gly Met Glu Arg Lys
305 310 315 320
Glu Asp Pro Ser Lys Ile Ala Arg Asn Gly Pro Ser Gln Gly Ser Gly
325 330 335
Lys Ser Ala Trp Cys Pro Val Glu Val Ser Lys Thr Ile Leu Trp Pro
340 345 350
Glu Ser Ile Ser Val Val Arg Cys Val Glu Leu Leu Glu Ala Pro Val
355 360 365
Glu Ser Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Lys Gly Ser Phe
370 375 380
Cys Pro Ser Pro Val Asn Leu Glu Asp Ser Phe Gln Glu Gly Arg Glu
385 390 395 400
Gly Ile Ala Ala Arg Leu Thr Glu Ser Leu Phe Met Asp Leu Leu Gly
405 410 415
Val Glu Lys Gly Gly Phe Gly Pro Gln Gly Ser Leu Glu Ser Trp Phe
420 425 430
Pro Pro Pro Ser Gly Ser Ala Gly Ala Gln Met Pro Trp Ala Glu Phe
435 440 445
Pro Gly Pro Gly Pro Gln Glu Ala Ser Pro Gln Gly Lys Glu Gln Pro
450 455 460
Phe Asp Pro Arg Ser Asp Pro Leu Ala Thr Leu Pro Gln Ser Pro Ala
465 470 475 480
Ser Pro Thr Phe Pro Glu Thr Pro Pro Val Val Thr Asp Asn Pro Ala
485 490 495
Tyr Arg Ser Phe Gly Thr Phe Gln Gly Arg Ser Ser Gly Pro Gly Glu
500 505 510
Cys Asp Ser Gly Pro Glu Leu Ala Gly Arg Leu Gly Glu Ala Asp Pro
515 520 525
Gly Ile Pro Ala Ala Pro Gln Pro Ser Glu Pro Pro Ser Ala Leu Gln
530 535 540
Pro Glu Ala Glu Thr Trp Glu Gln Ile Leu Arg Gln Arg Val Leu Gln
545 550 555 560
His Arg Gly Ala Pro Ala Pro Ala Pro Gly Ser Gly Tyr Arg Glu Phe
565 570 575
Val Cys Ala Val Arg Gln Gly Ser Thr Gln Asp Ser Arg Val Gly Asp
580 585 590
Phe Gly Pro Ser Glu Glu Ala Gly Tyr Lys Ala Phe Ser Ser Leu Leu
595 600 605
Thr Ser Gly Ala Val Cys Pro Glu Thr Ser Gly Gly Glu Ala Gly Ser
610 615 620
Gly Asp Gly Gly Tyr Lys Pro Phe Gln Ser Leu Thr Pro Gly Cys Pro
625 630 635 640
Gly Ala Pro Ala Pro Val Pro Val Pro Leu Phe Thr Phe Gly Leu Asp
645 650 655
Ala Glu Pro Pro His Cys Pro Gln Asp Ser Pro Leu Pro Gly Ser Ser
660 665 670
Pro Glu Pro Ala Gly Lys Ala Gln Asp Ser His Lys Thr Pro Pro Ala
675 680 685
Pro Glu Gln Ala Ala Asp Pro Leu Arg Asp Asp Leu Ala Ser Gly Ile
690 695 700
Val Tyr Ser Ala Leu Thr Cys His Leu Cys Gly His Leu Lys Gln Cys
705 710 715 720
His Gly Gln Glu Glu Gly Gly Glu Ala His Pro Val Ala Ser Pro Cys
725 730 735
Cys Gly Cys Cys Cys Gly Asp Arg Ser Ser Pro Leu Val Ser Pro Leu
740 745 750
Arg Ala Pro Asp Pro Leu Pro Gly Gly Val Pro Leu Glu Ala Ser Leu
755 760 765
Ser Pro Ala Ser Pro Ala Pro Leu Ala Val Ser Glu Glu Gly Pro Pro
770 775 780
Ser Leu Cys Phe Gln Pro Ala Leu Ser His Ala His Ser Ser Ser Gln
785 790 795 800
Thr Pro Lys Lys Val Ala Met Leu Ser Pro Glu Pro Thr Cys Thr Met
805 810 815
Ala Ser
<210> 96
<211> 809
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(809)
<223> 马类IL4R NCBI参考序列：NP_001075243.1
白细胞介素-4受体亚基α前体[家马(Equus caballus)]
<400> 96
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 Arg 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 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 Val 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> 97
<211> 810
<212> PRT
<213> 小家鼠(Mus musculus)
<220>
<221> 尚未归类的特征
<222> (1)..(810)
<223> 鼠类IL4R NCBI参考序列：NP_001008700.1
白细胞介素-4受体亚基α同种型1 前体[小家鼠(Mus musculus)]
<400> 97
Met Gly Arg Leu Cys Thr Lys Phe Leu Thr Ser Val Gly Cys Leu Ile
1 5 10 15
Leu Leu Leu Val Thr Gly Ser Gly Ser Ile Lys Val Leu Gly Glu Pro
20 25 30
Thr Cys Phe Ser Asp Tyr Ile Arg Thr Ser Thr Cys Glu Trp Phe Leu
35 40 45
Asp Ser Ala Val Asp Cys Ser Ser Gln Leu Cys Leu His Tyr Arg Leu
50 55 60
Met Phe Phe Glu Phe Ser Glu Asn Leu Thr Cys Ile Pro Arg Asn Ser
65 70 75 80
Ala Ser Thr Val Cys Val Cys His Met Glu Met Asn Arg Pro Val Gln
85 90 95
Ser Asp Arg Tyr Gln Met Glu Leu Trp Ala Glu His Arg Gln Leu Trp
100 105 110
Gln Gly Ser Phe Ser Pro Ser Gly Asn Val Lys Pro Leu Ala Pro Asp
115 120 125
Asn Leu Thr Leu His Thr Asn Val Ser Asp Glu Trp Leu Leu Thr Trp
130 135 140
Asn Asn Leu Tyr Pro Ser Asn Asn Leu Leu Tyr Lys Asp Leu Ile Ser
145 150 155 160
Met Val Asn Ile Ser Arg Glu Asp Asn Pro Ala Glu Phe Ile Val Tyr
165 170 175
Asn Val Thr Tyr Lys Glu Pro Arg Leu Ser Phe Pro Ile Asn Ile Leu
180 185 190
Met Ser Gly Val Tyr Tyr Thr Ala Arg Val Arg Val Arg Ser Gln Ile
195 200 205
Leu Thr Gly Thr Trp Ser Glu Trp Ser Pro Ser Ile Thr Trp Tyr Asn
210 215 220
His Phe Gln Leu Pro Leu Ile Gln Arg Leu Pro Leu Gly Val Thr Ile
225 230 235 240
Ser Cys Leu Cys Ile Pro Leu Phe Cys Leu Phe Cys Tyr Phe Ser Ile
245 250 255
Thr Lys Ile Lys Lys Ile Trp Trp Asp Gln Ile Pro Thr Pro Ala Arg
260 265 270
Ser Pro Leu Val Ala Ile Ile Ile Gln Asp Ala Gln Val Pro Leu Trp
275 280 285
Asp Lys Gln Thr Arg Ser Gln Glu Ser Thr Lys Tyr Pro His Trp Lys
290 295 300
Thr Cys Leu Asp Lys Leu Leu Pro Cys Leu Leu Lys His Arg Val Lys
305 310 315 320
Lys Lys Thr Asp Phe Pro Lys Ala Ala Pro Thr Lys Ser Leu Gln Ser
325 330 335
Pro Gly Lys Ala Gly Trp Cys Pro Met Glu Val Ser Arg Thr Val Leu
340 345 350
Trp Pro Glu Asn Val Ser Val Ser Val Val Arg Cys Met Glu Leu Phe
355 360 365
Glu Ala Pro Val Gln Asn Val Glu Glu Glu Glu Asp Glu Ile Val Lys
370 375 380
Glu Asp Leu Ser Met Ser Pro Glu Asn Ser Gly Gly Cys Gly Phe Gln
385 390 395 400
Glu Ser Gln Ala Asp Ile Met Ala Arg Leu Thr Glu Asn Leu Phe Ser
405 410 415
Asp Leu Leu Glu Ala Glu Asn Gly Gly Leu Gly Gln Ser Ala Leu Ala
420 425 430
Glu Ser Cys Ser Pro Leu Pro Ser Gly Ser Gly Gln Ala Ser Val Ser
435 440 445
Trp Ala Cys Leu Pro Met Gly Pro Ser Glu Glu Ala Thr Cys Gln Val
450 455 460
Thr Glu Gln Pro Ser His Pro Gly Pro Leu Ser Gly Ser Pro Ala Gln
465 470 475 480
Ser Ala Pro Thr Leu Ala Cys Thr Gln Val Pro Leu Val Leu Ala Asp
485 490 495
Asn Pro Ala Tyr Arg Ser Phe Ser Asp Cys Cys Ser Pro Ala Pro Asn
500 505 510
Pro Gly Glu Leu Ala Pro Glu Gln Gln Gln Ala Asp His Leu Glu Glu
515 520 525
Glu Glu Pro Pro Ser Pro Ala Asp Pro His Ser Ser Gly Pro Pro Met
530 535 540
Gln Pro Val Glu Ser Trp Glu Gln Ile Leu His Met Ser Val Leu Gln
545 550 555 560
His Gly Ala Ala Ala Gly Ser Thr Pro Ala Pro Ala Gly Gly Tyr Gln
565 570 575
Glu Phe Val Gln Ala Val Lys Gln Gly Ala Ala Gln Asp Pro Gly Val
580 585 590
Pro Gly Val Arg Pro Ser Gly Asp Pro Gly Tyr Lys Ala Phe Ser Ser
595 600 605
Leu Leu Ser Ser Asn Gly Ile Arg Gly Asp Thr Ala Ala Ala Gly Thr
610 615 620
Asp Asp Gly His Gly Gly Tyr Lys Pro Phe Gln Asn Pro Val Pro Asn
625 630 635 640
Gln Ser Pro Ser Ser Val Pro Leu Phe Thr Phe Gly Leu Asp Thr Glu
645 650 655
Leu Ser Pro Ser Pro Leu Asn Ser Asp Pro Pro Lys Ser Pro Pro Glu
660 665 670
Cys Leu Gly Leu Glu Leu Gly Leu Lys Gly Gly Asp Trp Val Lys Ala
675 680 685
Pro Pro Pro Ala Asp Gln Val Pro Lys Pro Phe Gly Asp Asp Leu Gly
690 695 700
Phe Gly Ile Val Tyr Ser Ser Leu Thr Cys His Leu Cys Gly His Leu
705 710 715 720
Lys Gln His His Ser Gln Glu Glu Gly Gly Gln Ser Pro Ile Val Ala
725 730 735
Ser Pro Gly Cys Gly Cys Cys Tyr Asp Asp Arg Ser Pro Ser Leu Gly
740 745 750
Ser Leu Ser Gly Ala Leu Glu Ser Cys Pro Glu Gly Ile Pro Pro Glu
755 760 765
Ala Asn Leu Met Ser Ala Pro Lys Thr Pro Ser Asn Leu Ser Gly Glu
770 775 780
Gly Lys Gly Pro Gly His Ser Pro Val Pro Ser Gln Thr Thr Glu Val
785 790 795 800
Pro Val Gly Ala Leu Gly Ile Ala Val Ser
805 810
<210> 98
<211> 825
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 尚未归类的特征
<222> (1)..(825)
<223> 人IL4R NCBI参考序列：NP_000409.1 白细胞介素-4
受体亚基α同种型a 前体[智人(Homo sapiens)]
<400> 98
Met Gly Trp Leu Cys Ser Gly Leu Leu Phe Pro Val Ser Cys Leu Val
1 5 10 15
Leu Leu Gln Val Ala Ser Ser Gly Asn Met Lys Val Leu Gln Glu Pro
20 25 30
Thr Cys Val Ser Asp Tyr Met Ser Ile Ser Thr Cys Glu Trp Lys Met
35 40 45
Asn Gly Pro Thr Asn Cys Ser Thr Glu Leu Arg Leu Leu Tyr Gln Leu
50 55 60
Val Phe Leu Leu Ser Glu Ala His Thr Cys Ile Pro Glu Asn Asn Gly
65 70 75 80
Gly Ala Gly Cys Val Cys His Leu Leu Met Asp Asp Val Val Ser Ala
85 90 95
Asp Asn Tyr Thr Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Lys
100 105 110
Gly Ser Phe Lys Pro Ser Glu His Val Lys Pro Arg Ala Pro Gly Asn
115 120 125
Leu Thr Val His Thr Asn Val Ser Asp Thr Leu Leu Leu Thr Trp Ser
130 135 140
Asn Pro Tyr Pro Pro Asp Asn Tyr Leu Tyr Asn His Leu Thr Tyr Ala
145 150 155 160
Val Asn Ile Trp Ser Glu Asn Asp Pro Ala Asp Phe Arg Ile Tyr Asn
165 170 175
Val Thr Tyr Leu Glu Pro Ser Leu Arg Ile Ala Ala Ser Thr Leu Lys
180 185 190
Ser Gly Ile Ser Tyr Arg Ala Arg Val Arg Ala Trp Ala Gln Cys Tyr
195 200 205
Asn Thr Thr Trp Ser Glu Trp Ser Pro Ser Thr Lys Trp His Asn Ser
210 215 220
Tyr Arg Glu Pro Phe Glu Gln His Leu Leu Leu Gly Val Ser Val Ser
225 230 235 240
Cys Ile Val Ile Leu Ala Val Cys Leu Leu Cys Tyr Val Ser Ile Thr
245 250 255
Lys Ile Lys Lys Glu Trp Trp Asp Gln Ile Pro Asn Pro Ala Arg Ser
260 265 270
Arg Leu Val Ala Ile Ile Ile Gln Asp Ala Gln Gly Ser Gln Trp Glu
275 280 285
Lys Arg Ser Arg Gly Gln Glu Pro Ala Lys Cys Pro His Trp Lys Asn
290 295 300
Cys Leu Thr Lys Leu Leu Pro Cys Phe Leu Glu His Asn Met Lys Arg
305 310 315 320
Asp Glu Asp Pro His Lys Ala Ala Lys Glu Met Pro Phe Gln Gly Ser
325 330 335
Gly Lys Ser Ala Trp Cys Pro Val Glu Ile Ser Lys Thr Val Leu Trp
340 345 350
Pro Glu Ser Ile Ser Val Val Arg Cys Val Glu Leu Phe Glu Ala Pro
355 360 365
Val Glu Cys Glu Glu Glu Glu Glu Val Glu Glu Glu Lys Gly Ser Phe
370 375 380
Cys Ala Ser Pro Glu Ser Ser Arg Asp Asp Phe Gln Glu Gly Arg Glu
385 390 395 400
Gly Ile Val Ala Arg Leu Thr Glu Ser Leu Phe Leu Asp Leu Leu Gly
405 410 415
Glu Glu Asn Gly Gly Phe Cys Gln Gln Asp Met Gly Glu Ser Cys Leu
420 425 430
Leu Pro Pro Ser Gly Ser Thr Ser Ala His Met Pro Trp Asp Glu Phe
435 440 445
Pro Ser Ala Gly Pro Lys Glu Ala Pro Pro Trp Gly Lys Glu Gln Pro
450 455 460
Leu His Leu Glu Pro Ser Pro Pro Ala Ser Pro Thr Gln Ser Pro Asp
465 470 475 480
Asn Leu Thr Cys Thr Glu Thr Pro Leu Val Ile Ala Gly Asn Pro Ala
485 490 495
Tyr Arg Ser Phe Ser Asn Ser Leu Ser Gln Ser Pro Cys Pro Arg Glu
500 505 510
Leu Gly Pro Asp Pro Leu Leu Ala Arg His Leu Glu Glu Val Glu Pro
515 520 525
Glu Met Pro Cys Val Pro Gln Leu Ser Glu Pro Thr Thr Val Pro Gln
530 535 540
Pro Glu Pro Glu Thr Trp Glu Gln Ile Leu Arg Arg Asn Val Leu Gln
545 550 555 560
His Gly Ala Ala Ala Ala Pro Val Ser Ala Pro Thr Ser Gly Tyr Gln
565 570 575
Glu Phe Val His Ala Val Glu Gln Gly Gly Thr Gln Ala Ser Ala Val
580 585 590
Val Gly Leu Gly Pro Pro Gly Glu Ala Gly Tyr Lys Ala Phe Ser Ser
595 600 605
Leu Leu Ala Ser Ser Ala Val Ser Pro Glu Lys Cys Gly Phe Gly Ala
610 615 620
Ser Ser Gly Glu Glu Gly Tyr Lys Pro Phe Gln Asp Leu Ile Pro Gly
625 630 635 640
Cys Pro Gly Asp Pro Ala Pro Val Pro Val Pro Leu Phe Thr Phe Gly
645 650 655
Leu Asp Arg Glu Pro Pro Arg Ser Pro Gln Ser Ser His Leu Pro Ser
660 665 670
Ser Ser Pro Glu His Leu Gly Leu Glu Pro Gly Glu Lys Val Glu Asp
675 680 685
Met Pro Lys Pro Pro Leu Pro Gln Glu Gln Ala Thr Asp Pro Leu Val
690 695 700
Asp Ser Leu Gly Ser Gly Ile Val Tyr Ser Ala Leu Thr Cys His Leu
705 710 715 720
Cys Gly His Leu Lys Gln Cys His Gly Gln Glu Asp Gly Gly Gln Thr
725 730 735
Pro Val Met Ala Ser Pro Cys Cys Gly Cys Cys Cys Gly Asp Arg Ser
740 745 750
Ser Pro Pro Thr Thr Pro Leu Arg Ala Pro Asp Pro Ser Pro Gly Gly
755 760 765
Val Pro Leu Glu Ala Ser Leu Cys Pro Ala Ser Leu Ala Pro Ser Gly
770 775 780
Ile Ser Glu Lys Ser Lys Ser Ser Ser Ser Phe His Pro Ala Pro Gly
785 790 795 800
Asn Ala Gln Ser Ser Ser Gln Thr Pro Lys Ile Val Asn Phe Val Ser
805 810 815
Val Gly Pro Thr Tyr Met Arg Val Ser
820 825
<210> 99
<211> 203
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(203)
<223> 犬类IL4R_ECD
<400> 99
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu
195 200
<210> 100
<211> 203
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(203)
<223> 猫类IL4R_ECD
<400> 100
Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr Phe
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu Asn
35 40 45
Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys Ser
50 55 60
Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His Leu
65 70 75 80
Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser Ser
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Val
100 105 110
Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu Asn
115 120 125
His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu Asp
130 135 140
Asp Pro Thr Asp Ser Arg Ile Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Val Ala Ala Ser Thr Leu Thr Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Ser Tyr Asn Ser Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp Leu Asn His Tyr Glu
195 200
<210> 101
<211> 206
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(206)
<223> 马类IL4R_ECD
<400> 101
Val Lys Val Leu Arg Leu Thr Ala Cys Phe Ser Asp Tyr Ile Ser Ala
1 5 10 15
Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys Ser Ala Gln
20 25 30
Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp Asn Leu Thr
35 40 45
Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys Arg Met Leu
50 55 60
Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp Leu Trp Ala
65 70 75 80
Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser Arg His Val
85 90 95
Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile Ser His Thr
100 105 110
Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn His Leu Trp
115 120 125
Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp Asp Pro Thr
130 135 140
Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr Leu Arg Val
145 150 155 160
Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala Arg Val Lys
165 170 175
Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp Ser Pro Ser
180 185 190
Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro Leu Glu Gln Arg
195 200 205
<210> 102
<211> 238
<212> PRT
<213> 小家鼠(Mus musculus)
<220>
<221> 尚未归类的特征
<222> (1)..(238)
<223> 鼠类IL4R_ECD
<400> 102
Ile Lys Val Leu Gly Glu Pro Thr Cys Phe Ser Asp Tyr Ile Arg Thr
1 5 10 15
Ser Thr Cys Glu Trp Phe Leu Asp Ser Ala Val Asp Cys Ser Ser Gln
20 25 30
Leu Cys Leu His Tyr Arg Leu Met Phe Phe Glu Phe Ser Glu Asn Leu
35 40 45
Thr Cys Ile Pro Arg Asn Ser Ala Ser Thr Val Cys Val Cys His Met
50 55 60
Glu Met Asn Arg Pro Val Gln Ser Asp Arg Tyr Gln Met Glu Leu Trp
65 70 75 80
Ala Glu His Arg Gln Leu Trp Gln Gly Ser Phe Ser Pro Ser Gly Asn
85 90 95
Val Lys Pro Leu Ala Pro Asp Asn Leu Thr Leu His Thr Asn Val Ser
100 105 110
Asp Glu Trp Leu Leu Thr Trp Asn Asn Leu Tyr Pro Ser Asn Asn Leu
115 120 125
Leu Tyr Lys Asp Leu Ile Ser Met Val Asn Ile Ser Arg Glu Asp Asn
130 135 140
Pro Ala Glu Phe Ile Val Tyr Asn Val Thr Tyr Lys Glu Pro Arg Leu
145 150 155 160
Ser Phe Pro Ile Asn Ile Leu Met Ser Gly Val Tyr Tyr Thr Ala Arg
165 170 175
Val Arg Val Arg Ser Gln Ile Leu Thr Gly Thr Trp Ser Glu Trp Ser
180 185 190
Pro Ser Ile Thr Trp Tyr Asn His Phe Gln Leu Pro Leu Ile Gln Arg
195 200 205
Leu Pro Leu Gly Val Thr Ile Ser Cys Leu Cys Ile Pro Leu Phe Cys
210 215 220
Leu Phe Cys Tyr Phe Ser Ile Thr Lys Ile Lys Lys Ile Trp
225 230 235
<210> 103
<211> 209
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 尚未归类的特征
<222> (1)..(209)
<223> 人IL4R_ECD
<400> 103
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Thr Asn Val
100 105 110
Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn
115 120 125
Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn Ile Trp Ser Glu Asn
130 135 140
Asp Pro Ala Asp Phe Arg Ile Tyr Asn Val Thr Tyr Leu Glu Pro Ser
145 150 155 160
Leu Arg Ile Ala Ala Ser Thr Leu Lys Ser Gly Ile Ser Tyr Arg Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Cys Tyr Asn Thr Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gln
195 200 205
His
<210> 104
<211> 835
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(835)
<223> 具有前导序列的犬类IL4R_C-FLAG
<400> 104
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 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 Gly Ser Gly Ser Asp Tyr Lys Asp Asp
820 825 830
Asp Asp Lys
835
<210> 105
<211> 812
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(812)
<223> 犬类IL4R_C-FLAG
<400> 105
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Trp Glu Gln His
195 200 205
Leu Pro Leu Gly Val Ser Ile Ser Cys Leu Val Ile Leu Ala Ile Cys
210 215 220
Leu Ser Cys Tyr Phe Ser Ile Ile Lys Ile Lys Lys Gly Trp Trp Asp
225 230 235 240
Gln Ile Pro Asn Pro Ala His Ser Pro Leu Val Ala Ile Val Ile Gln
245 250 255
Asp Ser Gln Val Ser Leu Trp Gly Lys Arg Ser Arg Gly Gln Glu Pro
260 265 270
Ala Lys Cys Pro His Trp Lys Thr Cys Leu Thr Lys Leu Leu Pro Cys
275 280 285
Leu Leu Glu His Gly Leu Gly Arg Glu Glu Glu Ser Pro Lys Thr Ala
290 295 300
Lys Asn Gly Pro Leu Gln Gly Pro Gly Lys Pro Ala Trp Cys Pro Val
305 310 315 320
Glu Val Ser Lys Thr Ile Leu Trp Pro Glu Ser Ile Ser Val Val Gln
325 330 335
Cys Val Glu Leu Ser Glu Ala Pro Val Asp Asn Glu Glu Glu Glu Glu
340 345 350
Val Glu Glu Asp Lys Arg Ser Leu Cys Pro Ser Leu Glu Gly Ser Gly
355 360 365
Gly Ser Phe Gln Glu Gly Arg Glu Gly Ile Val Ala Arg Leu Thr Glu
370 375 380
Ser Leu Phe Leu Asp Leu Leu Gly Gly Glu Asn Gly Gly Phe Cys Pro
385 390 395 400
Gln Gly Leu Glu Glu Ser Cys Leu Pro Pro Pro Ser Gly Ser Val Gly
405 410 415
Ala Gln Met Pro Trp Ala Gln Phe Pro Arg Ala Gly Pro Arg Ala Ala
420 425 430
Pro Glu Gly Pro Glu Gln Pro Arg Arg Pro Glu Ser Ala Leu Gln Ala
435 440 445
Ser Pro Thr Gln Ser Ala Gly Ser Ser Ala Phe Pro Glu Pro Pro Pro
450 455 460
Val Val Thr Asp Asn Pro Ala Tyr Arg Ser Phe Gly Ser Phe Leu Gly
465 470 475 480
Gln Ser Ser Asp Pro Gly Asp Gly Asp Ser Asp Pro Glu Leu Ala Asp
485 490 495
Arg Pro Gly Glu Ala Asp Pro Gly Ile Pro Ser Ala Pro Gln Pro Pro
500 505 510
Glu Pro Pro Ala Ala Leu Gln Pro Glu Pro Glu Ser Trp Glu Gln Ile
515 520 525
Leu Arg Gln Ser Val Leu Gln His Arg Ala Ala Pro Ala Pro Gly Pro
530 535 540
Gly Pro Gly Ser Gly Tyr Arg Glu Phe Thr Cys Ala Val Lys Gln Gly
545 550 555 560
Ser Ala Pro Asp Ala Gly Gly Pro Gly Phe Gly Pro Ser Gly Glu Ala
565 570 575
Gly Tyr Lys Ala Phe Cys Ser Leu Leu Pro Gly Gly Ala Thr Cys Pro
580 585 590
Gly Thr Ser Gly Gly Glu Ala Gly Ser Gly Glu Gly Gly Tyr Lys Pro
595 600 605
Phe Gln Ser Leu Thr Pro Gly Cys Pro Gly Ala Pro Thr Pro Val Pro
610 615 620
Val Pro Leu Phe Thr Phe Gly Leu Asp Thr Glu Pro Pro Gly Ser Pro
625 630 635 640
Gln Asp Ser Leu Gly Ala Gly Ser Ser Pro Glu His Leu Gly Val Glu
645 650 655
Pro Ala Gly Lys Glu Glu Asp Ser Arg Lys Thr Leu Leu Ala Pro Glu
660 665 670
Gln Ala Thr Asp Pro Leu Arg Asp Asp Leu Ala Ser Ser Ile Val Tyr
675 680 685
Ser Ala Leu Thr Cys His Leu Cys Gly His Leu Lys Gln Trp His Asp
690 695 700
Gln Glu Glu Arg Gly Lys Ala His Ile Val Pro Ser Pro Cys Cys Gly
705 710 715 720
Cys Cys Cys Gly Asp Arg Ser Ser Leu Leu Leu Ser Pro Leu Arg Ala
725 730 735
Pro Asn Val Leu Pro Gly Gly Val Leu Leu Glu Ala Ser Leu Ser Pro
740 745 750
Ala Ser Leu Val Pro Ser Gly Val Ser Lys Glu Gly Lys Ser Ser Pro
755 760 765
Phe Ser Gln Pro Ala Ser Ser Ser Ala Gln Ser Ser Ser Gln Thr Pro
770 775 780
Lys Lys Leu Ala Val Leu Ser Thr Glu Pro Thr Cys Met Ser Ala Ser
785 790 795 800
Gly Ser Gly Ser Asp Tyr Lys Asp Asp Asp Asp Lys
805 810
<210> 106
<211> 237
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(237)
<223> 具有前导序列的犬类IL4R-ECD_C-His6
<400> 106
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys 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 Gly Ser Gly Ser His His His His His His
225 230 235
<210> 107
<211> 214
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(214)
<223> 犬类IL4R-ECD_C-His6
<400> 107
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Gly Ser
195 200 205
His His His His His His
210
<210> 108
<211> 473
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(473)
<223> 具有前导序列的犬类IL4R-ECD_ C HuFc_His6
<400> 108
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys 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 Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys
225 230 235 240
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
245 250 255
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
260 265 270
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
275 280 285
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
290 295 300
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
305 310 315 320
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
325 330 335
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
340 345 350
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
355 360 365
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
370 375 380
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
385 390 395 400
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
405 410 415
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
420 425 430
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
435 440 445
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
450 455 460
Pro Gly Lys His His His His His His
465 470
<210> 109
<211> 450
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(450)
<223> 犬类IL4R-ECD_ C HuFc_His6
<400> 109
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 110
<211> 471
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(471)
<223> 具有前导序列的猫类IL4R-ECD_ C HuFc_His6
<400> 110
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys Gly Ser Val Lys Val Leu Arg Ala Pro Thr
20 25 30
Cys Phe Ser Asp Tyr Phe Ser Thr Ser Val Cys Gln Trp Asn Met Asp
35 40 45
Ala Pro Thr Asn Cys Ser Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn
50 55 60
Phe Met Gly Ser Glu Asn Arg Thr Cys Val Pro Glu Asn Gly Glu Gly
65 70 75 80
Ala Ala Cys Ala Cys Ser Met Leu Met Asp Asp Phe Val Glu Ala Asp
85 90 95
Val Tyr Gln Leu His Leu Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly
100 105 110
Ser Phe Lys Pro Ser Ser His Val Lys Pro Arg Ala Pro Gly Asn Leu
115 120 125
Thr Val His Pro Asn Val Ser His Thr Trp Leu Leu Arg Trp Ser Asn
130 135 140
Pro Tyr Pro Pro Glu Asn His Leu His Ala Glu Leu Thr Tyr Met Val
145 150 155 160
Asn Ile Ser Ser Glu Asp Asp Pro Thr Asp Ser Arg Ile Tyr Asn Val
165 170 175
Thr Tyr Met Gly Pro Thr Leu Arg Val Ala Ala Ser Thr Leu Thr Ser
180 185 190
Gly Ala Ser Tyr Ser Ala Arg Val Arg Ala Trp Ala Gln Ser Tyr Asn
195 200 205
Ser Thr Trp Ser Asp Trp Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr
210 215 220
Glu Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys
225 230 235 240
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
245 250 255
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
260 265 270
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
275 280 285
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
290 295 300
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
305 310 315 320
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
325 330 335
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
340 345 350
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
355 360 365
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
370 375 380
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
385 390 395 400
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
405 410 415
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
420 425 430
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
435 440 445
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
450 455 460
Lys His His His His His His
465 470
<210> 111
<211> 449
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(449)
<223> 猫类IL4R-ECD_ C HuFc_His6
<400> 111
Gly Ser Val Lys Val Leu Arg Ala Pro Thr Cys Phe Ser Asp Tyr Phe
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Asn Met Asp Ala Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asn Phe Met Gly Ser Glu Asn
35 40 45
Arg Thr Cys Val Pro Glu Asn Gly Glu Gly Ala Ala Cys Ala Cys Ser
50 55 60
Met Leu Met Asp Asp Phe Val Glu Ala Asp Val Tyr Gln Leu His Leu
65 70 75 80
Trp Ala Gly Thr Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser Ser
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Val
100 105 110
Ser His Thr Trp Leu Leu Arg Trp Ser Asn Pro Tyr Pro Pro Glu Asn
115 120 125
His Leu His Ala Glu Leu Thr Tyr Met Val Asn Ile Ser Ser Glu Asp
130 135 140
Asp Pro Thr Asp Ser Arg Ile Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Val Ala Ala Ser Thr Leu Thr Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Ser Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Gly Ser Glu Asn Leu
195 200 205
Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
210 215 220
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro
225 230 235 240
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
245 250 255
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
260 265 270
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
275 280 285
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
290 295 300
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
305 310 315 320
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
325 330 335
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
340 345 350
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
355 360 365
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
370 375 380
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
385 390 395 400
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
405 410 415
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
420 425 430
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His His
435 440 445
His
<210> 112
<211> 482
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(482)
<223> 具有前导序列的马类IL4R-ECD_ C HuFc_His6
<400> 112
Met Pro Ser Ser Val Ser Trp Gly Ile Leu Leu Leu Ala Gly Leu Cys
1 5 10 15
Cys Leu Val Pro Val Ser Leu Ala Val Lys Val Leu Arg Leu Thr Ala
20 25 30
Cys Phe Ser Asp Tyr Ile Ser Ala Ser Thr Cys Glu Trp Lys Met Asp
35 40 45
Arg Pro Thr Asn Cys Ser Ala Gln Leu Arg Leu Ser Tyr Gln Leu Asn
50 55 60
Asp Glu Phe Ser Asp Asn Leu Thr Cys Ile Pro Glu Asn Arg Glu Asp
65 70 75 80
Glu Val Cys Val Cys Arg Met Leu Met Asp Asn Ile Val Ser Glu Asp
85 90 95
Val Tyr Glu Leu Asp Leu Trp Ala Gly Asn Gln Leu Leu Trp Asn Ser
100 105 110
Ser Phe Lys Pro Ser Arg His Val Lys Pro Arg Ala Pro Gln Asn Leu
115 120 125
Thr Val His Ala Ile Ser His Thr Trp Leu Leu Thr Trp Ser Asn Pro
130 135 140
Tyr Pro Leu Lys Asn His Leu Trp Ser Glu Leu Thr Tyr Leu Val Asn
145 150 155 160
Ile Ser Lys Glu Asp Asp Pro Thr Asp Phe Lys Ile Tyr Asn Val Thr
165 170 175
Tyr Met Asp Pro Thr Leu Arg Val Thr Ala Ser Thr Leu Lys Ser Arg
180 185 190
Ala Thr Tyr Ser Ala Arg Val Lys Ala Arg Ala Gln Asn Tyr Asn Ser
195 200 205
Thr Trp Ser Glu Trp Ser Pro Ser Thr Thr Trp His Asn Tyr Tyr Glu
210 215 220
Gln Pro Leu Glu Gln Arg Gly Gly Gly Ser Gly Gly Gly Ser Glu Asn
225 230 235 240
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
245 250 255
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
260 265 270
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
275 280 285
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
290 295 300
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
305 310 315 320
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
325 330 335
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
340 345 350
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
355 360 365
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
370 375 380
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
385 390 395 400
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
405 410 415
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
420 425 430
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
435 440 445
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
450 455 460
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
465 470 475 480
His His
<210> 113
<211> 458
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(458)
<223> 马类IL4R-ECD_ C HuFc_His6
<400> 113
Val Lys Val Leu Arg Leu Thr Ala Cys Phe Ser Asp Tyr Ile Ser Ala
1 5 10 15
Ser Thr Cys Glu Trp Lys Met Asp Arg Pro Thr Asn Cys Ser Ala Gln
20 25 30
Leu Arg Leu Ser Tyr Gln Leu Asn Asp Glu Phe Ser Asp Asn Leu Thr
35 40 45
Cys Ile Pro Glu Asn Arg Glu Asp Glu Val Cys Val Cys Arg Met Leu
50 55 60
Met Asp Asn Ile Val Ser Glu Asp Val Tyr Glu Leu Asp Leu Trp Ala
65 70 75 80
Gly Asn Gln Leu Leu Trp Asn Ser Ser Phe Lys Pro Ser Arg His Val
85 90 95
Lys Pro Arg Ala Pro Gln Asn Leu Thr Val His Ala Ile Ser His Thr
100 105 110
Trp Leu Leu Thr Trp Ser Asn Pro Tyr Pro Leu Lys Asn His Leu Trp
115 120 125
Ser Glu Leu Thr Tyr Leu Val Asn Ile Ser Lys Glu Asp Asp Pro Thr
130 135 140
Asp Phe Lys Ile Tyr Asn Val Thr Tyr Met Asp Pro Thr Leu Arg Val
145 150 155 160
Thr Ala Ser Thr Leu Lys Ser Arg Ala Thr Tyr Ser Ala Arg Val Lys
165 170 175
Ala Arg Ala Gln Asn Tyr Asn Ser Thr Trp Ser Glu Trp Ser Pro Ser
180 185 190
Thr Thr Trp His Asn Tyr Tyr Glu Gln Pro Leu Glu Gln Arg Gly Gly
195 200 205
Gly Ser Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys His His His His His His
450 455
<210> 114
<211> 507
<212> PRT
<213> 小家鼠(Mus musculus)
<220>
<221> 尚未归类的特征
<222> (1)..(507)
<223> 具有前导序列的鼠类IL4R-ECD_ C HuFc_His6
<400> 114
Met Gly Trp Leu Cys Ser Gly Leu Leu Phe Pro Val Ser Cys Leu Val
1 5 10 15
Leu Leu Gln Val Ala Ser Ser Ile Lys Val Leu Gly Glu Pro Thr Cys
20 25 30
Phe Ser Asp Tyr Ile Arg Thr Ser Thr Cys Glu Trp Phe Leu Asp Ser
35 40 45
Ala Val Asp Cys Ser Ser Gln Leu Cys Leu His Tyr Arg Leu Met Phe
50 55 60
Phe Glu Phe Ser Glu Asn Leu Thr Cys Ile Pro Arg Asn Ser Ala Ser
65 70 75 80
Thr Val Cys Val Cys His Met Glu Met Asn Arg Pro Val Gln Ser Asp
85 90 95
Arg Tyr Gln Met Glu Leu Trp Ala Glu His Arg Gln Leu Trp Gln Gly
100 105 110
Ser Phe Ser Pro Ser Gly Asn Val Lys Pro Leu Ala Pro Asp Asn Leu
115 120 125
Thr Leu His Thr Asn Val Ser Asp Glu Trp Leu Leu Thr Trp Asn Asn
130 135 140
Leu Tyr Pro Ser Asn Asn Leu Leu Tyr Lys Asp Leu Ile Ser Met Val
145 150 155 160
Asn Ile Ser Arg Glu Asp Asn Pro Ala Glu Phe Ile Val Tyr Asn Val
165 170 175
Thr Tyr Lys Glu Pro Arg Leu Ser Phe Pro Ile Asn Ile Leu Met Ser
180 185 190
Gly Val Tyr Tyr Thr Ala Arg Val Arg Val Arg Ser Gln Ile Leu Thr
195 200 205
Gly Thr Trp Ser Glu Trp Ser Pro Ser Ile Thr Trp Tyr Asn His Phe
210 215 220
Gln Leu Pro Leu Ile Gln Arg Leu Pro Leu Gly Val Thr Ile Ser Cys
225 230 235 240
Leu Cys Ile Pro Leu Phe Cys Leu Phe Cys Tyr Phe Ser Ile Thr Lys
245 250 255
Ile Lys Lys Ile Trp Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys
260 265 270
Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu
275 280 285
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
290 295 300
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
305 310 315 320
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val
325 330 335
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser
340 345 350
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
355 360 365
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala
370 375 380
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
385 390 395 400
Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln
405 410 415
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
420 425 430
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
435 440 445
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu
450 455 460
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser
465 470 475 480
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
485 490 495
Leu Ser Pro Gly Lys His His His His His His
500 505
<210> 115
<211> 484
<212> PRT
<213> 小家鼠(Mus musculus)
<220>
<221> 尚未归类的特征
<222> (1)..(484)
<223> 鼠类IL4R-ECD_ C HuFc_His6
<400> 115
Ile Lys Val Leu Gly Glu Pro Thr Cys Phe Ser Asp Tyr Ile Arg Thr
1 5 10 15
Ser Thr Cys Glu Trp Phe Leu Asp Ser Ala Val Asp Cys Ser Ser Gln
20 25 30
Leu Cys Leu His Tyr Arg Leu Met Phe Phe Glu Phe Ser Glu Asn Leu
35 40 45
Thr Cys Ile Pro Arg Asn Ser Ala Ser Thr Val Cys Val Cys His Met
50 55 60
Glu Met Asn Arg Pro Val Gln Ser Asp Arg Tyr Gln Met Glu Leu Trp
65 70 75 80
Ala Glu His Arg Gln Leu Trp Gln Gly Ser Phe Ser Pro Ser Gly Asn
85 90 95
Val Lys Pro Leu Ala Pro Asp Asn Leu Thr Leu His Thr Asn Val Ser
100 105 110
Asp Glu Trp Leu Leu Thr Trp Asn Asn Leu Tyr Pro Ser Asn Asn Leu
115 120 125
Leu Tyr Lys Asp Leu Ile Ser Met Val Asn Ile Ser Arg Glu Asp Asn
130 135 140
Pro Ala Glu Phe Ile Val Tyr Asn Val Thr Tyr Lys Glu Pro Arg Leu
145 150 155 160
Ser Phe Pro Ile Asn Ile Leu Met Ser Gly Val Tyr Tyr Thr Ala Arg
165 170 175
Val Arg Val Arg Ser Gln Ile Leu Thr Gly Thr Trp Ser Glu Trp Ser
180 185 190
Pro Ser Ile Thr Trp Tyr Asn His Phe Gln Leu Pro Leu Ile Gln Arg
195 200 205
Leu Pro Leu Gly Val Thr Ile Ser Cys Leu Cys Ile Pro Leu Phe Cys
210 215 220
Leu Phe Cys Tyr Phe Ser Ile Thr Lys Ile Lys Lys Ile Trp Gly Ser
225 230 235 240
Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr
245 250 255
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe
260 265 270
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
275 280 285
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
290 295 300
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
305 310 315 320
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val
325 330 335
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
340 345 350
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
355 360 365
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
370 375 380
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
385 390 395 400
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
405 410 415
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
420 425 430
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
435 440 445
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
450 455 460
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His
465 470 475 480
His His His His
<210> 116
<211> 478
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 尚未归类的特征
<222> (1)..(478)
<223> 具有前导序列的人IL4R-ECD_ C HuFc_His6
<400> 116
Met Gly Trp Leu Cys Ser Gly Leu Leu Phe Pro Val Ser Cys Leu Val
1 5 10 15
Leu Leu Gln Val Ala Ser Ser Gly Asn Met Lys Val Leu Gln Glu Pro
20 25 30
Thr Cys Val Ser Asp Tyr Met Ser Ile Ser Thr Cys Glu Trp Lys Met
35 40 45
Asn Gly Pro Thr Asn Cys Ser Thr Glu Leu Arg Leu Leu Tyr Gln Leu
50 55 60
Val Phe Leu Leu Ser Glu Ala His Thr Cys Ile Pro Glu Asn Asn Gly
65 70 75 80
Gly Ala Gly Cys Val Cys His Leu Leu Met Asp Asp Val Val Ser Ala
85 90 95
Asp Asn Tyr Thr Leu Asp Leu Trp Ala Gly Gln Gln Leu Leu Trp Lys
100 105 110
Gly Ser Phe Lys Pro Ser Glu His Val Lys Pro Arg Ala Pro Gly Asn
115 120 125
Leu Thr Val His Thr Asn Val Ser Asp Thr Leu Leu Leu Thr Trp Ser
130 135 140
Asn Pro Tyr Pro Pro Asp Asn Tyr Leu Tyr Asn His Leu Thr Tyr Ala
145 150 155 160
Val Asn Ile Trp Ser Glu Asn Asp Pro Ala Asp Phe Arg Ile Tyr Asn
165 170 175
Val Thr Tyr Leu Glu Pro Ser Leu Arg Ile Ala Ala Ser Thr Leu Lys
180 185 190
Ser Gly Ile Ser Tyr Arg Ala Arg Val Arg Ala Trp Ala Gln Cys Tyr
195 200 205
Asn Thr Thr Trp Ser Glu Trp Ser Pro Ser Thr Lys Trp His Asn Ser
210 215 220
Tyr Arg Glu Pro Phe Glu Gln His Gly Ser Glu Asn Leu Tyr Phe Gln
225 230 235 240
Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
245 250 255
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
260 265 270
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
275 280 285
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
290 295 300
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
305 310 315 320
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
325 330 335
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala
340 345 350
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
355 360 365
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
370 375 380
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
385 390 395 400
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
405 410 415
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
420 425 430
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
435 440 445
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
450 455 460
Ser Leu Ser Leu Ser Pro Gly Lys His His His His His His
465 470 475
<210> 117
<211> 455
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 尚未归类的特征
<222> (1)..(455)
<223> 人IL4R-ECD_ C HuFc_His6
<400> 117
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Thr Asn Val
100 105 110
Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn
115 120 125
Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn Ile Trp Ser Glu Asn
130 135 140
Asp Pro Ala Asp Phe Arg Ile Tyr Asn Val Thr Tyr Leu Glu Pro Ser
145 150 155 160
Leu Arg Ile Ala Ala Ser Thr Leu Lys Ser Gly Ile Ser Tyr Arg Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Cys Tyr Asn Thr Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gln
195 200 205
His Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys His His His His His His
450 455
<210> 118
<211> 132
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(132)
<223> 犬类IL4 前体 NCBI参考号：NP_001003159.1
<400> 118
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 Lys Asp Val Phe Thr Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His Asn Cys Ser Asn Arg Tyr Leu Arg Gly Leu Tyr Arg Asn Leu
85 90 95
Ser Ser Met Ala Asn Lys Thr Cys Ser Met Asn Glu Ile Lys Lys Ser
100 105 110
Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Val Ile Met Gln Lys Lys
115 120 125
Tyr Tyr Arg His
130
<210> 119
<211> 133
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(133)
<223> 猫类IL4 前体 UniProtKB/Swiss-Prot参考号：P55030.1
<400> 119
Met Gly Leu Thr Tyr 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 Val Met Asp Val Leu Ala Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Thr Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His His Asn Cys Ser Thr Lys Phe Leu Lys Gly Leu Asp Arg Asn
85 90 95
Leu Ser Ser Met Ala Asn Arg Thr Cys Ser Val Asn Glu Val Lys Lys
100 105 110
Cys Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Ala Ile Met Gln Lys
115 120 125
Lys Tyr Ser Lys His
130
<210> 120
<211> 137
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(137)
<223> 马类IL4 前体NCBI参考号：NP_001075988.1
<400> 120
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> 121
<211> 132
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(132)
<223> 犬类IL4 前体NCBI参考号： NP_001003159.1
<400> 121
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 Lys Asp Val Phe Thr Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His Asn Cys Ser Asn Arg Tyr Leu Arg Gly Leu Tyr Arg Asn Leu
85 90 95
Ser Ser Met Ala Asn Lys Thr Cys Ser Met Asn Glu Ile Lys Lys Ser
100 105 110
Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Val Ile Met Gln Lys Lys
115 120 125
Tyr Tyr Arg His
130
<210> 122
<211> 133
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(133)
<223> 猫类IL4 前体NCBI参考号：NP_001036804.1
<400> 122
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 Val Met Asp Val Leu Ala Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Thr Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His His Asn Cys Ser Thr Lys Phe Leu Lys Gly Leu Asp Arg Asn
85 90 95
Leu Ser Ser Met Ala Asn Arg Thr Cys Ser Val Asn Glu Val Lys Lys
100 105 110
Cys Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Ala Ile Met Gln Lys
115 120 125
Lys Tyr Ser Lys His
130
<210> 123
<211> 139
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(139)
<223> 预测的马类IL4 前体NCBI参考号：XP_008536927.1
<400> 123
Met Gly Leu Ile Ser 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 Gln Ser
130 135
<210> 124
<211> 151
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(151)
<223> 具有前导序列的犬类IL4_N-His6
<400> 124
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 Ser Ser His His His His His His
20 25 30
Ser Ser Gly Leu Val Pro Arg Gly Ser His Met His Asn Phe Asn Ile
35 40 45
Thr Ile Lys Glu Ile Ile Lys Met Leu Asn Ile Leu Thr Ala Arg Asn
50 55 60
Asp Ser Cys Met Glu Leu Thr Val Lys Asp Val Phe Thr Ala Pro Lys
65 70 75 80
Asn Thr Ser Asp Lys Glu Ile Phe Cys Arg Ala Ala Thr Val Leu Arg
85 90 95
Gln Ile Tyr Thr His Asn Cys Ser Asn Arg Tyr Leu Arg Gly Leu Tyr
100 105 110
Arg Asn Leu Ser Ser Met Ala Asn Lys Thr Cys Ser Met Asn Glu Ile
115 120 125
Lys Lys Ser Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Val Ile Met
130 135 140
Gln Lys Lys Tyr Tyr Arg His
145 150
<210> 125
<211> 126
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(126)
<223> 犬类IL4_N-His6
<400> 125
Ser His His His His His His Ser Ser Gly Leu Val Pro Arg Gly Ser
1 5 10 15
His Met His Asn Phe Asn Ile Thr Ile Lys Glu Ile Ile Lys Met Leu
20 25 30
Asn Ile Leu Thr Ala Arg Asn Asp Ser Cys Met Glu Leu Thr Val Lys
35 40 45
Asp Val Phe Thr Ala Pro Lys Asn Thr Ser Asp Lys Glu Ile Phe Cys
50 55 60
Arg Ala Ala Thr Val Leu Arg Gln Ile Tyr Thr His Asn Cys Ser Asn
65 70 75 80
Arg Tyr Leu Arg Gly Leu Tyr Arg Asn Leu Ser Ser Met Ala Asn Lys
85 90 95
Thr Cys Ser Met Asn Glu Ile Lys Lys Ser Thr Leu Lys Asp Phe Leu
100 105 110
Glu Arg Leu Lys Val Ile Met Gln Lys Lys Tyr Tyr Arg His
115 120 125
<210> 126
<211> 137
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(137)
<223> 具有前导序列的犬类IL4_C-His6
<400> 126
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 Lys Asp Val Phe Thr Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His Asn Cys Ser Asn Arg Tyr Leu Arg Gly Leu Tyr Arg Asn Leu
85 90 95
Ser Ser Met Ala Asn Lys Thr Cys Ser Met Asn Glu Ile Lys Lys Ser
100 105 110
Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Val Ile Met Gln Lys Lys
115 120 125
Tyr Tyr Arg His His His His His His
130 135
<210> 127
<211> 117
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(117)
<223> 犬类IL4_C-His6
<400> 127
His Asn Phe Asn Ile Thr Ile Lys Glu Ile Ile Lys Met Leu Asn Ile
1 5 10 15
Leu Thr Ala Arg Asn Asp Ser Cys Met Glu Leu Thr Val Lys Asp Val
20 25 30
Phe Thr Ala Pro Lys Asn Thr Ser Asp Lys Glu Ile Phe Cys Arg Ala
35 40 45
Ala Thr Val Leu Arg Gln Ile Tyr Thr His Asn Cys Ser Asn Arg Tyr
50 55 60
Leu Arg Gly Leu Tyr Arg Asn Leu Ser Ser Met Ala Asn Lys Thr Cys
65 70 75 80
Ser Met Asn Glu Ile Lys Lys Ser Thr Leu Lys Asp Phe Leu Glu Arg
85 90 95
Leu Lys Val Ile Met Gln Lys Lys Tyr Tyr Arg Gly Ser Gly Ser His
100 105 110
His His His His His
115
<210> 128
<211> 143
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(143)
<223> 具有前导序列的猫类IL4_C-His6
<400> 128
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 Val Met Asp Val Leu Ala Ala Pro Lys Asn Thr Ser
50 55 60
Asp Lys Glu Ile Phe Cys Arg Ala Thr Thr Val Leu Arg Gln Ile Tyr
65 70 75 80
Thr His His Asn Cys Ser Thr Lys Phe Leu Lys Gly Leu Asp Arg Asn
85 90 95
Leu Ser Ser Met Ala Asn Arg Thr Cys Ser Val Asn Glu Val Lys Lys
100 105 110
Cys Thr Leu Lys Asp Phe Leu Glu Arg Leu Lys Ala Ile Met Gln Lys
115 120 125
Lys Tyr Ser Lys His Gly Ser Gly Ser His His His His His His
130 135 140
<210> 129
<211> 119
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(119)
<223> 猫类IL4_C-His6
<400> 129
Gln Asn Phe Asn Asn Thr Leu Lys Glu Ile Ile Lys Thr Leu Asn Ile
1 5 10 15
Leu Thr Ala Arg Asn Asp Ser Cys Met Glu Leu Thr Val Met Asp Val
20 25 30
Leu Ala Ala Pro Lys Asn Thr Ser Asp Lys Glu Ile Phe Cys Arg Ala
35 40 45
Thr Thr Val Leu Arg Gln Ile Tyr Thr His His Asn Cys Ser Thr Lys
50 55 60
Phe Leu Lys Gly Leu Asp Arg Asn Leu Ser Ser Met Ala Asn Arg Thr
65 70 75 80
Cys Ser Val Asn Glu Val Lys Lys Cys Thr Leu Lys Asp Phe Leu Glu
85 90 95
Arg Leu Lys Ala Ile Met Gln Lys Lys Tyr Ser Lys His Gly Ser Gly
100 105 110
Ser His His His His His His
115
<210> 130
<211> 148
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(148)
<223> 具有前导序列的马类IL4_C-His6
<400> 130
Met Gly Leu Ile Ser 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 Gln Gly Ser Gly Ser His His
130 135 140
His His His His
145
<210> 131
<211> 124
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<222> (1)..(124)
<223> 马类IL4_C-His6
<400> 131
Cys Lys Tyr Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Asn
1 5 10 15
Leu Thr Asp Gly Lys Gly Lys Asn Ser Cys Met Glu Leu Thr Val Ala
20 25 30
Asp Ala Phe Ala Gly Pro Lys Asn Thr Asp Gly Lys Glu Ile Cys Arg
35 40 45
Ala Ala Lys Val Leu Gln Gln Leu Tyr Lys Arg His Asp Arg Ser Leu
50 55 60
Ile Lys Glu Cys Leu Ser Gly Leu Asp Arg Asn Leu Lys Gly Met Ala
65 70 75 80
Asn Gly Thr Cys Cys Thr Val Asn Glu Ala Lys Lys Ser Thr Leu Lys
85 90 95
Asp Phe Leu Glu Arg Leu Lys Thr Ile Met Lys Glu Lys Tyr Ser Lys
100 105 110
Cys Gln Gly Ser Gly Ser His His His His His His
115 120
<210> 132
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性前导序列
<400> 132
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Arg Gly Ala Arg Cys
20
<210> 133
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体1 (杂合体1)
<400> 133
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Thr Asn Val
100 105 110
Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn
115 120 125
Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn Ile Trp Ser Glu Asn
130 135 140
Asp Pro Ala Asp Phe Arg Ile Tyr Asn Val Thr Tyr Leu Glu Pro Ser
145 150 155 160
Leu Arg Ile Ala Ala Ser Thr Leu Lys Ser Gly Ile Ser Tyr Arg Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Cys Tyr Asn Thr Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gln
195 200 205
His Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys His His His His His His
450 455
<210> 134
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体2(杂合体2)
<400> 134
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Thr Asn Val
100 105 110
Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn
115 120 125
Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn Ile Trp Ser Glu Asn
130 135 140
Asp Pro Ala Asp Phe Arg Ile Tyr Asn Val Thr Tyr Leu Glu Pro Ser
145 150 155 160
Leu Arg Ile Ala Ala Ser Thr Leu Lys Ser Gly Ile Ser Tyr Arg Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Cys Tyr Asn Thr Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gln
195 200 205
His Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys His His His His His His
450 455
<210> 135
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体3 (杂合体3)
<400> 135
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 136
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体4 (杂合体4)
<400> 136
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Thr Asn Val
100 105 110
Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn
115 120 125
Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn Ile Trp Ser Glu Asn
130 135 140
Asp Pro Ala Asp Phe Arg Ile Tyr Asn Val Thr Tyr Leu Glu Pro Ser
145 150 155 160
Leu Arg Ile Ala Ala Ser Thr Leu Lys Ser Gly Ile Ser Tyr Arg Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Cys Tyr Asn Thr Thr Trp Ser Glu Trp
180 185 190
Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gln
195 200 205
His Gly Ser Glu Asn Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys His His His His His His
450 455
<210> 137
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体5 (杂合体5)
<400> 137
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 138
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体6 (杂合体6)
<400> 138
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 139
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体7 (杂合体7)
<400> 139
Gly Asn Met Lys Val Leu Gln Glu Pro Thr Cys Val Ser Asp Tyr Met
1 5 10 15
Ser Ile Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 140
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 融合体8 (融合体8)
<400> 140
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 141
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C-HuFc_His6_ 杂合体9 (杂合体9)
<400> 141
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Leu Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 142
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C HuFc_His6_ 杂合体10 (杂合体
10)
<400> 142
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Val Phe Leu Leu Ser Glu Ala
35 40 45
His Thr Cys Ile Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 143
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C HuFc_His6_ 杂合体11 (杂合体
11)
<400> 143
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His
50 55 60
Leu Leu Met Asp Asp Val Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 144
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_C HuFc_His6_ 杂合体12 (杂合体
12)
<400> 144
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 145
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_C HuFc_His6_ 杂合体13 (杂合体
13)
<400> 145
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Lys Pro Ser Glu
85 90 95
His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 146
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类/人IL4R-ECD_ C HuFc_His6_ 杂合体14 (杂合体
14)
<400> 146
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Lys Gly Ser Phe Lys Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 147
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.A33T (突变体1)
<400> 147
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Thr Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 148
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.M44A (突变体2)
<400> 148
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Ala Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 149
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.G45A (突变体3)
<400> 149
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Ala Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 150
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.N48A (突变体4)
<400> 150
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Ala
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 151
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.S38A (突变体5)
<400> 151
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ala Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 152
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.D42A (突变体6)
<400> 152
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Ala Phe Met Gly Ser Glu Asn
35 40 45
His Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 153
<211> 450
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬类IL4R-ECD_ C HuFc_His6.H49A (突变体7)
<400> 153
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala Glu Leu Arg Leu Ser Tyr Gln Leu Asp Phe Met Gly Ser Glu Asn
35 40 45
Ala Thr Cys Val Pro Glu Asn Arg Glu Asp Ser Val Cys Val Cys Ser
50 55 60
Met Pro Ile Asp Asp Ala Val Glu Ala Asp Val Tyr Gln Leu Asp Leu
65 70 75 80
Trp Ala Gly Gln Gln Leu Leu Trp Ser Gly Ser Phe Gln Pro Ser Lys
85 90 95
His Val Lys Pro Arg Thr Pro Gly Asn Leu Thr Val His Pro Asn Ile
100 105 110
Ser His Thr Trp Leu Leu Met Trp Thr Asn Pro Tyr Pro Thr Glu Asn
115 120 125
His Leu His Ser Glu Leu Thr Tyr Met Val Asn Val Ser Asn Asp Asn
130 135 140
Asp Pro Glu Asp Phe Lys Val Tyr Asn Val Thr Tyr Met Gly Pro Thr
145 150 155 160
Leu Arg Leu Ala Ala Ser Thr Leu Lys Ser Gly Ala Ser Tyr Ser Ala
165 170 175
Arg Val Arg Ala Trp Ala Gln Thr Tyr Asn Ser Thr Trp Ser Asp Trp
180 185 190
Ser Pro Ser Thr Thr Trp Leu Asn Tyr Tyr Glu Pro Gly Ser Glu Asn
195 200 205
Leu Tyr Phe Gln Gly Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
210 215 220
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe
225 230 235 240
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
245 250 255
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
260 265 270
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
275 280 285
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
290 295 300
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
305 310 315 320
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
325 330 335
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
340 345 350
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
355 360 365
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
370 375 380
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
385 390 395 400
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
405 410 415
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
420 425 430
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys His His His His
435 440 445
His His
450
<210> 154
<211> 131
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(131)
<223> 犬类IL13 前体NCBI参考号：NP_001003384
<400> 154
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> 155
<211> 184
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(184)
<223> 猫类IL13 前体NCBI参考号： XP_006927648
<400> 155
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 Gln Tyr Cys Ala Ala Leu Glu Ser Leu Ile Asn Val Ser Asp Cys
115 120 125
Thr Ala Ile Gln Arg Thr Gln Arg Met Leu Lys Ala Leu Cys Thr Gln
130 135 140
Lys Pro Ser Ala Gly Gln Thr Ala Ser Glu Arg Ser Arg Asp Thr Lys
145 150 155 160
Ile Glu Val Ile Gln Leu Val Lys Asn Leu Leu Asn His Leu Arg Arg
165 170 175
Asn Phe Arg His Gly Asn Phe Lys
180
<210> 156
<211> 139
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(139)
<223> 具有前导序列的犬类IL13_C-His6
<400> 156
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 Gly Ser His His His His His His
130 135
<210> 157
<211> 121
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(121)
<223> 犬类IL13_C-His6
<400> 157
Ser Pro Ser Pro Val Thr Pro Ser Pro Thr Leu Lys Glu Leu Ile Glu
1 5 10 15
Glu Leu Val Asn Ile Thr Gln Asn Gln Ala Ser Leu Cys Asn Gly Ser
20 25 30
Met Val Trp Ser Val Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala Leu
35 40 45
Glu Ser Leu Ile Asn Val Ser Asp Cys Ser Ala Ile Gln Arg Thr Gln
50 55 60
Arg Met Leu Lys Ala Leu Cys Ser Gln Lys Pro Ala Ala Gly Gln Ile
65 70 75 80
Ser Ser Glu Arg Ser Arg Asp Thr Lys Ile Glu Val Ile Gln Leu Val
85 90 95
Lys Asn Leu Leu Thr Tyr Val Arg Gly Val Tyr Arg His Gly Asn Phe
100 105 110
Arg Gly Ser His His His His His His
115 120
<210> 158
<211> 144
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(144)
<223> 具有前导序列的猫类IL13_C-His6
<400> 158
Met Ala Leu Trp Leu Thr Val Val Ile Ala Leu Thr Cys Leu Gly Gly
1 5 10 15
Leu Ala Ser Pro Gly Pro His Ser Arg Arg Glu Leu Lys Glu Leu Ile
20 25 30
Glu Glu Leu Val Asn Ile Thr Gln Asn Gln Leu Leu Gln Val Ser Leu
35 40 45
Cys Asn Gly Ser Met Val Trp Ser Val Asn Leu Thr Thr Gly Met Gln
50 55 60
Tyr Cys Ala Ala Leu Glu Ser Leu Ile Asn Val Ser Asp Cys Thr Ala
65 70 75 80
Ile Gln Arg Thr Gln Arg Met Leu Lys Ala Leu Cys Thr Gln Lys Pro
85 90 95
Ser Ala Gly Gln Thr Ala Ser Glu Arg Ser Arg Asp Thr Lys Ile Glu
100 105 110
Val Ile Gln Leu Val Lys Asn Leu Leu Asn His Leu Arg Arg Asn Phe
115 120 125
Arg His Gly Asn Phe Lys Gly Ser Gly Ser His His His His His His
130 135 140
<210> 159
<211> 126
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(126)
<223> 猫类IL13_C-His6
<400> 159
Ser Pro Gly Pro His Ser Arg Arg Glu Leu Lys Glu Leu Ile Glu Glu
1 5 10 15
Leu Val Asn Ile Thr Gln Asn Gln Leu Leu Gln Val Ser Leu Cys Asn
20 25 30
Gly Ser Met Val Trp Ser Val Asn Leu Thr Thr Gly Met Gln Tyr Cys
35 40 45
Ala Ala Leu Glu Ser Leu Ile Asn Val Ser Asp Cys Thr Ala Ile Gln
50 55 60
Arg Thr Gln Arg Met Leu Lys Ala Leu Cys Thr Gln Lys Pro Ser Ala
65 70 75 80
Gly Gln Thr Ala Ser Glu Arg Ser Arg Asp Thr Lys Ile Glu Val Ile
85 90 95
Gln Leu Val Lys Asn Leu Leu Asn His Leu Arg Arg Asn Phe Arg His
100 105 110
Gly Asn Phe Lys Gly Ser Gly Ser His His His His His His
115 120 125
<210> 160
<211> 427
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(427)
<223> 犬类IL13R NCBI参考号：XP_538150.3
<400> 160
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> 161
<211> 315
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(315)
<223> 犬类IL13R ECD
<400> 161
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> 162
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型犬类IgG-A Fc 蛋白A - C1q
- CD16 -
<400> 162
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 163
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型犬类IgG-B Fc 蛋白A + C1q
+ CD16 +
<400> 163
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 164
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有铰链的示例性野生型犬类IgG-B Fc 蛋白A
+ C1q + CD16 +
<400> 164
Pro Lys Arg Glu Asn Gly Arg Val Pro Arg Pro Pro Asp Cys Pro Lys
1 5 10 15
Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr
35 40 45
Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser
50 55 60
Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn
100 105 110
Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg
115 120 125
Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu
130 135 140
Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe
145 150 155 160
Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
165 170 175
Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly
180 185 190
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
195 200 205
Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn
210 215 220
His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
225 230 235
<210> 165
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型犬类IgG-C Fc 蛋白A - C1q
+ CD16 +
<400> 165
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 166
<211> 235
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有铰链的示例性野生型犬类IgG-C Fc 蛋白A
- C1q + CD16 +
<400> 166
Ala Lys Glu Cys Glu Cys Lys Cys Asn Cys Asn Asn Cys Pro Cys Pro
1 5 10 15
Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys
20 25 30
Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys Val
35 40 45
Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp Phe
50 55 60
Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu Glu
65 70 75 80
Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His
85 90 95
Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn Lys
100 105 110
Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly Gln
115 120 125
Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu Met
130 135 140
Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe Pro
145 150 155 160
Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu
165 170 175
Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr
180 185 190
Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly
195 200 205
Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
210 215 220
Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
225 230 235
<210> 167
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型犬类IgG-D Fc 蛋白A - C1q
- CD16 -
<400> 167
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 168
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc C1q - 蛋白A +
I(21)T R(23)L T(25)A E(80)G T(205)A Q(207)H
<400> 168
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 169
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc C1q - 蛋白A +
I(21)T Q(207)H
<400> 169
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 170
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
K(93)R
<400> 170
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 171
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - M(5)P
<400> 171
Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 172
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - P(39)R
<400> 172
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 173
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - D(38)G
<400> 173
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 174
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - K(97)I
<400> 174
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Ile Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 175
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - A(98)G
<400> 175
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 176
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - D(38)G K(97)I A(98)G
<400> 176
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 177
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
CD16 - D(38)G K(93)R K(97)I A(98)G
<400> 177
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 178
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 - M(5)P P(39)R
<400> 178
Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 179
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
CD16 - M(5)P P(39)R K(93)R
<400> 179
Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 180
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc C1q + 蛋白A +
I(21)T V(23)L T(24)I
<400> 180
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 181
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc C1q + 蛋白A +
I(21)T
<400> 181
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 182
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A - C1q -
K(93)R
<400> 182
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 183
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc C1q - K(93)R
蛋白A + I(21)T V(23)L T(24)I
<400> 183
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 184
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - L(5)P
<400> 184
Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 185
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - P(39)R
<400> 185
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 186
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - D(38)G
<400> 186
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 187
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - K(97)I
<400> 187
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Ile Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 188
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - A(98)G
<400> 188
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 189
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - D(38)G K(97)I A(98)G
<400> 189
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 190
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q -
CD16 - D(38)G K(93)R K(97)I A(98)G
<400> 190
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Gly Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 191
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q +
CD16 - L(5)P P(39)R
<400> 191
Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 192
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 蛋白A + C1q -
CD16 - M(5)P P(39)R K(93)R
<400> 192
Pro Gly Cys Gly Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Arg Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Arg Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 193
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc C1q - 蛋白A +
I(21)T R(23)L T(25)A E(80)G Q(207)H
<400> 193
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 194
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc C1q - 蛋白A +
I(21)T Q(207)H
<400> 194
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 195
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc 双特异性杵
T(138)W
<400> 195
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Trp Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 196
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 双特异性杵
T(137)W
<400> 196
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Trp Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 197
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 双特异性杵
T(137)W
<400> 197
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Trp Cys Leu Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 198
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc 双特异性杵
T(138)W
<400> 198
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Trp Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 199
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc 双特异性臼
T(138)S L(140)A
<400> 199
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Ser Cys Ala Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Thr Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 200
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 双特异性臼
T(137)S L(139)A
<400> 200
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Ser Cys Ala Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 201
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-C Fc 双特异性臼
T(137)S L(139)A
<400> 201
Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro Thr Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr Gln Pro Arg Glu
50 55 60
Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser Lys Thr Pro Gly
100 105 110
Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro Ser Arg Asp Glu
115 120 125
Met Ser Lys Asn Thr Val Thr Leu Ser Cys Ala Val Lys Asp Phe Phe
130 135 140
Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 202
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc 双特异性臼
T(138)S L(140)A
<400> 202
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Glu
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Ser Cys Ala Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu Gln Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 203
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型猫类IgG1a Fc 蛋白A + C1q +
<400> 203
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 204
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型猫类IgG1a Fc 蛋白A + C1q +
<400> 204
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 205
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型猫类IgG1b Fc 蛋白A + C1q +
<400> 205
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 206
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型猫类IgG1b Fc 蛋白A + C1q +
<400> 206
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 207
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型猫类IgG2 Fc 蛋白A + C1q -
<400> 207
Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 208
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有修饰铰链的示例性变体猫类IgG1a Fc
K(16)P
<400> 208
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Pro
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 209
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 蛋白A + C1q -
P(198)A
<400> 209
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 210
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 蛋白A + C1q -
P(198)A
<400> 210
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 211
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有修饰铰链的示例性变体猫类IgG1b Fc
K(16)P
<400> 211
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Pro
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 212
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 蛋白A + C1q -
P(198)A
<400> 212
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 213
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 蛋白A + C1q -
P(198)A
<400> 213
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 214
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有修饰铰链的示例性变体猫类IgG2 Fc
铰链Cys G(14)C
<400> 214
Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Cys Pro Lys
1 5 10 15
Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 215
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有修饰铰链的示例性变体猫类IgG2 Fc
K(16)P
<400> 215
Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Pro
1 5 10 15
Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 216
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有猫类IgG1铰链的示例性变体猫类IgG2 Fc
<400> 216
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 217
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 双特异性杵
T(154)W
<400> 217
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 218
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 双特异性杵
T(154)W
<400> 218
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 219
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 双特异性杵
T(154)W
<400> 219
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 220
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 双特异性杵
T(154)W
<400> 220
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 221
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG2 Fc 双特异性杵
T(154)W
<400> 221
Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Trp Cys Leu Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 222
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 双特异性臼
T(154)S, L(156)A
<400> 222
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 223
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1a Fc 双特异性臼
T(154)S, L(156)A
<400> 223
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Lys Ser Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Val Tyr Ser Lys Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 224
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 双特异性臼
T(154)S, L(156)A
<400> 224
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Pro Cys Asp Cys Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 225
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG1b Fc 双特异性臼
T(154)S, L(156)A
<400> 225
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Pro Pro Glu Met Leu Gly Gly Pro Ser Ile Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asp Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Gln Val Tyr Thr Ala Lys Thr Ser Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Asp Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Ala Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Glu Gly Phe
145 150 155 160
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Arg Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser Arg Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 226
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体猫类IgG2 Fc 双特异性臼
T(154)S, L(156)A
<400> 226
Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys
1 5 10 15
Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro
20 25 30
Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr
35 40 45
Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr
50 55 60
Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg
65 70 75 80
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
85 90 95
Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn
100 105 110
Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys
115 120 125
Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu
130 135 140
Glu Leu Ser Glu Asn Lys Val Ser Val Ser Cys Ala Ile Lys Gly Phe
145 150 155 160
His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu
165 170 175
Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly
180 185 190
Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln
195 200 205
Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser
210 215 220
His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
225 230 235
<210> 227
<211> 98
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型犬类IgG-A CH1
<400> 227
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu Val Ser Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu His Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Val His Pro Ala Ser Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 228
<211> 98
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型犬类IgG-B CH1
<400> 228
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu Val Ser Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 229
<211> 98
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型犬类IgG-C CH1
<400> 229
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Gln Ser Gly Ser Thr Val Ala Leu Ala Cys Leu Val Ser Gly Tyr
20 25 30
Ile Pro Glu Pro Val Thr Val Ser Trp Asn Ser Val Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 230
<211> 98
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型犬类IgG-D CH1
<400> 230
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu Val Ser Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Thr Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Val His Pro Ala Ser Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 231
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体犬类IgG-A CH1 A(24)L S(30)D
<400> 231
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Leu Leu Ala Cys Leu Val Asp Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu His Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Val His Pro Ala Ser Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 232
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体犬类IgG-B CH1 A(24)L S(30)D
<400> 232
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Leu Leu Ala Cys Leu Val Asp Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 233
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体犬类IgG-C CH1 A(24)L S(30)D
<400> 233
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Gln Ser Gly Ser Thr Val Leu Leu Ala Cys Leu Val Asp Gly Tyr
20 25 30
Ile Pro Glu Pro Val Thr Val Ser Trp Asn Ser Val Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 234
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体犬类IgG-D CH1 A(24)L S(30)D
<400> 234
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Ser Thr Ser Gly Ser Thr Val Leu Leu Ala Cys Leu Val Asp Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ser Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Thr Val Thr Val Pro Ser Ser Arg Trp Pro Ser Glu Thr
65 70 75 80
Phe Thr Cys Asn Val Val His Pro Ala Ser Asn Thr Lys Val Asp Lys
85 90 95
Pro Val
<210> 235
<211> 110
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<222> (1)..(110)
<223> 野生型犬类κ恒定区
<400> 235
Arg Asn Asp Ala Gln Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp
1 5 10 15
Gln Leu His Thr Gly Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe
20 25 30
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln
35 40 45
Asp Thr Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser
65 70 75 80
His Glu Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr
85 90 95
Leu Ile Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
100 105 110
<210> 236
<211> 110
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体犬类κ恒定区F(11)A S(22)R
<400> 236
Arg Asn Asp Ala Gln Pro Ala Val Tyr Leu Ala Gln Pro Ser Pro Asp
1 5 10 15
Gln Leu His Thr Gly Arg Ala Ser Val Val Cys Leu Leu Asn Ser Phe
20 25 30
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln
35 40 45
Asp Thr Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser
65 70 75 80
His Glu Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr
85 90 95
Leu Ile Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
100 105 110
<210> 237
<211> 98
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型猫类IgG1 CH1
<400> 237
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu Val Ser Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ala Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Leu Ser Asp Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Thr Val
<210> 238
<211> 98
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(98)
<223> 野生型猫类IgG2 CH1
<400> 238
Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu Ser Leu Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Leu Ser Asp Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr Lys Val Asp Lys
85 90 95
Thr Val
<210> 239
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体猫类IgG1 CH1 A(24)L S(30)D
<400> 239
Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Thr Thr Ser Gly Ala Thr Val Leu Leu Ala Cys Leu Val Asp Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ala Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Leu Ser Asp Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Pro Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Thr Val
<210> 240
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体猫类IgG2 CH1 A(24)L S(29)D
<400> 240
Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala Pro Ser Cys Gly
1 5 10 15
Thr Thr Ser Gly Ala Thr Val Leu Leu Ala Cys Leu Asp Leu Gly Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp Leu Ser Asp Thr
65 70 75 80
Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr Lys Val Asp Lys
85 90 95
Thr Val
<210> 241
<211> 110
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<222> (1)..(110)
<223> 野生型猫类κ恒定区
<400> 241
Arg Ser Asp Ala Gln Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp
1 5 10 15
Glu Leu His Thr Gly Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe
20 25 30
Tyr Pro Lys Glu Val Asn Val Lys Trp Lys Val Asp Gly Val Val Gln
35 40 45
Asn Lys Gly Ile Gln Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln
65 70 75 80
Ser His Glu Lys Phe Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser
85 90 95
Thr Leu Val Lys Ser Phe Asn Arg Ser Glu Cys Gln Arg Glu
100 105 110
<210> 242
<211> 110
<212> PRT
<213> 人工序列
<220>
<223> 合成的：变体猫类κ恒定区F(11)A S(22)R
<400> 242
Arg Ser Asp Ala Gln Pro Ser Val Phe Leu Ala Gln Pro Ser Leu Asp
1 5 10 15
Glu Leu His Thr Gly Arg Ala Ser Ile Val Cys Ile Leu Asn Asp Phe
20 25 30
Tyr Pro Lys Glu Val Asn Val Lys Trp Lys Val Asp Gly Val Val Gln
35 40 45
Asn Lys Gly Ile Gln Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln
65 70 75 80
Ser His Glu Lys Phe Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser
85 90 95
Thr Leu Val Lys Ser Phe Asn Arg Ser Glu Cys Gln Arg Glu
100 105 110
<210> 243
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2和变体犬类
IgG-B Fc C1q - CD16 - 双特异性杵 变体CH1
<400> 243
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Leu Leu Ala Cys Leu
130 135 140
Val Asp Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Thr Leu Trp
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 244
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v2和变体犬类
κ恒定区
<400> 244
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Arg Asp Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Ala Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Arg Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 245
<211> 453
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化anti-犬类IL31 克隆M14可变HC和
变体犬类IgG-B Fc C1q - CD16 - 双特异性臼
<400> 245
Glu Val Gln Leu Val Glu Ser Gly Pro Ser Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ser Val Thr Gly Asp Ser Ile Thr Ser Gly
20 25 30
Tyr Trp Asn Trp Ile Arg Lys Phe Pro Gly Asn Lys Leu Glu Tyr Met
35 40 45
Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Asp Tyr Asn Pro Ser Leu Lys
50 55 60
Ser Arg Ile Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Tyr Tyr Leu
65 70 75 80
Gln Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys Ala
85 90 95
Arg Tyr Gly Asn Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala
130 135 140
Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser
180 185 190
Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser
195 200 205
Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val
210 215 220
Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu
245 250 255
Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg
260 265 270
Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met
275 280 285
Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly
305 310 315 320
Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile
325 330 335
Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val
340 345 350
Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Thr
355 360 365
Leu Ser Cys Ala Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu
370 375 380
Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr
385 390 395 400
Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
405 410 415
Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala
420 425 430
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser
435 440 445
His Ser Pro Gly Lys
450
<210> 246
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化抗犬类IL31 克隆M14可变LC和
犬类κ恒定区
<400> 246
Asp Ile Val Met Thr Gln Ser Pro Ala Ser Leu Ser Val Ser Leu Gly
1 5 10 15
Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Thr Tyr
20 25 30
Gly Asn Ser Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro
35 40 45
Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala
50 55 60
Arg Phe Gly Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp
65 70 75 80
Pro Val Gln Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr
85 90 95
Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
100 105 110
Asn Asp Ala Gln Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln
115 120 125
Leu His Thr Gly Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr
130 135 140
Pro Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp
145 150 155 160
Thr Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His
180 185 190
Glu Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu
195 200 205
Ile Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215 220
<210> 247
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG1 Fc
<400> 247
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
1 5 10 15
Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
20 25 30
Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu Val
35 40 45
Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro Ile
85 90 95
Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Ser Lys Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile Glu
130 135 140
Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 248
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG2 Fc
<400> 248
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp
20 25 30
Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val
35 40 45
His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile
85 90 95
Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu
130 135 140
Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser
195 200 205
Glu Ser Leu Gly Lys
210
<210> 249
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG3 Fc
<400> 249
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser His
20 25 30
Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu Val
35 40 45
Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn Gly
65 70 75 80
Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr Thr
145 150 155 160
Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Val
180 185 190
Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 250
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG4 Fc
<400> 250
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 251
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG5 Fc
<400> 251
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly His
20 25 30
Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
His Ser Pro Gly Lys
210
<210> 252
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG6 Fc
<400> 252
Gly Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
20 25 30
Gln Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
35 40 45
Ala His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg
65 70 75 80
Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Lys
100 105 110
Val Tyr Ile Leu Ala Pro His Arg Glu Glu Val Thr Lys Asn Thr Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val
130 135 140
Glu Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr
145 150 155 160
Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys
180 185 190
Val Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile
195 200 205
Thr Asn Phe Pro Gly Lys
210
<210> 253
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性野生型马类IgG7 Fc
<400> 253
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 254
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG1 Fc 双特异性杵
T(130)W
<400> 254
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
1 5 10 15
Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
20 25 30
Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu Val
35 40 45
Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro Ile
85 90 95
Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Ser Lys Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile Glu
130 135 140
Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 255
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG2 Fc 双特异性杵
T(130)W
<400> 255
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp
20 25 30
Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val
35 40 45
His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile
85 90 95
Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu
130 135 140
Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser
195 200 205
Glu Ser Leu Gly Lys
210
<210> 256
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG3 Fc 双特异性杵
T(130)W
<400> 256
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser His
20 25 30
Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu Val
35 40 45
Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn Gly
65 70 75 80
Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr Thr
145 150 155 160
Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Val
180 185 190
Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 257
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG4 Fc 双特异性杵
T(130)W
<400> 257
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 258
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG5 Fc 双特异性杵
T(130)W
<400> 258
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly His
20 25 30
Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
His Ser Pro Gly Lys
210
<210> 259
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG6 Fc 双特异性杵
T(130)W
<400> 259
Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
20 25 30
Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Ala
35 40 45
His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Lys Val
100 105 110
Tyr Ile Leu Ala Pro His Arg Glu Glu Val Thr Lys Asn Thr Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val Glu
130 135 140
Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys Val
180 185 190
Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile Thr
195 200 205
Asn Phe Pro Gly Lys
210
<210> 260
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG7 Fc 双特异性杵
T(130)W
<400> 260
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Trp Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 261
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG1 Fc 双特异性臼
T(130)S L(132)A
<400> 261
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
1 5 10 15
Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
20 25 30
Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Met Asp Gly Val Glu Val
35 40 45
Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro Ile
85 90 95
Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Ser Lys Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile Glu
130 135 140
Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 262
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG2 Fc 双特异性臼
T(130)S L(132)A
<400> 262
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp
20 25 30
Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val
35 40 45
His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile
85 90 95
Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu
130 135 140
Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser
195 200 205
Glu Ser Leu Gly Lys
210
<210> 263
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG3 Fc 双特异性臼
T(130)S L(132)A
<400> 263
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser His
20 25 30
Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu Val
35 40 45
Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn Gly
65 70 75 80
Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr Thr
145 150 155 160
Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Val
180 185 190
Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile Ser
195 200 205
Lys Asn Pro Gly Lys
210
<210> 264
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG4 Fc 双特异性臼
T(130)S L(132)A
<400> 264
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 265
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG5 Fc 双特异性臼
T(130)S L(132)A
<400> 265
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly His
20 25 30
Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val Glu
130 135 140
Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys Gly
180 185 190
Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val Ser
195 200 205
His Ser Pro Gly Lys
210
<210> 266
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG6 Fc 双特异性臼
T(130)S L(132)A
<400> 266
Arg Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln
20 25 30
Glu Asn Pro Asp Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Ala
35 40 45
His Thr Ala Thr Thr Lys Ala Lys Glu Lys Gln Asp Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Arg Arg Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Arg Ala Leu Pro Ala Pro Val
85 90 95
Glu Arg Thr Ile Thr Lys Ala Lys Gly Glu Leu Gln Asp Pro Lys Val
100 105 110
Tyr Ile Leu Ala Pro His Arg Glu Glu Val Thr Lys Asn Thr Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Asp Ile Asn Val Glu
130 135 140
Trp Gln Ser Asn Glu Glu Pro Glu Pro Glu Val Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asp Arg Trp Glu Gln Gly Glu Ser Phe Thr Cys Val
180 185 190
Val Met His Glu Ala Ile Arg His Thr Tyr Arg Gln Lys Ser Ile Thr
195 200 205
Asn Phe Pro Gly Lys
210
<210> 267
<211> 213
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体马类IgG7 Fc 双特异性臼
T(130)S L(132)A
<400> 267
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Met
1 5 10 15
Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly His
20 25 30
Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Thr
35 40 45
His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr Tyr
50 55 60
Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser Gly
65 70 75 80
Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro Val
85 90 95
Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln Val
100 105 110
Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val Ser
115 120 125
Val Ser Cys Ala Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile Glu
130 135 140
Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr Thr
145 150 155 160
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
165 170 175
Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys Ala
180 185 190
Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val Ser
195 200 205
Lys Ser Pro Gly Lys
210
<210> 268
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代CDR-H2
<220>
<221> 尚未归类的特征
<222> (5)..(5)
<223> X是K、A或N
<400> 268
Tyr Ile Asn Pro Xaa Asn Asp Gly Thr
1 5
<210> 269
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆B CDR-H2
<400> 269
Tyr Ile Asn Pro Lys Asn Asp Gly Thr
1 5
<210> 270
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆B HC-FR3
<400> 270
Phe Tyr Asn Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys
1 5 10 15
Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp
20 25 30
Ser Ala Val Tyr Tyr Cys Ala Ala
35 40
<210> 271
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-H2
<400> 271
Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe Gln
1 5 10 15
Gly
<210> 272
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-H2
<400> 272
Tyr Ile Asn Pro Asn Asn Asp Gly Thr
1 5
<210> 273
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I HC-FR3
<400> 273
Phe Tyr Asn Gly Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys
1 5 10 15
Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp
20 25 30
Ser Ala Val Tyr Tyr Cys Ala Ala
35 40
<210> 274
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v3
<400> 274
Glu Val Gln Leu Val Gln Ser Ala Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Gly Thr Thr Tyr
65 70 75 80
Thr Glu Leu Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 275
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v3
<400> 275
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Ala Gly Thr Lys Val Glu Leu Lys
100 105
<210> 276
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v3和变体犬类
IgG-B C1q -, CD16 -
<400> 276
Glu Val Gln Leu Val Gln Ser Ala Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Gly Thr Thr Tyr
65 70 75 80
Thr Glu Leu Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 277
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v3和犬类κ
轻恒定区
<400> 277
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Ala Gly Thr Lys Val Glu Leu Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 278
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-H1
<400> 278
Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr Ser Val His
1 5 10
<210> 279
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-H2
<400> 279
Gly Met Ile Trp Gly Gly Gly Ser Thr
1 5
<210> 280
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-H3
<400> 280
Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr
1 5
<210> 281
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 HC-FR1
<400> 281
Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln
1 5 10 15
Ser Leu Ser Ile Thr Cys
20
<210> 282
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 HC-FR2
<400> 282
Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu
1 5 10
<210> 283
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 HC-FR3
<400> 283
Asp Tyr Asn Ser Val Phe Lys Ser Arg Leu Ser Ile Ser Lys Asp Asn
1 5 10 15
Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp
20 25 30
Thr Ala Met Tyr Tyr Cys Ala Arg
35 40
<210> 284
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 HC-FR4
<400> 284
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
1 5 10
<210> 285
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-L1
<400> 285
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 286
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-L2
<400> 286
Tyr Tyr Thr Ser Arg Leu Gln Ser
1 5
<210> 287
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 CDR-L3
<400> 287
Gln Gln Ala Asn Thr Leu Pro Leu Thr
1 5
<210> 288
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 LC-FR1
<400> 288
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys
20
<210> 289
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 LC-FR2
<400> 289
Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
1 5 10
<210> 290
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 LC-FR3
<400> 290
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Cys
1 5 10 15
Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys
20 25 30
<210> 291
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3 LC-FR4
<400> 291
Phe Gly Ser Gly Thr Lys Leu Glu Leu Lys
1 5 10
<210> 292
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3可变HC
<400> 292
Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln
1 5 10 15
Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Phe Lys
50 55 60
Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu
65 70 75 80
Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Ser
100 105 110
Val Thr Val Ser Ser
115
<210> 293
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M3可变LC
<400> 293
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Cys Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Ala Asn Thr Leu Pro Leu
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 294
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-H1
<400> 294
Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr Ser Val His
1 5 10
<210> 295
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-H2
<400> 295
Gly Met Ile Trp Gly Gly Gly Ser Thr
1 5
<210> 296
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-H3
<400> 296
Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr
1 5
<210> 297
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 HC-FR1
<400> 297
Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln
1 5 10 15
Ser Leu Ser Ile Thr Cys
20
<210> 298
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 HC-FR2
<400> 298
Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu
1 5 10
<210> 299
<211> 40
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 HC-FR3
<400> 299
Asp Tyr Asn Ser Val Phe Lys Ser Arg Leu Ser Ile Ser Lys Asp Asn
1 5 10 15
Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp
20 25 30
Thr Ala Met Tyr Tyr Cys Ala Arg
35 40
<210> 300
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 HC-FR4
<400> 300
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
1 5 10
<210> 301
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-L1
<400> 301
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 302
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-L2
<400> 302
Tyr Tyr Thr Ser Arg Leu Gln Ser
1 5
<210> 303
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 CDR-L3
<400> 303
Gln Gln Ala Asn Thr Leu Pro Leu Thr
1 5
<210> 304
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 LC-FR1
<400> 304
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys
20
<210> 305
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 LC-FR2
<400> 305
Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
1 5 10
<210> 306
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 LC-FR3
<400> 306
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Cys
1 5 10 15
Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys
20 25 30
<210> 307
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5 LC-FR4
<400> 307
Phe Gly Ser Gly Thr Lys Leu Glu Leu Lys
1 5 10
<210> 308
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5可变HC
<400> 308
Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln
1 5 10 15
Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Phe Lys
50 55 60
Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu
65 70 75 80
Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Ser
100 105 110
Val Thr Val Ser Ser
115
<210> 309
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M5可变LC
<400> 309
Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Cys Leu Thr Ile Ser Asn Leu Glu Gln
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Ala Asn Thr Leu Pro Leu
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 310
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-H1
<400> 310
Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asp Ile Asn
1 5 10
<210> 311
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-H2
<400> 311
Gly Trp Ile Tyr Pro Gly Asp Gly Ser Thr Lys
1 5 10
<210> 312
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-H3
<400> 312
Ser Ser Phe Val Val
1 5
<210> 313
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 HC-FR1
<400> 313
Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Leu Val Lys Ile Ser Cys
20
<210> 314
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 HC-FR2
<400> 314
Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
1 5 10
<210> 315
<211> 39
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 HC-FR3
<400> 315
Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser
1 5 10 15
Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser
20 25 30
Ala Val Tyr Phe Cys Ala Arg
35
<210> 316
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 HC-FR4
<400> 316
Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 317
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-L1
<400> 317
Lys Ala Ser Asp Pro Ile Asn Asn Trp Leu Ala
1 5 10
<210> 318
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-L2
<400> 318
Ser Gly Ala Thr Ser Leu Glu Thr
1 5
<210> 319
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 CDR-L3
<400> 319
His Gln Tyr Trp Ser Ile Pro Tyr Thr
1 5
<210> 320
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 LC-FR1
<400> 320
Asp Ile Gln Met Thr Gln Ser Ser Ser Tyr Leu Ser Val Ser Leu Gly
1 5 10 15
Gly Arg Val Thr Ile Thr Cys
20
<210> 321
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 LC-FR2
<400> 321
Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile
1 5 10
<210> 322
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 LC-FR3
<400> 322
Gly Val Pro Ser Arg Ile Ser Gly Ser Gly Ser Gly Lys Asp Tyr Ser
1 5 10 15
Leu Ser Ile Thr Ser Leu Gln Thr Glu Asp Ile Ala Thr Tyr Tyr Cys
20 25 30
<210> 323
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8 LC-FR4
<400> 323
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
1 5 10
<210> 324
<211> 114
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8可变HC
<400> 324
Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Leu Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asp Ile Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Tyr Pro Gly Asp Gly Ser Thr Lys Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Ser Ser Phe Val Val Trp Gly Ala Gly Thr Thr Val Thr Val
100 105 110
Ser Ser
<210> 325
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M8可变LC
<400> 325
Asp Ile Gln Met Thr Gln Ser Ser Ser Tyr Leu Ser Val Ser Leu Gly
1 5 10 15
Gly Arg Val Thr Ile Thr Cys Lys Ala Ser Asp Pro Ile Asn Asn Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile
35 40 45
Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Ile Ser Gly
50 55 60
Ser Gly Ser Gly Lys Asp Tyr Ser Leu Ser Ile Thr Ser Leu Gln Thr
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys His Gln Tyr Trp Ser Ile Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 326
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-H1
<400> 326
Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe Gly Met His
1 5 10
<210> 327
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-H2
<400> 327
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr
1 5 10
<210> 328
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-H3
<400> 328
Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr
1 5 10
<210> 329
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 HC-FR1
<400> 329
Asp Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Arg Lys Leu Ser Cys
20
<210> 330
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 HC-FR2
<400> 330
Trp Val Arg Gln Ala Pro Glu Lys Gly Leu Glu Trp Val
1 5 10
<210> 331
<211> 39
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 HC-FR3
<400> 331
Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro
1 5 10 15
Lys Asn Thr Leu Phe Leu Gln Met Thr Ser Leu Arg Ser Glu Asp Thr
20 25 30
Ala Met Tyr Tyr Cys Ala Arg
35
<210> 332
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 HC-FR4
<400> 332
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala
1 5 10
<210> 333
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-L1
<400> 333
Ser Ala Ser Ser Ser Val Ser Ser Asn Tyr Leu His
1 5 10
<210> 334
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-L2
<400> 334
Tyr Arg Thr Ser Asn Leu Pro Ser
1 5
<210> 335
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 CDR-L3
<400> 335
Gln Gln Gly Ser Gly Met Leu Thr
1 5
<210> 336
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 LC-FR1
<400> 336
Glu Ile Val Leu Thr Gln Ser Pro Thr Thr Met Ala Ala Ser Pro Gly
1 5 10 15
Glu Lys Ile Thr Ile Thr Cys
20
<210> 337
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 LC-FR2
<400> 337
Trp Tyr Gln Gln Lys Pro Gly Phe Ser Pro Lys Leu Leu Ile
1 5 10
<210> 338
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 LC-FR3
<400> 338
Gly Val Pro Ala Arg Phe Phe Gly Ser Gly Ser Gly Thr Ser Tyr Ser
1 5 10 15
Leu Thr Ile Gly Thr Met Glu Ala Glu Asp Val Ala Thr Tyr Tyr Cys
20 25 30
<210> 339
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9 LC-FR4
<400> 339
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
1 5 10
<210> 340
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9可变HC
<400> 340
Asp Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Arg Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Glu Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Thr Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Thr Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ala
115 120
<210> 341
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：克隆M9可变LC
<400> 341
Glu Ile Val Leu Thr Gln Ser Pro Thr Thr Met Ala Ala Ser Pro Gly
1 5 10 15
Glu Lys Ile Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Ser Asn
20 25 30
Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Phe Ser Pro Lys Leu Leu
35 40 45
Ile Tyr Arg Thr Ser Asn Leu Pro Ser Gly Val Pro Ala Arg Phe Phe
50 55 60
Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Gly Thr Met Glu
65 70 75 80
Ala Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Gly Ser Gly Met Leu
85 90 95
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 342
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v1
<400> 342
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Ala Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 343
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v2
<400> 343
Glu Leu Thr Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Ile Arg Gln Pro Arg Gly Arg Gly Leu Glu Leu Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Pro Ala Phe Gln
50 55 60
Gly Arg Ile Ser Ile Thr Ala Asp Thr Ala Lys Asn Gln Phe Ser Leu
65 70 75 80
Gln Leu Ser Ser Met Thr Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 344
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变LC v1
<400> 344
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Gly Arg Val Glu Ala
65 70 75 80
Glu Asp Ala Gly Ile Tyr Phe Cys Gln Gln Ala Asn Thr Leu Pro Leu
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Val Arg
100 105
<210> 345
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v1
<400> 345
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 346
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v2
<400> 346
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 347
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变LC v1
<400> 347
Asp Ile Met Leu Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Ser Ala Ser Ser Ser Val Ser Ser Asn
20 25 30
Tyr Leu His Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu
35 40 45
Ile Tyr Arg Thr Ser Asn Leu Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Gly Arg Val Glu
65 70 75 80
Ala Glu Asp Ala Gly Ile Tyr Tyr Cys Gln Gln Gly Ser Gly Met Leu
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Val Arg
100 105
<210> 348
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v1和变体犬类
IgG-B C1q -, CD16 -
<400> 348
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Ala Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 349
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v2和变体犬类
IgG-B C1q -, CD16 -
<400> 349
Glu Leu Thr Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Ile Arg Gln Pro Arg Gly Arg Gly Leu Glu Leu Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Pro Ala Phe Gln
50 55 60
Gly Arg Ile Ser Ile Thr Ala Asp Thr Ala Lys Asn Gln Phe Ser Leu
65 70 75 80
Gln Leu Ser Ser Met Thr Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 350
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变LC v1和犬类κ
轻恒定区
<400> 350
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu Ile
35 40 45
Tyr Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Gly Arg Val Glu Ala
65 70 75 80
Glu Asp Ala Gly Ile Tyr Phe Cys Gln Gln Ala Asn Thr Leu Pro Leu
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Val Arg Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 351
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v1和变体犬类
IgG-B C1q -, CD16 -
<400> 351
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 352
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v2和变体犬类
IgG-B C1q -, CD16 -
<400> 352
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 353
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变LC v1和犬类κ
轻恒定区
<400> 353
Asp Ile Met Leu Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Ser Ala Ser Ser Ser Val Ser Ser Asn
20 25 30
Tyr Leu His Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu
35 40 45
Ile Tyr Arg Thr Ser Asn Leu Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Gly Arg Val Glu
65 70 75 80
Ala Glu Asp Ala Gly Ile Tyr Tyr Cys Gln Gln Gly Ser Gly Met Leu
85 90 95
Thr Phe Gly Gln Gly Thr Arg Leu Glu Val Arg Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 354
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 合成的：M3 犬类IL4R表位
<400> 354
Asp Phe Met Gly Ser Glu Asn His Thr Cys Val Pro Glu Asn
1 5 10
<210> 355
<211> 33
<212> PRT
<213> 人工序列
<220>
<223> 合成的：M8 犬类IL4R 表位1
<400> 355
Gly Ser Val Lys Val Leu His Glu Pro Ser Cys Phe Ser Asp Tyr Ile
1 5 10 15
Ser Thr Ser Val Cys Gln Trp Lys Met Asp His Pro Thr Asn Cys Ser
20 25 30
Ala
<210> 356
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 合成的：M8 犬类IL4R 表位2
<400> 356
Arg Glu Asp Ser Val Cys Val Cys Ser Met Pro Ile
1 5 10
<210> 357
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 合成的：M9 犬类IL4R表位
<400> 357
Arg Glu Asp Ser Val Cys Val Cys Ser Met Pro Ile Asp Asp Ala Val
1 5 10 15
Glu Ala Asp Val
20
<210> 358
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-H1
<400> 358
Gly Tyr Thr Phe Thr Ser Tyr Val Met Asn
1 5 10
<210> 359
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-H2
<400> 359
Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 360
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-L1
<400> 360
Arg Ala Ser Gln Glu Ile Ser Gly Tyr Leu Ala
1 5 10
<210> 361
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-L2
<400> 361
Ala Ala Ser Thr Leu Gln Thr
1 5
<210> 362
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代克隆I CDR-L2
<400> 362
Ala Ala Ser Thr Leu Asp Thr
1 5
<210> 363
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v4
<400> 363
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 364
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v4
<400> 364
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala
65 70 75 80
Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys
100 105
<210> 365
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v2
<400> 365
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Lys Gln Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 366
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v3
<400> 366
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 367
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v2
<400> 367
Glu Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Pro Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 368
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v3
<400> 368
Glu Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Pro Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 369
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v4
<400> 369
Glu Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 370
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v4和变体犬类
IgG-B C1q -, CD16 -
<400> 370
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 371
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变LC v4和犬类κ
轻恒定区
<400> 371
Met Ser Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr
1 5 10 15
Asp Ala Arg Cys Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser
20 25 30
Val Ser Pro Gly Glu Thr Ala Ser Ile Ser Cys Arg Ala Ser Gln Glu
35 40 45
Ile Ser Gly Tyr Leu Ser Trp Leu Gln Gln Lys Pro Gly Gly Thr Ile
50 55 60
Lys Arg Leu Ile Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp
65 70 75 80
Arg Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser
85 90 95
Arg Val Glu Ala Asp Asp Thr Gly Val Tyr Tyr Cys Leu Gln Tyr Ala
100 105 110
Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Leu Lys Arg
115 120 125
Asn Asp Ala Gln Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln
130 135 140
Leu His Thr Gly Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr
145 150 155 160
Pro Lys Asp Ile Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp
165 170 175
Thr Gly Ile Gln Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr
180 185 190
Ser Leu Ser Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His
195 200 205
Glu Leu Tyr Ser Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu
210 215 220
Ile Lys Ser Phe Gln Arg Ser Glu Cys Gln Arg Val Asp
225 230 235
<210> 372
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v2和具有铰链Cys修饰的变体猫类
IgG2
<400> 372
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Lys Gln Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys
210 215 220
Thr Gly Glu Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 373
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v3和具有铰链Cys修饰的变体猫类
IgG2
<400> 373
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys
210 215 220
Thr Gly Glu Cys Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 374
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v2和具有猫类IgG1铰链的变体猫类
IgG2
<400> 374
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Lys Gln Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Arg Lys Thr Asp His Pro Pro Gly Pro Lys
210 215 220
Pro Cys Asp Cys Pro Lys Cys Pro Pro Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 375
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变HC v3和具有猫类IgG1铰链的变体猫类
IgG2
<400> 375
Asp Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Thr Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Ser Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Thr Thr Ser Gly Ala Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Leu Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ala Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Leu Ser Asp Thr Phe Thr Cys Asn Val Ala His Arg Pro Ser Ser Thr
195 200 205
Lys Val Asp Lys Thr Val Arg Lys Thr Asp His Pro Pro Gly Pro Lys
210 215 220
Pro Cys Asp Cys Pro Lys Cys Pro Pro Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
260 265 270
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
275 280 285
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
355 360 365
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
370 375 380
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
405 410 415
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
420 425 430
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
435 440 445
Pro Gly Lys
450
<210> 376
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v2和猫类κ
轻恒定区
<400> 376
Glu Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Pro Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ser Asp Ala Gln
100 105 110
Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp Glu Leu His Thr Gly
115 120 125
Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe Tyr Pro Lys Glu Val
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Val Gln Asn Lys Gly Ile Gln
145 150 155 160
Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln Ser His Glu Lys Phe
180 185 190
Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser Thr Leu Val Lys Ser
195 200 205
Phe Asn Arg Ser Glu Cys Gln Arg Glu
210 215
<210> 377
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v3和猫类κ
轻恒定区
<400> 377
Glu Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Pro Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ser Asp Ala Gln
100 105 110
Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp Glu Leu His Thr Gly
115 120 125
Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe Tyr Pro Lys Glu Val
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Val Gln Asn Lys Gly Ile Gln
145 150 155 160
Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln Ser His Glu Lys Phe
180 185 190
Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser Thr Leu Val Lys Ser
195 200 205
Phe Asn Arg Ser Glu Cys Gln Arg Glu
210 215
<210> 378
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：猫源化克隆I可变LC v4和猫类κ
轻恒定区
<400> 378
Glu Ile Thr Met Thr Gln Ser Pro Gly Ser Leu Ala Gly Ser Pro Gly
1 5 10 15
Gln Gln Val Thr Met Asn Cys Arg Ala Ser Gln Glu Ile Ser Gly Tyr
20 25 30
Leu Ser Trp Leu Gln Gln Lys Pro Asp Gly Thr Ile Lys Arg Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Ala
65 70 75 80
Glu Asp Val Ala Ser Tyr Tyr Cys Leu Gln Tyr Ala Ser Tyr Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ser Asp Ala Gln
100 105 110
Pro Ser Val Phe Leu Phe Gln Pro Ser Leu Asp Glu Leu His Thr Gly
115 120 125
Ser Ala Ser Ile Val Cys Ile Leu Asn Asp Phe Tyr Pro Lys Glu Val
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Val Gln Asn Lys Gly Ile Gln
145 150 155 160
Glu Ser Thr Thr Glu Gln Asn Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Met Ser Ser Thr Glu Tyr Gln Ser His Glu Lys Phe
180 185 190
Ser Cys Glu Val Thr His Lys Ser Leu Ala Ser Thr Leu Val Lys Ser
195 200 205
Phe Asn Arg Ser Glu Cys Gln Arg Glu
210 215
<210> 379
<211> 305
<212> PRT
<213> 人工序列
<220>
<223> 合成的：具有聚His的示例性犬类FcRn
<400> 379
Met Gly Val Pro Arg Pro Arg Ser Trp Gly Leu Gly Phe Leu Leu Phe
1 5 10 15
Leu Leu Pro Thr Leu Arg Ala Ala Asp Ser His Leu Ser Leu Leu Tyr
20 25 30
His Leu Thr Ala Val Ser Ala Pro Pro Pro Gly Thr Pro Ala Phe Trp
35 40 45
Ala Ser Gly Trp Leu Gly Pro Gln Gln Tyr Leu Ser Tyr Asn Asn Leu
50 55 60
Arg Ala Gln Ala Glu Pro Tyr Gly Ala Trp Val Trp Glu Asn Gln Val
65 70 75 80
Ser Trp Tyr Trp Glu Lys Glu Thr Thr Asp Leu Arg Thr Lys Glu Gly
85 90 95
Leu Phe Leu Glu Ala Leu Lys Ala Leu Gly Asp Gly Gly Pro Tyr Thr
100 105 110
Leu Gln Gly Leu Leu Gly Cys Glu Leu Gly Pro Asp Asn Thr Ser Val
115 120 125
Pro Val Ala Lys Phe Ala Leu Asn Gly Glu Asp Phe Met Thr Phe Asp
130 135 140
Pro Lys Leu Gly Thr Trp Asn Gly Asp Trp Pro Glu Thr Glu Thr Val
145 150 155 160
Ser Lys Arg Trp Met Gln Gln Ala Gly Ala Val Ser Lys Glu Arg Thr
165 170 175
Phe Leu Leu Tyr Ser Cys Pro Gln Arg Leu Leu Gly His Leu Glu Arg
180 185 190
Gly Arg Gly Asn Leu Glu Trp Lys Glu Pro Pro Ser Met Arg Leu Lys
195 200 205
Ala Arg Pro Gly Ser Pro Gly Phe Ser Val Leu Thr Cys Ser Ala Phe
210 215 220
Ser Phe Tyr Pro Pro Glu Leu Gln Leu Arg Phe Leu Arg Asn Gly Leu
225 230 235 240
Ala Ala Gly Ser Gly Glu Gly Asp Phe Gly Pro Asn Gly Asp Gly Ser
245 250 255
Phe His Ala Trp Ser Ser Leu Thr Val Lys Ser Gly Asp Glu His His
260 265 270
Tyr Arg Cys Leu Val Gln His Ala Gly Leu Pro Gln Pro Leu Thr Val
275 280 285
Glu Leu Glu Ser Pro Ala Lys Ser Ser Gly Ser His His His His His
290 295 300
His
305
<210> 380
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性犬类B2M
<400> 380
Met Ala Pro Arg Pro Ala Leu Ala Thr Ala Gly Phe Leu Ala Leu Leu
1 5 10 15
Leu Ile Leu Leu Ala Ala Cys Arg Leu Asp Ala Val Gln His Pro Pro
20 25 30
Lys Ile Gln Val Tyr Ser Arg His Pro Ala Glu Asn Gly Lys Pro Asn
35 40 45
Phe Leu Asn Cys Tyr Val Ser Gly Phe His Pro Pro Glu Ile Glu Ile
50 55 60
Asp Leu Leu Lys Asn Gly Lys Glu Met Lys Ala Glu Gln Thr Asp Leu
65 70 75 80
Ser Phe Ser Lys Asp Trp Thr Phe Tyr Leu Leu Val His Thr Glu Phe
85 90 95
Thr Pro Asn Glu Gln Asp Glu Phe Ser Cys Arg Val Lys His Val Thr
100 105 110
Leu Ser Glu Pro Gln Ile Val Lys Trp Asp Arg Asp Asn
115 120 125
<210> 381
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 + L(23)F (F00)
<400> 381
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 382
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q +
CD16 + L(23)Y (Y00)
<400> 382
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 383
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc (F00; 蛋白A+;
C1q -; CD16 -) I(21)T; R(23)F; T(25)A; E(80)G; T(205)A; Q(207)H
<400> 383
Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 384
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-A Fc (蛋白A+; C1q +;
CD16 +) V2A; P5M; I21T; R23L; T25A; L35V; G38D; R39P; Q65E;
E80G; R93K; H96N; I97K; D98A; T205A; Q207H
<400> 384
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe
130 135 140
Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu
145 150 155 160
Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 385
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc (F00; 蛋白A+;
C1q -; CD16 -) I(21)T; R(23)F; T(25)A; E(80)G; Q(205)A; Q(207)H
<400> 385
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 386
<211> 221
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-D Fc (蛋白A+; C1q +;
CD16 +) V2A; S5M; I21T; R23L; T25A; L35V; G38D; R39P; Q65E;
E80G; R93K; H96N; I97K; G98A; Q207H
<400> 386
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
115 120 125
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
130 135 140
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
145 150 155 160
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
165 170 175
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
180 185 190
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
195 200 205
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 387
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc (0Y0) 蛋白A +
C1q + CD16 + Q(82)Y (0Y0)
<400> 387
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 388
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc (0YH) Gln82Tyr
Asn207His
<400> 388
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His His His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 389
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc (0YY) Gln82Tyr
Asn207Tyr
<400> 389
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Tyr His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 390
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc (00Y) Asn207Tyr
<400> 390
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Tyr His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 391
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc (YTE) Leu23Tyr
Ala25Thr Thr27Glu
<400> 391
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn
85 90 95
Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 392
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
CD16 - K(93)R K(97)I A(98)G L(23)F (F00)
<400> 392
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 393
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
CD16 - K(93)R K(97)I A(98)G L(23)Y (Y00)
<400> 393
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 394
<211> 220
<212> PRT
<213> 人工序列
<220>
<223> 合成的：示例性变体犬类IgG-B Fc 蛋白A + C1q -
CD16 - K(93)R K(97)I A(98)G Q(82)Y (0Y0)
<400> 394
Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
1 5 10 15
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys
20 25 30
Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp
35 40 45
Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu
50 55 60
Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
65 70 75 80
His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn
85 90 95
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
100 105 110
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu
115 120 125
Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe
130 135 140
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
145 150 155 160
Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
165 170 175
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg
180 185 190
Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His
195 200 205
Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 395
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v1和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 395
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 396
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 396
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 397
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v3和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 397
Glu Val Gln Leu Val Gln Ser Ala Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Gly Thr Thr Tyr
65 70 75 80
Thr Glu Leu Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 398
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v4和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 398
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 399
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v1和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 399
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 400
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 400
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 401
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v3和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 401
Glu Val Gln Leu Val Gln Ser Ala Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Gly Thr Thr Tyr
65 70 75 80
Thr Glu Leu Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 402
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v4和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 402
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 403
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v1和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 403
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 404
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v2和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 404
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 405
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v3和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 405
Glu Val Gln Leu Val Gln Ser Ala Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Gly Thr Thr Tyr
65 70 75 80
Thr Glu Leu Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 406
<211> 451
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆I可变HC v4和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 406
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Asp Gly Thr Phe Tyr Asn Gly Lys Phe
50 55 60
Gln Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ala Gly Asp Ile Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Phe Tyr Tyr Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys Leu
130 135 140
Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg Trp
180 185 190
Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys Thr
195 200 205
Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
210 215 220
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp
260 265 270
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
275 280 285
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln
305 310 315 320
Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg
325 330 335
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
340 345 350
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
355 360 365
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
370 375 380
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
385 390 395 400
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
405 410 415
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
435 440 445
Pro Gly Lys
450
<210> 407
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 合成的：替代M9 CDR-H1
<400> 407
Ala Ser Gly Phe Thr Phe Ser Ser Phe Gly Met His
1 5 10
<210> 408
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变LC v2
<400> 408
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Ser Ala Ser Ser Ser Val Ser Ser Asn
20 25 30
Tyr Leu His Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu
35 40 45
Ile Tyr Arg Thr Ser Asn Leu Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu
65 70 75 80
Ala Glu Asp Ala Gly Ile Tyr Tyr Cys Gln Gln Gly Ser Gly Met Leu
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 409
<211> 217
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变LC v2和犬类?轻
恒定区
<400> 409
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Ser Ala Ser Ser Ser Val Ser Ser Asn
20 25 30
Tyr Leu His Trp Tyr Leu Gln Lys Ala Gly Gln Ser Pro Arg Leu Leu
35 40 45
Ile Tyr Arg Thr Ser Asn Leu Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu
65 70 75 80
Ala Glu Asp Ala Gly Ile Tyr Tyr Cys Gln Gln Gly Ser Gly Met Leu
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Asn Asp Ala Gln
100 105 110
Pro Ala Val Tyr Leu Phe Gln Pro Ser Pro Asp Gln Leu His Thr Gly
115 120 125
Ser Ala Ser Val Val Cys Leu Leu Asn Ser Phe Tyr Pro Lys Asp Ile
130 135 140
Asn Val Lys Trp Lys Val Asp Gly Val Ile Gln Asp Thr Gly Ile Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Met Ser Ser Thr Glu Tyr Leu Ser His Glu Leu Tyr Ser
180 185 190
Cys Glu Ile Thr His Lys Ser Leu Pro Ser Thr Leu Ile Lys Ser Phe
195 200 205
Gln Arg Ser Glu Cys Gln Arg Val Asp
210 215
<210> 410
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v1和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 410
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Ala Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 411
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v2和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 411
Glu Leu Thr Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Ile Arg Gln Pro Arg Gly Arg Gly Leu Glu Leu Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Pro Ala Phe Gln
50 55 60
Gly Arg Ile Ser Ile Thr Ala Asp Thr Ala Lys Asn Gln Phe Ser Leu
65 70 75 80
Gln Leu Ser Ser Met Thr Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 412
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v1和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 412
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 413
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v2和变体犬类
IgG-B C1q -, CD16 -, F00
<400> 413
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 414
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v1和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 414
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Ala Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 415
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v2和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 415
Glu Leu Thr Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Ile Arg Gln Pro Arg Gly Arg Gly Leu Glu Leu Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Pro Ala Phe Gln
50 55 60
Gly Arg Ile Ser Ile Thr Ala Asp Thr Ala Lys Asn Gln Phe Ser Leu
65 70 75 80
Gln Leu Ser Ser Met Thr Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 416
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v1和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 416
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 417
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v2和变体犬类
IgG-B C1q -, CD16 -, Y00
<400> 417
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 418
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v1和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 418
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Ala Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Val Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 419
<211> 452
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M3可变HC v2和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 419
Glu Leu Thr Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Tyr
20 25 30
Ser Val His Trp Ile Arg Gln Pro Arg Gly Arg Gly Leu Glu Leu Leu
35 40 45
Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Pro Ala Phe Gln
50 55 60
Gly Arg Ile Ser Ile Thr Ala Asp Thr Ala Lys Asn Gln Phe Ser Leu
65 70 75 80
Gln Leu Ser Ser Met Thr Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Thr Tyr Arg Gly Tyr Ala Leu Asp Tyr Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala Leu Ala Cys
130 135 140
Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro Ser Ser Arg
180 185 190
Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro Ala Ser Lys
195 200 205
Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly Arg Val Pro
210 215 220
Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
245 250 255
Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu
260 265 270
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln
275 280 285
Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys
305 310 315 320
Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu
325 330 335
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
340 345 350
Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu
355 360 365
Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp
370 375 380
Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro
385 390 395 400
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
405 410 415
Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His
435 440 445
Ser Pro Gly Lys
450
<210> 420
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v1和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 420
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
<210> 421
<211> 455
<212> PRT
<213> 人工序列
<220>
<223> 合成的：犬源化克隆M9可变HC v2和变体犬类
IgG-B C1q -, CD16 -, 0Y0
<400> 421
Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Ser Phe
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val
35 40 45
Ala Tyr Ile Arg Ser Asp Ser Ser Thr Ile Tyr Tyr Ala Asp Ala Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Tyr Tyr Gly Ser Phe Ser Leu Thr Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Thr Ala Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Cys Gly Ser Thr Ser Gly Ser Thr Val Ala
130 135 140
Leu Ala Cys Leu Val Ser Gly Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ser Leu Thr Ser Gly Val His Thr Phe Pro Ser Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Met Val Thr Val Pro
180 185 190
Ser Ser Arg Trp Pro Ser Glu Thr Phe Thr Cys Asn Val Ala His Pro
195 200 205
Ala Ser Lys Thr Lys Val Asp Lys Pro Val Pro Lys Arg Glu Asn Gly
210 215 220
Arg Val Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met
225 230 235 240
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr
245 250 255
Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu
260 265 270
Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys
275 280 285
Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly
290 295 300
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu
305 310 315 320
Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser
325 330 335
Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro
340 345 350
Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr
355 360 365
Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp
370 375 380
Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg
385 390 395 400
Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
405 410 415
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile
420 425 430
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser
435 440 445
Leu Ser His Ser Pro Gly Lys
450 455
Claims (153)
1.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含LX10FMGSENX11T(SEQ ID NO:85)的氨基酸序列的表位结合，其中X10是D或N并且X11是H或R，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
2.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含RLSYQLX10FMGSENX11TCVPEN(SEQ ID NO:86)的氨基酸序列的表位结合，其中X10是D或N并且X11是H或R，其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
3.根据权利要求2所述的分离的抗体，其中所述抗体与包含LX10FMGSENX11T(SEQ IDNO:85)的氨基酸序列的表位结合，其中X10是D或N，并且X11是H或R。
4.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:88或SEQ ID NO:91的氨基酸序列的表位结合。
5.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:89或SEQ ID NO:92的氨基酸序列的表位结合。
6.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体与包含SMX12X13DDX14VEADVYQLX15LWAGX16Q(SEQ ID NO:87)的氨基酸序列的表位结合，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T。
7.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SMX12X13DDX14VEADVYQLX15LWAGX16Q(SEQ ID NO:87)的氨基酸序列的表位结合，其中X12是P或L，X13是I或M，X14是A或F，X15是D或H，并且X16是Q或T，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
8.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体与包含SEQ ID NO:90或SEQ ID NO:93的氨基酸序列的表位结合。
9.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
10.根据前述权利要求中任一项所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
11.根据前述权利要求中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
12.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体与单克隆克隆B或克隆I抗体竞争结合至犬类IL4R或猫类IL4R。
13.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
14.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
15.根据前述权利要求中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
16.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含重链，所述重链包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
17.根据前述权利要求中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F。
18.根据前述权利要求中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:7、SEQ ID NO:29或SEQ ID NO:358的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271、SEQID NO:359或SEQ ID NO:272的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:9或SEQ ID NO:31的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
19.根据前述权利要求中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1，其包含SEQ ID NO:7、SEQ ID NO:29或SEQ ID NO:358的氨基酸序列；
b)CDR-H2，其包含SEQ ID NO:8、SEQ ID NO:269、SEQ ID NO:30、SEQ ID NO:271、SEQID NO:359或SEQ ID NO:272的氨基酸序列；和
c)CDR-H3，其包含SEQ ID NO:9或SEQ ID NO:31的氨基酸序列。
20.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含轻链，所述轻链包含：
a)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
b)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
c)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
21.根据前述权利要求中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
b)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
c)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L。
22.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含：
a)CDR-H1序列，其与GYTFTSYVMX1(SEQ ID NO:1)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X1是H或N；
b)CDR-H2序列，其与以下氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性：YINPX2NDGTFYX3GX4X5X6G(SEQ ID NO:2)的氨基酸序列，其中X2是K、A或N，X3是N或A，X4是K或A，X5是F或V，并且X6是K或Q，或YINPX2NDGT(SEQ ID NO:268)的氨基酸序列，其中X2是K、A或N；和
c)CDR-H3序列，其与FX7YGX8AY(SEQ ID NO:3)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X7是N或Y，并且X8是I或F；
d)CDR-L1序列，其与RASQEISGYLX9(SEQ ID NO:4)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X9是S或A；
e)CDR-L2序列，其与AASX10X11DX12(SEQ ID NO:5)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X10是T或N，X11是R或L，并且X12是S或T；和
f)CDR-L3序列，其与X13QYASYPWT(SEQ ID NO:6)的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性，其中X13是V或L；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
23.根据前述权利要求中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:14、SEQ ID NO:36或SEQ ID NO:360的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:15、SEQ ID NO:37、SEQ ID NO:361或SEQ IDNO:362的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:16或SEQ ID NO:38的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
24.根据前述权利要求中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1，其包含SEQ ID NO:14、SEQ ID NO:36或SEQ ID NO:360的氨基酸序列；
b)CDR-L2，其包含SEQ ID NO:15、SEQ ID NO:37、SEQ ID NO:361或SEQ ID NO:362的氨基酸序列；和
c)CDR-L3，其包含SEQ ID NO:16或SEQ ID NO:38的氨基酸序列。
25.根据权利要求16至24中任一项所述的抗体，其还包含以下中的一项或多项：(a)SEQID NO:10或SEQ ID NO:32的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:11或SEQ IDNO:33的HC-FR2序列；(c)SEQ ID NO:12、SEQ ID NO:270、SEQ ID NO:34、SEQ ID NO:273的HC-FR3序列；(d)SEQ ID NO:13或SEQ ID NO:35的HC-FR4序列；(e)SEQ ID NO:17或SEQ IDNO:39的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:18或SEQ ID NO:40的LC-FR2序列；(g)SEQ ID NO:19或SEQ ID NO:41的LC-FR3序列；或(h)SEQ ID NO:20或SEQ ID NO:42的LC-FR4序列。
26.根据前述权利要求中任一项所述的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:21或SEQ ID NO:43的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:22或SEQ ID NO:44的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274或SEQ ID NO:363的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:61、SEQ ID NO:62、SEQ IDNO:65、SEQ ID NO:66、SEQ ID NO:275或SEQ ID NO:364的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
c.(i)可变重链序列，其与SEQ ID NO:67或SEQ ID NO:69的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:68或SEQ ID NO:70的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
27.根据前述权利要求中任一项所述的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:21、SEQ ID NO:43、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274、SEQ ID NO:363、SEQ ID NO:67或SEQ ID NO:69的氨基酸序列。
28.根据前述权利要求中任一项所述的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:22、SEQ ID NO:44、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:275、SEQ ID NO:364、SEQ ID NO:68或SEQ IDNO:70的氨基酸序列。
29.根据前述权利要求中任一项所述的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:21或SEQ ID NO:43的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:22或SEQ ID NO:44的氨基酸序列；
b)可变重链序列，所述可变重链序列包含SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274、SEQ ID NO:363的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:275、SEQ ID NO:364的氨基酸序列；或
c)可变重链序列，所述可变重链序列包含SEQ ID NO:67、SEQ ID NO:69、SEQ ID NO:365或SEQ ID NO:366的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ ID NO:369的氨基酸序列。
30.一种分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:21或SEQ ID NO:43的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:22或SEQ ID NO:44的氨基酸序列；
b)可变重链序列，所述可变重链序列包含SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:274或SEQ ID NO:363的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:65、SEQ ID NO:66、SEQ IDNO:275或SEQ ID NO:364的氨基酸序列；或
c)可变重链序列，所述可变重链序列包含SEQ ID NO:67、SEQ ID NO:69、SEQ ID NO:365或SEQ ID NO:366的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:68、SEQ ID NO:70、SEQ ID NO:367、SEQ ID NO:368或SEQ ID NO:369的氨基酸序列，并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
31.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SEQ ID NO:354的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
32.根据权利要求31所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10- 10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
33.根据权利要求31或权利要求32所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
34.根据权利要求31至33中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
35.根据权利要求31至34中任一项所述的分离的抗体，其中所述抗体与单克隆M3抗体竞争结合至犬类IL4R或猫类IL4R。
36.根据权利要求31至35中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
37.根据权利要求31至36中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
38.根据权利要求31至37中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
39.根据权利要求31至38中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:278的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:279的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:280的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
40.根据权利要求31至39中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:285的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:286的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:287的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
41.根据权利要求31至40中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:281的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:282的HC-FR2序列；(c)SEQ ID NO:283的HC-FR3序列；(d)SEQ ID NO:284的HC-FR4序列；(e)SEQ ID NO:288的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:289的LC-FR2序列；(g)SEQ ID NO:290的LC-FR3序列；或(h)SEQ ID NO:291的LC-FR4序列。
42.根据权利要求31至41中任一项所述的分离的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:292的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:293的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:342或SEQ ID NO:343的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:344的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
43.根据权利要求31至42中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:292、SEQ ID NO:342或SEQ ID NO:343的氨基酸序列。
44.根据权利要求31至43中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:293或SEQ ID NO:344的氨基酸序列。
45.根据权利要求31至44中任一项所述的分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:292的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:293的氨基酸序列；和/或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:342或SEQ ID NO:343的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:344的氨基酸序列。
46.一种分离的抗体，其包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:292的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:293的氨基酸序列；或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:342或SEQ ID NO:343的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:344的氨基酸序列；
并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
47.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体与包含SEQ ID NO:355的氨基酸序列的表位和/或包含SEQ ID NO:356的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
48.根据权利要求47所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10- 10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R或猫类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
49.根据权利要求47或权利要求48所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R或猫类IL4R结合。
50.根据权利要求47至49中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类和/或猫类IL4多肽和/或犬类和/或猫类IL13多肽与犬类IL4R和/或猫类IL4R的结合。
51.根据权利要求47至50中任一项所述的分离的抗体，其中所述抗体与单克隆M8抗体竞争结合至犬类IL4R或猫类IL4R。
52.根据权利要求47至51中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
53.根据权利要求47至52中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
54.根据权利要求47至53中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
55.根据权利要求47至54中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:310的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:311的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:312的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
56.根据权利要求47至55中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:317的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:318的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:319的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
57.根据权利要求47至56中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:313的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:314的HC-FR2序列；(c)SEQ ID NO:315的HC-FR3序列；(d)SEQ ID NO:316的HC-FR4序列；(e)SEQ ID NO:320的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:321的LC-FR2序列；(g)SEQ ID NO:322的LC-FR3序列；或(h)SEQ ID NO:323的LC-FR4序列。
58.根据权利要求47至57中任一项所述的分离的抗体，其中所述抗体包含：
(a)可变重链序列，其与SEQ ID NO:324的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
(b)可变轻链序列，其与SEQ ID NO:325的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或
(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
59.根据权利要求47至58中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:324的氨基酸序列。
60.根据权利要求47至59中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列。
61.根据权利要求47至60中任一项所述的分离的抗体，其中所述抗体包含：可变重链序列，所述可变重链序列包含SEQ ID NO:324的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列。
62.一种分离的抗体，其包含：可变重链序列，所述可变重链序列包含SEQ ID NO:324的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:325的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
63.一种与犬类IL4R结合的分离的抗体，其中所述抗体与包含SEQ ID NO:357的氨基酸序列的表位结合，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
64.根据权利要求63所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10- 10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
65.根据权利要求63或权利要求64所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R结合。
66.根据权利要求63至65中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类IL4多肽和/或犬类IL13多肽与犬类IL4R的结合。
67.根据权利要求63至66中任一项所述的分离的抗体，其中所述抗体与单克隆M9抗体竞争结合至犬类IL4R。
68.根据权利要求63至67中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
69.根据权利要求63至68中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
70.根据权利要求63至69中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
71.根据权利要求63至70中任一项所述的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:326或SEQ ID NO:407的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:327的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:328的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
72.根据权利要求63至71中任一项所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:333的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:334的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:335的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
73.根据权利要求63至72中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:329的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:330的HC-FR2序列；(c)SEQ ID NO:331的HC-FR3序列；(d)SEQ ID NO:332的HC-FR4序列；(e)SEQ ID NO:336的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:337的LC-FR2序列；(g)SEQ ID NO:338的LC-FR3序列；或(h)SEQ ID NO:339的LC-FR4序列。
74.根据权利要求63至73中任一项所述的分离的抗体，其中所述抗体包含：
a.(i)可变重链序列，其与SEQ ID NO:340的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ ID NO:341的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列；或
b.(i)可变重链序列，其与SEQ ID NO:345或SEQ ID NO:346的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；(ii)可变轻链序列，其与SEQ IDNO:347或SEQ ID NO:408的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或(iii)如(i)中的可变重链序列和如(ii)中的可变轻链序列。
75.根据权利要求63至74中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:340、SEQ ID NO:345或SEQ ID NO:346的氨基酸序列。
76.根据权利要求63至75中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:341、SEQ ID NO:347或SEQ ID NO:408的氨基酸序列。
77.根据权利要求63至76中任一项所述的分离的抗体，其中所述抗体包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:340的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:341的氨基酸序列；和/或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:345或SEQ ID NO:346的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:347或SEQ ID NO:408的氨基酸序列。
78.一种分离的抗体，其包含：
a)可变重链序列，所述可变重链序列包含SEQ ID NO:340的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:341的氨基酸序列；或
b)可变重链序列，所述可变重链序列包含SEQ ID NO:345或SEQ ID NO:346的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:347或SEQ ID NO:408的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
79.一种与犬类IL4R结合的分离的抗体，其包含重链，所述重链包含：
a)CDR-H1序列，其与SEQ ID NO:294的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-H2序列，其与SEQ ID NO:295的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-H3序列，其与SEQ ID NO:296的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
80.一种与犬类IL4R结合的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:301的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:302的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:303的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
81.根据权利要求79所述的分离的抗体，其包含轻链，所述轻链包含：
a)CDR-L1序列，其与SEQ ID NO:301的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
b)CDR-L2序列，其与SEQ ID NO:302的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；和
c)CDR-L3序列，其与SEQ ID NO:303的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性。
82.根据权利要求79至81中任一项所述的分离的抗体，其中所述抗体以小于5x10-6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与犬类IL4R结合，所述解离常数是通过生物膜层干涉法测量的。
83.根据权利要求79至82中任一项所述的抗体，其中如通过免疫印迹分析或生物膜层干涉法所确定的，所述抗体与犬类IL4R结合。
84.根据权利要求79至83中任一项所述的分离的抗体，其中如通过生物膜层干涉法所测量的，所述抗体减少犬类IL4多肽和/或犬类IL13多肽与犬类IL4R的结合。
85.根据权利要求79至84中任一项所述的分离的抗体，其中所述抗体与单克隆M5抗体竞争结合至犬类IL4R。
86.根据权利要求79至85中任一项所述的分离的抗体，其中所述抗体是单克隆抗体。
87.根据权利要求79至86中任一项所述的分离的抗体，其中所述抗体是犬类、犬源化、猫类、猫源化或嵌合抗体。
88.根据权利要求79至87中任一项所述的分离的抗体，其中所述抗体是包含一个或多个鼠类可变重链框架区或一个或多个鼠类可变轻链框架区的嵌合抗体。
89.根据权利要求79至88中任一项所述的分离的抗体，其还包含以下中的一项或多项：(a)SEQ ID NO:297的可变区重链框架1(HC-FR1)序列；(b)SEQ ID NO:298的HC-FR2序列；(c)SEQ ID NO:299的HC-FR3序列；(d)SEQ ID NO:300的HC-FR4序列；(e)SEQ ID NO:304的可变区轻链框架1(LC-FR1)序列；(f)SEQ ID NO:305的LC-FR2序列；(g)SEQ ID NO:306的LC-FR3序列；或(h)SEQ ID NO:307的LC-FR4序列。
90.根据权利要求79至89中任一项所述的分离的抗体，其中所述抗体包含：
(a)可变重链序列，其与SEQ ID NO:308的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；
(b)可变轻链序列，其与SEQ ID NO:309的氨基酸序列具有至少85％、至少90％、至少95％、至少98％或100％序列同一性；或
(c)如(a)中的可变重链序列和如(b)中的可变轻链序列。
91.根据权利要求79至90中任一项所述的分离的抗体，其中所述抗体包含可变重链序列，所述可变重链序列包含SEQ ID NO:308的氨基酸序列。
92.根据权利要求79至91中任一项所述的分离的抗体，其中所述抗体包含可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列。
93.根据权利要求79至92中任一项所述的分离的抗体，其中所述抗体包含：可变重链序列，所述可变重链序列包含SEQ ID NO:308的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列。
94.一种分离的抗体，其包含：可变重链序列，所述可变重链序列包含SEQ ID NO:308的氨基酸序列，和可变轻链序列，所述可变轻链序列包含SEQ ID NO:309的氨基酸序列，并且其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
95.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽是变体犬类IgG-A Fc多肽；变体犬类IgG-B Fc多肽；变体IgG-C Fc多肽；变体IgG-D Fc多肽；变体猫类IgG1a Fc多肽；变体猫类IgG1b Fc多肽；或变体猫类IgG2 Fc多肽。
96.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽相对于野生型IgG Fc多肽包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽相对于所述野生型IgG Fc多肽具有增加的对蛋白质A的结合亲和力；相对于所述野生型IgG Fc多肽具有降低的对C1q的结合亲和力；和/或相对于所述野生型IgG Fc多肽具有降低的对CD16的结合亲和力。
97.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽相对于野生型IgG Fc多肽包含对铰链区的至少一个氨基酸修饰，其中如在还原和/或非还原条件下通过SDS-PAGE分析所确定的，所述变体IgG Fc多肽相对于所述野生型IgG Fc多肽具有增加的重组产生和/或增加的铰链二硫化物形成。
98.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:162的位置21、23、25、80、205和/或207的位置处的至少一个氨基酸取代；
b)在对应于SEQ ID NO:163的位置5、38、39、94、97和/或98的位置处的至少一个氨基酸取代；
c)在对应于SEQ ID NO:165的位置5、21、23、24、38、39、93、97和/或98的位置处的至少一个氨基酸取代；
d)在对应于SEQ ID NO:167的位置21、23、25、80和/或207的位置处的至少一个氨基酸取代；
e)在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198的位置处的至少一个氨基酸取代；和/或
f)在对应于SEQ ID NO:207的位置14和/或16的位置处的至少一个氨基酸取代。
99.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:162的位置21、23、25、80、205和/或207处的至少一个氨基酸取代；
b)在SEQ ID NO:163的位置5、38、39、94、97和/或98处的至少一个氨基酸取代；
c)在SEQ ID NO:164的位置5、21、23、24、38、39、93、97和/或98处的至少一个氨基酸取代；
d)在SEQ ID NO:165的位置21、23、25、80和/或207处的至少一个氨基酸取代；
e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16和/或198处的至少一个氨基酸取代；和/或
f)在SEQ ID NO:207的位置14和/或16处的至少一个氨基酸取代。
100.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:162的位置21的位置处的苏氨酸、在对应于SEQ ID NO:162的位置23的位置处的亮氨酸、在对应于SEQ ID NO:162的位置25的位置处的丙氨酸、在对应于SEQ ID NO:162的位置80的位置处的甘氨酸、在对应于SEQ ID NO:162的位置205的位置处的丙氨酸、和/或在对应于SEQ ID NO:162的位置207的位置处的组氨酸；
b)在对应于SEQ ID NO:163的位置5的位置处的脯氨酸、在对应于SEQ ID NO:163的位置38的位置处的甘氨酸、在对应于SEQ ID NO:163的位置39的位置处的精氨酸、在对应于SEQ ID NO:163的位置93的位置处的精氨酸、在对应于SEQ ID NO:163的位置97的位置处的异亮氨酸、和/或在对应于SEQ ID NO:163的位置98的位置处的甘氨酸；
c)在对应于SEQ ID NO:164的位置5的位置处的脯氨酸、在对应于SEQ ID NO:164的位置21的位置处的苏氨酸、在对应于SEQ ID NO:164的位置23的位置处的亮氨酸、在对应于SEQ ID NO:164的位置24的位置处的异亮氨酸、在对应于SEQ ID NO:164的位置38的位置处的甘氨酸、在对应于SEQ ID NO:164的位置39的位置处的精氨酸、在对应于SEQ ID NO:164的位置93的位置处的精氨酸、在对应于SEQ ID NO:164的位置97的位置处的异亮氨酸、和/或在对应于SEQ ID NO:164的位置98的位置处的甘氨酸；
d)在对应于SEQ ID NO:165的位置21的位置处的苏氨酸、在对应于SEQ ID NO:165的位置23的位置处的亮氨酸、在对应于SEQ ID NO:165的位置25的位置处的丙氨酸、在对应于SEQ ID NO:165的位置80的位置处的甘氨酸、和/或在对应于SEQ ID NO:165的位置207的位置处的组氨酸；
e)在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16的位置处的脯氨酸和/或在对应于SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQID NO:206的位置198的位置处的丙氨酸；和/或
f)在对应于SEQ ID NO:207的位置14的位置处的半胱氨酸和/或在对应于SEQ ID NO:207的位置16的位置处的脯氨酸。
101.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:162的位置21处的苏氨酸、在SEQ ID NO:162的位置23处的亮氨酸、在SEQ ID NO:162的位置25处的丙氨酸、在SEQ ID NO:162的位置80处的甘氨酸、在SEQ IDNO:162的位置205处的丙氨酸、和/或在SEQ ID NO:162的位置207处的组氨酸；
b)在SEQ ID NO:163的位置5处的脯氨酸、在SEQ ID NO:163的位置38处的甘氨酸、在SEQ ID NO:163的位置39处的精氨酸、在SEQ ID NO:163的位置93处的精氨酸、在SEQ IDNO:163的位置97处的异亮氨酸、和/或在SEQ ID NO:163的位置98处的甘氨酸；
c)在SEQ ID NO:164的位置5处的脯氨酸、在SEQ ID NO:164的位置21处的苏氨酸、在SEQ ID NO:164的位置23处的亮氨酸、在SEQ ID NO:164的位置24处的异亮氨酸、在SEQ IDNO:164的位置38处的甘氨酸、在SEQ ID NO:164的位置39处的精氨酸、在SEQ ID NO:164的位置93处的精氨酸、在SEQ ID NO:164的位置97处的异亮氨酸、和/或在SEQ ID NO:164的位置98处的甘氨酸；
d)在SEQ ID NO:165的位置21处的苏氨酸、在SEQ ID NO:165的位置23处的亮氨酸、在SEQ ID NO:165的位置25处的丙氨酸、在SEQ ID NO:165的位置80处的甘氨酸、和/或在SEQID NO:165的位置207处的组氨酸；
e)在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置16处的脯氨酸和/或在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205或SEQ ID NO:206的位置198处的丙氨酸；和/或
f)在SEQ ID NO:207的位置14处的半胱氨酸和/或在SEQ ID NO:207的位置16处的脯氨酸。
102.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，所述CH1区包含相对于野生型犬类或猫类IgG CH1区的至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ IDNO:237的位置24和/或位置30的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:238的位置24和/或位置29的位置处的至少一个氨基酸取代。
103.一种抗体，所述抗体包含变体IgG Fc多肽，所述变体IgG Fc多肽包含CH1区，其相对于野生型犬类或猫类IgG CH1区包含至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ IDNO:237的位置24和/或位置30的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:238的位置24和/或位置29的位置处的至少一个氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
104.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，所述CH1区包含相对于野生型犬类或猫类IgG CH1区的至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24和/或位置30处的至少一个氨基酸取代；或
b)在SEQ ID NO:238的位置24和/或位置29处的至少一个氨基酸取代。
105.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，所述CH1区包含相对于野生型犬类或猫类IgG CH1区的至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ IDNO:237的位置24的位置处的亮氨酸和/或在对应于位置30的位置处的天冬酰胺；或
b)在对应于SEQ ID NO:238的位置24的位置处的亮氨酸和/或在对应于位置29的位置处的天冬酰胺。
106.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含CH1区，所述CH1区包含相对于野生型犬类或猫类IgG CH1区的至少一个氨基酸修饰，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230或SEQ ID NO:237的位置24处的亮氨酸和/或位置30处的天冬酰胺；或
b)在SEQ ID NO:238的位置24处的亮氨酸和/或位置29处的天冬酰胺。
107.根据前述权利要求中任一项所述的抗体，其中所述抗体包含野生型或变体犬类或猫类轻链恒定区。
108.根据前述权利要求中任一项所述的抗体，其中所述抗体包含野生型或变体犬类或猫类轻链κ恒定区。
109.根据权利要求107或权利要求108所述的抗体，其中所述变体轻链恒定区相对于野生型犬类或猫类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11和/或位置22的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:241的位置11和/或位置22的位置处的至少一个氨基酸取代。
110.一种包含变体轻链恒定区的抗体，所述变体轻链恒定区相对于野生型犬类或猫类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11和/或位置22的位置处的至少一个氨基酸取代；或
b)在对应于SEQ ID NO:241的位置11和/或位置22的位置处的至少一个氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
111.根据权利要求107至110中任一项所述的抗体，其中所述变体轻链恒定区相对于野生型猫类或犬类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在对应于SEQ ID NO:235的位置11的位置处的丙氨酸和/或在对应于其位置22的位置处的精氨酸；或
b)在对应于SEQ ID NO:241的位置11的位置处的丙氨酸和/或在对应于其位置22的位置处的精氨酸。
112.根据权利要求107至111中任一项所述的抗体，其中所述变体轻链恒定区相对于野生型猫类或犬类轻链κ恒定区包含至少一个氨基酸修饰，所述氨基酸修饰包含：
a)在SEQ ID NO:235的位置11处的丙氨酸和/或其位置22处的精氨酸；或
b)在SEQ ID NO:241的位置11处的丙氨酸和/或其位置22处的精氨酸。
113.根据权利要求107至112中任一项所述的抗体，其中所述轻链恒定区包含SEQ IDNO:235、236、241和/或242的氨基酸序列。
114.根据前述权利要求中任一项所述的抗体，其中所述抗体是双特异性抗体。
115.根据前述权利要求中任一项所述的抗体，其中所述抗体是双特异性抗体，所述双特异性抗体包含：
i)第一变体犬类IgG Fc多肽，其相对于第一野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体犬类IgG Fc多肽，其相对于第二野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的氨基酸取代，和/或
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138和/或位置140、SEQ ID NO:163的位置137和/或位置139、SEQ ID NO:165的位置137和/或位置139或SEQ ID NO:167的位置138和/或位置140的位置处的氨基酸取代；或
ii)第一变体猫类IgG Fc多肽，其相对于第一野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体猫类IgG Fc多肽，其相对于第二野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的氨基酸取代，和/或
b)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156的位置处的氨基酸取代。
116.一种抗体或双特异性抗体，其包含：
i)第一变体犬类IgG Fc多肽，其相对于第一野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体犬类IgG Fc多肽，其相对于第二野生型犬类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的氨基酸取代，和/或
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138和/或位置140、SEQ ID NO:163的位置137和/或位置139、SEQ ID NO:165的位置137和/或位置139或SEQ ID NO:167的位置138和/或位置140的位置处的氨基酸取代；
ii)第一变体猫类IgG Fc多肽，其相对于第一野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体猫类IgG Fc多肽，其相对于第二野生型猫类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的氨基酸取代，和/或
b)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156的位置处的氨基酸取代；或
iii)第一变体马类IgG Fc多肽，其相对于第一野生型马类IgG Fc多肽包含至少一个氨基酸修饰，和第二变体马类IgG Fc多肽，其相对于第二野生型马类IgG Fc多肽包含至少一个氨基酸修饰，其中：
a)所述第一变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的氨基酸取代，和/或
b)所述第二变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130和/或位置132的位置处的氨基酸取代；并且
其中所述抗体包含能够以相对于野生型Fc多肽增加的亲和力结合新生儿Fc受体(FcRn)的变体犬类或猫类IgG Fc多肽。
117.根据权利要求115或权利要求116所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138的位置处的色氨酸；
b)所述第二变体犬类IgG Fc多肽包含在对应于SEQ ID NO:162的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸、在对应于SEQ ID NO:163的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸、在对应于SEQ ID NO:165的位置137的位置处的丝氨酸和/或在对应于位置139的位置处的丙氨酸、或在对应于SEQ ID NO:167的位置138的位置处的丝氨酸和/或在对应于位置140的位置处的丙氨酸；
c)所述第一变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的色氨酸；
d)所述第二变体猫类IgG Fc多肽包含在对应于SEQ ID NO:203、SEQ ID NO:204、SEQID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154的位置处的丝氨酸和/或在对应于位置156的位置处的丙氨酸；
e)所述第一变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的色氨酸；和/或
f)所述第二变体马类IgG Fc多肽包含在对应于SEQ ID NO:254、SEQ ID NO:255、SEQID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130的位置处的丝氨酸和/或在对应于位置132的位置处的丙氨酸。
118.根据权利要求115至117中任一项所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138处的氨基酸取代；
b)所述第二变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138和/或位置140处的氨基酸取代、在SEQ ID NO:163的位置137和/或位置139处的氨基酸取代、在SEQ ID NO:165的位置137和/或位置139处的氨基酸取代，或在SEQ ID NO:167的位置138和/或位置140处的氨基酸取代；
c)所述第一变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的氨基酸取代；
d)所述第二变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154和/或位置156处的氨基酸取代；
e)所述第一变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的氨基酸取代；和/或
f)所述第二变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130和/或位置132处的氨基酸取代。
119.根据权利要求115至118中任一项所述的抗体，其中：
a)所述第一变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138、SEQ ID NO:163的位置137、SEQ ID NO:165的位置137或SEQ ID NO:167的位置138处的色氨酸；
b)所述第二变体犬类IgG Fc多肽包含在SEQ ID NO:162的位置138处的丝氨酸和/或位置140处的丙氨酸、在SEQ ID NO:163的位置137处的丝氨酸和/或位置139处的丙氨酸、在SEQ ID NO:165的位置137处的丝氨酸和/或位置139处的丙氨酸、或在SEQ ID NO:167的位置138处的丝氨酸和/或位置140处的丙氨酸；
c)所述第一变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的色氨酸；
d)所述第二变体猫类IgG Fc多肽包含在SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206或SEQ ID NO:207的位置154处的丝氨酸和/或位置156处的丙氨酸；
e)所述第一变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的色氨酸；和/或
f)所述第二变体马类IgG Fc多肽包含在SEQ ID NO:254、SEQ ID NO:255、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:259或SEQ ID NO:260的位置130处的丝氨酸和/或位置132处的丙氨酸。
120.根据权利要求115至119中任一项所述的抗体，其中所述第一野生型IgG Fc多肽和所述第二野生型IgG Fc多肽来自相同的IgG亚型。
121.根据权利要求115至117中任一项所述的抗体，其中所述第一野生型IgG Fc多肽和所述第二野生型IgG Fc多肽来自不同的IgG亚型。
122.根据前述权利要求中任一项所述的抗体，其中所述变体Fc多肽以比野生型IgG Fc多肽更大的亲和力与FcRn结合，所述亲和力是通过生物膜层干涉法、表面等离子体共振或任何蛋白质-蛋白质相互作用工具在约5.0至约6.5范围内的pH下，如在约5.0的pH、约5.2的pH、约5.5的pH、约6.0的pH、约6.2的pH或约6.5的pH下测量的。
123.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽以小于5x10- 6M、小于1x10-6M、小于5x10-7M、小于1x10-7M、小于5x10-8M、小于1x10-8M、小于5x10-9M、小于1x10-9M、小于5x10-10M、小于1x10-10M、小于5x10-11M、小于1x10-11M、小于5x10-12M或小于1x10-12M的解离常数(Kd)与FcRn结合，所述解离常数是通过生物膜层干涉法、表面等离子体共振或任何蛋白质-蛋白质相互作用工具在约5.0至约6.5范围内的pH下，如在约5.0的pH、约5.5的pH、约6.0的pH或约6.5的pH下测量的。
124.根据前述权利要求中任一项所述的抗体，其中所述抗体相对于具有野生型IgG Fc多肽的抗体具有增加的血清半衰期。
125.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:163的位置23的位置处的酪氨酸或苯丙氨酸；
b)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸；
c)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸和在对应于其位置207的位置处的组氨酸；
d)在对应于SEQ ID NO:163的位置82的位置处的酪氨酸和在对应于其位置207的位置处的酪氨酸；或
e)在对应于SEQ ID NO:163的位置207的位置处的酪氨酸。
126.根据前述权利要求中任一项所述的抗体，其中所述变体IgG Fc多肽包含：
a)在SEQ ID NO:163的位置23处的酪氨酸或苯丙氨酸；
b)在SEQ ID NO:163的位置82处的酪氨酸；
c)在SEQ ID NO:163的位置82处的酪氨酸和位置207处的组氨酸；
d)在SEQ ID NO:163的位置82处的酪氨酸和位置207处的酪氨酸，或
e)在SEQ ID NO:163的位置207处的酪氨酸。
127.根据前述权利要求中任一项所述的抗体，其中所述抗体包含IgG Fc多肽，所述IgGFc多肽包含SEQ ID NO:162、163、164、165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、228、229、230、231、232、233、234、237、238、239、240、254、255、256、257、258、259、260、261、262、263、264、265、266、267、381、382、383、384、385、386、387、388、389、390、391、392、393和/或394的氨基酸序列。
128.根据前述权利要求中任一项所述的抗体，其中所述抗体包含：
a.(i)SEQ ID NO:25或SEQ ID NO:47的重链氨基酸序列；(ii)SEQ ID NO:26或SEQ IDNO:48的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
b.(i)SEQ ID NO:51或SEQ ID NO:55的重链氨基酸序列；(ii)SEQ ID NO:52或SEQ IDNO:56的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
c.(i)SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:276、SEQ ID NO:370、SEQ ID NO:395、SEQ ID NO:396、SEQ ID NO:397、SEQ ID NO:398、SEQ IDNO:399、SEQ ID NO:400、SEQ ID NO:401、SEQ ID NO:402、SEQ ID NO:403、SEQ ID NO:404、SEQ ID NO:405、SEQ ID NO:406、SEQ ID NO:410、SEQ ID NO:411、SEQ ID NO:412、SEQ IDNO:413、SEQ ID NO:414、SEQ ID NO:415、SEQ ID NO:416、SEQ ID NO:417、SEQ ID NO:418、SEQ ID NO:419、SEQ ID NO:420、或SEQ ID NO:421的重链氨基酸序列；(ii)SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:277、SEQ ID NO:371的轻链氨基酸序列；或者(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
d.(i)SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:82、SEQ ID NO:372、SEQ ID NO:373、SEQ ID NO:83、SEQ ID NO:374、或SEQ ID NO:375的重链氨基酸序列；(ii)SEQ ID NO:81、SEQ ID NO:84、SEQ ID NO:376、SEQ ID NO:377、SEQ ID NO:378的轻链氨基酸序列；或者(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
e.(i)SEQ ID NO:243的重链氨基酸序列；(ii)SEQ ID NO:244的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列；
f.(i)SEQ ID NO:348或SEQ ID NO:349的重链氨基酸序列；(ii)SEQ ID NO:350的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链；或
g.(i)SEQ ID NO:351或SEQ ID NO:352的重链氨基酸序列；(ii)SEQ ID NO:253的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列。
129.一种与犬类IL4R或猫类IL4R结合的分离的抗体，其中所述抗体包含SEQ ID NO:408的可变轻链氨基酸序列和/或SEQ ID NO:409的轻链氨基酸序列。
130.根据前述权利要求中任一项所述的抗体，其中所述抗体是双特异性抗体，其结合IL4R和选自以下的一种或多种抗原：IL17、IL31、TNFα、CD20、CD19、CD25、IL4、IL13、IL23、IgE、CD11α、IL6R、α4-整合素、IL12、IL1β或BlyS。
131.根据前述权利要求中任一项所述的抗体，其中所述抗体包含(i)SEQ ID NO:245的重链氨基酸序列；(ii)SEQ ID NO:246的轻链氨基酸序列；或(iii)如(i)中的重链氨基酸序列和如(ii)中的轻链序列。
132.根据前述权利要求中任一项所述的抗体，其中所述抗体是抗体片段，如Fv、scFv、Fab、Fab'、F(ab')2或Fab'-SH片段。
133.一种分离的核酸，其编码根据前述权利要求中任一项所述的抗体。
134.一种宿主细胞，所述宿主细胞包含根据权利要求133所述的核酸。
135.一种宿主细胞，其表达根据权利要求1至134中任一项所述的抗体。
136.一种生产抗体的方法，其包括培养根据权利要求134或权利要求135所述的宿主细胞并且分离所述抗体。
137.一种药物组合物，其包含根据权利要求1至132中任一项的抗体和药学上可接受的载体。
138.一种治疗患有IL4/IL13诱导的病症的伴生动物物种的方法，所述方法包括向所述伴生动物物种施用治疗有效量的根据权利要求1至132中任一项所述的抗体或根据权利要求137所述的药物组合物。
139.根据权利要求138所述的方法，其中所述伴生动物物种是犬类、猫类或马类。
140.根据权利要求138或权利要求139所述的方法，其中所述IL4/IL13诱导的病症是瘙痒性病症或过敏性病症。
141.根据权利要求138至140中任一项所述的方法，其中所述IL4/IL13诱导的病症选自特应性皮炎、过敏性皮炎、瘙痒、哮喘、银屑病、硬皮病和湿疹。
142.根据权利要求138至141中任一项所述的方法，其中肠胃外施用所述抗体或所述药物组合物。
143.根据权利要求138至142中任一项所述的方法，其中所述抗体或所述药物组合物是通过肌内途径、腹膜内途径、脑脊髓内途径、皮下途径、动脉内途径、滑膜内途径、鞘内途径或吸入途径施用的。
144.根据权利要求138至143中任一项所述的方法，其中所述方法包括与所述抗体或所述药物组合物组合施用Jak抑制剂、PI3K抑制剂、ERK抑制剂。
145.根据权利要求138至144中任一项所述的方法，其中所述方法包括与所述抗体或所述药物组合物组合施用选自以下的一种或多种抗体：抗IL17抗体、抗IL31抗体、抗TNFα抗体、抗CD20抗体、抗CD19抗体、抗CD25抗体、抗IL4抗体、抗IL13抗体、抗IL23抗体、抗IgE抗体、抗CD11α抗体、抗IL6R抗体、抗α4-整合素抗体、抗IL12抗体、抗IL1β抗体和抗BlyS抗体。
146.一种降低细胞中IL4和/或IL13信号传导功能的方法，所述方法包括在允许根据权利要求1至132中任一项所述的抗体与细胞外IL4和/或IL13结合的条件下向所述细胞暴露所述抗体或根据权利要求137所述的药物组合物，从而降低IL4和/或IL13与IL4R的结合和/或降低所述细胞的IL4和/或IL13信号传导功能。
147.根据权利要求146所述的方法，其中将所述细胞离体暴露于所述抗体或所述药物组合物。
148.根据权利要求146所述的方法，其中将所述细胞在体内暴露于所述抗体或所述药物组合物。
149.根据权利要求146至148中任一项所述的方法，其中所述细胞是犬类细胞或猫类细胞。
150.根据权利要求146至149中任一项所述的方法，其中如通过STAT6磷酸化的减少所确定的，所述抗体降低所述细胞中的IL4和/或IL13信号传导功能。
151.根据权利要求146至150中任一项所述的方法，其中所述细胞是犬类DH82细胞。
152.一种用于检测来自伴生动物物种的样品中的IL4R的方法，所述方法包括在允许根据权利要求1至132中任一项所述的抗体与IL4R结合的条件下，使所述样品与所述抗体或根据权利要求137所述的药物组合物接触。
153.根据权利要求152所述的方法，其中所述样品是从犬类或猫类获得的生物样品。
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