CN113840831A - 医用ngf拮抗剂 - Google Patents
医用ngf拮抗剂 Download PDFInfo
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- CN113840831A CN113840831A CN202080035418.XA CN202080035418A CN113840831A CN 113840831 A CN113840831 A CN 113840831A CN 202080035418 A CN202080035418 A CN 202080035418A CN 113840831 A CN113840831 A CN 113840831A
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Abstract
提供了与来自伴生动物物种、结合NGF的TrkA ECD多肽相关的各种实施方案。此类多肽可用于治疗与诸如犬类、猫类和马类等伴生动物中的慢性疼痛和/或炎性疼痛相关的NGF诱导的病症的方法。
Description
本申请要求2019年3月20日提交的美国临时申请号62/821,438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。
技术领域
本公开文本涉及包含来自伴生动物物种的TrkA的细胞外结构域的、与NGF结合的多肽。本公开文本还涉及使用所述多肽例如用于例如在伴生动物，如犬类、猫类和马类中治疗NGF诱导的病症或降低细胞中的NGF信号传导活性的方法。
背景技术
神经生长因子(NGF)是一种神经营养因子，其对调节某些神经元的生长、维持、增殖和存活具有广泛作用。NGF还与慢性疼痛和炎性疼痛相关联。NGF与以下两类受体结合：原肌球蛋白(tropomyosine)受体激酶A(TrkA)和低亲和力NGF受体。当NGF(一种二聚体)与TrkA细胞外结构域结合时，它会引起受体二聚化，从而激活下游激酶活性。TrkA细胞外结构域可用于拮抗NGF活性、减少游离NGF和/或减弱与NGF相关疼痛相关的临床征象和症状。
伴生物种动物(如猫、狗和马)患有许多与人病症相似的病症，包括慢性疼痛和炎性疼痛。因此，仍然需要可以特异性地用于结合伴生动物NGF以治疗NGF诱导的病症和降低NGF信号传导活性的方法和物种特异性化合物。
发明内容
实施方案1.一种连续多肽，所述连续多肽包含来自伴生动物物种的TrkA多肽的至少一个细胞外结构域(TrkA ECD多肽)和融合配偶体。
实施方案2.根据实施方案1所述的连续多肽，其中所述连续多肽以通过生物膜层干涉法测量的小于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NGF多肽结合。
实施方案3.根据实施方案2所述的连续多肽，其中所述NGF多肽是人NGF多肽、犬类NGF多肽、猫类NGF多肽或马类多肽。
实施方案4.根据前述实施方案中任一项所述的连续多肽，其中所述连续多肽降低所述伴生动物物种中的NGF信号传导。
实施方案5.根据前述实施方案中任一项所述的连续多肽，其中所述伴生动物物种是犬类、猫类或马类。
实施方案6.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽的氨基酸序列与以下的氨基酸序列至少90％相同、至少91％相同、至少92％相同、至少93％相同、至少94％相同、至少95％相同、至少96％相同、至少97％相同、至少98％相同或至少99％相同：SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ IDNO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14或SEQ IDNO:15。
实施方案7.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89的位置处的半胱氨酸；或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和位置87的位置处的半胱氨酸。
实施方案8.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:7、SEQ ID NO:8、SEQID NO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89处的半胱氨酸；或
b)在SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和87处的半胱氨酸。
实施方案9.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含不存在于相应野生型TrkA ECD多肽中的至少一个N连接的糖基化位点，其中所述N连接的糖基化位点包含序列天冬酰胺-xaa-丝氨酸或天冬酰胺-xaa-苏氨酸，其中xaa是除脯氨酸外的任何氨基酸，并且其中一个N连接的糖基化位点不与另一个N连接的糖基化位点重叠。
实施方案10.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD包含在选自以下的一个或多个位置处的至少一个N连接的糖基化位点：
a)SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQID NO:14的氨基酸位置6-8、31-33、84-86、85-87、86-88、88-90、90-92、92-94和/或94-96；或
b)SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的氨基酸位置4-6、29-31、82-84、83-85、84-86、86-88、89-90、90-92和/或92-94。
实施方案11.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO13或SEQ ID NO:14的位置30和/或位置85的氨基酸位置处的除脯氨酸之外的氨基酸；和/或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28或位置83的氨基酸位置处的除脯氨酸之外的氨基酸。
实施方案12.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ ID NO:14的位置30和/或位置85的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸；和/或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28或位置83的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸。
实施方案13.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含表A中列出的一个或多个氨基酸修饰：
，其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)；
表B：
，其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)；和/或
表C：
，其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)。
实施方案14.根据前述实施方案中任一项所述的连续多肽，其中所述TrkA ECD多肽包含选自以下的氨基酸序列：SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32和SEQ ID NO:33。
实施方案15.根据前述实施方案中任一项所述的连续多肽，其中所述连续多肽包含接头。
实施方案16.根据实施方案15所述的连续多肽，其中所述接头包含选自以下的氨基酸序列：G、GG、GGG、S、SS、SSS、GS、GSGS(SEQ ID NO:143)、GSGSGS(SEQ ID NO:144)、GGS、GGSGGS(SEQ ID NO:145)、GGSGGSGGS(SEQ ID NO:146)、GGGS(SEQ ID NO:147)、GGGSGGGS(SEQ ID NO:148)、GGGSGGGSGGGS(SEQ ID NO:149)、GSS、GSSGSS(SEQ ID NO:150)、GSSGSSGSS(SEQ ID NO:151)、GGSS(SEQ ID NO:152)、GGSSGGSS(SEQ ID NO:153)、GGSSGGSSGGS(SEQ ID NO:154)、SGGSGGS(SEQ ID NO:155)和SGGGSGGGS(SEQ ID NO:156)。
实施方案17.根据前述实施方案中任一项所述的连续多肽，其中所述融合配偶体选自Fc多肽、白蛋白和白蛋白结合片段。
实施方案18.根据前述实施方案中任一项所述的连续多肽，其中所述融合配偶体是Fc多肽，其包含(a)野生型或变体犬类IgG-A、IgG-B、IgG-C或IgG-D多肽；(b)野生型或变体猫类IgG1a、IgG1b或IgG2多肽；或(c)野生型或变体马类IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7多肽。
实施方案19.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含：
式(I)：TrkA ECD 1-L1-Fc；
式(II)：Fc-L1-TrkA ECD 1；
式(III)：TrkA ECD 1-L1-Fc-L2-TrkA ECD 2；
式(IV)：TrkA ECD 1-L1-TrkA ECD 2-L2-Fc；或
式(V)：Fc-L1-TrkA ECD 1-L2-TrkA ECD 2，
其中TrkA ECD 1是第一TrkA ECD多肽，TrkA ECD 2是第二TrkA ECD多肽，L1和L2是任选的接头，并且Fc是伴生动物物种的野生型或变体IgG Fc多肽。
实施方案20.根据实施方案19所述的连续多肽，其中TrkA ECD 1和TrkA ECD 2是相同的多肽。
实施方案21.根据实施方案19所述的连续多肽，其中TrkA ECD 1和TrkA ECD 2是不同的多肽。
实施方案22.根据前述实施方案中任一项所述的连续多肽，其中所述融合配偶体或Fc是变体Fc多肽，其包含：
a)相对于伴生动物物种的野生型IgG Fc多肽的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A的结合亲和力；
b)相对于伴生动物物种的野生型IgG Fc多肽的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多肽具有降低的对C1q的结合亲和力；
c)相对于伴生动物物种的野生型IgG Fc多肽的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多肽具有降低的对CD16的结合亲和力；
d)铰链区，其包含相对于野生型猫类或马类IgG Fc多肽的至少一个氨基酸修饰；
e)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述至少一个氨基酸取代是半胱氨酸，并且其中所述变体IgG Fc多肽能够相对于所述野生型猫类IgG Fc多肽形成至少一个另外的链间二硫键；和/或
f)相对于源自伴生动物物种的野生型IgG Fc多肽的至少一个氨基酸取代，其中所述变体Fc多肽能够以相对于所述野生型Fc多肽增加的亲和力与新生儿Fc受体(FcRn)结合。
实施方案23.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以通过生物膜层干涉法测量的大于5x10-6M、大于1x10-5M、大于5x10-5M、大于1x10-4M、大于5x10-4M或大于1x10-3M的解离常数(Kd)与C1q和/或CD16结合。
实施方案24.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以通过生物膜层干涉法测量的小于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)与蛋白A结合。
实施方案25.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG 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26.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，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27.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以相对于所述野生型Fc多肽增加的亲和力与FcRn结合，并且其中所述连续多肽相对于包含野生型Fc多肽的连续多肽具有增加的血清半衰期。
实施方案28.根据前述实施方案中任一项所述的连续多肽，其中所述野生型IgGFc多肽是：
a)犬类IgG-A Fc、IgG-B Fc、IgG-C Fc或IgG-D Fc；
b)马类IgG1 Fc、IgG2 Fc、IgG3 Fc、IgG4 Fc、IgG5 Fc、IgG6 Fc或IgG7 Fc；或
c)猫类IgG1a Fc、IgG1b Fc或IgG2 Fc。
实施方案29.根据前述实施方案中任一项所述的连续多肽，其中所述野生型IgGFc多肽包含以下的氨基酸序列：SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72、SEQ IDNO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90。
实施方案30.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16的位置处的氨基酸取代；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处的氨基酸取代；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置20的位置处的氨基酸取代。
实施方案31.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16处的氨基酸取代；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:72的位置3处的氨基酸取代；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:72的位置20处的氨基酸取代。
实施方案32.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16的位置处或在SEQ ID NO:SEQ ID NO:86、SEQ ID NO:87、SEQ IDNO:88、SEQ ID NO:89或SEQ ID NO:90的位置16处的脯氨酸；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处或在SEQ ID NO:72的位置3处的丝氨酸；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置20的位置处或在SEQ ID NO:72的位置20处的脯氨酸。
实施方案33.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体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。
实施方案34.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含来自野生型猫类IgG-1Fc多肽或来自野生型马类IgG1 Fc多肽的铰链区或铰链区的一部分。
实施方案35.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在对应于SEQ ID NO:90的位置8、位置9、位置10、位置11、位置12、位置13、位置14、位置15或位置16的位置处的半胱氨酸。
实施方案36.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在对应于SEQ ID NO:90的位置14的位置处的半胱氨酸。
实施方案37.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在SEQ ID NO:90的位置14处的半胱氨酸。
实施方案38.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置23的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置25的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置80的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置205的位置处的氨基酸取代、和/或在对应于SEQ ID NO:34的位置207的位置处的氨基酸取代；
b)在对应于SEQ ID NO:37的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:37的位置23的位置处的氨基酸取代和/或在对应于SEQ ID NO:37的位置24的位置处的氨基酸取代；
c)在对应于SEQ ID NO:39的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置23的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置25的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置80的位置处的氨基酸取代和/或在对应于SEQ ID NO:39的位置207的位置处的氨基酸取代；
d)在对应于SEQ ID NO:71的位置15的位置处的氨基酸取代和/或在对应于SEQ IDNO:71的位置203的位置处的氨基酸取代；
e)在对应于SEQ ID NO:75的位置199的位置处的氨基酸取代和/或在对应于SEQID NO:75的位置200的位置处的氨基酸取代；和/或
f)在对应于SEQ ID NO:76的位置199的位置处的氨基酸取代、在对应于SEQ IDNO:76的位置200的位置处的氨基酸取代、在对应于SEQ ID NO:76的位置201的位置处的氨基酸取代和/或在对应于SEQ ID NO:76的位置202的位置处的氨基酸取代。
实施方案39.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34的位置21处的氨基酸取代、在SEQ ID NO:34的位置23处的氨基酸取代、在SEQ ID NO:34的位置25处的氨基酸取代、在SEQ ID NO:34的位置80处的氨基酸取代、在SEQ ID NO:34的位置205处的氨基酸取代和/或在SEQ ID NO:34的位置207处的氨基酸取代；
b)在SEQ ID NO:37的位置21处的氨基酸取代、在SEQ ID NO:37的位置23处的氨基酸取代和/或在SEQ ID NO:37的位置24处的氨基酸取代；
c)在SEQ ID NO:39的位置21处的氨基酸取代、在SEQ ID NO:39的位置23处的氨基酸取代、在SEQ ID NO:39的位置25处的氨基酸取代、在SEQ ID NO:39的位置80处的氨基酸取代和/或在SEQ ID NO:39的位置207处的氨基酸取代；
d)在SEQ ID NO:71的位置15处的氨基酸取代和/或在SEQ ID NO:71的位置203处的氨基酸取代；
e)在SEQ ID NO:75的位置199处的氨基酸取代和/或在SEQ ID NO:75的位置200处的氨基酸取代；和/或
f)在SEQ ID NO:76的位置199处的氨基酸取代、在SEQ ID NO:76的位置200处的氨基酸取代、在SEQ ID NO:76的位置201处的氨基酸取代和/或在SEQ ID NO:76的位置202处的氨基酸取代。
实施方案40.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34的位置21的位置处的苏氨酸、在对应于SEQ ID NO:34的位置23的位置处的亮氨酸、在对应于SEQ ID NO:34的位置25的位置处的丙氨酸、在对应于SEQ ID NO:34的位置80的位置处的甘氨酸、在对应于SEQ ID NO:34的位置205的位置处的丙氨酸和/或在对应于SEQ ID NO:34的位置207的位置处的组氨酸；
b)在对应于SEQ ID NO:37的位置21的位置处的苏氨酸、在对应于SEQ ID NO:37的位置23的位置处的亮氨酸和/或在对应于SEQ ID NO:37的位置24的位置处的异亮氨酸；
c)在对应于SEQ ID NO:39的位置21的位置处的苏氨酸、在对应于SEQ ID NO:39的位置23的位置处的亮氨酸、在对应于SEQ ID NO:39的位置25的位置处的丙氨酸、在对应于SEQ ID NO:39的位置80的位置处的甘氨酸和/或在对应于SEQ ID NO:39的位置207的位置处的组氨酸；
d)在对应于SEQ ID NO:71的位置15的位置处的苏氨酸或缬氨酸和/或在对应于SEQ ID NO:71的位置203的位置处的酪氨酸或缬氨酸；
e)在对应于SEQ ID NO:75的位置199的位置处的亮氨酸和/或在对应于SEQ IDNO:75的位置200的位置处的组氨酸；和/或
f)在对应于SEQ ID NO:76的位置199的位置处的亮氨酸、在对应于SEQ ID NO:76的位置200的位置处的组氨酸、在对应于SEQ ID NO:76的位置201的位置处的天冬酰胺和/或在对应于SEQ ID NO:76的位置202的位置处的组氨酸。
实施方案41.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34的位置21处的苏氨酸、在SEQ ID NO:34的位置23处的亮氨酸、在SEQ ID NO:34的位置25处的丙氨酸、在SEQ ID NO:34的位置80处的甘氨酸、在SEQ IDNO:34的位置205处的丙氨酸和/或在SEQ ID NO:34的位置207处的组氨酸；
b)在SEQ ID NO:37的位置21处的苏氨酸、在SEQ ID NO:37的位置23处的亮氨酸和/或在SEQ ID NO:37的位置24处的异亮氨酸；
c)在SEQ ID NO:39的位置21处的苏氨酸、在SEQ ID NO:39的位置23处的亮氨酸、在SEQ ID NO:39的位置25处的丙氨酸、在SEQ ID NO:39的位置80处的甘氨酸和/或在SEQID NO:39的位置207处的组氨酸；
d)在SEQ ID NO:71的位置15处的苏氨酸或缬氨酸和/或在SEQ ID NO:71的位置203处的酪氨酸或缬氨酸；
e)在SEQ ID NO:75的位置199处的亮氨酸和/或在SEQ ID NO:75的位置200处的组氨酸；和/或
f)在SEQ ID NO:76的位置199处的亮氨酸、在SEQ ID NO:76的位置200处的组氨酸、在SEQ ID NO:76的位置201处的天冬酰胺和/或在SEQ ID NO:76的位置202处的组氨酸。
实施方案42.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:35的位置93的位置处的氨基酸取代或在对应于SEQ IDNO:37的位置93的位置处的氨基酸取代；
b)在对应于SEQ ID NO:70的位置87的位置处的氨基酸取代、在对应于SEQ ID NO:73的位置87的位置处的氨基酸取代、在对应于SEQ ID NO:74的位置87的位置处的氨基酸取代或在对应于SEQ ID NO:77的位置87的位置处的氨基酸取代；或
c)在对应于SEQ ID NO:86的位置198的位置处的氨基酸取代、在对应于SEQ IDNO:87的位置198的位置处的氨基酸取代、在对应于SEQ ID NO:88的位置198的位置处的氨基酸取代或在对应于SEQ ID NO:89的位置198的位置处的氨基酸取代。
实施方案43.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:35的位置93处的氨基酸取代或在SEQ ID NO:37的位置93处的氨基酸取代；
b)在SEQ ID NO:70的位置87处的氨基酸取代、在SEQ ID NO:73的位置87处的氨基酸取代、在SEQ ID NO:74的位置87处的氨基酸取代或在SEQ ID NO:77的位置87处的氨基酸取代；或
c)在SEQ ID NO:86的位置198处的氨基酸取代、在SEQ ID NO:87的位置198处的氨基酸取代、在SEQ ID NO:88的位置198处的氨基酸取代或在SEQ ID NO:89的位置198处的氨基酸取代。
实施方案44.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:35的位置93的位置处的精氨酸或在对应于SEQ ID NO:37的位置93的位置处的精氨酸；
b)在对应于SEQ ID NO:70的位置87的位置处的丝氨酸、在对应于SEQ ID NO:73的位置87的位置处的丝氨酸取代、在对应于SEQ ID NO:74的位置87的位置处的丝氨酸或在对应于SEQ ID NO:77的位置87的位置处的丝氨酸；或
c)在对应于SEQ ID NO:86的位置198的位置处的丙氨酸、在对应于SEQ ID NO:87的位置198的位置处的丙氨酸、在对应于SEQ ID NO:88的位置198的位置处的丙氨酸或在对应于SEQ ID NO:89的位置198的位置处的丙氨酸。
实施方案45.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:35的位置93处的精氨酸或在SEQ ID NO:37的位置93处的精氨酸；
b)在SEQ ID NO:70的位置87处的丝氨酸、在SEQ ID NO:73的位置87处的丝氨酸、在SEQ ID NO:74的位置87处的丝氨酸或在SEQ ID NO:77的位置87处的丝氨酸；或
c)在SEQ ID NO:86的位置198处的丙氨酸、在SEQ ID NO:87的位置198处的丙氨酸、在SEQ ID NO:88的位置198处的丙氨酸或在SEQ ID NO:89的位置198处的丙氨酸。
实施方案46.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ IDNO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ IDNO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90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:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ IDNO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ IDNO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82的位置处的酪氨酸；
c)在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ IDNO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90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:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ IDNO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90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；
e)在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ IDNO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90的位置207的位置处的酪氨酸；
f)在对应于SEQ ID NO:34或SEQ ID NO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的组氨酸；
g)在对应于SEQ ID NO:34或SEQ ID NO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的酪氨酸；或
h)在对应于SEQ ID NO:34或SEQ ID NO:39的位置208的位置处的酪氨酸。
实施方案47.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置23处的酪氨酸或苯丙氨酸；
b)在SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸；
c)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的组氨酸；
d)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的酪氨酸；
e)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置207处的酪氨酸；
f)在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的组氨酸；
g)在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的酪氨酸；或
h)在SEQ ID NO:34或SEQ ID NO:39的位置208处的酪氨酸。
实施方案48.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含与以下的氨基酸序列具有至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性或至少99％同一性的氨基酸序列：SEQ IDNO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ IDNO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ IDNO:52、SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ IDNO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ IDNO:64、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ IDNO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ IDNO:84、SEQ ID NO:85、SEQ ID NO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ IDNO:95、SEQ ID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:197、SEQ ID NO:198、SEQID NO:199、SEQ ID NO:200、SEQ ID NO:201、SEQ ID NO:202、SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206、SEQ ID NO:207、SEQ ID NO:208、SEQ ID NO:209和/或SEQ ID NO:210。
实施方案49.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含以下的氨基酸序列：SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ IDNO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ IDNO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、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:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:78、SEQ IDNO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQ IDNO:85、SEQ ID NO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ IDNO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:197、SEQ ID NO:198、SEQ ID NO:199、SEQID NO:200、SEQ ID NO:201、SEQ ID NO:202、SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206、SEQ ID NO:207、SEQ ID NO:208、SEQ ID NO:209和/或SEQ ID NO:210。
实施方案50.根据前述实施方案中任一项所述的连续多肽，所述连续多肽还包含NGFR多肽的至少一个细胞外结构域(NGFR ECD多肽)。
实施方案51.根据前述实施方案中任一项所述的连续多肽，所述连续多肽还包含含有SEQ ID NO:135、SEQ ID NO:137和/或SEQ ID NO:139的氨基酸序列的至少一种NGFRECD多肽。
实施方案52.根据前述实施方案中任一项所述的连续多肽，所述连续多肽包含以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:110、SEQ IDNO:111、SEQ ID NO:112、SEQ ID NO:113、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ IDNO:122、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131、SEQ ID NO:132、SEQ IDNO:133、SEQ ID NO:140、SEQ ID NO:141、SEQ ID NO:142、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ ID NO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ IDNO:166、SEQ ID NO:167、SEQ ID NO:168、SEQ ID NO:169、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172、SEQ ID NO:173、SEQ ID NO:174、SEQ ID NO:175、SEQ ID NO:176、SEQ IDNO:177、SEQ ID NO:178、SEQ ID NO:179、SEQ ID NO:180、SEQ ID NO:181、SEQ ID NO:182、SEQ ID NO:183、SEQ ID NO:184、SEQ ID NO:185、SEQ ID NO:186、SEQ ID NO:187、SEQ IDNO:188、SEQ ID NO:189、SEQ ID NO:190、SEQ ID NO:191、SEQ ID NO:192、SEQ ID NO:193、SEQ ID NO:194、SEQ ID NO:211、SEQ ID NO:212、SEQ ID NO:213、SEQ ID NO:214、SEQ IDNO:215、SEQ ID NO:216、SEQ ID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220、SEQ ID NO:221、SEQ ID NO:222、SEQ ID NO:223、SEQ ID NO:224、SEQ ID NO:225、SEQ IDNO:226、SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230、SEQ ID NO:231、SEQ ID NO:232、SEQ ID NO:233、SEQ ID NO:234、SEQ ID NO:235、SEQ ID NO:236、SEQ IDNO:237、SEQ ID NO:238、SEQ ID NO:239、SEQ ID NO:240、SEQ ID NO:241、SEQ ID NO:242、SEQ ID NO:243、SEQ ID NO:244、SEQ ID NO:245或SEQ ID NO:246。
实施方案53.一种连续多肽，所述连续多肽包含以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ IDNO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:110、SEQ ID NO:111、SEQ ID NO:112、SEQID NO:113、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:122、SEQ ID NO:123、SEQID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131、SEQ ID NO:132、SEQ ID NO:133、SEQ ID NO:140、SEQID NO:141、SEQ ID NO:142、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ ID NO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166、SEQ ID NO:167、SEQID NO:168、SEQ ID NO:169、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172、SEQ ID NO:173、SEQ ID NO:174、SEQ ID NO:175、SEQ ID NO:176、SEQ ID NO:177、SEQ ID NO:178、SEQID NO:179、SEQ ID NO:180、SEQ ID NO:181、SEQ ID NO:182、SEQ ID NO:183、SEQ ID NO:184、SEQ ID NO:185、SEQ ID NO:186、SEQ ID NO:187、SEQ ID NO:188、SEQ ID NO:189、SEQID NO:190、SEQ ID NO:191、SEQ ID NO:192、SEQ ID NO:193、SEQ ID NO:194、SEQ ID NO:211、SEQ ID NO:212、SEQ ID NO:213、SEQ ID NO:214、SEQ ID NO:215、SEQ ID NO:216、SEQID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220、SEQ ID NO:221、SEQ ID NO:222、SEQ ID NO:223、SEQ ID NO:224、SEQ ID NO:225、SEQ ID NO:226、SEQ ID NO:227、SEQID NO:228、SEQ ID NO:229、SEQ ID NO:230、SEQ ID NO:231、SEQ ID NO:232、SEQ ID NO:233、SEQ ID NO:234、SEQ ID NO:235、SEQ ID NO:236、SEQ ID NO:237、SEQ ID NO:238、SEQID NO:239、SEQ ID NO:240、SEQ ID NO:241、SEQ ID NO:242、SEQ ID NO:243、SEQ ID NO:244、SEQ ID NO:245或SEQ ID NO:246。
实施方案54.根据前述实施方案中任一项所述的连续多肽，其中所述Trk A ECD多肽是糖基化的。
实施方案55.根据前述实施方案中任一项所述的连续多肽，其中所述Trk A ECD多肽包含至少一个聚糖部分。
实施方案56.根据前述实施方案中任一项所述的连续多肽，其中所述Trk A ECD多肽被聚乙二醇化。
实施方案57.根据前述实施方案中任一项所述的连续多肽，其中所述Trk A ECD多肽在聚糖处、在伯胺处和/或在N末端α-胺处被聚乙二醇化。
实施方案58.一种分离的核酸，所述分离的核酸编码根据前述实施方案中任一项所述的连续多肽。
实施方案59.一种宿主细胞，所述宿主细胞包含根据实施方案58所述的核酸。
实施方案60.一种产生多肽的方法，所述方法包括培养根据实施方案59所述的宿主细胞并分离所述连续多肽。
实施方案61.一种药物组合物，所述药物组合物包含根据实施方案1至57中任一项所述的连续多肽和药学上可接受的载体。
实施方案62.根据实施方案61所述的药物组合物，其中所述药学上可接受的载体包含约5至约50mM的柠檬酸钠；约5至约50mM的组氨酸；或约5至约50mM的乙酸钠。
实施方案63.根据实施方案61或实施方案62所述的药物组合物，其中所述药物组合物具有5至6的pH。
实施方案64.一种治疗患有NGF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52中任一项所述的连续多肽或根据实施方案61至63中任一项所述的药物组合物。
实施方案65.一种治疗患有疼痛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57中任一项所述的连续多肽或根据实施方案61至63中任一项所述的药物组合物。
实施方案66.根据实施方案64或实施方案65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67.根据实施方案64至66中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是慢性疼痛、急性疼痛和/或炎性疼痛。
实施方案68.根据实施方案64至67中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是骨关节炎疼痛、背痛、癌症疼痛和/或神经性疼痛。
实施方案69.根据实施方案64至68中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是与手术、断骨或骨折、牙科治疗、烧伤、割伤和/或分娩相关的疼痛。
实施方案70.根据实施方案64至69中任一项所述的方法，其中所述连续多肽或所述药物组合物是肠胃外施用的。
实施方案71.根据实施方案64至70中任一项所述的方法，其中所述连续多肽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72.根据实施方案64至71中任一项所述的方法，其中所述方法还包括施用NGF激酶抑制剂、PI3K抑制剂、ras抑制剂、CGRP抑制剂、TNF抑制剂、IL17抑制剂、EGFR抑制剂和/或磷脂酶C途径抑制剂。
实施方案73.根据实施方案64至72中任一项所述的方法，其中所述方法还包括施用一种或多种疼痛治疗药物，如皮质类固醇、非甾体抗炎药(NSAID)、环氧合酶抑制剂、阿片类物质和/或大麻素。
实施方案74.一种降低细胞中NGF信号传导活性的方法，所述方法包括在以下条件下将所述细胞暴露于根据实施方案1至57中任一项所述的连续多肽或根据实施方案61至63中任一项所述的药物组合物：所述条件允许所述连续多肽与NGF的结合。
实施方案75.根据实施方案74所述的方法，其中将所述细胞离体暴露于所述连续多肽或所述药物组合物。
实施方案76.根据实施方案74所述的方法，其中将所述细胞在体内暴露于所述连续多肽或所述药物组合物。
实施方案77.根据实施方案74至76中任一项所述的方法，其中所述细胞是犬类细胞、猫类细胞或马类细胞。
实施方案78.一种用于检测来自伴生动物物种的样品中的NGF的方法，所述方法包括在以下条件下使所述样品与根据实施方案1至57中任一项所述的连续多肽或根据实施方案61至63中任一项所述的药物组合物接触：所述条件允许所述连续多肽与NGF的结合；并且检测是否在所述多肽与所述样品中的NGF之间形成复合物。
实施方案79.根据实施方案78所述的方法，其中所述样品是从犬类、猫类或马类获得的生物样品。
附图说明
图1示出了比较犬类和猫类TrkA ECD v2和v3 IgG-Fc融合蛋白对NGF的亲和力的传感图。不相关的犬类或猫类IgG-Fc融合蛋白用作阴性对照。
图2示出了比较马类TrkA ECD v2和v3 IgG-Fc融合蛋白对NGF的亲和力的传感图。不相关的马类IgG-Fc融合蛋白用作阴性对照。
图3是示出了在如实施例4中所述进行的TF1细胞增殖测定中示例性马类TrkAECD-IgG Fc多肽(SEQ ID NO:22)中和NGF活性的图。不相关的单克隆抗体用作阴性对照。
图4是示出了在大鼠MIA诱导的骨关节炎模型中施用犬类TrkA-Fc多肽(1mg/kg和20mg/kg)后滑膜中NGF的浓度的图。
图5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6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7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8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9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10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11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12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13是示出了由如实施例19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
提供了连续多肽，所述连续多肽包含至少一种结合NGF多肽的TrkA ECD多肽。还提供了产生和纯化所述连续多肽的方法。提供了使用结合NGF并抑制NGF介导的信号传导的TrkA ECD多肽的治疗方法。此类方法包括但不限于治疗伴生动物物种的疼痛的方法。还提供了检测来自伴生动物物种的样品中的NGF的方法。
为方便读者，提供了以下本文所使用的术语的定义。
如本文所用，诸如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。
示例性TrkA多肽
提供了结合NGF的TrkA ECD多肽，例如结合NGF的犬类、猫类和马类TrkA ECD多肽。
“氨基酸序列”意指蛋白质中的氨基酸序列，并且包括其中序列的一个或多个氨基酸的侧基已经被化学修饰的氨基酸序列，以及如下的那些氨基酸序列：其中，相对于已知序列，一个或多个氨基酸已经被替代、插入或缺失，但并未由此消除所需特性，如结合EPO受体的能力。氨基酸序列也可称为肽、寡肽、多肽或蛋白质。
如本文所用，“TrkA”或“TrkA多肽”是包含能够与NGF结合的原肌球蛋白受体激酶A(TrkA)受体的全部或片段的多肽。
例如，除非另外指明，否则“TrkA”是指来自任何脊椎动物来源的TrkA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)。在一些实施方案中，TrkA是结合NGF的细胞外结构域片段。在一些此类实施方案中，TrkA可称为TrkA细胞外结构域(ECD)。在一些实施方案中，TrkA包含以下的氨基酸序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ IDNO:32或SEQ ID NO:33。
如本文所用，“NGF受体”或“NGFR”是包含结合NGF的低亲和力神经生长因子受体(也称为肿瘤坏死因子受体超家族成员16)的全部或部分的多肽。
例如，除非另外指明，否则“NGFR”是指来自任何脊椎动物来源的NGFR多肽，所述脊椎动物来源包括哺乳动物，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)。在一些实施方案中，NGFR是结合NGF的细胞外结构域片段。在一些此类实施方案中，NGFR可称为NGFR细胞外结构域(ECD)。在一些实施方案中，NGFR包含SEQ ID NO:134、SEQ ID NO:135、SEQ ID NO:136、SEQ ID NO:137、SEQ ID NO:138或SEQ ID NO:139的氨基酸序列。
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牛、猪等家畜。
“细胞外结构域”(“ECD”)是多肽的延伸超过跨膜结构域到细胞外空间中的一部分。如本文所用，术语“细胞外结构域”可包含完整的细胞外结构域或可包含缺失一个或多个与其配体结合的氨基酸的截短型细胞外结构域。所述细胞外结构域的组成可取决于用于确定哪些氨基酸在膜中的算法。对于给定的蛋白质，不同的算法可预测不同的细胞外结构域，并且不同的系统可表达不同的细胞外结构域。
TrkA多肽的细胞外结构域可以包含结合NGF的TrkA的完整细胞外结构域或截短型细胞外结构域。如本文所用，术语“TrkA多肽的细胞外结构域”或“TrkA ECD”是指不包含跨膜结构域或细胞质结构域的TrkA多肽，即使所述术语遵循开放的过渡词，如“包含(comprising)”、“包含(comprises)”等。在一些实施方案中，TrkA多肽的细胞外结构域是来自伴生物种动物的TrkA的细胞外结构域。例如，在一些实施方案中，TrkA多肽的细胞外结构域源自犬类TrkA、猫类TrkA或马类TrkA。在一些实施方案中，TRKA多肽的细胞外结构域包含以下的氨基酸序列：SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33或其任何片段。
NGFR多肽的细胞外结构域可以包含结合NGF的NGFR的完整细胞外结构域或截短型细胞外结构域。如本文所用，术语“NGFR多肽的细胞外结构域”或“NGFR ECD”是指不包含跨膜结构域或细胞质结构域的NGFR多肽，即使所述术语遵循开放的过渡词，如“包含(comprising)”、“包含(comprises)”等。在一些实施方案中，NGFR多肽的细胞外结构域是来自伴生物种动物的NGFR多肽的细胞外结构域。例如，在一些实施方案中，NGFR多肽的细胞外结构域源自犬类NGFR、猫类NGFR或马类NGFR。在一些实施方案中，NGFR多肽的细胞外结构域包含SEQ ID NO:135、SEQ ID NO:137、SEQ ID NO:139的氨基酸序列或其任何片段。
“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。
“变体”或“类似物”在本文中可互换地称为这样的多肽，其与参考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多肽的至少一种生物活性。
“生物活性”实体或具有“生物活性”的实体是如下实体：其具有与代谢或生理过程有关或相关的任何功能，和/或具有天然存在的分子的结构功能、调节功能或生化功能。生物活性多肽或其片段包括可以参与生物反应的一种，所述生物反应包括但不限于配体-受体相互作用或抗原-抗体结合。生物活性可以包括改善的期望活性或降低的不期望活性。在实体参与与另一种分子的分子相互作用时，在实体具有减轻疾病病症的治疗价值时，在实体具有诱导免疫应答的预防价值时，在实体具有确定分子的存在的诊断和/或预后价值时，所述实体可以展现生物活性。
如本文所用，关于多肽序列的“氨基酸序列同一性百分比(％)”和“同源性”被定义为，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)后，并且不将任何保守取代视为序列同一性的一部分，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MEGALIGNTM(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，在比对序列和引入空位(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91％序列同一性、至少约92％序列同一性、至少约93％序列同一性、至少约94％序列同一性、至少约95％序列同一性、至少约96％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99％序列同一性。
如本文所用，“对应于位置n的位置”(其中n是任何数)是指在比对主题多肽和参考多肽的氨基酸序列并引入空位后，与参考多肽的位置n对齐的主题多肽的氨基酸位置。用于确定主题多肽的位置是否对应于参考多肽的位置n的目的的比对可以以本领域技术范围内的各种方式实现，例如使用公众可获得的计算机软件，如BLAST、BLAST-2、CLUSTAL OMEGA、ALIGN或MEGALIGNTM(DNASTAR)软件。本领域技术人员可以确定用于比对的适当参数，包括为了在所比较的两个序列的全长上实现最大比对所需要的任何参数。在一些实施方案中，主题多肽和参考多肽具有不同的长度。
“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”可以包括但不限于用另一种氨基酸替代多肽中的一个氨基酸。示例性取代在表2中示出。可以将氨基酸取代引入目的分子中，并筛选产物的所需活性，例如，保留/改善的受体结合、降低的免疫原性、减少的ADCC和/或CDC、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？TableP age＝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，变体IgG Fc多肽包含用氨基酸衍生物进行的氨基酸取代。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。
在一些实施方案中，TrkA ECD多肽包含SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQID NO:13、SEQ ID NO:14或SEQ ID NO:15的氨基酸序列，不同之处在于存在不存在于SEQID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQ IDNO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14或SEQ ID NO:15中的至少一个N连接的糖基化位点。在一些实施方案中，所述至少一个N连接的糖基化位点包含序列天冬酰胺-xaa-丝氨酸，其中xaa是除脯氨酸外的任何氨基酸。在一些实施方案中，所述至少一个N连接的糖基化位点包含序列天冬酰胺-xaa-苏氨酸，其中xaa是除脯氨酸外的任何氨基酸。在一些实施方案中，所述至少一个N连接的糖基化位点不与另一个N连接的糖基化位点重叠。
在一些实施方案中，TrkA ECD多肽包含在SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ ID NO:14的氨基酸位置6-8、31-33、84-86、85-87、86-88、88-90、90-92、92-94和/或94-96处的N连接的糖基化位点。在一些实施方案中，TrkA ECD多肽包含在SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的氨基酸位置4-6、29-31、82-84、83-85、84-86、86-88、89-90、90-92和/或92-94处的N连接的糖基化位点。
在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:3、SEQ ID NO:4、SEQID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ ID NO:14的位置30或位置85的氨基酸位置处的除脯氨酸之外的氨基酸。在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28或位置83的氨基酸位置处的除脯氨酸之外的氨基酸。
在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:3、SEQ ID NO:4、SEQID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ ID NO:14的位置30和/或位置85的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸。在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28和/或位置83的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸。
在一些实施方案中，TrkA ECD多肽包含下文表3、表4或表5中列出的一个或多个氨基酸修饰。
表3.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
表4.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
表5.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
在一些实施方案中，TrkA ECD多肽包含一种或多种另外的二硫键。例如，在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ IDNO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89的位置处的半胱氨酸。在一些实施方案中，TrkA ECD多肽包含在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和位置87的位置处的半胱氨酸。在一些实施方案中，TrkA ECD多肽包含在SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:7、SEQ IDNO:8、SEQ ID NO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89处的半胱氨酸。在一些实施方案中，TrkA多肽包含在SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和位置87处的半胱氨酸。
在一些实施方案中，TrkA ECD多肽包含SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ IDNO:33的氨基酸序列。
如本文所用，“糖基化的”是指具有一个或多个共价附接的聚糖部分的多肽。
如本文所用，“聚糖”或“聚糖部分”是指糖苷连接的单糖。
聚糖以几种方式附接至糖肽，其中N连接至天冬酰胺和O连接至丝氨酸和苏氨酸对于重组治疗性糖蛋白是最相关的。N连接的糖基化发生在共有序列Asn-Xaa-Ser/Thr处，其中Xaa可以是除脯氨酸外的任何氨基酸。
如本文所用，“唾液酸化”是指多肽具有一个或多个共价附接的唾液酸部分。
已经开发了多种用于生产糖基化的和唾液酸化的蛋白质的方法。参见例如Savinova等人,Applied Biochem&Microbiol.51(8):827-33(2015)。
如本文所用，“聚乙二醇化”是指多肽具有一个或多个缔合或者共价或非共价附接的聚乙二醇(PEG)部分。
在一些实施方案中，TrkA ECD多肽被糖基化。在一些实施方案中，TrkA ECD多肽包含附接至N连接的糖基化位点的至少一个聚糖部分。在一些实施方案中，TrkA ECD多肽被唾液酸化。在一些实施方案中，TrkA ECD多肽被聚乙二醇化。在一些实施方案中，TrkA ECD多肽在聚糖处被聚乙二醇化。在一些实施方案中，TrkA ECD多肽在伯胺处被聚乙二醇化。在一些实施方案中，TrkA ECD多肽在N末端α胺处被聚乙二醇化。在一些实施方案中，TrkA ECD多肽被糖基化、唾液酸化和/或聚乙二醇化。
示例性变体IgG Fc多肽和融合分子
包含TrkA多肽的连续多肽可以包含融合配偶体，如野生型或变体IgG Fc多肽。
如本文所用，“融合分子”是指包含一个或多个“融合配偶体”的分子。在一些实施方案中，融合配偶体是共价连接(“融合”)的。如果两个融合配偶体均是多肽，则融合配偶体多肽可以是连续氨基酸序列(即，连续多肽)的一部分。第一融合配偶体多肽可以连接至第二融合配偶体的N末端或C末端。在一些实施方案中，融合配偶体由编码两个融合配偶体的编码序列翻译为单个多肽。融合配偶体可以通过其他手段，如除了肽键之外的化学连接而共价连接。可以使用许多已知的将多肽与其他分子(例如，融合配偶体)共价连接的方法。在其他实施方案中，融合配偶体通过“接头”融合，所述接头由至少一个氨基酸或化学部分构成。
在一些实施方案中，融合配偶体是白蛋白、白蛋白结合片段或免疫球蛋白分子的片段。融合配偶体可以包含寡聚化结构域，如重链免疫球蛋白的Fc结构域。在一些实施方案中，融合配偶体包含至少一种TrkA ECD多肽和一种IgG Fc多肽。在一些实施方案中，融合配偶体还包含一种或多种其他治疗性多肽，如NGFR ECD多肽。在一些实施方案中，TrkA ECD多肽可以连接至IgG Fc多肽的N末端或C末端。
本文中的术语“连续多肽”用于意指氨基酸的不间断序列。连续多肽通常从单个连续DNA序列翻译。它可以通过基因工程来制得，例如，通过从第一蛋白质的DNA序列中去除终止密码子，然后在框内附加第二蛋白质的DNA序列，使得DNA序列表达为单一蛋白质。通常，这是通过将cDNA与现有基因一起框内克隆至表达载体中来完成的。
“接头”是指连接第一多肽与第二多肽的一个或多个氨基酸残基。
在一些实施方案中，接头是柔性非结构性接头。在一些实施方案中，接头是富含甘氨酸、富含丝氨酸、或富含甘氨酸和丝氨酸的接头。在一些实施方案中，接头包含100％、至少95％、至少90％、或至少85％的丝氨酸和/或甘氨酸氨基酸残基。在一些实施方案中，接头是富含甘氨酸、富含丝氨酸或富含GS的柔性非结构性接头。在一些实施方案中，接头包含氨基酸G(Gly)和/或S(Ser)。例如，接头可以包含G或G的重复序列(例如，GG、GGG等)；GS或GS的重复序列(例如，GSGS(SEQ ID NO:143)、GSGSGS(SEQ ID NO:144)等)；GGS或GGS的重复序列(例如，GGSGGS(SEQ ID NO:145)、GGSGGSGGS(SEQ ID NO:146)等)；GGGS(SEQ ID NO:147)或GGGS(SEQ ID NO:147)的重复序列(例如，GGGSGGGS(SEQ ID NO:148)、GGGSGGGSGGGS(SEQID NO:149)等)；GSS或GSS的重复序列(例如，GSSGSS(SEQ ID NO:150)、GSSGSSGSS(SEQ IDNO:151)等)；GGSS(SEQ ID NO:152)或GGSS(SEQ ID NO:152)的重复(例如，GGSSGGSS(SEQID NO:153)、GGSSGGSSGGSS(SEQ ID NO:157)等)；SGGG(SEQ ID NO:158)或SGGG(SEQ IDNO:158)的重复序列(例如SGGGSGGGS(SEQ ID NO:156))。
如本文所用，“延伸部分”是指在C末端或N末端连接至多肽的一个或多个氨基酸残基。
在一些实施方案中，延伸部分是柔性的。在一些实施方案中，延伸部分向多肽增加柔性，而不干扰多肽的生物活性。在一些实施方案中，延伸部分增加多肽的溶解度。在一些实施方案中，延伸部分包含一个或多个甘氨酸残基。在一些实施方案中，延伸部分包含一个甘氨酸残基、两个甘氨酸残基、三个甘氨酸残基、四个甘氨酸残基、五个甘氨酸残基、六个甘氨酸残基、七个甘氨酸残基、八个甘氨酸残基或更多个甘氨酸残基。
如本文所用，“变体IgG Fc”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。
“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”是任何抗体响应于刺激而全部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”或“IgX Fc多肽”是指源自特定抗体同种型(例如，IgG、IgA、IgD、IgE、IgM等)的Fc多肽，其中“X”表示抗体同种型。因此，“IgG Fc”表示Fc多肽源自γ链，“IgAFc”表示Fc多肽源自α链，“IgD Fc”表示Fc多肽源自δ链，“IgE Fc”表示Fc多肽源自ε链，“IgMFc”表示Fc多肽源自μ链等。在一些实施方案中，IgG Fc多肽包含铰链、CH2和CH3，但不包含CH1或CL。在一些实施方案中，IgG Fc多肽包含CH2和CH3，但不包含CH1、铰链或CL。在一些实施方案中，IgG Fc多肽包含CH1、铰链、CH2、CH3，具有或不具有CL。在一些实施方案中，IgGFc多肽包含CH1、铰链、CH2和CH3，具有或不具有CL1。在一些实施方案中，Fc多肽(如IgG Fc多肽)缺少一个或多个C末端氨基酸，如1至20、1至15、1至10、1至5或1至2个氨基酸，同时保留生物活性。在一些实施方案中，生物活性是结合FcRn的能力。Fc多肽的“效应子功能”是任何抗体响应于刺激而全部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。“IgX-NFc”或“IgGXN Fc”表示Fc多肽源自抗体同种型的特定子类(如犬类IgG子类IgG-A、IgG-B、IgG-C或IgG-D；猫类IgG子类IgG1a、IgG1b或IgG2；或马类IgG子类IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7等)，其中“N”表示子类。
“铰链”是指Fc多肽或变体Fc多肽的任何部分，所述任何部分富含脯氨酸并且包含位于全长重链恒定区的CH1与CH2之间的至少一个半胱氨酸残基。
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，IgX或IgXN区源自诸如狗、猫或马等伴生动物。在一些实施方案中，IgG区分离自犬类γ重链，如IgGA、IgGB、IgGC或IgGD。在一些情况下，IgG Fc区分离自猫类γ重链，如IgG1、IgG2a或IgG2b。在其他情况下，IgG区分离自马类γ重链，如IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7。包含IgGA、IgGB、IgGC或IgGD的Fc区的多肽可以在重组生产系统中提供更高的表达水平。
在一些实施方案中，IgX Fc多肽或IgX-N Fc多肽源自诸如狗、猫或马等伴生动物。在一些实施方案中，IgG Fc多肽分离自犬类γ重链，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IgG1a、IgG1b或IgG2。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。
在一些实施方案中，野生型IgG Fc多肽包含以下的氨基酸序列：SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ IDNO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQID NO:90。
“变体Fc多肽”是如下的Fc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Fc多肽保留了参考Fc多肽的至少一种生物活性。在一些实施方案中，变体Fc多肽(例如，变体犬类IgG-A Fc、变体犬类IgG-CFc、变体犬类IgG-D Fc、变体马类IgG2 Fc、变体马类IgG5 Fc、或变体马类IgG6 Fc)具有参考Fc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、变体犬类IgG-CFc、变体犬类IgG-D Fc、变体马类IgG2 Fc、变体马类IgG5 Fc或变体马类IgG6 Fc结合蛋白A。
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。
具有修饰的蛋白A结合的示例性变体IgG Fc多肽
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多肽包含在对应于SEQ ID NO:34的位置21、位置23、位置25、位置80、位置205和/或位置207的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置21、位置23和/或位置24的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:39的位置21、位置23、位置25、位置80和/或位置207的位置处的氨基酸取代。
在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:71的位置15和/或位置203的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ IDNO:75的位置199和/或位置200的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:76的位置199、位置200、位置201和/或202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:34的位置21、位置23、位置25、位置80、位置205和/或位置207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:37的位置21、位置23和/或位置24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:39的位置21、位置23、位置25、位置80和/或位置207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:71的位置15和/或位置203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:75的位置199和/或位置200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:76的位置199、位置200、位置201和/或位置202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:34的位置21的位置处的苏氨酸、在对应于SEQ ID NO:34的位置23的位置处的亮氨酸、在对应于SEQ ID NO:34的位置25的位置处的丙氨酸、在对应于SEQ ID NO:34的位置80的位置处的甘氨酸、在对应于SEQ ID NO:34的位置205的位置处的丙氨酸和/或在对应于SEQ ID NO:34的位置207的位置处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置21的位置处的苏氨酸、在对应于SEQ ID NO:37的位置23的位置处的亮氨酸和/或在对应于SEQID NO:37的位置24的位置处的异亮氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:39的位置21的位置处的苏氨酸、在对应于SEQ ID NO:39的位置23的位置处的亮氨酸、在对应于SEQ ID NO:39的位置25的位置处的丙氨酸、在对应于SEQ ID NO:39的位置80的位置处的甘氨酸和/或在对应于SEQ ID NO:39的位置207的位置处的组氨酸。
在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:71的位置15的位置处的苏氨酸或缬氨酸和/或在对应于SEQ ID NO:71的位置203的位置处的酪氨酸或缬氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:75的位置199的位置处的亮氨酸和/或在对应于SEQ ID NO:75的位置200的位置处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:76的位置199的位置处的异亮氨酸、在对应于SEQ IDNO:76的位置200的位置处的组氨酸、在对应于SEQ ID NO:76的位置201的位置处的天冬酰胺和/或在对应于SEQ ID NO:76的位置202的位置处的组氨酸。
在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34的位置21处的苏氨酸、在SEQ ID NO:34的位置23处的亮氨酸、在SEQ ID NO:34的位置25处的丙氨酸、在SEQ IDNO:34的位置80处的甘氨酸、在SEQ ID NO:34的位置205处的丙氨酸和/或在SEQ ID NO:34的位置207处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:47的位置21处的苏氨酸、在SEQ ID NO:47的位置23处的亮氨酸和/或在SEQ ID NO:47的位置24处的异亮氨酸。在一些实施方案中，变体IgG Fc多肽在SEQ ID NO:39的位置21处的苏氨酸、在SEQID NO:39的位置23处的亮氨酸、在SEQ ID NO:39的位置25处的丙氨酸、在SEQ ID NO:39的位置80处的甘氨酸和/或在SEQ ID NO:39的位置207处的组氨酸。
在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:71的位置15处的苏氨酸或缬氨酸和/或在SEQ ID NO:71的位置203处的酪氨酸或缬氨酸。在一些实施方案中，变体IgGFc多肽包含在SEQ ID NO:75的位置199处的亮氨酸和/或在SEQ ID NO:75的位置200处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:76的位置199处的异亮氨酸、在SEQ ID NO:76的位置200处的组氨酸、在SEQ ID NO:76的位置201处的天冬酰胺和/或在SEQ ID NO:76的位置202处的组氨酸。
具有修饰的CD16结合的示例性变体IgG Fc多肽
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多肽包含在对应于SEQ ID NO:35的位置5、位置38、位置39、位置97和/或位置98的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置5、位置38、位置39、位置97和/或位置98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:35的位置5、位置38、位置39、位置97和/或位置98处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在SEQID NO:37的位置5、位置38、位置39、位置97和/或位置98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:36的位置5的位置处的脯氨酸、在对应于其位置38的位置处的甘氨酸、在对应于其位置39的位置处的精氨酸、在对应于其位置97的位置处的异亮氨酸和/或在对应于其位置98的位置处的甘氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置5的位置处的脯氨酸、在对应于其位置38的位置处的甘氨酸、在对应于其位置39的位置处的精氨酸、在对应于其位置97的位置处的异亮氨酸和/或在对应于其位置98的位置处的甘氨酸。
在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:35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97处的异亮氨酸和/或位置98处的甘氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:37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97处的异亮氨酸和/或位置98处的甘氨酸。
具有修饰的C1q结合的示例性变体IgG Fc多肽
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多肽包含在对应于SEQ ID NO:35的位置93的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置93的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:70的位置87的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQID NO:73的位置87的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:74的位置87的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:77的位置87的位置处的氨基酸取代。在一些实施方案中，变体IgGFc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89的位置198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:35的位置93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:37的位置93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:70的位置87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:73的位置87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:74的位置87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:77的位置87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:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89的位置198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:35的位置93的位置处的精氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:37的位置93的位置处的精氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:70的位置87的位置处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:73的位置87的位置处的丝氨酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ IDNO:74的位置87的位置处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQID NO:77的位置87的位置处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89的位置198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:35的位置93处的精氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:37的位置93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:70的位置87处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:73的位置87处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:74的位置87处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:77的位置87处的丝氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89的位置198处的丙氨酸。
具有修饰的FcRn结合的示例性变体IgG Fc多肽
在一些实施方案中，变体IgG Fc多肽具有修饰的新生儿受体(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。
在一些实施方案中，变体IgG 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。
在一些实施方案中，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。
在一些实施方案中，连续多肽包含能够以相对于野生型Fc多肽增加的亲和力与FcRn结合的变体IgG Fc多肽，并且其中所述连续多肽相对于包含野生型Fc多肽的连续多肽具有增加的血清半衰期。
在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ IDNO:90的位置23的位置处的酪氨酸或苯丙氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ IDNO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ IDNO:86、SEQ ID NO:88或SEQ ID NO:90的位置82的位置处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90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。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:35、SEQ IDNO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ IDNO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90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。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置207的位置处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:34或SEQ ID NO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:34或SEQ IDNO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:34或SEQ ID NO:39的位置208的位置处的酪氨酸。
在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34、SEQ ID NO:35、SEQ IDNO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置23处的酪氨酸或苯丙氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34、SEQID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ IDNO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ IDNO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ IDNO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置207处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的组氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的酪氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:34或SEQ ID NO:39的位置208处的酪氨酸。
具有修饰的链间二硫键的示例性变体IgG Fc多肽
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。在一些实施方案中，变体猫类IgG Fc多肽在铰链区中具有至少一个另外的链间二硫键。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多肽具有对铰链区的至少一个氨基酸修饰。在一些实施方案中，野生型IgG Fc多肽是野生型猫类或马类IgG Fc多肽。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多肽包含来自野生型猫类IgG-1a Fc多肽、来自野生型猫类IgG-1b Fc多肽或来自野生型马类IgG1 Fc多肽的铰链区。在一些实施方案中，变体IgG2 Fc多肽相对于野生型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。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多肽包含在对应于SEQ ID NO:90的位置8、位置9、位置10、位置11、位置12、位置13、位置14、位置15或位置16的位置处的半胱氨酸。在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:90的位置8、位置9、位置10、位置11、位置12、位置13、位置14、位置15或位置16处的半胱氨酸。
在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16的位置处的氨基酸取代。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处和/或在对应于其位置20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:86、SEQ ID NO:87、SEQ IDNO:88、SEQ ID NO:89或SEQ ID NO:90的位置16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:72的位置3处和/或在对应于其位置20的位置处的氨基酸取代。
在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16的位置处的脯氨酸。在一些实施方案中，变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处的丝氨酸和/或在对应于其位置20的位置处的脯氨酸。
在一些实施方案中，变体IgG Fc多肽包含在SEQ ID NO:86、SEQ ID NO:87、SEQ IDNO:88、SEQ ID NO:89或SEQ ID NO:90的位置16处的脯氨酸。在一些实施方案中，变体IgGFc多肽包含在SEQ ID NO:72的位置3处的丝氨酸和/或位置20处的脯氨酸。
在一些实施方案中，变体IgG Fc多肽包含以下的氨基酸序列：SEQ ID NO:40、SEQID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:78、SEQID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQID NO:85、SEQ ID NO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105、SEQ ID NO:106、SEQ IDNO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:197、SEQ ID NO:198、SEQ ID NO:199、SEQ ID NO:200、SEQ ID NO:201、SEQ ID NO:202、SEQ ID NO:203、SEQ ID NO:204、SEQ IDNO:205、SEQ ID NO:206、SEQ ID NO:207、SEQ ID NO:208、SEQ ID NO:209和/或SEQ ID NO:210。
在一些实施方案中，可以基于以下式制备包含至少一种TrkA ECD多肽(例如，ECDv1、v2、v3和/或v4)和本文所述的野生型或变体犬类、猫类或马类IgG Fc多肽的连续多肽：
式(I)：TrkA ECD 1-L1-Fc；
式(II)：Fc-L1-TrkA ECD 1；
式(III)：TrkA ECD 1-L1-Fc-L2-TrkA ECD 2；
式(IV)：TrkA ECD 1-L1-TrkA ECD 2-L2-Fc；或
式(V)：Fc-L1-TrkA ECD 1-L2-TrkA ECD 2，
其中TrkA ECD 1是第一TrkA ECD多肽，TrkA ECD 2是第二TrkA ECD多肽(例如，相同的TrkA ECD多肽或不同的TrkA ECD多肽)，L1和L2是任选的接头；并且Fc是伴生动物物种的野生型或变体IgG Fc多肽。任选地，连续多肽包含信号序列。式I-V的示例性构建体可以包含在任何TrkA ECD 1或TrkA ECD 2之后或之前的第三、第四或第五等TrkA ECD。第三、第四或第五等TrkA ECD可以是与TrkA ECD 1或TrkA ECD 2相同的TrkA ECD多肽或不同的TrkA ECD多肽。
例如，连续多肽可以包含至少一种犬类TrkA ECD多肽(例如，SEQ ID NO:2、3、4、5、25、26或27)和野生型犬类IgG多肽(例如，SEQ ID NO:34、35、36、37、38或39)、变体犬类IgG-A Fc多肽(例如，SEQ ID NO:40、43、199或200)、变体犬类IgG-B Fc多肽(例如，SEQ ID NO:46、48、49、50、51、52、53、54、55、64、65、66、67、197、198、203、204、205、206、207、208、209或210)、变体犬类IgG-C Fc多肽(例如，SEQ ID NO:41、44、47、56、57、58、59、60、61、52、63、68或69)或变体犬类IgG-D Fc多肽(例如，SEQ ID NO:42、45、201或202)，如本文所述。
连续多肽可以包含至少一种猫类TrkA ECD多肽(例如，SEQ ID NO:7、8、9、10、28、29或30)和野生型猫类IgG Fc多肽(例如，86、87、88、89或90)、变体猫类IgG1a Fc多肽(例如，SEQ ID NO:91、92、96或97)、变体猫类IgG1b Fc多肽(例如，SEQ ID NO:93、94、98或99)或变体猫类IgG2 Fc多肽(例如，SEQ ID NO:95、100或107)，如本文所述。
连续多肽可以包含至少一种马类TrkA ECD多肽(例如，SEQ ID NO:12、13、14、15、31、32或33)和野生型马类IgG Fc多肽(例如，SEQ ID NO:70、71、72、73、74、75、76或77)、变体马类IgG1Fc多肽(例如，SEQ ID NO:82)、变体马类IgG2 Fc多肽(例如，SEQ ID NO:78、79、101、102、103、104、105、106、108或109)、变体马类IgG3 Fc多肽(例如，SEQ ID NO:83)、变体马类IgG4 Fc多肽(例如，SEQ ID NO:84)、变体马类IgG5 Fc多肽(例如，SEQ ID NO:80)、变体马类IgG6 Fc多肽(例如，SEQ ID NO:81)或变体马类IgG7 Fc多肽(例如，SEQ ID NO:85)。
在一些实施方案中，包含TrkA ECD多肽的连续多肽还可以包含至少一种NGFR ECD多肽。在一些实施方案中，NGFR ECD多肽包含SEQ ID NO:135、SEQ ID NO:137和/或SEQ IDNO:139的氨基酸序列。
在一些实施方案中，连续多肽包含以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ IDNO:23、SEQ ID NO:24、SEQ ID NO:110、SEQ ID NO:111、SEQ ID NO:112、SEQ ID NO:113、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ IDNO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:122、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ IDNO:130、SEQ ID NO:131、SEQ ID NO:132、SEQ ID NO:133、SEQ ID NO:140、SEQ ID NO:141、SEQ ID NO:142、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ IDNO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166、SEQ ID NO:167、SEQ ID NO:168、SEQ ID NO:169、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172、SEQ ID NO:173、SEQ IDNO:174、SEQ ID NO:175、SEQ ID NO:176、SEQ ID NO:177、SEQ ID NO:178、SEQ ID NO:179、SEQ ID NO:180、SEQ ID NO:181、SEQ ID NO:182、SEQ ID NO:183、SEQ ID NO:184、SEQ IDNO:185、SEQ ID NO:186、SEQ ID NO:187、SEQ ID NO:188、SEQ ID NO:189、SEQ ID NO:190、SEQ ID NO:191、SEQ ID NO:192、SEQ ID NO:193、SEQ ID NO:194、SEQ ID NO:211、SEQ IDNO:212、SEQ ID NO:213、SEQ ID NO:214、SEQ ID NO:215、SEQ ID NO:216、SEQ ID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220、SEQ ID NO:221、SEQ ID NO:222、SEQ IDNO:223、SEQ ID NO:224、SEQ ID NO:225、SEQ ID NO:226、SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230、SEQ ID NO:231、SEQ ID NO:232、SEQ ID NO:233、SEQ IDNO:234、SEQ ID NO:235、SEQ ID NO:236、SEQ ID NO:237、SEQ ID NO:238、SEQ ID NO:239、SEQ ID NO:240、SEQ ID NO:241、SEQ ID NO:242、SEQ ID NO:243、SEQ ID NO:244、SEQ IDNO:245、SEQ ID NO:246。
可以使用以下形式进一步构建分子：R-(接头)-Fc-TrkA。R可以是任何蛋白质，如TNFR、IL13R、IL4R、IL17R等。双特异性形式可以提供另外的治疗益处。
也可以将TrkA与抗体，例如与IgG重链C末端融合。抗体可以是抗TNF、抗CGRP、抗IL17、抗IL4R、抗EGFR等。抗体融合体可以对治疗具有增强的效果。
示例性TrkA ECD多肽表达和产生
提供具有或不具有信号序列的编码TrkA多肽的全部或部分(例如，细胞外结构域)的多核苷酸序列。如果在核酸分子的构建中不使用同源信号序列(即，TRKA的信号序列)，则可以使用另一信号序列，例如，PCT US06/02951中所述的信号序列中的任何一种。
通常，将编码目的多肽(如TrkA多肽)的核苷酸序列插入到适合于在所选宿主细胞中表达的表达载体中。
“载体”是可用于将DNA序列从一种生物体转移至另一种生物体或用于表达目的基因的质粒。载体通常包括复制起点和调节目的基因表达的调节序列，并且可以携带或可以不携带选择性标记基因，如抗生素抗性基因。载体适用于要在其中表达它的宿主细胞。当目的基因存在于载体中时，载体可以称为“重组载体”。
“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(如尺寸排阻色谱、离子交换色谱、蛋白质A柱色谱、疏水相互作用色谱和CHT色谱)分离TrkA多肽。
术语“标记”和“可检测标记”意指与TrkA多肽附接以使其可检测的部分。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。
作为诱饵受体陷阱的示例性TrkA多肽
本发明的TRKA多肽可以充当诱饵受体用于捕获NGF并抑制其与细胞表面上的NGF和TRKA的相互作用。诱饵受体(如本发明的那些)以高亲和力和特异性识别其配体，但在结构上不能传导信号。它们与野生型受体竞争配体结合并参与配体/受体相互作用，从而调节功能受体的活性或数量和/或受体下游的细胞活性。诱饵受体可以充当激动剂配体的分子陷阱且从而抑制配体诱导的受体激活。
如本文所用，“NGF”是指由细胞中NGF的表达和加工产生的任何天然NGF。除非另外指明，否则所述术语包括来自任何脊椎动物来源的NGF，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)和啮齿动物(例如，小鼠和大鼠)和伴生动物(例如，狗、猫和马类)。所述术语还包括天然存在的NGF变体，例如剪接变体或等位基因变体。
本发明提供了作为治疗剂的TrkA ECD多肽。本发明的TrkA ECD多肽与本文更详细描述的NGF(其已被证明与慢性疼痛或炎性疼痛相关)结合。在各种实施方案中，TrkA多肽可以以高亲和力结合NGF。在各种实施方案中，TrkA多肽可以干扰NGF信号传导。
术语“亲和力”意指在分子(例如，受体)的单个结合位点与其结合配偶体(例如，配体)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”可互换用于指受体融合体-配体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 ForteBioLLC，加利福尼亚州弗里蒙特)等的生物传感器，通过使用生物膜层干涉测定来测量融合分子与其配体的Kd。简而言之，将生物素化的抗原与传感器尖端结合，并且监测融合分子的缔合持续90秒，并且监测解离持续600秒。用于稀释和结合步骤的缓冲液是20mM磷酸盐、150mMNaCl，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”是指分子X与其配偶体Y的缔合的速率常数，而术语“koff”是指分子X或配偶体Y与分子X/配偶体Y复合物解离的速率常数。
术语与物质“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，TrkA多肽以通过生物膜层干涉法测量的小于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NGF、猫类NGF、马类NGF或人NGF结合。在一些实施例中，TRKA多肽以通过生物膜层干涉法测量的如下Kd与犬类NGF、猫类NGF、或马类NGF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、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、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、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,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、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、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或在1x10-11M与1x10-12M之间。在一些实施方案中，TRKA多肽与犬类NGF、猫类NGF和/或马类NGF结合。
“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。
在一些实施方案中，与不存在融合分子时的NGF信号传导相比，TrkA多肽可以将伴生动物物种中的NGF信号传导降低至少10％、至少15％、至少20％、至少25％、至少30％、至少35％、至少40、至少45％、至少50％、至少60％、至少70％、至少80％、至少90％或100％。在一些实施方案中，信号传导通过NGF依赖性TF-1细胞增殖的降低来测量。在一些实施方案中，NGF信号传导的降低或增殖的降低在10％与15％之间、10％与20％之间、10％与25％之间、10％与30％之间、10％与35％之间、10％与40％之间、10％与45％之间、10％与50％之间、10％与60％之间、10％与70％之间、10％与80％之间、10％与90％之间、10％与100％之间、15％与20％之间、15％与25％之间、15％与30％之间、15％与35％之间、15％与40％之间、15％与45％之间、15％与50％之间、15％与60％之间、15％与70％之间、15％与80％之间、15％与90％之间、15％与100％之间、20％与25％之间、20％与30％之间、20％与35％之间、20％与40％之间、20％与45％之间、20％与50％之间、20％与60％之间、20％与70％之间、20％与80％之间、20％与90％之间、20％与100％之间、25％与30％之间、25％与35％之间、25％与40％之间、25％与45％之间、25％与50％之间、25％与60％之间、25％与70％之间、25％与80％之间、25％与90％之间、25％与100％之间、30％与35％之间、30％与40％之间、30％与45％之间、30％与50％之间、30％与60％之间、30％与70％之间、30％与80％之间、30％与90％之间、30％与100％之间、35％与40％之间、35％与45％之间、35％与50％之间、35％与60％之间、35％与70％之间、35％与80％之间、35％与90％之间、35％与100％之间、40％与45％之间、40％与50％之间、40％与60％之间、40％与70％之间、40％与80％之间、40％与90％之间、40％与100％之间、45％与50％之间、45％与60％之间、45％与70％之间、45％与80％之间、45％与90％之间、45％与100％之间、50％与60％之间、50％与70％之间、50％与80％之间、50％与90％之间、50％与100％之间、60％与70％之间、60％与80％之间、60％与90％之间、60％与100％之间、70％与80％之间、70％与90％之间、70％与100％之间、80％与90％之间、80％与100％之间或90％与100％之间。
示例性药物组合物
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的血清蛋白；诸如磷酸盐、柠檬酸盐、氨丁三醇或HEPES缓冲液等的缓冲液；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的电解质；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，特别是当融合分子对热变性和氧化变性而言高度稳定时，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。
TrkA多肽和药物组合物的示例性用途
TrkA多肽或包含本发明的TrkA多肽的药物组合物可用于治疗NGF诱导的病症。如本文所用，“NGF诱导的病症”意指与NGF的水平升高或分布改变相关、由其引起或表征的疾病。此类NGF诱导的病症包括但不限于骨关节炎疼痛、癌症疼痛、下背痛。在一些实施方案中，NGF诱导的病症是慢性疼痛或炎性疼痛。NGF诱导的病症可以在伴生动物中展现出来，所述伴生动物包括但不限于犬类、猫类或马类。
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TrkA多肽或包含它的药物组合物来治疗NGF诱导的病症。在一些实施方案中，将TrkA多肽或药物组合物施用于伴生动物如犬类、猫类或马类，以治疗NGF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，TrkA多肽或包含TrkA多肽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，TrkA多肽或包含TrkA多肽的药物组合物作为推注或通过在一段时间中连续输注来施用。在一些实施方案中，TrkA多肽或包含TrkA多肽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。
可以将本文所述的TrkA多肽以在每剂量0.1mg/kg体重至100mg/kg体重范围内的量来施用。在一些实施方案中，可以将TrkA融合体以每剂量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，可以将TrkA融合体以每剂量1mg/kg体重至10mg/kg体重范围内的量施用。在一些实施方案中，可以将融合分子以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体重范围内或5mg/kg体重至50mg/kg体重范围内的量施用。
可以将TrkA多肽或包含TrkA多肽的药物组合物一次或经过一系列治疗施用于伴生动物。例如，可以将TrkA多肽或包含TrkA的药物组合物施用至少一次、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TrkA多肽或包含TrkA多肽的药物组合物组合施用NGF激酶抑制剂、PI3K抑制剂、ras抑制剂和/或磷脂酶C途径抑制剂。在一些实施方案中，所述方法还包括施用一种或多种疼痛治疗药物，如皮质类固醇、非甾体抗炎药(NSAID)、环氧合酶抑制剂、阿片类物质和/或大麻素。
本文提供了在允许与NGF结合的条件下，向细胞暴露TrkA多肽或包含TrkA多肽的药物组合物的方法。在一些实施方案中，将所述细胞离体暴露于TrkA多肽或药物组合物。在一些实施方案中，将所述细胞在体内暴露于TrkA多肽或药物组合物。在一些实施方案中，将细胞暴露于TrkA多肽。在一些实施方案中，在以下条件下将细胞暴露于TrkA多肽或所述药物组合物：所述条件允许所述融合分子与细胞外NGF结合。在一些实施方案中，可以将细胞通过本文所述的任何一种或多种施用方法在体内暴露于TrkA多肽或所述药物组合物，所述施用方法包括但不限于腹膜内、肌内、静脉注射至受试者体内。在一些实施方案中，可以通过以下方式将细胞离体暴露于TrkA多肽或所述药物组合物：将所述细胞暴露于包含所述融合分子或所述药物组合物的培养基。在一些实施方案中，在将所述细胞暴露于包含所述融合分子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。
在一些实施方案中，所述暴露导致所述细胞的NGF信号传导功能的降低。在一些实施方案中，与不存在TrkA多肽时的NGF信号传导功能相比，TrkA多肽可以将细胞中的NGF信号传导降低至少10％、至少15％、至少20％、至少25％、至少30％、至少35％、至少40、至少45％、至少50％、至少60％、至少70％、至少80％、至少90％或100％。在一些实施方案中，NGF信号传导的降低或TF-1增殖的降低在10％与15％之间、10％与20％之间、10％与25％之间、10％与30％之间、10％与35％之间、10％与40％之间、10％与45％之间、10％与50％之间、10％与60％之间、10％与70％之间、10％与80％之间、10％与90％之间、10％与100％之间、15％与20％之间、15％与25％之间、15％与30％之间、15％与35％之间、15％与40％之间、15％与45％之间、15％与50％之间、15％与60％之间、15％与70％之间、15％与80％之间、15％与90％之间、15％与100％之间、20％与25％之间、20％与30％之间、20％与35％之间、20％与40％之间、20％与45％之间、20％与50％之间、20％与60％之间、20％与70％之间、20％与80％之间、20％与90％之间、20％与100％之间、25％与30％之间、25％与35％之间、25％与40％之间、25％与45％之间、25％与50％之间、25％与60％之间、25％与70％之间、25％与80％之间、25％与90％之间、25％与100％之间、30％与35％之间、30％与40％之间、30％与45％之间、30％与50％之间、30％与60％之间、30％与70％之间、30％与80％之间、30％与90％之间、30％与100％之间、35％与40％之间、35％与45％之间、35％与50％之间、35％与60％之间、35％与70％之间、35％与80％之间、35％与90％之间、35％与100％之间、40％与45％之间、40％与50％之间、40％与60％之间、40％与70％之间、40％与80％之间、40％与90％之间、40％与100％之间、45％与50％之间、45％与60％之间、45％与70％之间、45％与80％之间、45％与90％之间、45％与100％之间、50％与60％之间、50％与70％之间、50％与80％之间、50％与90％之间、50％与100％之间、60％与70％之间、60％与80％之间、60％与90％之间、60％与100％之间、70％与80％之间、70％与90％之间、70％与100％之间、80％与90％之间、80％与100％之间或90％与100％之间。
本文提供了使用TrkA多肽和多核苷酸用于检测、诊断和监测NGF诱导的病症的方法。本文提供了确定伴生动物是否将对TrkA多肽疗法有反应的方法。在一些实施方案中，所述方法包括使用TrkA多肽检测动物是否具有表达NGF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，所述方法可以用于确定本文所述的TrkA多肽是否是对受试动物而言适当的治疗。
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TrkA多肽接触，并测定TrkA多肽与细胞之间的结合。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TrkA多肽的治疗。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附接到主题抗体上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p-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，帕洛阿尔托，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TrkA多肽，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。将标记与多肽缀合的方法是本领域已知的。在一些实施方案中，TrkA多肽不需要被标记，并且可以例如使用与TrkA多肽结合的抗体检测其存在。在一些实施方案中，TRKA多肽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中。Zola,Monoclonal Antibodies:AManual of Techniques,第147-158页(CRC Press,Inc.1987)。抗NGF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，TRKA多肽还可以用作病理学中的染色试剂。
在一些实施方案中，TrkA多肽用于诊断剂并且TrkA多肽用作治疗剂。在一些实施方案中，第一TrkA多肽和第二TrkA多肽是不同的。
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
TrkA的细胞外结构域
鉴定出负责结合犬类、猫类和马类NGF的犬类、猫类和马类TrkA的细胞外结构域并对其定义边界。从相应的全长多肽序列(分别为SEQ ID NO:1、SEQ ID NO:6和SEQ ID NO:11)鉴定出犬类TrkA(SEQ ID NO:2)、猫类TrkA(SEQ ID NO:7)和马类TrkA(SEQ ID NO:12)的全长细胞外结构域(ECD v1)。鉴定出假定保留NGF结合的犬类TrkA、猫类TrkA和马类TrkA的示例性截短型细胞外结构域多肽(示例性ECD v2、v3和v4)(例如，SEQ ID NO:3、4和5(犬类TrkA ECD v2、v3和v4)；SEQ ID NO:8、9和10(猫类TrkA ECD v2、v3和v4)；和SEQ ID NO:13、14和15(马类TrkA ECD v2、v3和v4)。
实施例2
来自CHO细胞的TrkA ECD多肽的设计、表达、纯化和稳定性
为了增强体内半衰期、NGF结合亲合力和纯化，将示例性TrkA ECD融合至用接头桥接的IgG Fc多肽。优选地，IgG Fc多肽可以结合蛋白A。
设计、化学合成编码信号序列、犬类TrkA ECD v2(SEQ ID NO:3)或犬类TrkA ECDv3(SEQ ID NO:4)、接头和野生型犬类IgG-B Fc多肽的核苷酸序列，并将其插入到适合于转染至CHO宿主细胞中的表达载体中。此外，类似地设计、合成编码以下的单独核苷酸序列，并将其克隆至表达载体中：(1)信号序列、猫类TrkA ECD v2(SEQ ID NO:8)或猫类TrkA ECDv3(SEQ ID NO:9)、接头和野生型猫类IgG-2Fc多肽；和(2)信号序列、马类TrkA ECD v2(SEQID NO:13)或马类TrkA ECD v3(SEQ ID NO:14)以及变体马类IgG-2Fc多肽(SEQ ID NO:104；蛋白A+、C1q-、CD16-)。在转染至CHO细胞中并培养后，通过单步蛋白A柱色谱将融合蛋白(分别为SEQ ID NO:16、17、19、20、22和23)从培养基中纯化出来。
使用差示扫描荧光测定法来评估TrkA ECD v2和TrkA ECD v3在不同pH下的稳定性，如通过平均熔点温度所反映的(下表6)。在该实施例中，比较了上文制备的马类TrkAECD v2和马类TrkA ECD v3融合多肽(SEQ ID NO:22和SEQ ID NO:23)。在测试的pH中，在热稳定性方面，马类TrkA ECD v3(SEQ ID NO:23)比马类TrkA ECD v2(SEQ ID NO:22)稍微更稳定。
表6.
实施例3
NGF结合活性的证明
考虑了实施例2中制备的犬类、猫类和马类TrkA ECD v2和v3融合多肽(SEQ IDNO:16、17、19、20、22和23)与可商购的人NGF的结合活性。使用生物传感器Octet进行如下结合分析。简而言之，将人NGF(Sino Biological,Inc.；目录号11050-HNAC)生物素化。通过广泛透析从生物素化的NGF中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NGF。监测NGF与TrkA-Fc(25ug/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，pH7.2。
图1和图2是示出犬类、猫类和马类TrkA ECD v2和v3融合多肽均结合NGF的传感图。图1示出了比较犬类和猫类TrkA v2和v3与NGF的结合亲和力的传感图。不相关的犬类和猫类IgG-Fc融合蛋白用作阴性对照。图2示出了比较马类TrkA v2和v3与NGF的结合亲和力的传感图。在三个物种中，所有TrkA ECD和NGF的Kd在1x10-9M范围内。
实施例4
TrkA ECD-IgG Fc多肽的细胞功能活性
将TF1细胞(ATCC目录号CRL-2003)(一种在细胞表面表达NGF受体的人红白血病细胞系)用于增殖测定。在不存在其他必要的生长因子(例如，红细胞生成素、IL3或GM-CSF)时，重组人NGF刺激TF-1细胞的细胞增殖。参见Kitamura,T.等人,“Establishment andcharacterization of a unique human cell line that proliferates dependently onGM-CSF,IL-3,or erythropoietin.”J.Cell Physiol.140(2):323-34(1989)；rndsystems.com/prod ucts/recombinant-human-beta-ngf-protein_256-gf#product-details。使细胞在RP MI1640(Gibco，目录号11875)中生长，所述RPMI1640补充有10％热灭活的胎牛血清(Sigma，目录号2868)和2nM/ml人GM-CSF(R&D System，目录号215-GM-010)。将指数生长期时的细胞用PBS洗涤，重悬于不含GM-C SF的上述培养基中，且铺板在96孔板中。将马类TrkA ECD v2-变体马类IgG2 Fc(SEQ ID NO:22；蛋白A+、C1q-、CD16-)以一系列稀释液添加，之后以10ng/ml添加NGF(Sino Biological,Inc.；目录号11050-HNAC)。不相关的单克隆抗体用作阴性对照。
将细胞以100μl的总体积在37℃、5％CO2中孵育48小时。在孵育结束时，将细胞在室温中冷却并通过使用CellTiter-
发光法细胞活力测定(Promega，目录号G7570)测量细胞ATP含量来分析增殖/活力。在该测定中，将100μl预混合试剂A和B添加至每个孔中。在定轨摇床上振荡大约2分钟后，裂解细胞。在细胞中出现的Mg2+和ATP的存在下，通过萤光素酶催化荧光素的单氧化，从而产生与细胞中的ATP量成比例的发光信号。ATP的量正比于在培养物中存在的细胞的数目。将板在室温下孵育10分钟以稳定发光信号，并且使用Synergy HT微板读数器(Biotek，威努斯基，佛蒙特州)检测发光。使用4参数逻辑拟合分析数据，并证明TrkA ECD-IgG Fc多肽在该TF1细胞增殖测定中中和了NGF活性。TrkA ECD-Fc多肽的IC50是5.4nM。参见图3。
实施例5
对TrkA ECD多肽的N连接的糖基化工程化
为了进一步增强TrkA ECD多肽的药代动力学，可以将另外的N连接的糖基化位点引入野生型犬类TrkA、猫类TrkA和马类TrkA中。例如，可以将一个、两个、三个或四个另外的N连接的糖基化位点在非重叠位置处引入TrkA ECD氨基酸序列中。N连接的糖基化位点可以具有Asn-Xaa-Ser/Thr的共有序列，其中Xaa是除脯氨酸外的任何氨基酸。添加一个或多个糖基化位点可以增加TrkA ECD多肽的分子大小，提供更多唾液酸化位点，和/或改善所述多肽在动物血清中的半衰期。
TrkA ECD多肽可以由哺乳动物细胞在增强唾液酸化的条件下产生。此外，TrkAECD多肽可以通过胺缀合或在聚糖上进一步聚乙二醇化或聚唾液酸化。例如，可以将化学聚唾液酸化引入糖基化位点。
表7列出犬类TrkA ECD v2、v3和v4的氨基酸取代，其可以用于产生一个或多个另外的N连接的糖基化位点。
表7.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
表8列出猫类TrkA ECD v2、v3和v4的氨基酸取代，其可以用于产生一个或多个另外的N连接的糖基化位点。
表8.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
表9列出马类TrkA ECD v2、v3和v4的氨基酸取代，其可以用于产生一个或多个另外的N连接的糖基化位点。
表9.
*X指示除脯氨酸外的任何氨基酸(如E、V、A、I等)。
实施例6
TrkA ECD分子内二硫化物
为了增加TrkA ECD多肽的稳定性，通过三维蛋白质建模和分析来鉴定用于另外的分子内二硫化物结合的合适位置。另外的二硫化物结合可以防止TrkA ECD多肽解折叠并增强蛋白酶抗性，从而导致增强的产物保质期稳定性和增强的体内药代动力学。例如，可以将半胱氨酸残基在SEQ ID NO:3、4、8、9、13或14的氨基酸位置7和89处并入犬类、猫类或马类TrkA ECD v2或v3中(V7C和A89C(对于犬类或猫类序列)或D89C(对于马类序列))。也可以将半胱氨酸残基在SEQ ID NO:5、10或15的氨基酸位置5和87处并入犬类、猫类或马类TrkAECD v4中(V5C和A87C(对于犬类或猫类序列)或D87C(对于马类序列))。具有另外的二硫化物对的示例性TrkA ECD多肽包括SEQ ID NO:25、26、27、28、29、30、31、32和33。
实施例7
包含TrkA ECD和IgG Fc的示例性连续多肽
可以设计、表达和纯化包含犬类、猫类或马类TrkA ECD v1、v2、v3或v4多肽(例如，SEQ ID NO:2、3、4、5、7、8、9、10、12、13、14、15、25、26、27、28、29、30、31、32或33)和相应伴生动物的野生型IgG Fc多肽或变体IgG Fc多肽的连续多肽用于表征。优选将与具有蛋白A结合、与C1q的降低或不可测量结合(例如，以降低CDC功能)和/或与CD16的降低或不可测量结合(例如，以降低ADCC功能)的IgG Fc多肽连接的TrkA ECD用于施用于患有NGF诱导的疼痛的伴生动物。示例性野生型犬类、猫类和马类IgG Fc多肽包含SEQ ID NO:33-39、70-77或86-90的氨基酸序列。示例性变体犬类、猫类和马类IgG Fc多肽包含诸如实施例8至11中描述的那些的氨基酸序列(例如，SEQ ID NO:40-69、78-85或91-109)。
可以基于以下式制备包含至少一种TrkA ECD多肽(例如，ECD v1、v2、v3和/或v4)和本文所述的野生型或变体犬类、猫类或马类IgG Fc多肽的连续多肽：
式(I)：TrkA ECD 1-L1-Fc；
式(II)：Fc-L1-TrkA ECD 1；
式(III)：TrkA ECD 1-L1-Fc-L2-TrkA ECD 2；
式(IV)：TrkA ECD 1-L1-TrkA ECD 2-L2-Fc；或
式(V)：Fc-L1-TrkA ECD 1-L2-TrkA ECD 2，
其中TrkA ECD 1是第一TrkA ECD多肽，TrkA ECD 2是第二TrkA ECD多肽(例如，相同的TrkA ECD多肽或不同的TrkA ECD多肽)，L1和L2是任选的接头；并且Fc是伴生动物物种的野生型或变体IgG Fc多肽。任选地，连续多肽包含信号序列。式I-V的示例性构建体可以包含在任何TrkA ECD 1或TrkA ECD 2之后或之前的第三、第四或第五等TrkA ECD。第三、第四或第五等TrkA ECD可以是与TrkA ECD 1或TrkA ECD 2相同的TrkA ECD多肽或不同的TrkA ECD多肽。
例如，连续多肽可以包含至少一种犬类TrkA ECD多肽(例如，SEQ ID NO:2、3、4、5、25、26或27)和野生型犬类IgG多肽(例如，SEQ ID NO:34、35、36、37、38或39)、变体犬类IgG-A Fc多肽(例如，SEQ ID NO:40、43、199或200)、变体犬类IgG-B Fc多肽(例如，SEQ ID NO:46、48、49、50、51、52、53、54、55、64、65、66、67、197、198、203、204、205、206、207、208、209或210)、变体犬类IgG-C Fc多肽(例如，SEQ ID NO:41、44、47、56、57、58、59、60、61、52、63、68或69)或变体犬类IgG-DFc多肽(例如，SEQ ID NO:42、45、201或202)，如本文所述。
连续多肽可以包含至少一种猫类TrkA ECD多肽(例如，SEQ ID NO:7、8、9、10、28、29或30)和野生型猫类IgG Fc多肽(例如，86、87、88、89或90)、变体猫类IgG1a Fc多肽(例如，SEQ ID NO:91、92、96或97)、变体猫类IgG1b Fc多肽(例如，SEQ ID NO:93、94、98或99)或变体猫类IgG2Fc多肽(例如，SEQ ID NO:95、100或107)，如本文所述。
连续多肽可以包含至少一种马类TrkA ECD多肽(例如，SEQ ID NO:12、13、14、15、31、32或33)和野生型马类IgG Fc多肽(例如，SEQ ID NO:70、71、72、73、74、75、76或77)、变体马类IgG1Fc多肽(例如，SEQ ID NO:82)、变体马类IgG2 Fc多肽(例如，SEQ ID NO:78、79、101、102、103、104、105、106、108或109)、变体马类IgG3 Fc多肽(例如，SEQ ID NO:83)、变体马类IgG4 Fc多肽(例如，SEQ ID NO:84)、变体马类IgG5 Fc多肽(例如，SEQ ID NO:80)、变体马类IgG6 Fc多肽(例如，SEQ ID NO:81)或变体马类IgG7 Fc多肽(例如，SEQ ID NO:85)。
接头可以是柔性非结构性接头，如富含甘氨酸和/或丝氨酸的接头。可以将柔性延伸部分添加至连续多肽的C末端。延伸部分可以包含一个、两个、三个、四个、五个、六个、七个、八个或更多个甘氨酸残基。
包含TrkA ECD的连续多肽还可以包含NGFR多肽的至少一个ECD，如SEQ ID NO:135、SEQ ID NO:137或SEQ ID NO:139。
可以使用蛋白A柱(
蛋白A亲和树脂，Repligen)亲和纯化包含具有蛋白A结合的Fc IgG多肽的连续多肽。还可以经由其他色谱方法分离连续多肽，所述其他色谱方法如离子交换柱色谱、疏水相互作用柱色谱、混合模式柱色谱(如CHT)或多峰模式柱色谱(如CaptoMMC)。可以应用低pH或其他病毒灭活和病毒去除步骤。可以将纯化的蛋白质与赋形剂混合，并通过过滤灭菌以制备本发明的药物组合物。
可以通过HPLC凝胶过滤和/或在不存在和存在还原剂(DTT)的情况下的SDS-PAGE分析来评估所得蛋白质的二聚化、聚集和/或硫化物连接的存在。
实施例8
用于增加的蛋白A结合和/或降低的补体结合
和/或降低的CD16结合的变体犬类IgG Fc多肽
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:35或SEQ ID NO:36)具有蛋白A结合亲和力。犬类IgG-A Fc(例如，SEQ ID NO:34)、IgG-C Fc(例如，SEQ ID NO:37或SEQ ID NO:38)和IgG-D Fc(例如，SEQID NO:39)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10汇总了犬类IgG Fc亚型的蛋白A、C1q和CD16结合特征。值得注意的是，野生型犬类IgG Fc亚型均不结合蛋白A并且缺乏C1q结合和/或CD16结合。
表10.
(-)表示低的或无可测量的结合活性。
使用三维蛋白质建模和蛋白质序列分析，鉴定了可能与蛋白A接触的犬类IgG-BFc的序列。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:40、SEQ ID NO:41和SEQ ID NO:42)。对于第二种途径，将变体犬类IgG-A Fc I(21)T/Q(207)H(SEQ ID NO:43)、变体犬类IgG-CFc I(21)T(SEQ ID NO:44)和变体犬类IgG-D Fc I(21)T/Q(207)H(SEQ ID NO:45)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11中列出的一个或多个氨基酸取代。
表11.
*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:35或SEQ ID NO:37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。这些氨基酸取代在犬类IgG-B Fc和IgG-C Fc与犬类IgG-A Fc和IgG-D Fc(了解它们未展现出补体活性)相比的蛋白质序列分析和3-D结构建模之后鉴定出。例如，可以制备变体犬类IgG-B Fc K(93)R(SEQ ID NO:46)和变体犬类IgG-C Fc K(93)R(SEQ ID NO:47)。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12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(例如，SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ IDNO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ IDNO:59、SEQ ID NO:60、SEQ ID NO:61和/或SEQ ID NO:62)。所述一个或多个氨基酸取代在犬类IgG-B和IgG-C与IgG-A和IgG-D(了解它们未展现出ADCC活性)相比的蛋白质序列分析和3-D结构建模之后鉴定出。
表12.
*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A结合并且具有C1q结合，因此可以通过将表11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的结合的双重变体犬类IgG-C Fc(例如，SEQ ID NO:63)。可以通过将表12中列出的一个或多个氨基酸取代与K(93)R取代或K(93)R取代(其中X是除Lys外的任何氨基酸)组合来制备具有降低的与C1q的结合和降低的与CD16的结合的双重变体犬类IgG-B Fc或双重变体犬类IgG-C Fc(例如，SEQ ID NO:65、SEQ IDNO:66、SEQ ID NO:67、SEQ ID NO:68和/或SEQ ID NO:69)。可以通过将表11中列出的一个或多个氨基酸取代和表12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。
实施例9
用于增加的蛋白A结合
和/或降低的补体结合的变体马类IgG Fc多肽
在马类IgG的七种亚型中，IgG1 Fc(例如，SEQ ID NO:70)、IgG3 Fc(例如，SEQ IDNO:73)、IgG4 Fc(例如，SEQ ID NO:74)、IgG7 Fc(例如，SEQ ID NO:77)具有蛋白A结合亲和力。马类IgG2 Fc(例如，SEQ ID NO:71或SEQ ID NO:72)、IgG5 Fc(例如，SEQ ID NO:75)和IgG6 Fc(例如，SEQ ID NO:76)具有弱或无可测量的蛋白A结合亲和力。设计了变体马类IgG2 Fc、IgG5 Fc和IgG6 Fc多肽以用于改变蛋白A结合。
此外，马类IgG2 Fc、IgG5 Fc和IgG6 Fc具有弱的或无可测量的对C1q的结合亲和力，而马类IgG1 Fc、IgG3 Fc、IgG4 Fc和IgG7 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，设计了变体马类IgG1 Fc、IgG3 Fc、IgG4 Fc和IgG7 Fc多肽。
下表13汇总了马类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13.
(-)表示低的或无可测量的结合活性。
使用三维蛋白质建模和蛋白质序列分析，鉴定了可能与蛋白A接触的马类IgG1Fc、IgG3 Fc、IgG4 Fc和IgG7 Fc的序列。可以制备具有增加的蛋白A结合的变体马类IgG2Fc、IgG5 Fc和IgG6 Fc多肽，其具有表14中列出的一个或多个氨基酸取代。
表14.
*列出的氨基酸位置是相对于所指示的SEQ ID NO.
例如，将变体马类IgG2 Fc、IgG5 Fc和IgG6 Fc多肽设计为在蛋白A结合区中具有一个或多个氨基酸取代，以与结合蛋白A的野生型马类IgG Fc的氨基酸序列相对应。可以制备具有增加的蛋白A结合的变体马类IgG2 Fc F(203)Y(SEQ ID NO:78)；变体马类IgG2 FcA(15)T/F(203)Y(SEQ ID NO:79)；变体马类IgG5 Fc V(199)L/E(200)Y(SEQ ID NO:80)；和变体马类IgG6Fc I(199)L/R(200)H/H(201)N/T(202)H(SEQ ID NO:81)。
为了潜在地降低C1q与马类IgG1 Fc、IgG3 Fc、IgG4 Fc和IgG7 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IgG1 Fc、IgG3 Fc、IgG4 Fc和IgG7 Fc多肽，其分别在对应于SEQ ID NO:70、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:77的位置87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。这些氨基酸取代在马类IgG1 Fc、IgG3 Fc、IgG4 Fc和IgG7 Fc与马类IgG2 Fc、IgG5 Fc和IgG6 Fc(了解它们未展现出补体活性)相比的蛋白质序列分析和3-D结构建模之后鉴定出。例如，可以制备变体马类IgG1 Fc K(87)S(SEQ ID NO:82)、变体马类IgG3 Fc K(87)S(SEQ ID NO:83)、变体马类IgG4 Fc K(87)S(SEQ ID NO:84)和变体马类IgG7 Fc K(87)S(SEQ ID NO:85)。
可以确定任何变体马类IgG Fc与蛋白A和/或C1q的结合，并且将其与另一种IgGFc(例如，相应的野生型马类IgG Fc、另一种野生型或变体马类IgG Fc、或另一种伴生动物的野生型或变体IgG Fc等)与蛋白A和/或C1q的结合进行比较。可以使用实施例8中描述的结合测定。
实施例10
用于减少补体结合的变体猫类IgG Fc多肽
猫类IgG、IgG1a Fc(SEQ ID NO:86或SEQ ID NO:87)、IgG1b Fc(SEQ ID NO:88或SEQ ID NO:89)和IgG2 Fc(SEQ ID NO:90)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IgG1a Fc、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15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15.
(-)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:86、SEQ ID NO:87、SEQ ID NO:88或SEQ ID NO:89的位置198的氨基酸位置处具有用除Pro外的任何氨基酸对Pro的氨基酸取代。这些氨基酸取代在猫类IgG1a Fc和IgG1b Fc与猫类IgG2Fc(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IgG1a Fc P(198)A(例如，SEQ ID NO:91或SEQ ID NO:92)和变体猫类IgG1b Fc P(198)A(例如，SEQ ID NO:93或SEQ ID NO:94)。
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8中描述的结合测定。
实施例11
用于增加和/或增强二硫化物形成的变体IgG Fc多肽
使用若干种直系同源铰链结构的三维蛋白质建模分析来确定用于修饰猫类IgG2铰链以增加二硫化物形成的大致位置。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，可以通过在对应于SEQ ID NO:90的位置14的氨基酸位置处用半胱氨酸取代甘氨酸来制备具有修饰铰链的变体猫类IgG2 Fc(SEQID NO:95)。可以制备具有修饰铰链的其他变体猫类IgG2 Fc多肽，所述修饰铰链包含在对应于SEQ ID NO:90的位置8、位置9、位置10、位置11、位置12、位置13、位置15或位置16的氨基酸位置处的半胱氨酸。
使用对若干种直系同源铰链结构的另外三维蛋白质建模分析来修饰猫类和马类IgG铰链以增强二硫化物形成。为了增强猫类IgG铰链处的二硫化物形成，可以通过以下方式来修饰铰链序列：在对应于野生型或变体猫类IgG1a(例如，SEQ ID NO:86或SEQ ID NO:87)、猫类IgG1b(例如，SEQ ID NO:88或SEQ ID NO:89)、或猫类IgG2(例如，SEQ ID NO:90)的位置16的位置处用脯氨酸取代赖氨酸(例如，K16P)。具有修饰铰链的变体猫类IgG多肽的氨基酸序列的例子包括SEQ ID NO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99和SEQID NO:100。
为了增强马类IgG铰链处的二硫化物形成，可以通过以下方式来修饰铰链序列：在对应于具有铰链的野生型或变体马类IgG(例如，IgG2 Fc(SEQ ID NO:72))的位置3的位置处用丝氨酸取代半胱氨酸和/或在对应于具有铰链的马类IgG(例如，IgG2 Fc(SEQ ID NO:72)的位置20的位置处用脯氨酸取代谷氨酰胺(例如，C3S和/或Q20P)。具有修饰铰链的变体马类IgG多肽的氨基酸序列的例子包括SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105和SEQ ID NO:106。
可以将上述氨基酸取代掺入至本文所述的野生型或变体Fc多肽的铰链中。
使用三维蛋白质建模来设计猫类和马类变体IgG Fc多肽，其包含来自不同IgG同种型的铰链区的序列以用于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:107)。此外，可以制备包含来自马类IgG1铰链区的序列的变体马类IgG2 Fc多肽(例如，SEQ ID NO:108和SEQ ID NO:109)。
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。
实施例12
TrkA-Fc缓冲液配制品
分析了各种缓冲液配制品中犬类TrkA-Fc的热稳定性。考虑了含有20mM磷酸钠(pH6.2、6.6、7.2和7.6)、20mM柠檬酸钠(pH 4.4、5.2、5.8和6.4)、20mM组氨酸(pH 5.5、6.0和6.5)和20mM乙酸钠(pH 5.2)的缓冲液。在所有缓冲液中使用终浓度为40mM或140mM的氯化钠。通过差示扫描荧光技术从20℃至95℃一式两份测量每种缓冲液中浓度为6μg/μL的示例性犬类TrkA-Fc多肽(SEQ ID NO:126)的熔解温度(Tm 1和Tm 2)。表16列出了测试的各种缓冲液中犬类TrkA的平均Tm值。
表16.
*来自一个样品的结果
含有较低浓度的柠檬酸钠、组氨酸或乙酸钠缓冲液和在5与6之间的pH的配制品6A、7B、9A和12B对于TrkA ECD融合多肽可能是更希望的。
使用配制品6A、7B、9A、12B和PBS(pH 7.2)来研究在45℃下应激下储存3天的示例性犬类TrkA-Fc多肽(SEQ ID NO:126)样品的稳定性。通过HPLC凝胶过滤分析评价五个样品的聚集状态，并且没有鉴定出明显的聚集。然后将五个样品在55℃下再储存一天。在PBS(pH7.2)中储存的样品中观察到明显的聚集，但在配制品6A、7B、9A和12B中储存的样品中未观察到。
实施例13
在用TrkA-Fc多肽的情况下NGF的体内减少
NGF水平在患有各种类型的慢性关节炎的人患者的滑液中是升高的。参见Aloe L等人,“Nerve growth factor in the synovial fluid of patients with chronicarthritis,”Arthritis Rheum.1992,35(3):351-5。在大鼠MIA诱导的骨关节炎模型中测试犬类TrkA-Fc多肽对NGF水平的影响。
所述研究方案由机构动物伦理委员会(Institutional Animal EthicsCommittee)(IAEC)审查和批准(批准号：B-070)。将雄性斯普拉-道来(Sprague Dawley)大鼠用异氟醚麻醉，并通过右膝(骨关节炎)的髌下韧带给予3mg碘乙酸单钠(Sigma，目录号I2512，圣路易，密苏里州)的单次关节内注射。将MIA溶解在生理盐水中并使用30号、0.5英寸针头以50μl的体积施用。参见Combe R等人,“The monosodium iodoacetate model ofosteoarthritis:a model of chronic nociceptive pain in rats？”NeurosciLett.2004,370(2-3):236-40。向对照大鼠注射等体积的盐水并使其恢复。从程序中恢复后，将动物以三只为一组返回至笼中，使用12h光照/黑暗循环并随意进食和饮水。
在MIA注射后第8、15和22天，进行犬类TrkA-Fc多肽(1mg/kg(第3组)和10mg/kg(第4组))的每周一次施用。在第28天，测量滑膜NGF水平。治疗组汇总在下表17中。
表17.
在完成行为和膝关节直径测量后，收集来自每个治疗组的3-4只大鼠的膝关节样品。收集膝关节内软组织的修剪样品(同侧膝关节外侧囊的滑膜和前部)并将其切碎成约2mm大小的小块，在PBS中充分冲洗，并在液氮中冷冻直至使用。将组织样品压碎成粉末，并且在具有蛋白酶抑制剂(cOmpleteTM，不含EDTA的蛋白酶抑制剂混合物，目录号4693132001，Sigma-Aldrich)的200-μl裂解试剂(CelLyticTMMT细胞裂解试剂(C3228)，Sigma-Aldrich)中匀浆。将样品在4℃下以14,000rpm离心10min，且然后收集上清液用于测定。使用ELISA试剂盒(Millipore，特曼库拉，加利福尼亚州)测量NGF的浓度。使用BCA蛋白质测定试剂盒(目录号BCA1-1KT，Sigma，美国)测量所有样品中的总蛋白质浓度。
图4示出了四个动物组中每一个的滑膜中NGF的浓度。与未经治疗的MIA诱导对照组(第2组)相比，接受犬类TrkA-Fc多肽的MIA诱导动物组(第3组和第4组)显示出滑膜中NGF浓度的剂量依赖性降低。由于仍在研究中的原因，在该实验中，经治疗的动物并未显示疼痛的相应减少，如已经基于已公布的涉及使用NGF抗体和TrkA-IgG融合分子治疗动物的疼痛的研究所预期的那样。参见Ro LS等人,“Effect of NGF and anti-NGF on neuropathicpain in rats following chronic constriction injury of the sciatic nerve.”Pain.1999,79(2-3):265-74；Gearing D等人,“A fully caninised anti-NGF monoclonalantibody for pain relief in dogs.”BMC Vet Res.2013,9:226doi:10.1186/1746-6148-9-226；Gearing D等人,“In vitro and in vivo characterization of a fullyfelinized therapeutic anti-nerve growth factor monoclonal antibody for thetreatment of pain in cats.”J Vet Intern Med.2016,30(4):1129-37；McMahon SB等人,“The biological effects of endogenous nerve growth factor on adult sensoryneurons revealed by a trkA-IgG fusion molecule.”Nat Med.1995,1(8):774-80。
实施例14
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:195)和犬类B2M(SEQ ID NO:196)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:35或SEQ ID NO:36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:198；“Y00”)；L(23)F(SEQ IDNO:197；“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5至图9中。野生型犬类IgG-B Fc多肽的稳态Kd是1.25x10-6(图5)；变体犬类IgG-B Fc多肽L(23)Y(“Y00”)的稳态Kd是1.13x10-7(图6)；变体犬类IgG-B Fc多肽L(23)F(“F00”)的稳态Kd是3.67x10-7(图7)；并且变体犬类IgG-B Fc多肽L(23)M的稳态Kd是4.06x10-7(图8)；并且变体犬类IgG-B Fc多肽YTE的稳态Kd是8.62x10-8(图9)。
实施例15
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:199(F00；蛋白A+；C1q-；CD16-)或SEQ ID NO:200(蛋白A+；C1q+；CD16+)的变体犬类IgG-A Fc多肽和与包含SEQ ID NO:201(F00；蛋白A+；C1q-；CD16-)或SEQ ID NO:202(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10，C)和不具有Phe突变的IgG-D(图10，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10，A)和IgG-D“F00”抗体(图10，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10，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16
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11)。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17
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18
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:35)、变体犬类IgG-BFc多肽0Y0(包含SEQ ID NO:203)、变体犬类IgG-B Fc多肽0YH(包含SEQ ID NO:204)、变体犬类IgG-B Fc多肽0YY(包含SEQ ID NO:205)以及变体犬类IgG-B Fc多肽00Y(包含SEQ IDNO:206)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12)。
实施例19
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:35)、变体犬类IgG-B Fc多肽YTE(包含SEQ ID NO:207)、变体犬类IgG-B Fc多肽0Y0(包含SEQ ID NO:203)、变体犬类IgG-B Fc多肽F00(包含SEQ ID NO:197)、变体犬类IgG-B Fc多肽0YH(包含SEQ ID NO:204)和变体犬类IgG-B Fc多肽Y00(包含SEQ ID NO:198)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18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18：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。
序列表
<110> 金德雷德生物科学股份有限公司
<120> 医用NGF拮抗剂
<130> 01157-0018-00PCT
<150> US 62/821,438
<151> 2019-03-20
<160> 246
<170> PatentIn 3.5版
<210> 1
<211> 796
<212> PRT
<213> 家犬(Canis lupus familiaris)
<220>
<221> 尚未归类的特征
<223> 犬类TrkA
<400> 1
Met Leu Arg Gly Gly Arg Leu Gly Gln Arg Gly Gly His Gly Arg Ala
1 5 10 15
Ala Gly Pro Gly Ser Leu Leu Ala Trp Leu Val Leu Ala Ser Ala Gly
20 25 30
Ala Ala Pro Cys Pro Asp Val Cys Cys Pro His Gly Pro Ser Gly Leu
35 40 45
Arg Cys Thr Arg Ala Gly Ala Leu Gln Ser Leu His Arg Leu Pro Gly
50 55 60
Val Glu Asn Leu Thr Glu Leu Tyr Ile Asp Asn Gln Glu His Leu Gln
65 70 75 80
His Leu Asp Ala Val His Leu Lys Gly Leu Gly Met Leu Arg Asp Leu
85 90 95
Thr Ile Val Lys Ser Gly Leu Arg Ser Val Ala Pro Asp Ala Phe His
100 105 110
Phe Thr Pro Arg Leu Arg Arg Leu Asn Leu Ser Phe Asn Ala Leu Glu
115 120 125
Ser Leu Ser Trp Lys Thr Val Gln Gly Leu Pro Leu Gln Glu Leu Val
130 135 140
Leu Ser Gly Asn Pro Leu His Cys Ser Cys Ala Leu His Trp Leu Leu
145 150 155 160
Arg Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Gly Gln Arg Leu Gln
165 170 175
Cys Pro Gly Gln Gly Pro Leu Ala Leu Leu Ser Asn Ala Ser Cys Gly
180 185 190
Val Pro Val Leu Lys Val Gln Met Pro Asn Ala Ser Val Glu Val Gly
195 200 205
Asp Asp Val Leu Leu Gln Cys Gln Val Glu Gly Arg Gly Leu Glu Arg
210 215 220
Ala Gly Trp Ile Leu Pro Glu Val Glu Glu Leu Ala Thr Val Thr Pro
225 230 235 240
Ser Gly Asp Leu Pro Ser Leu Gly Leu Ile Leu Ala Asn Val Thr Ser
245 250 255
Asp Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly
260 265 270
Arg Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val
275 280 285
Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser
290 295 300
Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser
305 310 315 320
Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val
325 330 335
Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr
340 345 350
His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly
355 360 365
Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu
370 375 380
Phe Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr
385 390 395 400
Asn Ser Thr Ser Gly Asp Pro Val Glu Lys Lys Gly Gln Thr Pro Phe
405 410 415
Gly Val Ser Val Ala Val Gly Leu Ala Val Phe Ala Cys Leu Phe Leu
420 425 430
Ser Thr Leu Phe Leu Ala Leu Asn Lys Cys Gly Arg Arg Asn Lys Phe
435 440 445
Gly Gly Asn Arg Ala Val Val Leu Ala Pro Glu Asp Gly Leu Ala Met
450 455 460
Ser Leu His Phe Met Thr Leu Gly Gly Ser Ser Leu Ser Pro Thr Glu
465 470 475 480
Gly Lys Gly Ser Gly Leu Gln Gly His Ile Ile Glu Asn Pro Gln Tyr
485 490 495
Phe Ser Asp Ala Cys Val His His Ile Lys Arg Gln Asp Ile Val Leu
500 505 510
Lys Trp Glu Leu Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu
515 520 525
Cys His Asn Leu Leu Pro Glu Gln Asp Lys Met Leu Val Ala Val Lys
530 535 540
Ala Leu Lys Glu Val Ser Glu Ser Ala Arg Gln Asp Phe Gln Arg Glu
545 550 555 560
Ala Gln Leu Leu Thr Met Leu Gln His Gln His Ile Val Arg Phe Phe
565 570 575
Gly Val Cys Thr Glu Gly Arg Pro Leu Leu Met Val Phe Glu Tyr Met
580 585 590
Arg His Gly Asp Leu Asn Arg Phe Leu Arg Ser His Gly Pro Asp Ala
595 600 605
Lys Leu Leu Ala Gly Gly Glu Asp Val Ala Pro Gly Pro Leu Gly Leu
610 615 620
Gly Gln Leu Leu Ala Val Ala Ser Gln Val Ala Ala Gly Met Val Tyr
625 630 635 640
Leu Ala Gly Leu His Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys
645 650 655
Leu Val Gly Gln Gly Leu Val Val Lys Ile Gly Asp Phe Gly Met Ser
660 665 670
Arg Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg Val Gly Gly Arg Thr Met
675 680 685
Leu Pro Ile Arg Trp Met Pro Pro Glu Ser Ile Leu Tyr Arg Lys Phe
690 695 700
Thr Thr Glu Ser Asp Val Trp Ser Phe Gly Val Val Leu Trp Glu Ile
705 710 715 720
Phe Thr Tyr Gly Lys Gln Pro Trp Tyr Gln Leu Ser Asn Thr Glu Ala
725 730 735
Ile Glu Cys Ile Thr Gln Gly Arg Glu Leu Glu Arg Pro Arg Ala Cys
740 745 750
Pro Pro Glu Val Tyr Ala Ile Met Arg Gly Cys Trp Gln Arg Glu Pro
755 760 765
Gln Gln Arg His Ser Ile Lys Asp Val His Ala Arg Leu Gln Ala Leu
770 775 780
Ala Gln Ala Pro Pro Val Tyr Leu Asp Val Leu Gly
785 790 795
<210> 2
<211> 417
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v1)
<400> 2
Met Leu Arg Gly Gly Arg Leu Gly Gln Arg Gly Gly His Gly Arg Ala
1 5 10 15
Ala Gly Pro Gly Ser Leu Leu Ala Trp Leu Val Leu Ala Ser Ala Gly
20 25 30
Ala Ala Pro Cys Pro Asp Val Cys Cys Pro His Gly Pro Ser Gly Leu
35 40 45
Arg Cys Thr Arg Ala Gly Ala Leu Gln Ser Leu His Arg Leu Pro Gly
50 55 60
Val Glu Asn Leu Thr Glu Leu Tyr Ile Asp Asn Gln Glu His Leu Gln
65 70 75 80
His Leu Asp Ala Val His Leu Lys Gly Leu Gly Met Leu Arg Asp Leu
85 90 95
Thr Ile Val Lys Ser Gly Leu Arg Ser Val Ala Pro Asp Ala Phe His
100 105 110
Phe Thr Pro Arg Leu Arg Arg Leu Asn Leu Ser Phe Asn Ala Leu Glu
115 120 125
Ser Leu Ser Trp Lys Thr Val Gln Gly Leu Pro Leu Gln Glu Leu Val
130 135 140
Leu Ser Gly Asn Pro Leu His Cys Ser Cys Ala Leu His Trp Leu Leu
145 150 155 160
Arg Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Gly Gln Arg Leu Gln
165 170 175
Cys Pro Gly Gln Gly Pro Leu Ala Leu Leu Ser Asn Ala Ser Cys Gly
180 185 190
Val Pro Val Leu Lys Val Gln Met Pro Asn Ala Ser Val Glu Val Gly
195 200 205
Asp Asp Val Leu Leu Gln Cys Gln Val Glu Gly Arg Gly Leu Glu Arg
210 215 220
Ala Gly Trp Ile Leu Pro Glu Val Glu Glu Leu Ala Thr Val Thr Pro
225 230 235 240
Ser Gly Asp Leu Pro Ser Leu Gly Leu Ile Leu Ala Asn Val Thr Ser
245 250 255
Asp Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly
260 265 270
Arg Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val
275 280 285
Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser
290 295 300
Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser
305 310 315 320
Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val
325 330 335
Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr
340 345 350
His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly
355 360 365
Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu
370 375 380
Phe Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr
385 390 395 400
Asn Ser Thr Ser Gly Asp Pro Val Glu Lys Lys Gly Gln Thr Pro Phe
405 410 415
Gly
<210> 3
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v2)
<400> 3
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp
115 120 125
<210> 4
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v3)
<400> 4
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 5
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v4)
<400> 5
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro
<210> 6
<211> 795
<212> PRT
<213> 家猫(Felis catus)
<220>
<221> 尚未归类的特征
<223> 猫类TrkA
<400> 6
Met Leu Arg Gly Gly Arg Gly Pro Arg Gly Gly His Gly Arg Ala Ala
1 5 10 15
Gly Pro Gly Ser Leu Leu Ala Trp Leu Met Leu Ala Ser Ala Gly Ala
20 25 30
Ala Pro Cys Ala Asp Val Cys Cys Pro His Gly Pro Ser Gly Leu Arg
35 40 45
Cys Thr Arg Ala Gly Ala Leu Glu Ser Leu Arg Arg Leu Pro Gly Ala
50 55 60
Glu Asn Leu Thr Glu Leu Tyr Ile Glu Asn Gln Glu Arg Leu Arg His
65 70 75 80
Leu Glu Pro Ser Asp Leu Arg Gly Leu Gly Glu Leu Arg Gly Leu Thr
85 90 95
Ile Val Lys Ser Gly Leu Arg Phe Val Ala Pro Asp Val Phe His Phe
100 105 110
Thr Pro Arg Leu Ser Arg Leu Asn Leu Ser Phe Asn Ala Leu Glu Ser
115 120 125
Leu Ser Trp Lys Thr Val Gln Gly Leu Ser Leu Gln Glu Leu Val Leu
130 135 140
Ser Gly Asn Pro Leu Arg Cys Ser Cys Ala Leu His Trp Leu Leu Arg
145 150 155 160
Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Ala Gln Arg Leu Gln Cys
165 170 175
Pro Gly Gln Gly Pro Leu Ala Leu Leu Ser Asn Ala Ser Cys Gly Val
180 185 190
Pro Val Leu Lys Val Gln Thr Pro Asn Ala Ser Val Asn Val Gly Asp
195 200 205
Asp Val Leu Leu Gln Cys Gln Val Glu Gly Arg Gly Leu Glu Gln Ala
210 215 220
Gly Trp Ile Leu Thr Glu Leu Glu Glu Ser Ala Thr Val Thr Gln Ser
225 230 235 240
Gly Ala Leu Pro Ser Leu Gly Leu Thr Leu Ala Asn Val Thr Ser Asp
245 250 255
Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly Arg
260 265 270
Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val Gln
275 280 285
Leu His Ala Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val
290 295 300
Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val
305 310 315 320
Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala Ala
325 330 335
Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His
340 345 350
Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg
355 360 365
Ala Ala Ala Ser Val Leu Ala Ala Phe Met Asp Asn Pro Phe Glu Phe
370 375 380
Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Ser Asn
385 390 395 400
Ser Thr Ser Gly Asp Pro Val Glu Lys Lys Asp Glu Thr Pro Phe Gly
405 410 415
Val Ser Val Ala Val Gly Leu Ala Val Phe Ala Cys Leu Leu Leu Ser
420 425 430
Ala Phe Phe Leu Val Leu Asn Lys Cys Gly Arg Arg Asn Lys Phe Gly
435 440 445
Ile Asn Arg Thr Ala Val Leu Ala Pro Glu Asp Gly Leu Ala Met Ser
450 455 460
Leu His Phe Met Thr Leu Gly Gly Ser Ser Leu Ser Pro Thr Glu Gly
465 470 475 480
Lys Gly Ser Gly Leu Gln Gly His Ile Ile Glu Asn Pro Gln Tyr Phe
485 490 495
Ser Asp Ala Cys Val His His Ile Lys Arg Arg Asp Ile Val Leu Lys
500 505 510
Trp Glu Leu Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu Cys
515 520 525
Tyr Asn Leu Leu Pro Glu Gln Asp Lys Met Leu Val Ala Val Lys Ala
530 535 540
Leu Lys Glu Val Ser Glu Ser Ala Arg Gln Asp Phe Gln Arg Glu Ala
545 550 555 560
Gln Leu Leu Thr Val Leu Gln His Gln His Ile Val Arg Phe Phe Gly
565 570 575
Val Cys Thr Glu Gly Arg Pro Leu Leu Met Val Phe Glu Tyr Met Arg
580 585 590
His Gly Asp Leu Asn Arg Phe Leu Arg Ser His Gly Pro Asp Ala Lys
595 600 605
Leu Leu Ala Gly Arg Glu Asp Val Ala Pro Gly Pro Leu Gly Leu Ser
610 615 620
Gln Leu Leu Ala Val Ala Ser Gln Val Ala Ala Gly Met Val Tyr Leu
625 630 635 640
Ala Gly Leu His Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys Leu
645 650 655
Val Gly Gln Gly Leu Val Val Lys Ile Gly Asp Phe Gly Met Ser Arg
660 665 670
Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg Val Gly Gly Arg Thr Met Leu
675 680 685
Pro Ile Arg Trp Met Pro Pro Glu Ser Ile Leu Tyr Arg Lys Phe Thr
690 695 700
Thr Glu Ser Asp Val Trp Ser Phe Gly Val Val Leu Trp Glu Ile Phe
705 710 715 720
Thr Tyr Gly Lys Gln Pro Trp Tyr Gln Leu Ser Asn Thr Glu Ala Ile
725 730 735
Glu Cys Ile Thr Gln Gly Arg Glu Leu Glu Arg Pro Arg Ala Cys Pro
740 745 750
Pro Glu Val Tyr Ala Ile Met Arg Gly Cys Trp Gln Arg Glu Pro Gln
755 760 765
Gln Arg His Ser Ile Lys Glu Val His Ala Arg Leu Gln Ala Leu Ala
770 775 780
Gln Ala Pro Pro Val Tyr Leu Asp Val Leu Gly
785 790 795
<210> 7
<211> 416
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v1)
<400> 7
Met Leu Arg Gly Gly Arg Gly Pro Arg Gly Gly His Gly Arg Ala Ala
1 5 10 15
Gly Pro Gly Ser Leu Leu Ala Trp Leu Met Leu Ala Ser Ala Gly Ala
20 25 30
Ala Pro Cys Ala Asp Val Cys Cys Pro His Gly Pro Ser Gly Leu Arg
35 40 45
Cys Thr Arg Ala Gly Ala Leu Glu Ser Leu Arg Arg Leu Pro Gly Ala
50 55 60
Glu Asn Leu Thr Glu Leu Tyr Ile Glu Asn Gln Glu Arg Leu Arg His
65 70 75 80
Leu Glu Pro Ser Asp Leu Arg Gly Leu Gly Glu Leu Arg Gly Leu Thr
85 90 95
Ile Val Lys Ser Gly Leu Arg Phe Val Ala Pro Asp Val Phe His Phe
100 105 110
Thr Pro Arg Leu Ser Arg Leu Asn Leu Ser Phe Asn Ala Leu Glu Ser
115 120 125
Leu Ser Trp Lys Thr Val Gln Gly Leu Ser Leu Gln Glu Leu Val Leu
130 135 140
Ser Gly Asn Pro Leu Arg Cys Ser Cys Ala Leu His Trp Leu Leu Arg
145 150 155 160
Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Ala Gln Arg Leu Gln Cys
165 170 175
Pro Gly Gln Gly Pro Leu Ala Leu Leu Ser Asn Ala Ser Cys Gly Val
180 185 190
Pro Val Leu Lys Val Gln Thr Pro Asn Ala Ser Val Asn Val Gly Asp
195 200 205
Asp Val Leu Leu Gln Cys Gln Val Glu Gly Arg Gly Leu Glu Gln Ala
210 215 220
Gly Trp Ile Leu Thr Glu Leu Glu Glu Ser Ala Thr Val Thr Gln Ser
225 230 235 240
Gly Ala Leu Pro Ser Leu Gly Leu Thr Leu Ala Asn Val Thr Ser Asp
245 250 255
Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly Arg
260 265 270
Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val Gln
275 280 285
Leu His Ala Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val
290 295 300
Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val
305 310 315 320
Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala Ala
325 330 335
Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His
340 345 350
Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg
355 360 365
Ala Ala Ala Ser Val Leu Ala Ala Phe Met Asp Asn Pro Phe Glu Phe
370 375 380
Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Ser Asn
385 390 395 400
Ser Thr Ser Gly Asp Pro Val Glu Lys Lys Asp Glu Thr Pro Phe Gly
405 410 415
<210> 8
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v2)
<400> 8
Val Ser Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Ser Asn Ser Thr Ser Gly Asp
115 120 125
<210> 9
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v3)
<400> 9
Val Ser Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 10
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v4)
<400> 10
Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala Phe Met
85 90 95
Asp Asn Pro
<210> 11
<211> 796
<212> PRT
<213> 家马(Equus caballus)
<220>
<221> 尚未归类的特征
<223> 马类TrkA
<400> 11
Met Leu Arg Gly Gly Arg Arg Gly Gln Leu Gly Trp His Gly Arg Ala
1 5 10 15
Thr Gly Pro Gly Ser Leu Leu Ala Trp Leu Met Leu Ala Ser Ala Gly
20 25 30
Ala Ala Pro Cys Pro Asp Ala Cys Cys Pro His Gly Pro Ser Gly Leu
35 40 45
Arg Cys Thr Gln Pro Gly Ala Leu Asp Ser Leu Arg His Leu Pro Gly
50 55 60
Ala Glu Asn Leu Thr Glu Leu Tyr Ile Glu Asn Gln Gln Asn Leu Gln
65 70 75 80
Arg Leu Glu Arg Asn Asp Leu Arg Gly Leu Gly Glu Leu Arg Asn Leu
85 90 95
Thr Ile Val Lys Ser Gly Leu His Phe Val Ala Pro Asp Ala Phe His
100 105 110
Phe Thr Pro Arg Leu Ser Arg Leu Asn Leu Ser Phe Asn Ala Leu Lys
115 120 125
Ser Leu Ser Trp Lys Thr Val Gln Gly Leu Ser Leu Gln Gln Leu Val
130 135 140
Leu Leu Gly Asn Pro Leu Asp Cys Ser Cys Ala Leu Arg Trp Leu Gln
145 150 155 160
Arg Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Glu Gln Lys Leu Gln
165 170 175
Cys His Gln Gln Gly Pro Leu Ala Leu Met Ser Asn Thr Asn Cys Gly
180 185 190
Val Pro Leu Leu Lys Val Gln Val Pro Asn Ala Ser Val Asp Val Gly
195 200 205
Asp Asn Val Trp Leu Gln Cys Gln Val Glu Gly Gln Gly Leu Glu Gln
210 215 220
Ala Gly Trp Ile Leu Thr Glu Leu Glu Glu Ser Ala Thr Val Met Gln
225 230 235 240
Ser Gly Gly Leu Pro Ser Leu Gly Leu Thr Leu Ala Asn Val Thr Ser
245 250 255
Asp Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly
260 265 270
Arg Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val
275 280 285
His Leu Gln Thr Ala Val Glu Gln His His Trp Cys Ile Pro Phe Ser
290 295 300
Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser
305 310 315 320
Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala
325 330 335
Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr
340 345 350
His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly
355 360 365
Gln Asp Ser Ala Ser Val Met Val Ala Phe Met Asp Asn Pro Phe Glu
370 375 380
Phe Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr
385 390 395 400
Asn Ser Thr Ser Arg Asp Pro Val Glu Lys Lys Asp Glu Thr His Phe
405 410 415
Gly Val Ser Val Ala Val Gly Leu Ala Val Phe Ala Cys Leu Phe Leu
420 425 430
Ser Thr Leu Phe Leu Val Leu Asn Lys Cys Gly Arg Arg Asn Lys Phe
435 440 445
Gly Ile Asn Arg Pro Ala Val Leu Ala Pro Glu Asp Gly Leu Ala Met
450 455 460
Ser Leu His Phe Met Thr Leu Gly Gly Ser Ser Leu Ser Pro Thr Glu
465 470 475 480
Gly Lys Gly Ser Gly Leu Gln Gly His Ile Ile Glu Asn Pro Gln Tyr
485 490 495
Phe Ser Asp Ala Cys Val His His Ile Lys Arg Arg Asp Ile Val Leu
500 505 510
Lys Trp Glu Leu Gly Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu
515 520 525
Cys His Asn Leu Leu Pro Glu Gln Asp Lys Met Leu Val Ala Val Lys
530 535 540
Ala Leu Lys Glu Val Ser Glu Ser Ala Arg Gln Asp Phe Gln Arg Glu
545 550 555 560
Ala Glu Leu Leu Thr Met Leu Gln His Gln His Ile Val Arg Phe Phe
565 570 575
Gly Val Cys Thr Glu Gly Arg Pro Leu Leu Met Val Phe Glu Tyr Met
580 585 590
Arg His Gly Asp Leu Asn Arg Phe Leu Arg Ser His Gly Pro Asp Ala
595 600 605
Lys Leu Leu Ala Gly Gly Glu Asp Val Ala Pro Gly Pro Leu Gly Leu
610 615 620
Gly Gln Leu Leu Ala Val Ala Ser Gln Val Ala Ala Gly Met Val Tyr
625 630 635 640
Leu Ala Gly Leu His Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys
645 650 655
Leu Val Gly Gln Gly Leu Val Val Lys Ile Gly Asp Phe Gly Met Ser
660 665 670
Arg Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg Val Gly Gly Arg Thr Met
675 680 685
Leu Pro Ile Arg Trp Met Pro Pro Glu Ser Ile Leu Tyr Arg Lys Phe
690 695 700
Thr Thr Glu Ser Asp Val Trp Ser Phe Gly Val Val Leu Trp Glu Ile
705 710 715 720
Phe Thr Tyr Gly Lys Gln Pro Trp Tyr Gln Leu Ser Asn Thr Glu Ala
725 730 735
Ile Glu Cys Ile Thr Gln Gly Arg Glu Leu Glu Arg Pro Arg Ala Cys
740 745 750
Pro Pro Glu Val Tyr Ala Ile Met Arg Gly Cys Trp Gln Arg Glu Pro
755 760 765
Gln Gln Arg His Ser Ile Lys Asp Val His Ala Arg Leu Gln Ala Leu
770 775 780
Val Gln Ala Pro Pro Val Tyr Leu Asp Val Leu Gly
785 790 795
<210> 12
<211> 417
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v1)
<400> 12
Met Leu Arg Gly Gly Arg Arg Gly Gln Leu Gly Trp His Gly Arg Ala
1 5 10 15
Thr Gly Pro Gly Ser Leu Leu Ala Trp Leu Met Leu Ala Ser Ala Gly
20 25 30
Ala Ala Pro Cys Pro Asp Ala Cys Cys Pro His Gly Pro Ser Gly Leu
35 40 45
Arg Cys Thr Gln Pro Gly Ala Leu Asp Ser Leu Arg His Leu Pro Gly
50 55 60
Ala Glu Asn Leu Thr Glu Leu Tyr Ile Glu Asn Gln Gln Asn Leu Gln
65 70 75 80
Arg Leu Glu Arg Asn Asp Leu Arg Gly Leu Gly Glu Leu Arg Asn Leu
85 90 95
Thr Ile Val Lys Ser Gly Leu His Phe Val Ala Pro Asp Ala Phe His
100 105 110
Phe Thr Pro Arg Leu Ser Arg Leu Asn Leu Ser Phe Asn Ala Leu Lys
115 120 125
Ser Leu Ser Trp Lys Thr Val Gln Gly Leu Ser Leu Gln Gln Leu Val
130 135 140
Leu Leu Gly Asn Pro Leu Asp Cys Ser Cys Ala Leu Arg Trp Leu Gln
145 150 155 160
Arg Trp Glu Glu Glu Gly Leu Gly Gly Val Arg Glu Gln Lys Leu Gln
165 170 175
Cys His Gln Gln Gly Pro Leu Ala Leu Met Ser Asn Thr Asn Cys Gly
180 185 190
Val Pro Leu Leu Lys Val Gln Val Pro Asn Ala Ser Val Asp Val Gly
195 200 205
Asp Asn Val Trp Leu Gln Cys Gln Val Glu Gly Gln Gly Leu Glu Gln
210 215 220
Ala Gly Trp Ile Leu Thr Glu Leu Glu Glu Ser Ala Thr Val Met Gln
225 230 235 240
Ser Gly Gly Leu Pro Ser Leu Gly Leu Thr Leu Ala Asn Val Thr Ser
245 250 255
Asp Leu Asn Arg Lys Asn Val Thr Cys Trp Ala Glu Asn Asp Val Gly
260 265 270
Arg Ala Glu Val Ser Val Gln Val Asn Val Ser Phe Pro Ala Ser Val
275 280 285
His Leu Gln Thr Ala Val Glu Gln His His Trp Cys Ile Pro Phe Ser
290 295 300
Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser
305 310 315 320
Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala
325 330 335
Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr
340 345 350
His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly
355 360 365
Gln Asp Ser Ala Ser Val Met Val Ala Phe Met Asp Asn Pro Phe Glu
370 375 380
Phe Asn Pro Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr
385 390 395 400
Asn Ser Thr Ser Arg Asp Pro Val Glu Lys Lys Asp Glu Thr His Phe
405 410 415
Gly
<210> 13
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v2)
<400> 13
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg Asp
115 120 125
<210> 14
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v3)
<400> 14
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 15
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v4)
<400> 15
Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala Phe Met
85 90 95
Asp Asn Pro
<210> 16
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 野生型犬类
IgG-B Fc 蛋白A+ C1q + CD16 +
<400> 16
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 17
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 野生型犬类
IgG-B Fc 蛋白A+ C1q + CD16 +
<400> 17
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 18
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 野生型犬类
IgG-B Fc 蛋白A+ C1q + CD16 +
<400> 18
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 19
<211> 393
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性猫类TrkA ECD v2 - 野生型猫类
IgG2 Fc 蛋白A + C1q - CD16 -
<400> 19
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Ala Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Ser Val Leu Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Ser Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys Thr Ala
145 150 155 160
Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys Cys Pro Val Pro
165 170 175
Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
180 185 190
Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Leu Val Val
195 200 205
Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr Trp Phe Val Asp
210 215 220
Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe
225 230 235 240
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Leu His Gln Asp
245 250 255
Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn Ser Lys Ser Leu
260 265 270
Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Pro His
275 280 285
Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu
290 295 300
Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe His Pro Pro Asp
305 310 315 320
Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn
325 330 335
Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu
340 345 350
Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln Arg Gly Asn Thr
355 360 365
Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser His His Thr Gln
370 375 380
Lys Ser Leu Thr Gln Ser Pro Gly Lys
385 390
<210> 20
<211> 369
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性猫类TrkA ECD v3 - 野生型猫类
IgG2 Fc 蛋白A + C1q - CD16 -
<400> 20
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Ala Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Ser Val Leu Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly
130 135 140
Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val
145 150 155 160
Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr
165 170 175
Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn
180 185 190
Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys
195 200 205
Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
210 215 220
Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys
225 230 235 240
Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile
245 250 255
Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro
260 265 270
Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu
275 280 285
Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr
290 295 300
Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu
305 310 315 320
Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg
325 330 335
Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu
340 345 350
Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly
355 360 365
Lys
<210> 21
<211> 367
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性猫类TrkA ECD v4 - 野生型猫类
IgG2 Fc 蛋白A + C1q - CD16 -
<400> 21
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 Phe Pro Ala Ser Val Gln Leu His Ala Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser
100 105 110
Val Leu Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly
130 135 140
Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile
145 150 155 160
Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu
165 170 175
Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln
180 185 190
Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg
195 200 205
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
210 215 220
Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys
225 230 235 240
Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys
245 250 255
Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr
260 265 270
Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys
275 280 285
Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln
290 295 300
Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser
305 310 315 320
Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His
325 330 335
Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu
340 345 350
His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
355 360 365
<210> 22
<211> 389
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v2 - 变体马类
IgG2 Fc 蛋白A + C1q - CD16 -
<400> 22
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala
20 25 30
Val Glu Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser
100 105 110
Val Met Val Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp
115 120 125
Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg
130 135 140
Asp Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser
145 150 155 160
Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly
165 170 175
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
180 185 190
Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp
195 200 205
Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val
210 215 220
His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr
225 230 235 240
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
245 250 255
Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile
260 265 270
Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val
275 280 285
Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser
290 295 300
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu
305 310 315 320
Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr
325 330 335
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
340 345 350
Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala
355 360 365
Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser
370 375 380
Glu Ser Leu Gly Lys
385
<210> 23
<211> 365
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v3 - 变体马类
IgG2 Fc 蛋白A + C1q - CD16 -
<400> 23
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala
20 25 30
Val Glu Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser
100 105 110
Val Met Val Ala Phe Met Asp Asn Pro Pro Pro Cys Val Leu Ser Ala
115 120 125
Glu Gly Val Ile Pro Ile Pro Ser Val Pro Lys Pro Gln Cys Pro Pro
130 135 140
Tyr Thr His Ser Lys Phe Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
145 150 155 160
Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr
165 170 175
Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser
180 185 190
Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg
195 200 205
Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
210 215 220
Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr
225 230 235 240
Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys
245 250 255
Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp
260 265 270
Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe
275 280 285
Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu
290 295 300
Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly
305 310 315 320
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln
325 330 335
Gln Val Glu Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
340 345 350
His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys
355 360 365
<210> 24
<211> 363
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v4 - 变体马类
IgG2 Fc 蛋白A + C1q - CD16 -
<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 Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu
20 25 30
Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro
35 40 45
Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe
50 55 60
Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His
65 70 75 80
Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr
85 90 95
Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met
100 105 110
Val Ala Phe Met Asp Asn Pro Pro Pro Cys Val Leu Ser Ala Glu Gly
115 120 125
Val Ile Pro Ile Pro Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr
130 135 140
His Ser Lys Phe Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn
145 150 155 160
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val
165 170 175
Val Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr
180 185 190
Val Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala
195 200 205
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His
210 215 220
Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val
225 230 235 240
Gly Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro
245 250 255
Ser Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu
260 265 270
Ala Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro
275 280 285
Pro Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu
290 295 300
Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr
305 310 315 320
Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val
325 330 335
Glu Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
340 345 350
Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys
355 360
<210> 25
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v2) 额外的二硫化物
<400> 25
Val Ser Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp
115 120 125
<210> 26
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v3) 额外的二硫化物
<400> 26
Val Ser Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 27
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD (v4) 额外的二硫化物
<400> 27
Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro
<210> 28
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v2) 额外的二硫化物
<400> 28
Val Ser Phe Pro Ala Ser Cys Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Ser Asn Ser Thr Ser Gly Asp
115 120 125
<210> 29
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v3) 额外的二硫化物
<400> 29
Val Ser Phe Pro Ala Ser Cys Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 30
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD (v4) 额外的二硫化物
<400> 30
Phe Pro Ala Ser Cys Gln Leu His Ala Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Cys Ala Ala Ser Val Leu Ala Ala Phe Met
85 90 95
Asp Asn Pro
<210> 31
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v2) 额外的二硫化物
<400> 31
Val Ser Phe Pro Ala Ser Cys His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Cys Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg Asp
115 120 125
<210> 32
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v3) 额外的二硫化物
<400> 32
Val Ser Phe Pro Ala Ser Cys His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Cys Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro
100
<210> 33
<211> 99
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD (v4) 额外的二硫化物
<400> 33
Phe Pro Ala Ser Cys His Leu Gln Thr Ala Val Glu Gln His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Thr Asn Pro Tyr Gly Gln Cys Ser Ala Ser Val Met Val Ala Phe Met
85 90 95
Asp Asn Pro
<210> 34
<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> 34
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> 35
<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> 35
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> 36
<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> 36
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> 37
<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> 37
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> 38
<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> 38
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> 39
<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> 39
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> 40
<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 - CD16 -
蛋白A + I(21)T R(23)L T(25)A E(80)G T(205)A Q(207)H
<400> 40
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> 41
<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> 41
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> 42
<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 - CD16 -
蛋白A + I(21)T R(23)L T(25)A E(80)G Q(207)H
<400> 42
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> 43
<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 - CD16 -
蛋白A + I(21)T Q(207)H
<400> 43
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> 44
<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> 44
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> 45
<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> 45
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> 46
<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> 46
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> 47
<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(93)R
<400> 47
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> 48
<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> 48
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> 49
<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> 49
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> 50
<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> 50
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> 51
<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 P(39)R
<400> 51
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 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> 52
<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> 52
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> 53
<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> 53
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> 54
<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> 54
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> 55
<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> 55
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> 56
<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> 56
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> 57
<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> 57
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> 58
<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> 58
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> 59
<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> 59
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> 60
<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> 60
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> 61
<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> 61
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> 62
<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> 62
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> 63
<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> 63
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> 64
<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
<400> 64
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
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> 65
<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> 65
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> 66
<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> 66
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> 67
<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 D(38)G P(39)R K(93)R
<400> 67
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 Gly 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> 68
<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> 68
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> 69
<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> 69
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> 70
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG1 Fc 蛋白A + C1q +
<400> 70
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu
1 5 10 15
Met Ile Thr 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 Met Asp Gly Val Glu
35 40 45
Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Gln Pro
85 90 95
Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile
130 135 140
Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr
145 150 155 160
Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val
195 200 205
Ser Lys Asn Pro Gly Lys
210
<210> 71
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG2 Fc 蛋白A - C1q -
<400> 71
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser
20 25 30
Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu
35 40 45
Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro
85 90 95
Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val
130 135 140
Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly 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 Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile
195 200 205
Ser Glu Ser Leu Gly Lys
210
<210> 72
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有铰链的示例性野生型马类IgG2 Fc 蛋白
A - C1q -
<400> 72
Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 73
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG3 Fc 蛋白A + C1q+
<400> 73
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser
20 25 30
His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu
35 40 45
Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn
65 70 75 80
Gly Lys Lys Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val
130 135 140
Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr
145 150 155 160
Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile
195 200 205
Ser Lys Asn Pro Gly Lys
210
<210> 74
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG4 Fc 蛋白A + C1q +
<400> 74
Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly
20 25 30
His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile
130 135 140
Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr
145 150 155 160
Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val
195 200 205
Ser Lys Ser Pro Gly Lys
210
<210> 75
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG5 Fc 蛋白A - C1q -
<400> 75
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly
20 25 30
His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val
130 135 140
Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr
145 150 155 160
Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys
180 185 190
Gly Val Met His Glu Ala Val Glu Asn His Tyr Thr Gln Lys Asn Val
195 200 205
Ser His Ser Pro Gly Lys
210
<210> 76
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG6 Fc 蛋白A - C1q -
<400> 76
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 Gln
100 105 110
Val Tyr Ile Leu Ala Pro His Pro Asp 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> 77
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性野生型马类IgG7 Fc 蛋白A + C1q +
<400> 77
Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly
20 25 30
His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Gln Ala Leu Pro Ala Pro
85 90 95
Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile
130 135 140
Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr 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 Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val
195 200 205
Ser Lys Ser Pro Gly Lys
210
<210> 78
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG2 Fc C1q - 蛋白A +
F(203)Y
<400> 78
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser
20 25 30
Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu
35 40 45
Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro
85 90 95
Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val
130 135 140
Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly 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 Ser Leu Glu Thr Ser Arg Trp Gln Gln Gly Glu Ser Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile
195 200 205
Ser Glu Ser Leu Gly Lys
210
<210> 79
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG2 Fc C1q - 蛋白A +
A(15)T F(203)Y
<400> 79
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser
20 25 30
Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu
35 40 45
Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro
85 90 95
Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val
130 135 140
Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly 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 Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile
195 200 205
Ser Glu Ser Leu Gly Lys
210
<210> 80
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG5 Fc C1q - 蛋白A +
V(199)L E(200)H
<400> 80
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Lys Pro Glu Val Thr Cys Val Val Val Asp Leu Gly
20 25 30
His Asp Asp Pro Asp Val Gln Phe Thr Trp Phe Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Glu Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Thr Ser Lys Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Leu Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ala Lys Asn Thr Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asp Val
130 135 140
Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Ser Thr
145 150 155 160
Thr Pro Ala Gln Leu Asn Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Ser Val Glu Thr Ser Arg Trp Lys Gln Gly Glu Ser Phe Thr Cys
180 185 190
Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val
195 200 205
Ser His Ser Pro Gly Lys
210
<210> 81
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG6 Fc C1q - 蛋白A +
I(199)L R(200)H H(201)N T(202)H
<400> 81
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 Gln
100 105 110
Val Tyr Ile Leu Ala Pro His Pro Asp 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 Leu His Asn His Tyr Arg Gln Lys Ser Ile
195 200 205
Thr Asn Phe Pro Gly Lys
210
<210> 82
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG1 Fc 蛋白A + C1q -
K(87)S
<400> 82
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Asn Pro Lys Asp Thr Leu
1 5 10 15
Met Ile Thr 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 Met Asp Gly Val Glu
35 40 45
Val Arg Thr Ala Thr Thr Arg Pro Lys Glu Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Gln Pro
85 90 95
Ile Glu Arg Thr Ile Thr Lys Thr Lys Gly Arg Ser Gln Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Ser Lys Lys Ser Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Glu Ile Asn Ile
130 135 140
Glu Trp Gln Ser Asn Gly Gln Pro Glu Leu Glu Thr Lys Tyr Ser Thr
145 150 155 160
Thr Gln Ala Gln Gln Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Ser Val Asp Arg Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Asn Val
195 200 205
Ser Lys Asn Pro Gly Lys
210
<210> 83
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG3 Fc 蛋白A + C1q -
K(87)S
<400> 83
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Thr Arg Met Pro Glu Val Thr Cys Leu Val Val Asp Val Ser
20 25 30
His Asp Ser Ser Asp Val Leu Phe Thr Trp Tyr Val Asp Gly Thr Glu
35 40 45
Val Lys Thr Ala Lys Thr Met Pro Asn Glu Glu Gln Asn Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Arg Ile Gln His Gln Asp Trp Leu Asn
65 70 75 80
Gly Lys Lys Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Lys Ala Thr Gly Gln Thr Arg Val Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Thr Val
130 135 140
Glu Trp Gln Ser Asn Glu His Pro Glu Pro Glu Gly Lys Tyr Arg Thr
145 150 155 160
Thr Glu Ala Gln Lys Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Thr Val Glu Lys Asp Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Val Val Met His Glu Ala Leu His Asn His Val Met Gln Lys Asn Ile
195 200 205
Ser Lys Asn Pro Gly Lys
210
<210> 84
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG4 Fc 蛋白A + C1q -
K(87)S
<400> 84
Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly
20 25 30
His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Phe Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Lys Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Lys Ala Leu Pro Ala Pro
85 90 95
Val Glu Arg Thr Ile Ser Ala Pro Thr Gly Gln Pro Arg Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Arg Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile
130 135 140
Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr Lys Tyr Ser Thr
145 150 155 160
Thr Pro Ala Gln Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
165 170 175
Leu Thr Val Glu Thr Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val
195 200 205
Ser Lys Ser Pro Gly Lys
210
<210> 85
<211> 214
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG7 Fc 蛋白A + C1q -
K(87)S
<400> 85
Val Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu
1 5 10 15
Met Ile Ser Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Val Gly
20 25 30
His Asp Phe Pro Asp Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
35 40 45
Thr His Thr Ala Thr Thr Glu Pro Lys Gln Glu Gln Asn Asn Ser Thr
50 55 60
Tyr Arg Val Val Ser Ile Leu Ala Ile Gln His Lys Asp Trp Leu Ser
65 70 75 80
Gly Lys Glu Phe Lys Cys Ser Val Asn Asn Gln Ala Leu Pro Ala Pro
85 90 95
Val Gln Lys Thr Ile Ser Lys Pro Thr Gly Gln Pro Arg Glu Pro Gln
100 105 110
Val Tyr Val Leu Ala Pro His Pro Asp Glu Leu Ser Lys Asn Lys Val
115 120 125
Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Asp Ile
130 135 140
Glu Trp Lys Ser Asn Gly Gln Pro Glu Pro Glu Thr 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 Asn Arg Trp Gln Gln Gly Thr Thr Phe Thr Cys
180 185 190
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Glu Lys Ser Val
195 200 205
Ser Lys Ser Pro Gly Lys
210
<210> 86
<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> 86
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> 87
<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> 87
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> 88
<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> 88
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> 89
<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> 89
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> 90
<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> 90
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> 91
<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> 91
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> 92
<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> 92
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> 93
<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> 93
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> 94
<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> 94
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> 95
<211> 237
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体猫类IgG2 Fc 铰链 Cys G(14)C
<400> 95
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> 96
<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> 96
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly 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> 97
<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> 97
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> 98
<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> 98
Arg Lys Thr Asp His Pro Pro Gly Pro Lys Thr Gly Glu Gly 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> 99
<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> 99
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> 100
<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> 100
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> 101
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有修饰铰链的示例性变体马类IgG2 Fc
蛋白A - C1q - Q(20)P
<400> 101
Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 102
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有修饰铰链的示例性变体马类IgG2 Fc
蛋白A - C1q - C(3)S
<400> 102
Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 103
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有修饰铰链的示例性变体马类IgG2 Fc
蛋白A - C1q - C(3)S Q(20)P
<400> 103
Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 104
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有铰链的示例性变体马类IgG2 Fc 蛋白A
+ C1q - A(45)T F(233)Y
<400> 104
Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 105
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有修饰铰链的示例性变体马类IgG2 Fc
蛋白A + C1q - Q(20)P A(45)T F(233)Y
<400> 105
Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 106
<211> 244
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有修饰铰链的示例性变体马类IgG2 Fc
蛋白A + C1q - C(3)S Q(20)P A(45)T F(233)Y
<400> 106
Pro Pro Ser Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val
1 5 10 15
Pro Lys Pro Pro Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly
20 25 30
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile
35 40 45
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
50 55 60
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
65 70 75 80
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
85 90 95
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
100 105 110
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
115 120 125
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
130 135 140
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
145 150 155 160
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
165 170 175
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
180 185 190
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
195 200 205
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
210 215 220
Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu
225 230 235 240
Ser Leu Gly Lys
<210> 107
<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> 107
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> 108
<211> 228
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类Fc IgG2 (具有马类IgG1
铰链) 蛋白A - C1q -
<400> 108
Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly
1 5 10 15
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Ala Leu Met Ile
20 25 30
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
35 40 45
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
50 55 60
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
65 70 75 80
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
85 90 95
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
100 105 110
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
115 120 125
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
130 135 140
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
145 150 155 160
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
165 170 175
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
180 185 190
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
195 200 205
Met His Glu Ala Leu His Asn His Phe Thr Lys Thr Asp Ile Ser Glu
210 215 220
Ser Leu Gly Lys
225
<210> 109
<211> 228
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体马类IgG2 Fc (具有马类IgG1
铰链) C1q - 蛋白A + A(29)T F(217)Y
<400> 109
Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly
1 5 10 15
Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile
20 25 30
Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln
35 40 45
Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His
50 55 60
Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg
65 70 75 80
Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys
85 90 95
Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser
100 105 110
Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr
115 120 125
Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val
130 135 140
Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp
145 150 155 160
Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro
165 170 175
Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
180 185 190
Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val
195 200 205
Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu
210 215 220
Ser Leu Gly Lys
225
<210> 110
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A+ C1q - CD16 -
<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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 111
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A+ C1q - CD16 -
<400> 111
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 112
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A+ C1q - CD16 -
<400> 112
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 113
<211> 388
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-A Fc C1q - 蛋白A +
<400> 113
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Phe Asn Glu Cys
145 150 155 160
Arg Cys Thr Asp Thr Pro Cys Pro Val Pro Glu Pro Leu Gly Gly Pro
165 170 175
Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
180 185 190
Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp
195 200 205
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr
210 215 220
Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr Arg Val
225 230 235 240
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr Gly Lys Glu
245 250 255
Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile Glu Arg
260 265 270
Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val Tyr Val
275 280 285
Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Ser Ile
290 295 300
Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val Glu Trp
305 310 315 320
Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met Thr Pro
325 330 335
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
340 345 350
Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys Ala Val
355 360 365
Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser Leu Ser His
370 375 380
Ser Pro Gly Lys
385
<210> 114
<211> 364
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-A Fc C1q - 蛋白A +
<400> 114
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Phe Asn Glu Cys Arg Cys Thr Asp Thr Pro Cys Pro
130 135 140
Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys
145 150 155 160
Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val
165 170 175
Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe
180 185 190
Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln
195 200 205
Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His
210 215 220
Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile
225 230 235 240
Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg
245 250 255
Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu
260 265 270
Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr
275 280 285
Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro
290 295 300
Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser
305 310 315 320
Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln
325 330 335
Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His
340 345 350
Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 115
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-A Fc C1q - 蛋白A +
<400> 115
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Phe Asn Glu Cys Arg Cys Thr Asp Thr Pro Cys Pro Val Pro
130 135 140
Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys
145 150 155 160
Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Leu
165 170 175
Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp
180 185 190
Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe
195 200 205
Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp
210 215 220
Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu
225 230 235 240
Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His
245 250 255
Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser
260 265 270
Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg
290 295 300
Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp
325 330 335
Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 116
<211> 389
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-D Fc C1q - 蛋白A +
<400> 116
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys Glu Ser
145 150 155 160
Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu Gly Gly
165 170 175
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
180 185 190
Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp Leu Gly Arg Glu
195 200 205
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His
210 215 220
Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn Ser Thr Tyr Arg
225 230 235 240
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr Gly Lys
245 250 255
Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro Ile Glu
260 265 270
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
275 280 285
Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Thr
290 295 300
Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu
305 310 315 320
Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys Tyr His Thr Thr
325 330 335
Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
340 345 350
Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala
355 360 365
Val Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser Leu Ser
370 375 380
His Ser Pro Gly Lys
385
<210> 117
<211> 365
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-D Fc C1q - 蛋白A +
<400> 117
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys
130 135 140
Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro
145 150 155 160
Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys
165 170 175
Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp
180 185 190
Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu
195 200 205
Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly
210 215 220
His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His
225 230 235 240
Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly
245 250 255
Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu
260 265 270
Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe
275 280 285
Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu
290 295 300
Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly
305 310 315 320
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln
325 330 335
Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
340 345 350
His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360 365
<210> 118
<211> 363
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-D Fc C1q - 蛋白A +
<400> 118
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val
130 135 140
Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val
165 170 175
Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln
195 200 205
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser
260 265 270
Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro
275 280 285
Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu
290 295 300
Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr
305 310 315 320
Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly
325 330 335
Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
340 345 350
Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 119
<211> 373
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v2 - 具有IgG1
铰链的变体马类IgG2 C1q - 蛋白A +
<400> 119
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala
20 25 30
Val Glu Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser
100 105 110
Val Met Val Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp
115 120 125
Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg
130 135 140
Asp Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly
145 150 155 160
Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met
165 170 175
Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp
180 185 190
Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val
195 200 205
His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr
210 215 220
Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly
225 230 235 240
Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile
245 250 255
Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val
260 265 270
Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser
275 280 285
Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu
290 295 300
Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr
305 310 315 320
Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
325 330 335
Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala
340 345 350
Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser
355 360 365
Glu Ser Leu Gly Lys
370
<210> 120
<211> 349
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v3 - 具有IgG1
铰链的变体马类IgG2 C1q - 蛋白A +
<400> 120
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala
20 25 30
Val Glu Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser
100 105 110
Val Met Val Ala Phe Met Asp Asn Pro Asp Met Ser Lys Cys Pro Lys
115 120 125
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
130 135 140
Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr
145 150 155 160
Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser
165 170 175
Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg
180 185 190
Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
195 200 205
Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr
210 215 220
Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys
225 230 235 240
Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp
245 250 255
Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe
260 265 270
Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu
275 280 285
Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly
290 295 300
Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln
305 310 315 320
Gln Val Glu Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn
325 330 335
His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys
340 345
<210> 121
<211> 347
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性马类TrkA ECD v4 - 具有IgG1
铰链的变体马类IgG2 C1q - 蛋白A +
<400> 121
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu
20 25 30
Gln His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro
35 40 45
Thr Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe
50 55 60
Ile Phe Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His
65 70 75 80
Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr
85 90 95
Thr Leu Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met
100 105 110
Val Ala Phe Met Asp Asn Pro Asp Met Ser Lys Cys Pro Lys Cys Pro
115 120 125
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn
130 135 140
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val
145 150 155 160
Val Val Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr
165 170 175
Val Asp Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala
180 185 190
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His
195 200 205
Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val
210 215 220
Gly Val Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro
225 230 235 240
Ser Arg Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu
245 250 255
Ala Lys Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro
260 265 270
Pro Asp Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu
275 280 285
Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr
290 295 300
Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val
305 310 315 320
Glu Ser Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
325 330 335
Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly Lys
340 345
<210> 122
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 122
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 Val Ser Phe Pro Ala Ser Cys Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 123
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 123
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 Val Ser Phe Pro Ala Ser Cys Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 124
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 124
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 Phe Pro Ala Ser Cys Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 125
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 125
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 126
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 126
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 127
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 127
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 128
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 128
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 129
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 129
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 130
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 130
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly
165 170 175
Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 131
<211> 470
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 x2 - 变体犬类
IgG-B Fc 蛋白A + C1q - CD16 -
<400> 131
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala
130 135 140
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
145 150 155 160
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
165 170 175
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
180 185 190
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
195 200 205
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
210 215 220
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
225 230 235 240
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro 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 Gly
275 280 285
Arg 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 Arg 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> 132
<211> 367
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性变体犬类IgG-B Fc - 犬类
TrkA ECD v3 蛋白A + C1q - CD16 -
<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 Pro Lys Arg Glu Asn Gly Arg Val Pro Arg
20 25 30
Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro
35 40 45
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
50 55 60
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp
65 70 75 80
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr
85 90 95
Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val
100 105 110
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln
115 120 125
Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg
130 135 140
Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val
145 150 155 160
Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr
165 170 175
Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln
180 185 190
Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro
195 200 205
Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val
210 215 220
Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met
225 230 235 240
His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser
245 250 255
Pro Gly Lys Ser Gly Gly Gly Ser Gly Gly Val Ser Phe Pro Ala Ser
260 265 270
Val Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe
275 280 285
Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly
290 295 300
Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro
305 310 315 320
Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro
325 330 335
Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser
340 345 350
Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro
355 360 365
<210> 133
<211> 468
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc - 犬类TrkA ECD v3 蛋白A + C1q - CD16 -
<400> 133
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys Ser Gly Gly Gly Ser Gly Gly Val
355 360 365
Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His
370 375 380
Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg
385 390 395 400
Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr
405 410 415
Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu
420 425 430
Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu
435 440 445
Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe
450 455 460
Met Asp Asn Pro
465
<210> 134
<211> 541
<212> PRT
<213> 家犬
<220>
<221> 尚未归类的特征
<223> 犬类NGFR
<400> 134
Met Ala Ile Ala Gly Asp Asn Arg Val Ala Val Thr Val Ala Met Gly
1 5 10 15
Arg Ile Val Gly Val Val Ala Met Ala Val Val Ala Val Val Val Leu
20 25 30
Val Val Met Pro Val Ser Trp Leu Arg Gly Gly Arg Ala Arg Phe Arg
35 40 45
Gly Trp Ala Gly Trp Ala Gly Arg Arg Arg Gly Arg Arg Thr Gly Phe
50 55 60
Ser Gln Pro Leu Pro Pro Ser Ala Arg Ala Ser Gly Ala Ser Ala Ser
65 70 75 80
Ser Gly Gly Arg Ala Leu Glu Arg Ser Ala Ala Gln Pro Tyr Pro Ser
85 90 95
Ala Glu Arg Thr Pro Leu Glu Ala Glu Arg Cys His Arg Arg Arg Ala
100 105 110
Val Gly Ala Gly Ala Ala Gly Cys Ala Met Asp Gly Pro Arg Leu Leu
115 120 125
Leu Leu Leu Leu Leu Leu Leu Gly Val Ser Leu Gly Gly Ala Lys Glu
130 135 140
Ala Cys Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys Cys Lys Ala
145 150 155 160
Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln Thr
165 170 175
Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val Ser
180 185 190
Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln Ser
195 200 205
Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys Ala
210 215 220
Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys Arg
225 230 235 240
Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Arg Gln
245 250 255
Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu Ala
260 265 270
Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr Glu
275 280 285
Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu Glu
290 295 300
Ile Pro Gly Arg Trp Ile Thr Arg Ser Thr Pro Ser Glu Asp Ser Asp
305 310 315 320
Ser Thr Ala Pro Ser Thr Glu Glu Pro Glu Leu Pro Pro Asp Gln Glu
325 330 335
Ile Ile Ala Ser Thr Met Ala Asp Val Val Thr Thr Val Met Gly Ser
340 345 350
Ser Gln Pro Val Val Thr Arg Gly Thr Ala Asp Asn Leu Ile Pro Val
355 360 365
Tyr Cys Ser Ile Leu Ala Ala Val Val Val Gly Leu Val Ala Tyr Ile
370 375 380
Ala Phe Lys Arg Trp Asn Ser Cys Lys Gln Asn Lys Gln Gly Ala Asn
385 390 395 400
Ser Arg Pro Val Asn Gln Thr Pro Pro Pro Glu Gly Glu Lys Leu His
405 410 415
Ser Asp Ser Gly Ile Ser Val Asp Ser Gln Ser Leu His Asp Gln Gln
420 425 430
Pro His Thr Gln Thr Ala Ala Gly Gln Ala Leu Lys Gly Asp Gly Gly
435 440 445
Leu Tyr Ser Ser Leu Pro Pro Ala Lys Arg Glu Glu Val Glu Lys Leu
450 455 460
Leu Asn Gly Ser Ala Gly Asp Thr Trp Arg His Leu Ala Gly Glu Leu
465 470 475 480
Gly Tyr Gln Pro Glu His Ile Asp Ser Phe Thr His Glu Ala Cys Pro
485 490 495
Ala Arg Ala Leu Leu Ala Ser Trp Ala Ala Gln Asp Ser Ala Thr Leu
500 505 510
Asp Ala Leu Leu Ala Ala Leu Arg Arg Ile Gln Arg Ala Asp Ile Val
515 520 525
Glu Ser Leu Cys Ser Glu Ser Thr Ala Thr Ser Pro Val
530 535 540
<210> 135
<211> 163
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类NGFR ECD
<400> 135
Ala Lys Glu Ala Cys Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys
1 5 10 15
Cys Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala
20 25 30
Asn Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp
35 40 45
Val Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly
50 55 60
Leu Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys
65 70 75 80
Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu
85 90 95
Ala Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln
100 105 110
Asp Arg Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser
115 120 125
Asp Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu
130 135 140
Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu
145 150 155 160
Cys Glu Glu
<210> 136
<211> 430
<212> PRT
<213> 家猫
<220>
<221> 尚未归类的特征
<223> 猫类NGFR
<400> 136
Met Gly Ala Gly Ala Ala Gly Arg Ala Met Asp Gly Pro Arg Pro Leu
1 5 10 15
Leu Leu Leu Leu Pro Leu Leu Leu Gly Val Ser Leu Gly Gly Ala Lys
20 25 30
Glu Ala Cys Pro Thr Gly Leu Phe Thr His Ser Gly Glu Cys Cys Lys
35 40 45
Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln
50 55 60
Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val
65 70 75 80
Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln
85 90 95
Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys
100 105 110
Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys
115 120 125
Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Arg
130 135 140
Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu
145 150 155 160
Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr
165 170 175
Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu
180 185 190
Glu Ile Pro Gly Arg Trp Ile Thr Arg Ser Thr Pro Ser Glu Gly Ser
195 200 205
Asp Ser Thr Ala Pro Ser Thr Glu Glu Pro Glu Val Pro Pro Glu Gln
210 215 220
Asp Leu Ile Ala Ser Thr Val Ala Asp Val Val Thr Thr Val Met Gly
225 230 235 240
Ser Ser Gln Pro Val Val Thr Arg Gly Thr Ala Asp Asn Leu Ile Pro
245 250 255
Val Tyr Cys Ser Ile Leu Ala Ala Val Val Val Gly Leu Val Ala Tyr
260 265 270
Ile Ala Phe Lys Arg Trp Asn Ser Cys Lys Gln Asp Lys Gln Gly Ala
275 280 285
Asn Ser Arg Pro Val Asn Gln Thr Pro Pro Pro Glu Gly Glu Lys Leu
290 295 300
His Ser Asp Ser Gly Ile Ser Val Asp Ser Gln Ser Leu His Asp Gln
305 310 315 320
Gln Ser His Thr Gln Thr Ala Ala Gly Gln Ala Leu Lys Gly Asp Gly
325 330 335
Gly Leu Tyr Ser Ser Leu Pro Ser Ala Lys Arg Glu Glu Val Glu Lys
340 345 350
Leu Leu Asn Gly Ser Ala Gly Asp Thr Trp Arg His Leu Ala Gly Glu
355 360 365
Leu Gly Tyr Gln Pro Glu His Ile Asp Ser Phe Thr Arg Glu Ala Cys
370 375 380
Pro Ala Arg Ala Leu Leu Ala Ser Trp Ala Ala Gln Asp Ser Ala Thr
385 390 395 400
Leu Asp Ala Leu Leu Ala Ala Leu Arg Arg Ile Gln Arg Ala Asp Ile
405 410 415
Val Glu Ser Leu Cys Ser Glu Ser Thr Ala Thr Ser Pro Val
420 425 430
<210> 137
<211> 163
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类NGFR ECD
<400> 137
Ala Lys Glu Ala Cys Pro Thr Gly Leu Phe Thr His Ser Gly Glu Cys
1 5 10 15
Cys Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala
20 25 30
Asn Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp
35 40 45
Val Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly
50 55 60
Leu Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys
65 70 75 80
Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu
85 90 95
Ala Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln
100 105 110
Asp Arg Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser
115 120 125
Asp Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu
130 135 140
Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu
145 150 155 160
Cys Glu Glu
<210> 138
<211> 429
<212> PRT
<213> 家马
<220>
<221> 尚未归类的特征
<223> 马类NGFR
<400> 138
Met Arg Ala Gly Ala Ala Asp Cys Ala Met Asp Gly Pro Arg Leu Leu
1 5 10 15
Leu Leu Leu Leu Leu Leu Gly Val Cys Leu Leu Gly Gly Ala Lys Glu
20 25 30
Val Cys Pro Thr Asp Leu Tyr Thr His Ser Gly Glu Cys Cys Lys Ala
35 40 45
Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln Thr
50 55 60
Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val Ser
65 70 75 80
Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln Ser
85 90 95
Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys Ala
100 105 110
Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys Gln
115 120 125
Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Lys Gln
130 135 140
Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu Ala
145 150 155 160
Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr Glu
165 170 175
Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu Glu
180 185 190
Ile Pro Ser Arg Trp Ile Thr Arg Ala Thr Pro Pro Glu Gly Ser Asp
195 200 205
Ser Thr Ala Pro Ser Thr Gln Glu Pro Glu Gly Pro Pro Glu Lys Asp
210 215 220
Leu Val Ala Ser Thr Val Ala Asp Val Val Thr Thr Val Met Gly Ser
225 230 235 240
Ser Gln Pro Val Val Thr Arg Gly Thr Thr Asp Asn Leu Ile Pro Val
245 250 255
Tyr Cys Ser Ile Leu Ala Ala Val Val Val Gly Leu Val Ala Tyr Ile
260 265 270
Ala Phe Lys Arg Trp Asn Ser Cys Lys Gln Asn Lys Gln Gly Ala Asn
275 280 285
Ser Arg Pro Val Asn Gln Thr Pro Pro Pro Glu Gly Glu Lys Leu His
290 295 300
Ser Asp Ser Gly Ile Ser Val Asp Ser Gln Ser Leu His Asp Gln Gln
305 310 315 320
Pro His Thr Gln Thr Ala Ala Gly Gln Ala Leu Lys Gly Asp Gly Gly
325 330 335
Leu Tyr Ser Ser Leu Pro Leu Ala Lys Arg Glu Glu Val Glu Lys Leu
340 345 350
Leu Asn Gly Ser Ala Gly Asp Thr Trp Arg His Leu Ala Gly Glu Leu
355 360 365
Gly Tyr Gln Pro Glu His Ile Asp Ser Phe Thr His Glu Ala Cys Pro
370 375 380
Val Arg Ala Leu Leu Ala Ser Trp Ala Ala Gln Asp Ser Ala Thr Phe
385 390 395 400
Asp Ala Leu Leu Thr Ala Leu Arg Arg Ile Gln Arg Ala Asp Ile Val
405 410 415
Glu Ser Leu Cys Ser Glu Ser Thr Ala Thr Ser Pro Val
420 425
<210> 139
<211> 163
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类NGFR ECD
<400> 139
Ala Lys Glu Val Cys Pro Thr Asp Leu Tyr Thr His Ser Gly Glu Cys
1 5 10 15
Cys Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala
20 25 30
Asn Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp
35 40 45
Val Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly
50 55 60
Leu Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys
65 70 75 80
Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu
85 90 95
Ala Cys Gln Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln
100 105 110
Asp Lys Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser
115 120 125
Asp Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu
130 135 140
Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu
145 150 155 160
Cys Glu Glu
<210> 140
<211> 631
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 犬类NGFR ECD -
变体犬类IgG-B Fc - 犬类TrkA ECD v3
蛋白A + C1q - CD16 -
<400> 140
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Ala Lys Glu Ala Cys Pro Thr Gly Leu Tyr Thr His
130 135 140
Ser Gly Glu Cys Cys Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln
145 150 155 160
Pro Cys Gly Ala Asn Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val
165 170 175
Thr Phe Ser Asp Val Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr
180 185 190
Glu Cys Val Gly Leu Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp
195 200 205
Asp Ala Val Cys Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr
210 215 220
Gly Arg Cys Glu Ala Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val
225 230 235 240
Phe Ser Cys Gln Asp Arg Gln Asn Thr Val Cys Glu Glu Cys Pro Asp
245 250 255
Gly Thr Tyr Ser Asp Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys
260 265 270
Thr Val Cys Glu Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp
275 280 285
Ala Asp Ala Glu Cys Glu Glu Arg Pro Pro Asp Cys Pro Lys Cys Pro
290 295 300
Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys
305 310 315 320
Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val
325 330 335
Val Val Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe
340 345 350
Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu
355 360 365
Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His
370 375 380
Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys
385 390 395 400
Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln
405 410 415
Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu
420 425 430
Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro
435 440 445
Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu
450 455 460
Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr
465 470 475 480
Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly
485 490 495
Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
500 505 510
Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys Ser Gly Gly Gly Ser
515 520 525
Gly Gly Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu
530 535 540
Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro
545 550 555 560
Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe
565 570 575
Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His
580 585 590
Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr
595 600 605
Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met
610 615 620
Ala Ala Phe Met Asp Asn Pro
625 630
<210> 141
<211> 631
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类NGFR ECD - 犬类
TrkA ECD v3 - 变体犬类IgG-B Fc - 犬类TrkA ECD v3
蛋白A + C1q - CD16 -
<400> 141
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 Ala Lys Glu Ala Cys Pro Thr Gly Leu Tyr
20 25 30
Thr His Ser Gly Glu Cys Cys Lys Ala Cys Asn Leu Gly Glu Gly Val
35 40 45
Ala Gln Pro Cys Gly Ala Asn Gln Thr Val Cys Glu Pro Cys Leu Asp
50 55 60
Ser Val Thr Phe Ser Asp Val Val Ser Ala Thr Glu Pro Cys Lys Pro
65 70 75 80
Cys Thr Glu Cys Val Gly Leu Gln Ser Met Ser Ala Pro Cys Val Glu
85 90 95
Ala Asp Asp Ala Val Cys Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu
100 105 110
Thr Thr Gly Arg Cys Glu Ala Cys Arg Val Cys Glu Ala Gly Ser Gly
115 120 125
Leu Val Phe Ser Cys Gln Asp Arg Gln Asn Thr Val Cys Glu Glu Cys
130 135 140
Pro Asp Gly Thr Tyr Ser Asp Glu Ala Asn His Val Asp Pro Cys Leu
145 150 155 160
Pro Cys Thr Val Cys Glu Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr
165 170 175
Arg Trp Ala Asp Ala Glu Cys Glu Glu Ser Gly Gly Gly Ser Gly Gly
180 185 190
Gly Ser Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu
195 200 205
Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro
210 215 220
Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe
225 230 235 240
Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His
245 250 255
Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr
260 265 270
Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met
275 280 285
Ala Ala Phe Met Asp Asn Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro
290 295 300
Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys
305 310 315 320
Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val
325 330 335
Val Val Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe
340 345 350
Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu
355 360 365
Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His
370 375 380
Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys
385 390 395 400
Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln
405 410 415
Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu
420 425 430
Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro
435 440 445
Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu
450 455 460
Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr
465 470 475 480
Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly
485 490 495
Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr
500 505 510
Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys Ser Gly Gly Gly Ser
515 520 525
Gly Gly Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu
530 535 540
Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro
545 550 555 560
Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe
565 570 575
Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His
580 585 590
Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr
595 600 605
Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met
610 615 620
Ala Ala Phe Met Asp Asn Pro
625 630
<210> 142
<211> 530
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 -变体犬类
IgG-B Fc - 犬类NGFR ECD 蛋白A + C1q - CD16 -
<400> 142
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys Ser Gly Gly Gly Ser Gly Gly Ala
355 360 365
Lys Glu Ala Cys Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys Cys
370 375 380
Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn
385 390 395 400
Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val
405 410 415
Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu
420 425 430
Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg
435 440 445
Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala
450 455 460
Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp
465 470 475 480
Arg Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp
485 490 495
Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp
500 505 510
Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys
515 520 525
Glu Glu
530
<210> 143
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 143
Gly Ser Gly Ser
1
<210> 144
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 144
Gly Ser Gly Ser Gly Ser
1 5
<210> 145
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 145
Gly Gly Ser Gly Gly Ser
1 5
<210> 146
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 146
Gly Gly Ser Gly Gly Ser Gly Gly Ser
1 5
<210> 147
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 147
Gly Gly Gly Ser
1
<210> 148
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 148
Gly Gly Gly Ser Gly Gly Gly Ser
1 5
<210> 149
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 149
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
1 5 10
<210> 150
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 150
Gly Ser Ser Gly Ser Ser
1 5
<210> 151
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 151
Gly Ser Ser Gly Ser Ser Gly Ser Ser
1 5
<210> 152
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 152
Gly Gly Ser Ser
1
<210> 153
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 153
Gly Gly Ser Ser Gly Gly Ser Ser
1 5
<210> 154
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 154
Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser
1 5 10
<210> 155
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 155
Ser Gly Gly Ser Gly Gly Ser
1 5
<210> 156
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 156
Ser Gly Gly Gly Ser Gly Gly Gly Ser
1 5
<210> 157
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 157
Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser
1 5 10
<210> 158
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性接头
<400> 158
Ser Gly Gly Gly
1
<210> 159
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 野生型犬类IgG-B
Fc 蛋白A+ C1q + CD16 +
<400> 159
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 160
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 野生型犬类IgG-B
Fc 蛋白A+ C1q + CD16 +
<400> 160
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 161
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 野生型犬类IgG-B
Fc 蛋白A+ C1q + CD16 +
<400> 161
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 162
<211> 371
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD v2 - 野生型猫类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 162
Val Ser Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Ser Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Pro Lys Thr Ala Ser Thr Ile Glu Ser Lys
130 135 140
Thr Gly Glu Gly Pro Lys Cys Pro Val Pro Glu Ile Pro Gly Ala Pro
145 150 155 160
Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Ser Ile Ser
165 170 175
Arg Thr Pro Glu Val Thr Cys Leu Val Val Asp Leu Gly Pro Asp Asp
180 185 190
Ser Asn Val Gln Ile Thr Trp Phe Val Asp Asn Thr Glu Met His Thr
195 200 205
Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val
210 215 220
Val Ser Val Leu Pro Ile Leu His Gln Asp Trp Leu Lys Gly Lys Glu
225 230 235 240
Phe Lys Cys Lys Val Asn Ser Lys Ser Leu Pro Ser Ala Met Glu Arg
245 250 255
Thr Ile Ser Lys Ala Lys Gly Gln Pro His Glu Pro Gln Val Tyr Val
260 265 270
Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu Asn Lys Val Ser Val Thr
275 280 285
Cys Leu Ile Lys Gly Phe His Pro Pro Asp Ile Ala Val Glu Trp Glu
290 295 300
Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn Tyr Gln Thr Thr Pro Pro
305 310 315 320
Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu Tyr Ser Arg Leu Ser Val
325 330 335
Asp Arg Ser His Trp Gln Arg Gly Asn Thr Tyr Thr Cys Ser Val Ser
340 345 350
His Glu Ala Leu His Ser His His Thr Gln Lys Ser Leu Thr Gln Ser
355 360 365
Pro Gly Lys
370
<210> 163
<211> 347
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD v3 - 野生型猫类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 163
Val Ser Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys
100 105 110
Thr Ala Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys Cys Pro
115 120 125
Val Pro Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro Pro Lys
130 135 140
Pro Lys Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Leu
145 150 155 160
Val Val Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr Trp Phe
165 170 175
Val Asp Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg Glu Glu
180 185 190
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Leu His
195 200 205
Gln Asp Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn Ser Lys
210 215 220
Ser Leu Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln
225 230 235 240
Pro His Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu Glu Leu
245 250 255
Ser Glu Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe His Pro
260 265 270
Pro Asp Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu Pro Glu
275 280 285
Asn Asn Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly Thr Tyr
290 295 300
Phe Leu Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln Arg Gly
305 310 315 320
Asn Thr Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser His His
325 330 335
Thr Gln Lys Ser Leu Thr Gln Ser Pro Gly Lys
340 345
<210> 164
<211> 345
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性猫类TrkA ECD v4 - 野生型猫类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 164
Phe Pro Ala Ser Val Gln Leu His Ala Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Ala Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Ser Val Leu Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys Thr Ala
100 105 110
Ser Thr Ile Glu Ser Lys Thr Gly Glu Gly Pro Lys Cys Pro Val Pro
115 120 125
Glu Ile Pro Gly Ala Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys
130 135 140
Asp Thr Leu Ser Ile Ser Arg Thr Pro Glu Val Thr Cys Leu Val Val
145 150 155 160
Asp Leu Gly Pro Asp Asp Ser Asn Val Gln Ile Thr Trp Phe Val Asp
165 170 175
Asn Thr Glu Met His Thr Ala Lys Thr Arg Pro Arg Glu Glu Gln Phe
180 185 190
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Leu His Gln Asp
195 200 205
Trp Leu Lys Gly Lys Glu Phe Lys Cys Lys Val Asn Ser Lys Ser Leu
210 215 220
Pro Ser Ala Met Glu Arg Thr Ile Ser Lys Ala Lys Gly Gln Pro His
225 230 235 240
Glu Pro Gln Val Tyr Val Leu Pro Pro Thr Gln Glu Glu Leu Ser Glu
245 250 255
Asn Lys Val Ser Val Thr Cys Leu Ile Lys Gly Phe His Pro Pro Asp
260 265 270
Ile Ala Val Glu Trp Glu Ile Thr Gly Gln Pro Glu Pro Glu Asn Asn
275 280 285
Tyr Gln Thr Thr Pro Pro Gln Leu Asp Ser Asp Gly Thr Tyr Phe Leu
290 295 300
Tyr Ser Arg Leu Ser Val Asp Arg Ser His Trp Gln Arg Gly Asn Thr
305 310 315 320
Tyr Thr Cys Ser Val Ser His Glu Ala Leu His Ser His His Thr Gln
325 330 335
Lys Ser Leu Thr Gln Ser Pro Gly Lys
340 345
<210> 165
<211> 369
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v2 - 变体马类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 165
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg Asp Pro Pro Cys
115 120 125
Val Leu Ser Ala Glu Gly Val Ile Pro Ile Pro Ser Val Pro Lys Pro
130 135 140
Gln Cys Pro Pro Tyr Thr His Ser Lys Phe Leu Gly Gly Pro Ser Val
145 150 155 160
Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
165 170 175
Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro Asp
180 185 190
Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala Ile
195 200 205
Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
210 215 220
Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys
225 230 235 240
Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala Ile
245 250 255
Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu Pro
260 265 270
Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys Leu
275 280 285
Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser Asn
290 295 300
Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu
305 310 315 320
Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr
325 330 335
Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val Met His Glu
340 345 350
Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly
355 360 365
Lys
<210> 166
<211> 345
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v3 - 变体马类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 166
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile
100 105 110
Pro Ile Pro Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser
115 120 125
Lys Phe Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys
130 135 140
Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val
145 150 155 160
Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp
165 170 175
Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe
180 185 190
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp
195 200 205
Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val
210 215 220
Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg
225 230 235 240
Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys
245 250 255
Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp
260 265 270
Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys
275 280 285
Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu
290 295 300
Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser
305 310 315 320
Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys
325 330 335
Thr Asp Ile Ser Glu Ser Leu Gly Lys
340 345
<210> 167
<211> 343
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v4 - 变体马类IgG2 Fc
蛋白A + C1q - CD16 -
<400> 167
Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala Phe Met
85 90 95
Asp Asn Pro Pro Pro Cys Val Leu Ser Ala Glu Gly Val Ile Pro Ile
100 105 110
Pro Ser Val Pro Lys Pro Gln Cys Pro Pro Tyr Thr His Ser Lys Phe
115 120 125
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr
130 135 140
Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu
145 150 155 160
Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr
165 170 175
Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser
180 185 190
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu
195 200 205
Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln
210 215 220
Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro
225 230 235 240
Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys
245 250 255
Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser
260 265 270
Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser
275 280 285
Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser
290 295 300
Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr
305 310 315 320
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp
325 330 335
Ile Ser Glu Ser Leu Gly Lys
340
<210> 168
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A+ C1q - CD16 -
<400> 168
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 169
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A+ C1q - CD16 -
<400> 169
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 170
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A+ C1q - CD16 -
<400> 170
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 171
<211> 366
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-A Fc
C1q - 蛋白A +
<400> 171
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Phe Asn Glu Cys Arg Cys Thr Asp Thr Pro
130 135 140
Cys Pro Val Pro Glu Pro Leu Gly Gly Pro Ser Val Leu Ile Phe Pro
145 150 155 160
Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr
165 170 175
Cys Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser
180 185 190
Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Ser Arg
195 200 205
Glu Gln Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile
210 215 220
Gly His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn
225 230 235 240
His Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg
245 250 255
Gly Arg Ala His Lys Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys
260 265 270
Glu Leu Ser Ser Ser Asp Thr Val Ser Ile Thr Cys Leu Ile Lys Asp
275 280 285
Phe Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln
290 295 300
Glu Pro Glu Arg Lys His Arg Met Thr Pro Pro Gln Leu Asp Glu Asp
305 310 315 320
Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp
325 330 335
Gln Gln Gly Asp Pro Phe Thr Cys Ala Val Met His Glu Ala Leu His
340 345 350
Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360 365
<210> 172
<211> 342
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-A Fc
C1q - 蛋白A +
<400> 172
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Phe Asn
100 105 110
Glu Cys Arg Cys Thr Asp Thr Pro Cys Pro Val Pro Glu Pro Leu Gly
115 120 125
Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu
130 135 140
Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg
145 150 155 160
Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val
165 170 175
His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr
180 185 190
Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr Gly
195 200 205
Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile
210 215 220
Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val
225 230 235 240
Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val
245 250 255
Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val
260 265 270
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met
275 280 285
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
290 295 300
Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys
305 310 315 320
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser Leu
325 330 335
Ser His Ser Pro Gly Lys
340
<210> 173
<211> 340
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-A Fc
C1q - 蛋白A +
<400> 173
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Phe Asn Glu Cys
100 105 110
Arg Cys Thr Asp Thr Pro Cys Pro Val Pro Glu Pro Leu Gly Gly Pro
115 120 125
Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala
130 135 140
Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp
145 150 155 160
Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr
165 170 175
Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr Arg Val
180 185 190
Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr Gly Lys Glu
195 200 205
Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile Glu Arg
210 215 220
Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val Tyr Val
225 230 235 240
Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Ser Ile
245 250 255
Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val Glu Trp
260 265 270
Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met Thr Pro
275 280 285
Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser
290 295 300
Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys Ala Val
305 310 315 320
Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser Leu Ser His
325 330 335
Ser Pro Gly Lys
340
<210> 174
<211> 367
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-D Fc
C1q - 蛋白A +
<400> 174
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Pro Lys Glu Ser Thr Cys Lys Cys Ile Ser
130 135 140
Pro Cys Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe
145 150 155 160
Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile
165 170 175
Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile
180 185 190
Ser Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro
195 200 205
Arg Glu Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro
210 215 220
Ile Gly His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val
225 230 235 240
Asn His Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala
245 250 255
Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro
260 265 270
Lys Glu Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys
275 280 285
Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln
290 295 300
Pro Glu Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu
305 310 315 320
Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg
325 330 335
Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu
340 345 350
His Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
355 360 365
<210> 175
<211> 343
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-D Fc
C1q - 蛋白A +
<400> 175
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys
100 105 110
Glu Ser Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu
115 120 125
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
130 135 140
Leu Ile Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp Leu Gly
145 150 155 160
Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu
165 170 175
Val His Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn Ser Thr
180 185 190
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr
195 200 205
Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro
210 215 220
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
225 230 235 240
Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr
245 250 255
Val Thr Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp
260 265 270
Val Glu Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys Tyr His
275 280 285
Thr Thr Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser
290 295 300
Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr
305 310 315 320
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser
325 330 335
Leu Ser His Ser Pro Gly Lys
340
<210> 176
<211> 341
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-D Fc
C1q - 蛋白A +
<400> 176
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Pro Lys Glu Ser
100 105 110
Thr Cys Lys Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu Gly Gly
115 120 125
Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile
130 135 140
Ala Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp Leu Gly Arg Glu
145 150 155 160
Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His
165 170 175
Thr Ala Lys Thr Gln Pro Arg Glu Gln Gln Phe Asn Ser Thr Tyr Arg
180 185 190
Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Thr Gly Lys
195 200 205
Glu Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro Ile Glu
210 215 220
Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr
225 230 235 240
Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Thr
245 250 255
Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu
260 265 270
Trp Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys Tyr His Thr Thr
275 280 285
Ala Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
290 295 300
Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala
305 310 315 320
Val Met His Glu Ala Leu His Asn His Tyr Thr Asp Leu Ser Leu Ser
325 330 335
His Ser Pro Gly Lys
340
<210> 177
<211> 353
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v2 - 具有IgG1铰链的变体
马类 IgG2 C1q - 蛋白A +
<400> 177
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Arg Asp Asp Met Ser
115 120 125
Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val
130 135 140
Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
145 150 155 160
Pro Val Val Thr Cys Val Val Val Asn Leu Ser Asp Gln Tyr Pro Asp
165 170 175
Val Gln Phe Ser Trp Tyr Val Asp Asn Thr Glu Val His Ser Ala Ile
180 185 190
Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
195 200 205
Val Leu Pro Ile Gln His Gln Asp Trp Leu Ser Gly Lys Glu Phe Lys
210 215 220
Cys Ser Val Thr Asn Val Gly Val Pro Gln Pro Ile Ser Arg Ala Ile
225 230 235 240
Ser Arg Gly Lys Gly Pro Ser Arg Val Pro Gln Val Tyr Val Leu Pro
245 250 255
Pro His Pro Asp Glu Leu Ala Lys Ser Lys Val Ser Val Thr Cys Leu
260 265 270
Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser Val Glu Trp Gln Ser Asn
275 280 285
Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser Thr Thr Pro Ala Gln Leu
290 295 300
Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Leu Glu Thr
305 310 315 320
Ser Arg Trp Gln Gln Val Glu Ser Phe Thr Cys Ala Val Met His Glu
325 330 335
Ala Leu His Asn His Tyr Thr Lys Thr Asp Ile Ser Glu Ser Leu Gly
340 345 350
Lys
<210> 178
<211> 329
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v3 - 具有IgG1 铰链的变体
马类IgG2 C1q - 蛋白A +
<400> 178
Val Ser Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala
85 90 95
Phe Met Asp Asn Pro Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro
100 105 110
Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val
130 135 140
Asn Leu Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp
145 150 155 160
Asn Thr Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp
180 185 190
Trp Leu Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val
195 200 205
Pro Gln Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg
210 215 220
Val Pro Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys
225 230 235 240
Ser Lys Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp
245 250 255
Ile Ser Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys
260 265 270
Tyr Ser Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu
275 280 285
Tyr Ser Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser
290 295 300
Phe Thr Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys
305 310 315 320
Thr Asp Ile Ser Glu Ser Leu Gly Lys
325
<210> 179
<211> 327
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性马类TrkA ECD v4 - 具有IgG1 铰链的变体马类
IgG2 C1q - 蛋白A +
<400> 179
Phe Pro Ala Ser Val His Leu Gln Thr Ala Val Glu Gln His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Thr Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Ser Ala Ala Asn Glu Thr Met Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Thr Asn Pro Tyr Gly Gln Asp Ser Ala Ser Val Met Val Ala Phe Met
85 90 95
Asp Asn Pro Asp Met Ser Lys Cys Pro Lys Cys Pro Ala Pro Glu Leu
100 105 110
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Asn Pro Lys Asp Thr
115 120 125
Leu Met Ile Ser Arg Thr Pro Val Val Thr Cys Val Val Val Asn Leu
130 135 140
Ser Asp Gln Tyr Pro Asp Val Gln Phe Ser Trp Tyr Val Asp Asn Thr
145 150 155 160
Glu Val His Ser Ala Ile Thr Lys Gln Arg Glu Ala Gln Phe Asn Ser
165 170 175
Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gln His Gln Asp Trp Leu
180 185 190
Ser Gly Lys Glu Phe Lys Cys Ser Val Thr Asn Val Gly Val Pro Gln
195 200 205
Pro Ile Ser Arg Ala Ile Ser Arg Gly Lys Gly Pro Ser Arg Val Pro
210 215 220
Gln Val Tyr Val Leu Pro Pro His Pro Asp Glu Leu Ala Lys Ser Lys
225 230 235 240
Val Ser Val Thr Cys Leu Val Lys Asp Phe Tyr Pro Pro Asp Ile Ser
245 250 255
Val Glu Trp Gln Ser Asn Arg Trp Pro Glu Leu Glu Gly Lys Tyr Ser
260 265 270
Thr Thr Pro Ala Gln Leu Asp Gly Asp Gly Ser Tyr Phe Leu Tyr Ser
275 280 285
Lys Leu Ser Leu Glu Thr Ser Arg Trp Gln Gln Val Glu Ser Phe Thr
290 295 300
Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Lys Thr Asp
305 310 315 320
Ile Ser Glu Ser Leu Gly Lys
325
<210> 180
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 180
Val Ser Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 181
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 181
Val Ser Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 182
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
额外的二硫化物 蛋白A+ C1q - CD16 -
<400> 182
Phe Pro Ala Ser Cys Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Cys Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Arg Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 183
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 183
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 184
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 184
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 185
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 185
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 186
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 186
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Pro Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 187
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 187
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 188
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 -
<400> 188
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 189
<211> 448
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 x2 - 变体犬类IgG-B
Fc 蛋白A + C1q - CD16 -
<400> 189
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Val Ser
100 105 110
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
115 120 125
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
130 135 140
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
145 150 155 160
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
165 170 175
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
180 185 190
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
195 200 205
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
210 215 220
Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser Val Phe
225 230 235 240
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro Glu Val
260 265 270
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
275 280 285
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
290 295 300
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
305 310 315 320
Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
325 330 335
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
340 345 350
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
355 360 365
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
370 375 380
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
385 390 395 400
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
405 410 415
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
435 440 445
<210> 190
<211> 345
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性变体犬类IgG-B Fc - 犬类TrkA ECD v3
蛋白A + C1q - CD16 -
<400> 190
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 Pro 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 Gly Arg 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 Arg 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 Ser Gly Gly
225 230 235 240
Gly Ser Gly Gly Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala
245 250 255
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
260 265 270
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
275 280 285
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
290 295 300
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
305 310 315 320
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
325 330 335
Val Met Ala Ala Phe Met Asp Asn Pro
340 345
<210> 191
<211> 446
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
- 犬类TrkA ECD v3 蛋白A + C1q - CD16 -
<400> 191
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys Ser Gly Gly Gly Ser Gly Gly Val Ser Phe Pro Ala Ser Val
340 345 350
Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser
355 360 365
Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser
370 375 380
Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val
385 390 395 400
Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr
405 410 415
His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly
420 425 430
Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro
435 440 445
<210> 192
<211> 609
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 犬类NGFR ECD -
变体犬类IgG-B Fc - 犬类TrkA ECD v3 蛋白A + C1q -
CD16 -
<400> 192
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Ala Lys
100 105 110
Glu Ala Cys Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys Cys Lys
115 120 125
Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln
130 135 140
Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val
145 150 155 160
Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln
165 170 175
Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys
180 185 190
Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys
195 200 205
Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Arg
210 215 220
Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu
225 230 235 240
Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr
245 250 255
Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu
260 265 270
Glu Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly
275 280 285
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu
290 295 300
Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg
305 310 315 320
Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met
325 330 335
Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr
340 345 350
Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly
355 360 365
Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile
370 375 380
Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val
385 390 395 400
Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser
405 410 415
Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu
420 425 430
Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr
435 440 445
Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
450 455 460
Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala
465 470 475 480
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser
485 490 495
His Ser Pro Gly Lys Ser Gly Gly Gly Ser Gly Gly Val Ser Phe Pro
500 505 510
Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile
515 520 525
Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe
530 535 540
Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu
545 550 555 560
Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn
565 570 575
Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn
580 585 590
Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn
595 600 605
Pro
<210> 193
<211> 609
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类NGFR ECD - 犬类TrkA ECD v3
-变体犬类IgG-B Fc - 犬类TrkA ECD v3 蛋白A + C1q -
CD16 -
<400> 193
Ala Lys Glu Ala Cys Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys
1 5 10 15
Cys Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala
20 25 30
Asn Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp
35 40 45
Val Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly
50 55 60
Leu Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys
65 70 75 80
Arg Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu
85 90 95
Ala Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln
100 105 110
Asp Arg Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser
115 120 125
Asp Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu
130 135 140
Asp Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu
145 150 155 160
Cys Glu Glu Ser Gly Gly Gly Ser Gly Gly Gly Ser Val Ser Phe Pro
165 170 175
Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile
180 185 190
Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe
195 200 205
Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu
210 215 220
Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn
225 230 235 240
Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn
245 250 255
Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn
260 265 270
Pro Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly
275 280 285
Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu
290 295 300
Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg
305 310 315 320
Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met
325 330 335
Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr
340 345 350
Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly
355 360 365
Lys Gln Phe Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile
370 375 380
Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val
385 390 395 400
Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser
405 410 415
Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu
420 425 430
Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr
435 440 445
Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu
450 455 460
Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala
465 470 475 480
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser
485 490 495
His Ser Pro Gly Lys Ser Gly Gly Gly Ser Gly Gly Val Ser Phe Pro
500 505 510
Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp Cys Ile
515 520 525
Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe
530 535 540
Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu
545 550 555 560
Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg Leu Asn
565 570 575
Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn
580 585 590
Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met Asp Asn
595 600 605
Pro
<210> 194
<211> 508
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 -变体犬类IgG-B Fc
- 犬类NGFR ECD 蛋白A + C1q - CD16 -
<400> 194
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Pro Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Gly Arg Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys Ser Gly Gly Gly Ser Gly Gly Ala Lys Glu Ala Cys Pro Thr
340 345 350
Gly Leu Tyr Thr His Ser Gly Glu Cys Cys Lys Ala Cys Asn Leu Gly
355 360 365
Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln Thr Val Cys Glu Pro
370 375 380
Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val Ser Ala Thr Glu Pro
385 390 395 400
Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln Ser Met Ser Ala Pro
405 410 415
Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys Ala Tyr Gly Tyr Tyr
420 425 430
Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys Arg Val Cys Glu Ala
435 440 445
Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Arg Gln Asn Thr Val Cys
450 455 460
Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu Ala Asn His Val Asp
465 470 475 480
Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr Glu Arg Gln Leu Arg
485 490 495
Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu Glu
500 505
<210> 195
<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> 195
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> 196
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类B2M
<400> 196
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> 197
<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> 197
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> 198
<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> 198
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> 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 (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> 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 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> 200
<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> 200
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> 201
<211> 222
<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> 201
Cys Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
1 5 10 15
Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Ile Thr
20 25 30
Cys Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln Ile Ser
35 40 45
Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg
50 55 60
Glu Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
65 70 75 80
Gly His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg Val Asn
85 90 95
His Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg
100 105 110
Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys
115 120 125
Glu Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp
130 135 140
Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro
145 150 155 160
Glu Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp
165 170 175
Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp
180 185 190
Gln Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His
195 200 205
Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 202
<211> 222
<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> 202
Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro
1 5 10 15
Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Ile Thr
20 25 30
Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser
35 40 45
Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln Pro Arg
50 55 60
Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Pro Ile
65 70 75 80
Gly His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Lys Val Asn
85 90 95
Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg
100 105 110
Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Pro Lys
115 120 125
Glu Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile Lys Asp
130 135 140
Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Pro
145 150 155 160
Glu Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp Glu Asp
165 170 175
Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp
180 185 190
Gln Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala Leu His
195 200 205
Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly Lys
210 215 220
<210> 203
<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> 203
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> 204
<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> 204
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> 205
<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> 205
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> 206
<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> 206
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> 207
<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> 207
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> 208
<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> 208
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> 209
<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> 209
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> 210
<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> 210
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> 211
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)F (F00)
<400> 211
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 212
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)F (F00)
<400> 212
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 213
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)F (F00)
<400> 213
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 214
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)F (F00)
<400> 214
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 215
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的 示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)F (F00)
<400> 215
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 216
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)F (F00)
<400> 216
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 217
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 217
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 218
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 218
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 219
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 219
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 220
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 220
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 221
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 221
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 222
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + L(23)Y (Y00)
<400> 222
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 223
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 223
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 224
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 224
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 225
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 225
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 226
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 226
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 227
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 变体犬类
IgG-B Fc 蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 227
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 228
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q + CD16 + Q(82)Y (0Y0)
<400> 228
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 229
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 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> 229
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 230
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 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> 230
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 231
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 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> 231
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 232
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 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> 232
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 233
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 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> 233
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Phe Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 234
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 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> 234
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Phe Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 235
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 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> 235
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 236
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 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> 236
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 237
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 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> 237
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 238
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 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> 238
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 239
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 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> 239
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Tyr Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 240
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 变体犬类IgG-B Fc
蛋白A + C1q - CD16 - K(93)R K(97)I A(98)G L(23)F (Y00)
<400> 240
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
<210> 241
<211> 384
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v2 - 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> 241
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Phe Glu Phe Asn Pro
115 120 125
Glu Asp Pro Ile Pro Val Ser Phe Ser Pro Val Asp Thr Asn Ser Thr
130 135 140
Ser Gly Asp Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
145 150 155 160
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
165 170 175
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
180 185 190
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
195 200 205
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
210 215 220
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
225 230 235 240
Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
245 250 255
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
260 265 270
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
275 280 285
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
290 295 300
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
305 310 315 320
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
325 330 335
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
340 345 350
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
355 360 365
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
370 375 380
<210> 242
<211> 362
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v2 - 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> 242
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Phe Glu Phe Asn Pro Glu Asp Pro Ile Pro Val
100 105 110
Ser Phe Ser Pro Val Asp Thr Asn Ser Thr Ser Gly Asp Ser Gly Gly
115 120 125
Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala
130 135 140
Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro
145 150 155 160
Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val
165 170 175
Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val
180 185 190
Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln
195 200 205
Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr
210 215 220
Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly
225 230 235 240
Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala
245 250 255
His Gln Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser
260 265 270
Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro
275 280 285
Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser
290 295 300
Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe
305 310 315 320
Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp
325 330 335
Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr
340 345 350
Gln Glu Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 243
<211> 360
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v3 - 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> 243
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 Val Ser Phe Pro Ala Ser Val Gln Leu His
20 25 30
Glu Ala Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly
35 40 45
Gln Pro Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn
50 55 60
Glu Thr Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu
65 70 75 80
Thr Val Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn
85 90 95
Asn Gly Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala
100 105 110
Ala Phe Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu
130 135 140
Met Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp
145 150 155 160
Thr Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
165 170 175
Leu Asp Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly
180 185 190
Lys Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn
195 200 205
Gly Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp
210 215 220
Leu Lys Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro
225 230 235 240
Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln
245 250 255
Pro Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn
260 265 270
Thr Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile
275 280 285
Asp Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr
290 295 300
Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr
305 310 315 320
Ser Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe
325 330 335
Ile Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu
340 345 350
Ser Leu Ser His Ser Pro Gly Lys
355 360
<210> 244
<211> 338
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v3 - 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> 244
Val Ser Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His
1 5 10 15
His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu
20 25 30
Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe
35 40 45
Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys
50 55 60
Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu
65 70 75 80
Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala
85 90 95
Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro
100 105 110
Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser
115 120 125
Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg
130 135 140
Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro
145 150 155 160
Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala
165 170 175
Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val
180 185 190
Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe
195 200 205
Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr
210 215 220
Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu
225 230 235 240
Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys
245 250 255
Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser
260 265 270
Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln
275 280 285
Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp
290 295 300
Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His
305 310 315 320
Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro
325 330 335
Gly Lys
<210> 245
<211> 358
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 具有信号序列的示例性犬类TrkA ECD v4 - 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> 245
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 Phe Pro Ala Ser Val Gln Leu His Glu Ala
20 25 30
Val Glu Leu His His Trp Cys Ile Pro Phe Ser Val Asp Gly Gln Pro
35 40 45
Ala Pro Ser Leu Arg Trp Leu Phe Asn Gly Ser Val Leu Asn Glu Thr
50 55 60
Ser Phe Ile Phe Thr Glu Phe Leu Glu Pro Val Ala Asn Glu Thr Val
65 70 75 80
Arg His Gly Cys Leu Arg Leu Asn Gln Pro Thr His Val Asn Asn Gly
85 90 95
Asn Tyr Thr Leu Leu Ala Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe
100 105 110
Val Met Ala Ala Phe Met Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Arg Pro Pro Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu
130 135 140
Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu
145 150 155 160
Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp
165 170 175
Pro Glu Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln
180 185 190
Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr
195 200 205
Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Tyr Asp Trp Leu Lys
210 215 220
Gly Lys Gln Phe Thr Cys Arg Val Asn Asn Ile Gly Leu Pro Ser Pro
225 230 235 240
Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser
245 250 255
Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val
260 265 270
Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val
275 280 285
Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr
290 295 300
Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys
305 310 315 320
Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys
325 330 335
Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu
340 345 350
Ser His Ser Pro Gly Lys
355
<210> 246
<211> 336
<212> PRT
<213> 人工序列
<220>
<223> 合成的: 示例性犬类TrkA ECD v4 - 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> 246
Phe Pro Ala Ser Val Gln Leu His Glu Ala Val Glu Leu His His Trp
1 5 10 15
Cys Ile Pro Phe Ser Val Asp Gly Gln Pro Ala Pro Ser Leu Arg Trp
20 25 30
Leu Phe Asn Gly Ser Val Leu Asn Glu Thr Ser Phe Ile Phe Thr Glu
35 40 45
Phe Leu Glu Pro Val Ala Asn Glu Thr Val Arg His Gly Cys Leu Arg
50 55 60
Leu Asn Gln Pro Thr His Val Asn Asn Gly Asn Tyr Thr Leu Leu Ala
65 70 75 80
Ala Asn Pro Ser Gly Arg Ala Ala Ala Phe Val Met Ala Ala Phe Met
85 90 95
Asp Asn Pro Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Pro Pro Asp
100 105 110
Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe
115 120 125
Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro
130 135 140
Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val
145 150 155 160
Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr
165 170 175
Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val
180 185 190
Leu Pro Ile Gly His Tyr Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys
195 200 205
Arg Val Asn Asn Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser
210 215 220
Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro Pro
225 230 235 240
Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile
245 250 255
Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly
260 265 270
Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp
275 280 285
Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser
290 295 300
Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala
305 310 315 320
Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly Lys
325 330 335
Claims (79)
1.一种连续多肽，所述连续多肽包含来自伴生动物物种的TrkA多肽的至少一个细胞外结构域(TrkAECD多肽)和融合配偶体。
2.根据权利要求1所述的连续多肽，其中所述连续多肽以通过生物膜层干涉法测量的小于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NGF多肽结合。
3.根据权利要求2所述的连续多肽，其中所述NGF多肽是人NGF多肽、犬类NGF多肽、猫类NGF多肽或马类多肽。
4.根据前述权利要求中任一项所述的连续多肽，其中所述连续多肽减少所述伴生动物物种中的NGF信号传导。
5.根据前述权利要求中任一项所述的连续多肽，其中所述伴生动物物种是犬类、猫类或马类。
6.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽的氨基酸序列与以下的氨基酸序列至少90％相同、至少91％相同、至少92％相同、至少93％相同、至少94％相同、至少95％相同、至少96％相同、至少97％相同、至少98％相同或至少99％相同：SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14或SEQ ID NO:15。
7.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:7、SEQ ID NO:8、SEQID NO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89的位置处的半胱氨酸；或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和位置87的位置处的半胱氨酸。
8.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:7、SEQ ID NO:8、SEQ IDNO:9、SEQ ID NO:12、SEQ ID NO:13或SEQ ID NO:14的位置7和位置89处的半胱氨酸；或
b)在SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置5和87处的半胱氨酸。
9.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含不存在于相应野生型TrkA ECD多肽中的至少一个N连接的糖基化位点，其中所述N连接的糖基化位点包含序列天冬酰胺-xaa-丝氨酸或天冬酰胺-xaa-苏氨酸，其中xaa是除脯氨酸外的任何氨基酸，并且其中一个N连接的糖基化位点不与另一个N连接的糖基化位点重叠。
10.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD包含在选自以下的一个或多个位置处的至少一个N连接的糖基化位点：
a)SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ IDNO:14的氨基酸位置6-8、31-33、84-86、85-87、86-88、88-90、90-92、92-94和/或94-96；或
b)SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的氨基酸位置4-6、29-31、82-84、83-85、84-86、86-88、89-90、90-92和/或92-94。
11.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO 13或SEQ ID NO:14的位置30和/或位置85的氨基酸位置处的除脯氨酸之外的氨基酸；和/或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28或位置83的氨基酸位置处的除脯氨酸之外的氨基酸。
12.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含：
a)在对应于SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:13或SEQ ID NO:14的位置30和/或位置85的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸；和/或
b)在对应于SEQ ID NO:5、SEQ ID NO:10或SEQ ID NO:15的位置28或位置83的氨基酸位置处的缬氨酸、谷氨酸、丙氨酸或异亮氨酸。
13.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含表A中列出的一个或多个氨基酸修饰：
其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)；
表B：
其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)；和/或
表C：
其中*X指示除脯氨酸外的任何氨基酸(如E、V、A或I)。
14.根据前述权利要求中任一项所述的连续多肽，其中所述TrkA ECD多肽包含选自以下的氨基酸序列：SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32和SEQ ID NO:33。
15.根据前述权利要求中任一项所述的连续多肽，其中所述连续多肽包含接头。
16.根据权利要求15所述的连续多肽，其中所述接头包含选自以下的氨基酸序列：G、GG、GGG、S、SS、SSS、GS、GSGS(SEQ ID NO:143)、GSGSGS(SEQ ID NO:144)、GGS、GGSGGS(SEQID NO:145)、GGSGGSGGS(SEQ ID NO:146)、GGGS(SEQ ID NO:147)、GGGSGGGS(SEQ ID NO:148)、GGGSGGGSGGGS(SEQ ID NO:149)、GSS、GSSGSS(SEQ ID NO:150)、GSSGSSGSS(SEQ IDNO:151)、GGSS(SEQ ID NO:152)、GGSSGGSS(SEQ ID NO:153)、GGSSGGSSGGS(SEQ ID NO:154)、SGGSGGS(SEQ ID NO:155)和SGGGSGGGS(SEQ ID NO:156)。
17.根据前述权利要求中任一项所述的连续多肽，其中所述融合配偶体选自Fc多肽、白蛋白和白蛋白结合片段。
18.根据前述权利要求中任一项所述的连续多肽，其中所述融合配偶体是Fc多肽，其包含(a)野生型或变体犬类IgG-A、IgG-B、IgG-C或IgG-D多肽；(b)野生型或变体猫类IgG1a、IgG1b或IgG2多肽；或(c)野生型或变体马类IgG1、IgG2、IgG3、IgG4、IgG5、IgG6或IgG7多肽。
19.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含：
式(I)：TrkA ECD 1-L1-Fc；
式(II)：Fc-L1-TrkA ECD 1；
式(III)：TrkA ECD 1-L1-Fc-L2-TrkA ECD 2；
式(IV)：TrkA ECD 1-L1-TrkA ECD 2-L2-Fc；或
式(V)：Fc-L1-TrkA ECD 1-L2-TrkA ECD 2，
其中TrkA ECD 1是第一TrkA ECD多肽，TrkA ECD 2是第二TrkA ECD多肽，L1和L2是任选的接头，并且Fc是伴生动物物种的野生型或变体IgG Fc多肽。
20.根据权利要求19所述的连续多肽，其中TrkA ECD 1和TrkA ECD 2是相同的多肽。
21.根据权利要求19所述的连续多肽，其中TrkA ECD 1和TrkA ECD 2是不同的多肽。
22.根据前述权利要求中任一项所述的连续多肽，其中所述融合配偶体或Fc是变体Fc多肽，其包含：
a)相对于伴生动物物种的野生型IgG Fc多肽的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A的结合亲和力；
b)相对于伴生动物物种的野生型IgG Fc多肽的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多肽具有降低的对C1q的结合亲和力；
c)相对于伴生动物物种的野生型IgG Fc多肽的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多肽具有降低的对CD16的结合亲和力；
d)铰链区，其包含相对于野生型猫类或马类IgG Fc多肽的至少一个氨基酸修饰；
e)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述至少一个氨基酸取代是半胱氨酸，并且其中所述变体IgG Fc多肽能够相对于所述野生型猫类IgG Fc多肽形成至少一个另外的链间二硫键；
f)相对于源自伴生动物物种的野生型IgG Fc多肽的至少一个氨基酸取代，其中所述变体Fc多肽能够以相对于所述野生型Fc多肽增加的亲和力与新生儿Fc受体(FcRn)结合。
23.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以通过生物膜层干涉法测量的大于5x10-6M、大于1x10-5M、大于5x10- 5M、大于1x10-4M、大于5x10-4M或大于1x10-3M的解离常数(Kd)与C1q和/或CD16结合。
24.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以通过生物膜层干涉法测量的小于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)与蛋白A结合。
25.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG 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。
26.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，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。
27.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽以相对于所述野生型Fc多肽增加的亲和力与FcRn结合，并且其中所述连续多肽相对于包含野生型Fc多肽的连续多肽具有增加的血清半衰期。
28.根据前述权利要求中任一项所述的连续多肽，其中所述野生型IgG Fc多肽是：
a)犬类IgG-A Fc、IgG-B Fc、IgG-C Fc或IgG-D Fc；
b)马类IgG1 Fc、IgG2 Fc、IgG3 Fc、IgG4 Fc、IgG5 Fc、IgG6 Fc或IgG7Fc；或
c)猫类IgG1a Fc、IgG1b Fc或IgG2 Fc。
29.根据前述权利要求中任一项所述的连续多肽，其中所述野生型IgG Fc多肽包含以下的氨基酸序列：SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ IDNO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:87、SEQ IDNO:88、SEQ ID NO:89或SEQ ID NO:90。
30.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16的位置处的氨基酸取代；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处的氨基酸取代；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置20的位置处的氨基酸取代。
31.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16处的氨基酸取代；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:72的位置3处的氨基酸取代；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在SEQ ID NO:72的位置20处的氨基酸取代。
32.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)相对于野生型猫类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQID NO:90的位置16的位置处或在SEQ ID NO:SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或SEQ ID NO:90的位置16处的脯氨酸；
b)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置3的位置处或在SEQ ID NO:72的位置3处的丝氨酸；和/或
c)相对于野生型马类IgG Fc多肽的至少一个氨基酸取代，其中所述变体IgG Fc多肽包含在对应于SEQ ID NO:72的位置20的位置处或在SEQ ID NO:72的位置20处的脯氨酸。
33.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体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。
34.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含来自野生型猫类IgG-1Fc多肽或来自野生型马类IgG1 Fc多肽的铰链区或铰链区的一部分。
35.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在对应于SEQ ID NO:90的位置8、位置9、位置10、位置11、位置12、位置13、位置14、位置15或位置16的位置处的半胱氨酸。
36.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在对应于SEQ ID NO:90的位置14的位置处的半胱氨酸。
37.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含在SEQ ID NO:90的位置14处的半胱氨酸。
38.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置23的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置25的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置80的位置处的氨基酸取代、在对应于SEQ ID NO:34的位置205的位置处的氨基酸取代、和/或在对应于SEQ ID NO:34的位置207的位置处的氨基酸取代；
b)在对应于SEQ ID NO:37的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:37的位置23的位置处的氨基酸取代和/或在对应于SEQ ID NO:37的位置24的位置处的氨基酸取代；
c)在对应于SEQ ID NO:39的位置21的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置23的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置25的位置处的氨基酸取代、在对应于SEQ ID NO:39的位置80的位置处的氨基酸取代和/或在对应于SEQ ID NO:39的位置207的位置处的氨基酸取代；
d)在对应于SEQ ID NO:71的位置15的位置处的氨基酸取代和/或在对应于SEQ ID NO:71的位置203的位置处的氨基酸取代；
e)在对应于SEQ ID NO:75的位置199的位置处的氨基酸取代和/或在对应于SEQ IDNO:75的位置200的位置处的氨基酸取代；和/或
f)在对应于SEQ ID NO:76的位置199的位置处的氨基酸取代、在对应于SEQ ID NO:76的位置200的位置处的氨基酸取代、在对应于SEQ ID NO:76的位置201的位置处的氨基酸取代和/或在对应于SEQ ID NO:76的位置202的位置处的氨基酸取代。
39.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34的位置21处的氨基酸取代、在SEQ ID NO:34的位置23处的氨基酸取代、在SEQ ID NO:34的位置25处的氨基酸取代、在SEQ ID NO:34的位置80处的氨基酸取代、在SEQ ID NO:34的位置205处的氨基酸取代和/或在SEQ ID NO:34的位置207处的氨基酸取代；
b)在SEQ ID NO:37的位置21处的氨基酸取代、在SEQ ID NO:37的位置23处的氨基酸取代和/或在SEQ ID NO:37的位置24处的氨基酸取代；
c)在SEQ ID NO:39的位置21处的氨基酸取代、在SEQ ID NO:39的位置23处的氨基酸取代、在SEQ ID NO:39的位置25处的氨基酸取代、在SEQ ID NO:39的位置80处的氨基酸取代和/或在SEQ ID NO:39的位置207处的氨基酸取代；
d)在SEQ ID NO:71的位置15处的氨基酸取代和/或在SEQ ID NO:71的位置203处的氨基酸取代；
e)在SEQ ID NO:75的位置199处的氨基酸取代和/或在SEQ ID NO:75的位置200处的氨基酸取代；和/或
f)在SEQ ID NO:76的位置199处的氨基酸取代、在SEQ ID NO:76的位置200处的氨基酸取代、在SEQ ID NO:76的位置201处的氨基酸取代和/或在SEQ ID NO:76的位置202处的氨基酸取代。
40.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34的位置21的位置处的苏氨酸、在对应于SEQ ID NO:34的位置23的位置处的亮氨酸、在对应于SEQ ID NO:34的位置25的位置处的丙氨酸、在对应于SEQID NO:34的位置80的位置处的甘氨酸、在对应于SEQ ID NO:34的位置205的位置处的丙氨酸和/或在对应于SEQ ID NO:34的位置207的位置处的组氨酸；
b)在对应于SEQ ID NO:37的位置21的位置处的苏氨酸、在对应于SEQ ID NO:37的位置23的位置处的亮氨酸和/或在对应于SEQ ID NO:37的位置24的位置处的异亮氨酸；
c)在对应于SEQ ID NO:39的位置21的位置处的苏氨酸、在对应于SEQ ID NO:39的位置23的位置处的亮氨酸、在对应于SEQ ID NO:39的位置25的位置处的丙氨酸、在对应于SEQID NO:39的位置80的位置处的甘氨酸和/或在对应于SEQ ID NO:39的位置207的位置处的组氨酸；
d)在对应于SEQ ID NO:71的位置15的位置处的苏氨酸或缬氨酸和/或在对应于SEQ IDNO:71的位置203的位置处的酪氨酸或缬氨酸；
e)在对应于SEQ ID NO:75的位置199的位置处的亮氨酸和/或在对应于SEQ ID NO:75的位置200的位置处的组氨酸；和/或
f)在对应于SEQ ID NO:76的位置199的位置处的亮氨酸、在对应于SEQ ID NO:76的位置200的位置处的组氨酸、在对应于SEQ ID NO:76的位置201的位置处的天冬酰胺和/或在对应于SEQ ID NO:76的位置202的位置处的组氨酸。
41.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34的位置21处的苏氨酸、在SEQ ID NO:34的位置23处的亮氨酸、在SEQID NO:34的位置25处的丙氨酸、在SEQ ID NO:34的位置80处的甘氨酸、在SEQ ID NO:34的位置205处的丙氨酸和/或在SEQ ID NO:34的位置207处的组氨酸；
b)在SEQ ID NO:37的位置21处的苏氨酸、在SEQ ID NO:37的位置23处的亮氨酸和/或在SEQ ID NO:37的位置24处的异亮氨酸；
c)在SEQ ID NO:39的位置21处的苏氨酸、在SEQ ID NO:39的位置23处的亮氨酸、在SEQID NO:39的位置25处的丙氨酸、在SEQ ID NO:39的位置80处的甘氨酸和/或在SEQ ID NO:39的位置207处的组氨酸；
d)在SEQ ID NO:71的位置15处的苏氨酸或缬氨酸和/或在SEQ ID NO:71的位置203处的酪氨酸或缬氨酸；
e)在SEQ ID NO:75的位置199处的亮氨酸和/或在SEQ ID NO:75的位置200处的组氨酸；和/或
f)在SEQ ID NO:76的位置199处的亮氨酸、在SEQ ID NO:76的位置200处的组氨酸、在SEQ ID NO:76的位置201处的天冬酰胺和/或在SEQ ID NO:76的位置202处的组氨酸。
42.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:35的位置93的位置处的氨基酸取代或在对应于SEQ ID NO:37的位置93的位置处的氨基酸取代；
b)在对应于SEQ ID NO:70的位置87的位置处的氨基酸取代、在对应于SEQ ID NO:73的位置87的位置处的氨基酸取代、在对应于SEQ ID NO:74的位置87的位置处的氨基酸取代或在对应于SEQ ID NO:77的位置87的位置处的氨基酸取代；或
c)在对应于SEQ ID NO:86的位置198的位置处的氨基酸取代、在对应于SEQ ID NO:87的位置198的位置处的氨基酸取代、在对应于SEQ ID NO:88的位置198的位置处的氨基酸取代或在对应于SEQ ID NO:89的位置198的位置处的氨基酸取代。
43.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:35的位置93处的氨基酸取代或在SEQ ID NO:37的位置93处的氨基酸取代；
b)在SEQ ID NO:70的位置87处的氨基酸取代、在SEQ ID NO:73的位置87处的氨基酸取代、在SEQ ID NO:74的位置87处的氨基酸取代或在SEQ ID NO:77的位置87处的氨基酸取代；或
c)在SEQ ID NO:86的位置198处的氨基酸取代、在SEQ ID NO:87的位置198处的氨基酸取代、在SEQ ID NO:88的位置198处的氨基酸取代或在SEQ ID NO:89的位置198处的氨基酸取代。
44.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:35的位置93的位置处的精氨酸或在对应于SEQ ID NO:37的位置93的位置处的精氨酸；
b)在对应于SEQ ID NO:70的位置87的位置处的丝氨酸、在对应于SEQ ID NO:73的位置87的位置处的丝氨酸取代、在对应于SEQ ID NO:74的位置87的位置处的丝氨酸或在对应于SEQ ID NO:77的位置87的位置处的丝氨酸；或
c)在对应于SEQ ID NO:86的位置198的位置处的丙氨酸、在对应于SEQ ID NO:87的位置198的位置处的丙氨酸、在对应于SEQ ID NO:88的位置198的位置处的丙氨酸或在对应于SEQ ID NO:89的位置198的位置处的丙氨酸。
45.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:35的位置93处的精氨酸或在SEQ ID NO:37的位置93处的精氨酸；
b)在SEQ ID NO:70的位置87处的丝氨酸、在SEQ ID NO:73的位置87处的丝氨酸、在SEQID NO:74的位置87处的丝氨酸或在SEQ ID NO:77的位置87处的丝氨酸；或
c)在SEQ ID NO:86的位置198处的丙氨酸、在SEQ ID NO:87的位置198处的丙氨酸、在SEQ ID NO:88的位置198处的丙氨酸或在SEQ ID NO:89的位置198处的丙氨酸。
46.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在对应于SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ IDNO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90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:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ IDNO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82的位置处的酪氨酸；
c)在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90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:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90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；
e)在对应于SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ IDNO:88或SEQ ID NO:90的位置207的位置处的酪氨酸；
f)在对应于SEQ ID NO:34或SEQ ID NO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的组氨酸；
g)在对应于SEQ ID NO:34或SEQ ID NO:39的位置82的位置处的酪氨酸和在对应于其位置208的位置处的酪氨酸；或
h)在对应于SEQ ID NO:34或SEQ ID NO:39的位置208的位置处的酪氨酸。
47.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含：
a)在SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置23处的酪氨酸或苯丙氨酸；
b)在SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:70、SEQID NO:71、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸；
c)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的组氨酸；
d)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置82处的酪氨酸和位置207处的酪氨酸；
e)在SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:73、SEQID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:86、SEQ ID NO:88或SEQ ID NO:90的位置207处的酪氨酸；
f)在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的组氨酸；
g)在SEQ ID NO:34或SEQ ID NO:39的位置82处的酪氨酸和位置208处的酪氨酸；或
h)在SEQ ID NO:34或SEQ ID NO:39的位置208处的酪氨酸。
48.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，所述变体IgG Fc多肽包含与以下的氨基酸序列具有至少90％同一性、至少91％同一性、至少92％同一性、至少93％同一性、至少94％同一性、至少95％同一性、至少96％同一性、至少97％同一性、至少98％同一性或至少99％同一性的氨基酸序列：SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ IDNO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ IDNO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、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:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:78、SEQ IDNO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQ IDNO:85、SEQ ID NO:91、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ IDNO:96、SEQ ID NO:97、SEQ ID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:197、SEQ ID NO:198、SEQ ID NO:199、SEQID NO:200、SEQ ID NO:201、SEQ ID NO:202、SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206、SEQ ID NO:207、SEQ ID NO:208、SEQ ID NO:209和/或SEQ ID NO:210。
49.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含变体IgG Fc多肽，变体IgG Fc多肽包含以下的氨基酸序列：SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ ID NO:53、SEQ ID NO:54、SEQID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:65、SEQ ID NO:66、SEQID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQ ID NO:85、SEQ ID NO:91、SEQID NO:92、SEQ ID NO:93、SEQ ID NO:94、SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:97、SEQID NO:98、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101、SEQ ID NO:102、SEQ ID NO:103、SEQ ID NO:104、SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQID NO:109、SEQ ID NO:197、SEQ ID NO:198、SEQ ID NO:199、SEQ ID NO:200、SEQ ID NO:201、SEQ ID NO:202、SEQ ID NO:203、SEQ ID NO:204、SEQ ID NO:205、SEQ ID NO:206、SEQID NO:207、SEQ ID NO:208、SEQ ID NO:209和/或SEQ ID NO:210。
50.根据前述权利要求中任一项所述的连续多肽，所述连续多肽还包含NGFR多肽的至少一个细胞外结构域(NGFR ECD多肽)。
51.根据前述权利要求中任一项所述的连续多肽，所述连续多肽还包含含有SEQ IDNO:135、SEQ ID NO:137和/或SEQ ID NO:139的氨基酸序列的至少一种NGFR ECD多肽。
52.根据前述权利要求中任一项所述的连续多肽，所述连续多肽包含以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:110、SEQ ID NO:111、SEQID NO:112、SEQ ID NO:113、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:122、SEQID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131、SEQ ID NO:132、SEQ ID NO:133、SEQID NO:140、SEQ ID NO:141、SEQ ID NO:142、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ ID NO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166、SEQID NO:167、SEQ ID NO:168、SEQ ID NO:169、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172、SEQ ID NO:173、SEQ ID NO:174、SEQ ID NO:175、SEQ ID NO:176、SEQ ID NO:177、SEQID NO:178、SEQ ID NO:179、SEQ ID NO:180、SEQ ID NO:181、SEQ ID NO:182、SEQ ID NO:183、SEQ ID NO:184、SEQ ID NO:185、SEQ ID NO:186、SEQ ID NO:187、SEQ ID NO:188、SEQID NO:189、SEQ ID NO:190、SEQ ID NO:191、SEQ ID NO:192、SEQ ID NO:193、SEQ ID NO:194、SEQ ID NO:211、SEQ ID NO:212、SEQ ID NO:213、SEQ ID NO:214、SEQ ID NO:215、SEQID NO:216、SEQ ID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220、SEQ ID NO:221、SEQ ID NO:222、SEQ ID NO:223、SEQ ID NO:224、SEQ ID NO:225、SEQ ID NO:226、SEQID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230、SEQ ID NO:231、SEQ ID NO:232、SEQ ID NO:233、SEQ ID NO:234、SEQ ID NO:235、SEQ ID NO:236、SEQ ID NO:237、SEQID NO:238、SEQ ID NO:239、SEQ ID NO:240、SEQ ID NO:241、SEQ ID NO:242、SEQ ID NO:243、SEQ ID NO:244、SEQ ID NO:245或SEQ ID NO:246。
53.一种连续多肽，所述连续多肽包含以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ IDNO:23、SEQ ID NO:24、SEQ ID NO:110、SEQ ID NO:111、SEQ ID NO:112、SEQ ID NO:113、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ IDNO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:122、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ IDNO:130、SEQ ID NO:131、SEQ ID NO:132、SEQ ID NO:133、SEQ ID NO:140、SEQ ID NO:141、SEQ ID NO:142、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ IDNO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166、SEQ ID NO:167、SEQ ID NO:168、SEQ ID NO:169、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172、SEQ ID NO:173、SEQ IDNO:174、SEQ ID NO:175、SEQ ID NO:176、SEQ ID NO:177、SEQ ID NO:178、SEQ ID NO:179、SEQ ID NO:180、SEQ ID NO:181、SEQ ID NO:182、SEQ ID NO:183、SEQ ID NO:184、SEQ IDNO:185、SEQ ID NO:186、SEQ ID NO:187、SEQ ID NO:188、SEQ ID NO:189、SEQ ID NO:190、SEQ ID NO:191、SEQ ID NO:192、SEQ ID NO:193、SEQ ID NO:194、SEQ ID NO:211、SEQ IDNO:212、SEQ ID NO:213、SEQ ID NO:214、SEQ ID NO:215、SEQ ID NO:216、SEQ ID NO:217、SEQ ID NO:218、SEQ ID NO:219、SEQ ID NO:220、SEQ ID NO:221、SEQ ID NO:222、SEQ IDNO:223、SEQ ID NO:224、SEQ ID NO:225、SEQ ID NO:226、SEQ ID NO:227、SEQ ID NO:228、SEQ ID NO:229、SEQ ID NO:230、SEQ ID NO:231、SEQ ID NO:232、SEQ ID NO:233、SEQ IDNO:234、SEQ ID NO:235、SEQ ID NO:236、SEQ ID NO:237、SEQ ID NO:238、SEQ ID NO:239、SEQ ID NO:240、SEQ ID NO:241、SEQ ID NO:242、SEQ ID NO:243、SEQ ID NO:244、SEQ IDNO:245或SEQ ID NO:246。
54.根据前述权利要求中任一项所述的连续多肽，其中所述Trk A ECD多肽是糖基化的。
55.根据前述权利要求中任一项所述的连续多肽，其中所述Trk A ECD多肽包含至少一个聚糖部分。
56.根据前述权利要求中任一项所述的连续多肽，其中所述Trk A ECD多肽被聚乙二醇化。
57.根据前述权利要求中任一项所述的连续多肽，其中所述Trk A ECD多肽在聚糖处、在伯胺处和/或在N末端α-胺处被聚乙二醇化。
58.一种分离的核酸，所述分离的核酸编码根据前述权利要求中任一项所述的连续多肽。
59.一种宿主细胞，所述宿主细胞包含根据权利要求58所述的核酸。
60.一种产生多肽的方法，所述方法包括培养根据权利要求59所述的宿主细胞并分离所述连续多肽。
61.一种药物组合物，所述药物组合物包含根据权利要求1至57中任一项所述的连续多肽和药学上可接受的载体。
62.根据权利要求61所述的药物组合物，其中所述药学上可接受的载体包含约5至约50mM的柠檬酸钠；约5至约50mM的组氨酸；或约5至约50mM的乙酸钠。
63.根据权利要求61或权利要求62所述的药物组合物，其中所述药物组合物具有5至6的pH。
64.一种治疗患有NGF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57中任一项所述的连续多肽或根据权利要求61至63中任一项所述的药物组合物。
65.一种治疗患有疼痛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57中任一项所述的连续多肽或根据权利要求61至63中任一项所述的药物组合物。
66.根据权利要求64或权利要求65所述的方法，其中所述伴生动物物种是犬类、猫类或马类。
67.根据权利要求64至66中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是慢性疼痛、急性疼痛和/或炎性疼痛。
68.根据权利要求64至67中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是骨关节炎疼痛、背痛、癌症疼痛和/或神经性疼痛。
69.根据权利要求64至68中任一项所述的方法，其中所述NGF诱导的病症或所述疼痛是与手术、断骨或骨折、牙科治疗、烧伤、割伤和/或分娩相关的疼痛。
70.根据权利要求64至69中任一项所述的方法，其中所述连续多肽或所述药物组合物是肠胃外施用的。
71.根据权利要求64至70中任一项所述的方法，其中所述连续多肽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。
72.根据权利要求64至71中任一项所述的方法，其中所述方法还包括施用NGF激酶抑制剂、PI3K抑制剂、ras抑制剂、CGRP抑制剂、TNF抑制剂、IL17抑制剂、EGFR抑制剂和/或磷脂酶C途径抑制剂。
73.根据权利要求64至72中任一项所述的方法，其中所述方法还包括施用一种或多种疼痛治疗药物，如皮质类固醇、非甾体抗炎药(NSAID)、环氧合酶抑制剂、阿片类物质和/或大麻素。
74.一种降低细胞中NGF信号传导活性的方法，所述方法包括在以下条件下将所述细胞暴露于根据权利要求1至57中任一项所述的连续多肽或根据权利要求61至63中任一项所述的药物组合物：所述条件允许所述连续多肽与NGF的结合。
75.根据权利要求74所述的方法，其中将所述细胞离体暴露于所述连续多肽或所述药物组合物。
76.根据权利要求74所述的方法，其中将所述细胞在体内暴露于所述连续多肽或所述药物组合物。
77.根据权利要求74至76中任一项所述的方法，其中所述细胞是犬类细胞、猫类细胞或马类细胞。
78.一种用于检测来自伴生动物物种的样品中的NGF的方法，所述方法包括在以下条件下使所述样品与根据权利要求1至57中任一项所述的连续多肽或根据权利要求61至63中任一项所述的药物组合物接触：所述条件允许所述连续多肽与NGF的结合；并且检测是否在所述多肽与所述样品中的NGF之间形成复合物。
79.根据权利要求78所述的方法，其中所述样品是从犬类、猫类或马类获得的生物样品。
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| WO2014093387A1 (en) * | 2012-12-10 | 2014-06-19 | Kindred Biosciences, Inc. | Vegf receptor fusion proteins for veterinary use |
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| US20030097667A1 (en) * | 1998-04-09 | 2003-05-22 | Robertson Alan George Simpson | Therapeutic agent |
| US20070162990A1 (en) * | 2006-01-11 | 2007-07-12 | Yuan-Jang Tsai | Neurodegenerative non-human transgenic mammal expressing TrkA fusion protein |
| WO2014093387A1 (en) * | 2012-12-10 | 2014-06-19 | Kindred Biosciences, Inc. | Vegf receptor fusion proteins for veterinary use |
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