CN111867627A - 抗IL-6抗体例如克拉扎珠单抗(Clazakizumab)用于使实体器官移植接受者脱敏和/或用于预防、稳定或减轻抗体介导的排斥(ABMR)的用途 - Google Patents
抗IL-6抗体例如克拉扎珠单抗(Clazakizumab)用于使实体器官移植接受者脱敏和/或用于预防、稳定或减轻抗体介导的排斥(ABMR)的用途 Download PDFInfo
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Abstract
提供了涉及使用抗IL‑6抗体例如克拉扎珠单抗来预防、稳定、减轻或遏止接受实体器官移植的患者中抗体介导的排斥反应的新型治疗方案，所述患者例如是接受所移植肾、心脏、肝、肺、胰腺、肠或任何前述各物的组合的患者。此外，提供了涉及使用抗IL‑6抗体例如克拉扎珠单抗作为脱敏方案的一部分来治疗等待同种异体移植物移植和/或在同种异体移植物移植之后的高度敏化受试者的新型治疗方案，所述受试者例如是将接受实体器官移植体例如肾、心脏、肝、肺、胰腺、肠、皮肤或任何前述各物的组合的患者。前述治疗可与一种或多种其他免疫抑制方案或其他脱敏程序组合实行。
Description
优先权要求
本发明要求2018年1月4日提交的美国临时申请号62/613,447；2018年6月14日提交的美国临时申请号62/684,870；2018年9月25日提交的美国临时申请号62/736,205；以及2018年11月30日提交的美国临时申请号62/773,630的优先权。这些临时申请中的每一者的内容以引用的方式整体并入本文。
序列表
本发明含有序列表，所述序列表含有适用于所要求保护的疗法中的示例性抗IL-6抗体的序列。
技术领域
本发明涉及抗IL-6抗体例如克拉扎珠单抗用以预防、稳定或减轻接受实体器官移植的患者中抗体介导的排斥反应的用途，所述患者例如是接受所移植肾、心脏、肝、肺、胰腺、肠、皮肤或任何前述各物的组合的患者。
本发明还涉及抗IL-6抗体或抗IL-6抗体片段例如克拉扎珠单抗作为脱敏方案的一部分用于治疗等待同种异体移植物移植或在同种异体移植物移植之后的高度敏化受试者的用途，所述受试者例如是将接受实体器官移植体例如肾、心脏、肝、肺、胰腺、肠、皮肤、胃、胆囊或任何前述各物的组合的患者。前述治疗可与一种或多种其他免疫抑制方案或其他脱敏程序组合实行。
背景技术
尽管在移植前和移植后护理方面得到了显著改进，但短期移植物存活率与长期移植物存活率两者均在当前未达到最优。等待移植的许多患者对存在于供者器官中的抗原(例如人白细胞抗原(HLA)抗原和非HLA抗原)是敏化的，并且可能长期保持在等待名单表上。这些患者通常由于输血史、妊娠或先前移植而变得敏化，并且产生预先形成的针对供者器官的供者特异性抗体(DSA)。所述患者处于在移植之后发生急性和慢性排斥、同种异体移植物衰竭以及死亡的高风险下。为达成成功移植，这些患者必须经受移植前脱敏程序以移除或降低这些DSA。然而，这些治疗并不总是成功的，并且许多患者仍然是敏化的，或必须在对他们进行移植之前经受延长脱敏。
此外，许多患者无论是否在移植前是敏化的都在移植之后显现抗体介导的排斥(ABMR)。ABMR现时被认定为是移植后同种异体移植物衰竭的最大单一原因。无痛性ABMR可开始于移植之后不久，但经常在移植程序之后许多个月或甚至许多年导致同种异体移植物功能异常以及最终移植物衰竭的临床征象。此外，尽管有实验室测试可用于预测患者处于ABMR的风险下以及诊断ABMR，但ABMR不可用当前护理标准免疫抑制性药物治疗。
ABMR的潜在病理生理学指示产生针对存在于供者器官中的HLA抗原和非HLA抗原的DSA的B细胞和浆细胞具有主要作用。这些抗体通过补体和非补体路径来损害器官。新近开发的诊断测试允许预测和早期诊断ABMR：这些测试包括用以检测预先形成和新生HLADSA的测定(尤其是检测补体结合DSA的那些测定诸如C1q测定)以及针对与ABMR相关的非HLA抗体的测定。在肾同种异体移植物活检体中，抗体损害的组织学特征包括以下迹象：微血管炎症、补体沉积(C4d)在肾小管周毛细血管中、肾小管周毛细血管炎、肾小球炎和移植肾小球病变(双重肾小球基底膜轮廓)。在其他所移植器官中观察到由ABMR引起的类似组织学特征。活动性抗体介导的排斥(ABMR)，尤其是慢性活动性抗体介导的排斥(CABMR)，现时被认定为是在成功肾移植之后同种异体移植物衰竭的最常见原因。当前护理标准抗排斥治疗靶向细胞介导的(即T细胞介导的排斥(TCMR))过程而不影响这个抗体介导的过程。当前，不存在用于包括CABMR的活动性ABMR的核准治疗。
发明内容
本发明涉及抗IL-6单克隆抗体(mAb)例如克拉扎珠单抗用于通过抑制DSA同种异体免疫应答的产生来治疗移植接受者例如肾移植接受者中AMBR或CABMR的用途。克拉扎珠单抗包含以下阐述的重链和轻链序列：
(重链)SEQ ID NO：745
(轻链)SEQ ID NO：746
本发明的一目标在于提供用于通过使用特异性抗IL-6抗体和抗IL-6抗体片段来治疗或预防有需要的患者中ABMR或CAMBR的治疗方案，所述患者特别是接受实体器官移植的那些。
本发明的另一目标在于提供用于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来使等待同种异体移植物移植以及在同种异体移植物移植之后的高度敏化受试者脱敏的新型方案。
更特别地，本发明的目标在于提供预防、稳定或减轻将接受或已接受实体器官移植的受试者中抗体介导的排斥(ABMR)的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗IL-6抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽，例如其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽，并且优选地，其中所述抗体是克拉扎珠单抗。在示例性实施方案中，实体器官选自肾、心脏、肝、肺、胰腺、皮肤、肠、胃、皮肤、胆囊、膀胱或任何前述各物的组合，或优选地是肾。
本发明的一目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中评估所述患者以诊断ABMR的发生或进展，例如其中评估包括以下中的一者或多者：检测预先形成和新生HLA DSA(尤其是检测补体结合DSA的那些评估诸如C1q评估)，检测与ABMR相关的非HLA抗体，或鉴定至少一种为抗体介导的器官损害所特有的组织学特征。
本发明的一目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中评估所述患者的为抗体介导的器官损害所特有的组织学特征，所述组织学特征通过从所移植器官获得活检体来检测，并且任选地，为抗体介导的器官损害所特有的所述组织学特征包括微血管炎症、补体沉积(C4d)和毛细血管炎中的任一者。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中评估所述患者以诊断ABMR的发生或进展，例如其中评估包括以下中的一者或多者：检测预先形成和新生HLA DSA(尤其是检测补体结合DSA的那些评估诸如C1q评估)，检测与ABMR相关的非HLA抗体，或鉴定至少一种为抗体介导的器官损害所特有的组织学特征，其中所移植器官是肾，并且为抗体介导的器官损害所特有的所述组织学特征包括微血管炎症、补体沉积(C4d)在肾小管周毛细血管中、肾小管周毛细血管炎、肾小球炎和移植肾小球病变(双重肾小球基底膜轮廓)中的任一者。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中治疗还包括施用至少一种其他免疫抑制剂，例如护理标准移植前或移植后免疫抑制性药物，任选地，抗胸腺细胞球蛋白(thymoglobulin)、巴利昔单抗(basiliximab)、霉酚酸吗啉乙酯(mycophenolate mofetil)、他克莫司(tacrolimus)、抗CD20 mAb诸如利妥昔单抗(rituximab)和皮质类固醇(corticosteroid)中的任一者。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗体在静脉内或在皮下施用。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗IL-6抗体在约0.01mg-5000mg，更通常在0.1-1000mg，并且甚至更通常在1-500mg的范围内的剂量下优选地通过静脉内或皮下施用来施用。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗体在静脉内在约5mg-50mg的范围内的剂量下或在皮下在约10mg-50mg的范围内的剂量下施用。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗体约每4周、8周、12周、16周、20周或24周加以施用。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗体在检测ABMR的征象的约一个月内施用。
本发明的另一更特定目标在于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR，所述患者特别是接受实体器官移植的那些，其中所述抗体在移植之前持续数月以及在移植之后持续数月或甚至数年加以施用以预防或降低抗体介导的对所移植器官的损害。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述抗体或抗体片段包含：含有SEQID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽，例如其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽，并且优选地是克拉扎珠单抗。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述抗体或抗体片段包含：含有SEQID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽，其中所述实体器官选自肾、心脏、肝、肺、胰腺、皮肤、肠、胃或任何前述各物的组合，或所述实体器官是肾。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中患者由于输血史、妊娠或先前移植而处于敏化的风险下或是敏化的。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中患者产生预先形成的针对供者器官的供者特异性抗体(DSA)。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，所述方法还包括移植前脱敏程序以移除或降低这些同种异体抗体(DSA)。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述脱敏治疗包括血浆除去或血浆交换，任选地与静脉内免疫球蛋白、抗B细胞剂诸如利妥昔单抗(抗CD20 mAb)以及浆细胞抑制剂诸如硼替佐米(bortezomib)(蛋白体抑制剂)中的任一者组合。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述抗体在静脉内或在皮下施用。
本发明的另一目标在于提供一种通过使用特异性抗IL-6抗体和抗体片段来预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，例如其中所述抗体在约0.01mg-5000mg，更通常在0.1-1000mg，并且甚至更通常在1-500mg的范围内的剂量下优选地通过静脉内或皮下施用来施用。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述抗体在静脉内在5mg-50mg的剂量下或在皮下在10mg-50mg的剂量下施用。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中所述抗体约每4或8周加以施用，在移植之前数月(例如6个月)开始。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中在脱敏前通过各种抗体检测方法(例如细胞毒性交叉配型、流式细胞计量交叉配型、Luminex抗体测试)定期评估患者以检测在脱敏治疗过程期间DSA的水平。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中正性响应(例如阳性细胞毒性交叉配型转变成阴性细胞毒性交叉配型)用于确定患者对于移植来说是合格的并且可进行移植。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中患者在移植前和/或移植后用所述抗体优选地是克拉扎珠单抗加以治疗。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中在移植后持续数月或数年继续所述抗体施用以预防或治疗早期急性或晚期慢性排斥。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中监测患者的临床排斥征象(诸如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低)或新的DSA(新生DSA)的产生。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中监测患者的组织学器官排斥征象。
本发明的另一目标在于提供一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的如上所述的抗人白介素-6(IL-6)抗体或抗体片段例如克拉扎珠单抗，其中ABMR器官损害通过活检迹象(例如微血管炎症、间质性纤维化、移植肾小球病变、CD4沉积)确认。
本发明的另一目标在于使用任何以上提及的方法与通常在移植前和移植后向患者施用的护理标准免疫抑制方案(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司和皮质类固醇)的组合。
本发明的另一目标在于使用任何以上提及的方法，其中抗IL-6抗体或抗体片段含有已被修饰来改变效应功能、半衰期、蛋白水解和/或糖基化的Fc区。
本发明的另一目标在于使用任何以上提及的方法，其中抗IL-6抗体选自人源化、单链或嵌合抗体，并且抗体片段选自Fab、Fab′、F(ab′)2、Fv或scFv。
本发明的另一目标在于使用任何以上提及的方法，其中抗IL-6抗体剂量在每kg接受患者体重约0.001与100mg，更优选地在每kg体重0.01至20mg之间。
本发明的另一目标在于使用任何以上提及的方法，其中抗体或片段抑制IL-6与gp130的结合和/或I1-6与IL-6R1的结合。
本发明的另一目标在于使用任何以上提及的方法，其中抗IL-6抗体或抗体片段例如克拉扎珠单抗包含人恒定区。
本发明的另一目标在于使用任何以上提及的方法，其中抗I1-6抗体例如克拉扎珠单抗包含人恒定区诸如IgG1、IgG2、IgG3或IgG4恒定区，或优选地包含人IgG1恒定区。
本发明的另一目标在于提供一种预防、稳定或减轻将接受，正接受，或已接受实体器官移植的受试者中抗体介导的排斥(ABMR)的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗人I1-6抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
本发明的另一目标在于提供一种逆转、稳定和/或减缓有需要的移植接受者中活动性抗体介导的排斥(AMBR)的进展的方法，所述方法包括施用有效量的抗IL-6抗体或抗体片段，任选地，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗人IL-6抗体包含SEQ ID NO：704或745的重链多肽，并且包含SEQ ID NO：702或746的轻链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少1年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少2年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少3年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少4年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少5年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中持续超过5年施用抗人IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中任选地，当开始治疗时，任选地，在跨越治疗之前1-6个月的时期内至少一次，移植接受者包含活动性抗体介导的排斥(AMBR)或慢性活动性抗体介导的排斥(CABMR)。
本发明的另一目标在于提供如上鉴定的方法，其中移植接受者在抗IL-6抗体施用之前已被诊断为具有AMBR或CAMBR。
本发明的另一目标在于提供如上鉴定的方法，其中用抗IL-6抗体进行的治疗使在治疗期间，任选地在整个治疗时期中的估计肾小球滤过率(eGFR)稳定或增加。
本发明的另一目标在于提供如上鉴定的方法，其中用抗IL-6抗体进行的治疗使在治疗期间，任选地在整个治疗时期中的估计肾小球滤过率(eGFR)稳定或增加，并且此外，任选地，其中在治疗已结束之后，eGFR的所述稳定或增加维持至少3、6、9或12个月。
本发明的另一目标在于提供如上鉴定的方法，其中当开始治疗时和/或在治疗方案期间，所治疗患者不包含嗜中性白细胞减少症(小于1,000mm3)或血小板减少症(小于50,000mm3)。
本发明的另一目标在于提供如上鉴定的方法，其中在跨越治疗之前0-6个月的时期内，所治疗患者不-接受静脉内免疫球蛋白。
本发明的另一目标在于提供如上鉴定的方法，其中所治疗患者在治疗之前包含人白细胞抗原(HLA)DSA，任选地，其中这已在跨越治疗之前0-6个月的时期内通过检测人白细胞抗原(HLA)DSA的测定加以确认。
本发明的另一目标在于提供如上鉴定的方法，其中治疗引发以下中的一者或多者：
(i)使供者特异性抗体(DSA)的数目降低或消除供者特异性抗体(DSA)，
(ii)使CCL2水平降低；
(iii)使补体活化降低和/或使检测到的C5b.C9和/或C5b/C9复合物的量降低；
(iv)使分泌DSA的浆细胞的数目降低；
(v)防止同种异体移植物失功；
(vi)防止恢复透析，
(vii)防止同种异体移植物肾切除，和/或
(viii)防止对再移植的需要，
(ix)维持或增加估计肾小球滤过率(eGFR)以使它是至少≥15mL/min/1.73m2。
本发明的另一目标在于提供如上鉴定的方法，其中移植体包括实体器官。
本发明的另一目标在于提供如上鉴定的方法，其中实体器官包括肾、心脏、肺、膀胱、胰腺、肝、胆囊、甲状腺、皮肤或前述各物的任何组合。
本发明的另一目标在于提供如上鉴定的方法，其中实体器官包括肾或由肾组成。
本发明的另一目标在于提供如上鉴定的方法，其中移植体来自活体或死亡供者。
本发明的另一目标在于提供如上鉴定的方法，其中治疗是有效的，在治疗期间或之后的功效至少部分地通过检测eGFR值，任选地使用肾病膳食改进4(MDRD4)方程来评估。
本发明的另一目标在于提供如上鉴定的方法，其中功效至少部分地通过根据Banff 2015病变分级评分评估肾活检体的组织学来评估。
本发明的另一目标在于提供如上鉴定的方法，其中功效至少部分地通过检测DSA效价和/或平均荧光强度(MFI)评分来评估。
本发明的另一目标在于提供如上鉴定的方法，其中功效至少部分地通过评估急性排斥事件(TCMR和ABMR)的发生来评估。
本发明的另一目标在于提供如上鉴定的方法，其中功效至少部分地通过评估治疗对白蛋白尿的影响来评估。
本发明的另一目标在于提供如上鉴定的方法，其中功效至少部分地通过相较于对照和/或常规AMBR或CAMBR治疗评估存活率来评估。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体包含人IgG1恒定区，例如其中所述人IgG1恒定区包含SEQ ID NO：586的恒定轻多肽和SEQ ID NO：588的恒定重多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体包含SEQ ID NO：657的可变重链多肽和SEQ ID NO：709的可变轻链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体包含SEQ ID NO：704或745的重链多肽和SEQ ID NO：702或746的轻链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体每4周或每月在静脉内或在皮下给药。
本发明的另一目标在于提供如上鉴定的方法，其中每4周或每月在静脉内或在皮下施用25mg或12.5mg剂量的抗IL-6抗体。
本发明的另一目标在于提供如上鉴定的方法，其中每4周或每月在皮下施用25mg或12.5mg剂量的克拉扎珠单抗。
本发明的另一目标在于提供如上鉴定的方法，其中持续至少1年、2年、3年、4年或5年实行治疗，而无选自恢复透析、同种异体移植物肾切除、再移植或eGFR≤15mL/min/1.73m2的不利事件。
本发明的另一目标在于提供如上鉴定的方法，其中移植接受者任选地还用以下中的任一者治疗：
(i)咪唑硫嘌呤(azathioprine)(例如1.0-2.0mg/kg/天)，
(ii)钙调神经磷酸酶(calcineurin)抑制剂(CNI)，
(iii)霉酚酸吗啉乙酯(MMF)(例如1.0-2.0g/天)/霉酚酸(MPA)(例如720-1440mg/天)，
(iv)mTOR抑制剂(例如他克莫司、(例如目标谷底水平5-8ng/ml)依维莫司(everolimus)、西罗莫司(sirolimus))，
(v)低剂量皮质类固醇(例如泼尼松(prednisone)/泼尼松龙(prednisolone)≤10mg/天)，
(vi)抗高血压剂(例如血管紧张素转化酶抑制剂(ACEI))，
(vii)血管紧张素II受体阻断剂(ARB)，
(viii)环孢灵(cyclosporine)(例如目标谷底水平50-150ng/ml)
(ix)抗糖尿病发生剂；
(x)或任何前述各物的组合。
本发明的另一目标在于提供如上鉴定的方法，其中移植接受者任选地还用耶氏肺囊虫(pneumocystis jiroveci)肺炎(PJP)防治剂治疗，所述防治剂例如是甲氧苄啶(trimethoprim)(例如80mg，每日，丸剂)，和/或磺胺甲噁唑(sulfamethoxazole)(例如160mg，每周3次，丸剂)、吸入型喷他脒(pentamidine)或口服达普松(dapsone)(任选地在治疗的至少1周内开始)。
如前述权利要求中任一项所述的方法，其中如果移植接受者经历急性TCMR，那么例如用脉冲类固醇诸如口服泼尼松(例如200mg/天)对所述急性TCMR进行治疗。
本发明的另一目标在于提供如上鉴定的方法，其中在抗IL-6抗体治疗期间以及任选地在跨越开始治疗之前0、1、2、3、4、5或6个月的时期内，移植接受者不用以下中的任一者治疗：
(i)利妥昔单抗，
(ii)依库珠单抗(eculizumab)，
(iii)蛋白酶体抑制剂，
(iv)静脉内免疫球蛋白(IVIG)(除治疗低γ球蛋白血症之外)，
(v)血浆交换(PLEX)、贝拉西普(belatacept)，
(vi)抗IL-6R抗体和/或
(vii)前述各物的任何组合。
本发明的另一目标在于提供如上鉴定的方法，其中移植接受者包含以下中的任一者或全部：
(i)是18-75岁，
(ii)距离移植时间≥6个月开始治疗，
(iii)根据BANFF 2015诊断准则对CABMR的诊断，包括以下事项：活检证明的CABMR(即慢性肾小球病变(cg)＞0)，伴有/不伴有C4d染色(如果先前活检不在筛选的6个月内，那么进行重复活检)，
(iv)如果受试者已接受针对ABMR(包括CABMR)或TCMR的治疗，那么进行重复活检(以显示CABMR的持续性)，其中根据光学显微术不具有慢性组织损伤迹象，但根据电子显微术具有肾小球基底膜双重轮廓(cg1a)的受试者是合格的；
(v)在移植后存在人白细胞抗原(HLA)DSA(使用基于珠粒的单抗原测定)。
本发明的另一目标在于提供如上鉴定的方法，其中移植接受者不包含以下中的一者或多者：
(i)尚未在跨越IL-6抗体治疗或筛选的0-3个月或0-6个月的时期内进行针对ABMR或CABMR或TCMR的治疗；
(ii)不正在接受任何T细胞消减剂，在筛选或治疗的3个月内未针对ABMR(包括CABMR)或TCMR进行治疗；
(iii)尚未在筛选或IL-6抗体治疗的3个月内接受T细胞消减剂(例如阿来珠单抗(alemtuzumab)、抗胸腺细胞球蛋白)；
(iv)没有活检显示单纯性TCMR或晚期间质性纤维化(ci3)，
(v)无晚期肾小管萎缩(ct3)；
(vi)无血管纤维内膜增厚(cv3)或肾功能异常的其他重大原因(例如多瘤BK病毒(BKV)肾病变、肾小球性肾炎)；
(vii)无归因于所移植同种异体移植物中的病症(例如肾动脉狭窄、肾盂积水)的肾功能受损；
(viii)无eGFR＜25mL/min/1.73m2或＞65mL/min/1.73m2(MDRD4)，(viii)无规定为随机尿蛋白肌酸酐比率(UPCR)≥3,000mg/g(≥300mg/mmol)或随机尿白蛋白肌酸酐比率(UACR)≥2,200mg/g(≥220mg/mmol)的肾病范围蛋白尿；
(ix)不处于妊娠或哺乳中；
(x)无过敏症史；
(xi)肝功能测试(LFT)无异常(丙氨酸转氨酶(ALT)/天冬氨酸转氨酶(AST)/胆红素＞1.5倍正常值上限)或无其他重大肝病；
(xii)无活动性结核(TB)史；
(xiii)在不具有活动性TB史的情况下无潜伏性TB史(例如Quantiferon TB测试呈阳性)，除非受试者已完成防治性治疗的全过程，
(xiv)无人免疫缺陷病毒(HIV)感染史或关于HIV呈阳性；
(xv)关于乙型肝炎表面抗原(HBsAg)不呈血清阳性；
(xvi)不是丙型肝炎病毒(HCV)RNA阳性的；
(xvii)无已知艾伯斯坦-巴尔病毒(Epstein-Barr virus，EBV)不匹配：供者血清阳性，接受者血清阴性；
(xviii)无胃肠穿孔、憩室病或憩室炎、或炎症性肠病史；
(xix)无嗜中性白细胞减少症(＜1,000/mm3)或血小板减少症(＜50,000/mm3)；
(xx)无需要全身性抗微生物剂并且在筛选之前未消退的活动性感染；
(xxi)无历史或当前侵袭性真菌性感染或其他机会性感染，所述感染包括(但不限于)以下：非结核性分枝杆菌感染、曲霉病、肺囊虫病和弓形虫病；(xxii)基于聚合酶链式反应(PCR)测试，无活动性病毒性感染诸如BKV、巨细胞病毒(CMV)或EBV；
(xxii)无当前或新近(在跨越治疗之前0-3或0-6个月的时期中)，
(xxiii)在筛选的6周内未施用活疫苗，包括但不限于以下：腺病毒疫苗、麻疹疫苗、腮腺炎疫苗和风疹疫苗、口服脊髓灰质炎疫苗、口服伤寒疫苗、轮状病毒疫苗、水痘带状疱疹疫苗、黄热病疫苗，无酒精或非法物质(包括大麻)滥用史；
(xxiv)无目前或先前(在3年内)恶性肿瘤，除基底细胞癌、完全切除的皮肤鳞状细胞癌、或非复发性(在5年内)原位宫颈癌之外；
(xxv)不存在可损害安全性或预期寿命的状况或异常(即不受标准治疗控制的在临床上重大的内分泌、自体免疫、代谢、神经、精神病/心理、肾、胃肠、肝和血液或任何其他系统异常)；
(xxvi)无甲氧苄啶和/或磺胺甲噁唑不耐受史，先前未用抗IL-6抗体治疗，和/或
(xxvii)前述事项的任何组合。
本发明的另一目标在于提供预防、稳定或降低有需要的受试者中的补体活性的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，例如以下抗体或抗体片段：其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中在治疗之前、期间或之后测量受试者中的补体活性。
本发明的另一目标在于提供如上鉴定的方法，其中抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗体包含分别与SEQ ID NO：704或745以及702或746的多肽至少90、95、96、97、98或99％同一的重链多肽和轻多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗体是克拉扎珠单抗。
本发明的另一目标在于提供如上鉴定的方法，其中实体器官选自肾、心脏、肝、肺、胰腺、胆囊、皮肤、肠、胃或任何前述各物的组合。
本发明的另一目标在于提供如上鉴定的方法，其中实体器官包括肾或由肾组成。
本发明的另一目标在于提供如上鉴定的方法，其中患者在治疗之前被评估，并且已被诊断为具有ABMR或CAMBR，例如其中评估包括以下中的一者或多者：检测预先形成和新生HLA DSA(尤其是检测补体结合DSA的那些评估诸如C1q评估)，检测与ABMR相关的非HLA抗体，和/或鉴定至少一种为抗体介导的器官损害所特有的组织学特征，和/或为抗体介导的器官损害所特有的所述组织学特征通过从所移植器官获得活检体来检测，和/或为抗体介导的器官损害所特有的所述组织学特征包括微血管炎症、补体沉积(C4d)和毛细血管炎中的任一者。
本发明的另一目标在于提供如上鉴定的方法，其中患者具有由肾组成的所移植器官，并且为抗体介导的器官损害所特有的组织学特征包括微血管炎症、补体沉积(C4d)在肾小管周毛细血管中、肾小管周毛细血管炎、肾小球炎和移植肾小球病变(双重肾小球基底膜轮廓)中的任一者。
本发明的另一目标在于提供如上鉴定的方法，其中治疗还包括施用至少一种其他免疫抑制剂，例如其中所述至少一种其他免疫抑制剂是护理标准移植前或移植后免疫抑制性药物。
本发明的另一目标在于提供如上鉴定的方法，其中治疗还包括施用至少一种其他免疫抑制剂，例如所述至少一种其他免疫抑制剂包括抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司、抗CD20 mAb诸如利妥昔单抗和皮质类固醇中的任一者。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在静脉内或在皮下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在0.01-5000mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在0.1-1000mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在1-500mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在静脉内在约5mg-50mg的范围内的剂量下或在皮下在约10mg-50mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在约25mg的剂量下施用，所述剂量约每2周、4周、6周、8周、12周、16周、20周、24周、每月、每两月、每2个月、每3个月、每4个月、每5个月、每6个月、每年或以更小频率加以给药。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体约每4周、8周、12周、16周、20周或24周加以施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在25mg或12.5mg的剂量下每4周或每月在皮下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在检测ABMR或CAMBR的征象的约1、2或3个月内施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在移植之前持续数月以及在移植之后持续数月或数年加以施用以预防、稳定或降低抗体介导的对所移植器官的损害。
本发明的另一目标在于提供预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体包含分别与SEQ IDNO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗体包含与SEQ ID NO：657和709的多肽同一的VH多肽和VL多肽。
本发明的另一目标在于提供如上鉴定的方法，其中抗体包含分别与SEQ ID NO：702或746以及704或745的多肽同一的轻链多肽和重链多肽。
本发明的另一目标在于提供如上鉴定的方法，其中患者已用实体器官移植，所述实体器官选自肾、心脏、肝、肺、胰腺、皮肤、肠、胃或任何前述各物的组合。
本发明的另一目标在于提供如上鉴定的方法，其中实体器官包括肾或由肾组成。
本发明的另一目标在于提供如上鉴定的方法，其中患者由于输血史、妊娠或先前移植而处于敏化的风险下或是敏化的。
本发明的另一目标在于提供如上鉴定的方法，其中患者在抗IL-6抗体治疗之前和/或期间包含预先形成的针对供者器官的供者特异性抗体(DSA)。
本发明的另一目标在于提供如上鉴定的方法，所述方法还包括移植前脱敏程序以移除或降低供者特异性同种异体抗体(DSA)，例如其中所述脱敏治疗包括血浆除去或血浆交换，任选地与静脉内免疫球蛋白、抗B细胞剂诸如利妥昔单抗(抗CD20 mAb)以及浆细胞抑制剂诸如硼替佐米(蛋白体抑制剂)中的任一者组合。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在静脉内或在皮下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在0.01-5000mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在0.1-1000mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在1-500mg的范围内的剂量下施用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体在约25mg的剂量下施用，所述剂量约每2周、4周、6周、8周、12周、16周、20周、24周、每月、每两月、每2个月、每3个月、每4个月、每5个月、每6个月、每年或以更小频率加以给药。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体约每4或8周加以施用，在移植之前数月(例如在跨越0-6个月的时期内)开始。
本发明的另一目标在于提供如上鉴定的方法，其中在脱敏前在治疗期间通过一种或多种抗体检测方法(例如细胞毒性交叉配型、流式细胞计量交叉配型、Luminex抗体测试)定期评估患者以检测在脱敏治疗过程期间DSA的水平，例如其中正性响应(例如阳性细胞毒性交叉配型转变成阴性细胞毒性交叉配型)用于确定患者对于IL-6抗体治疗和/或移植来说是合格的或仍然是合格的。
本发明的另一目标在于提供如上鉴定的方法，其中患者在移植后用抗IL-6抗体例如克拉扎珠单抗加以治疗。
本发明的另一目标在于提供如上鉴定的方法，其中在移植后持续数月或数年继续所述抗IL-6抗体施用以预防或治疗早期急性或晚期慢性排斥。
本发明的另一目标在于提供如上鉴定的方法，其中监测患者的临床排斥征象(诸如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低)或新的DSA(新生DSA)的产生。
本发明的另一目标在于提供如上鉴定的方法，其中监测患者的组织学器官排斥征象。
本发明的另一目标在于提供如上鉴定的方法，其中对之前、期间和/或之后ABMR器官损害的预防、稳定或降低通过活检迹象(例如微血管炎症、间质性纤维化、移植肾小球病变、CD4沉积)确认。
本发明的另一目标在于提供如上鉴定的方法，其中克拉扎珠单抗与通常在移植前和移植后向患者施用的护理标准免疫抑制方案(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司、皮质类固醇)组合使用。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体或抗体片段含有已被修饰来改变效应功能、半衰期、蛋白水解和/或糖基化的Fc区。
如先前权利要求中任一项所述的方法，其中抗I1-6抗体选自人源化、单链或嵌合抗体，并且抗体片段选自Fab、Fab′、F(ab′)2、Fv或scFv。
本发明的另一目标在于提供如上鉴定的方法，其中抗体剂量在每kg接受患者体重约0.001与100mg之间。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体剂量在每kg接受患者体重约0.1与20mg之间，或包括约25mg。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体或片段抑制IL-6与gp130和/或与IL-6R1的结合。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体或抗体片段包含人恒定区，例如其中所述人恒定区包括IgG1、IgG2、IgG3或IgG4恒定区，或所述人恒定区包括IgG1恒定区。
本发明的另一目标在于提供如上鉴定的方法，其中抗IL-6抗体是克拉扎珠单抗。
本发明的另一目标在于提供如上鉴定的方法，其中所治疗受试者具有晚期或后期AMBR(根据Banff 2015分类的急性/活动性或慢性/活动性表型)。
本发明的另一目标在于提供如上鉴定的方法，其中施用的抗IL-6抗体是克拉扎珠单抗，并且所治疗受试者具有晚期或后期AMBR(根据Banff2015分类的急性/活动性或慢性/活动性表型)。
本发明的另一目标在于提供如上鉴定的方法，其中所治疗受试者患有选自以下的补体相关疾患：年龄相关以及退变性疾病诸如年龄相关的黄斑变性(AMD)(湿性和干性)、阿尔茨海默氏病(Alzheimer’s Disease)、肾小球疾病例如非典型溶血性尿毒综合征(aHUS)、由志贺(Shiga)毒素产生性大肠杆菌(E.coli)引起的溶血性尿毒综合征(STEC-HUS)、血栓性血小板减少性紫癜(TTP)、全身性红斑狼疮(SLE)、抗磷脂抗体综合征(APS)、抗嗜中性白细胞细胞质抗体(ANCA)诱发的血管炎、由针对嗜中性白细胞组分的自体抗体引起的炎症性小血管病症；涉及C5a介导的对胎盘血管生成的损害的抗体依赖性(即在具有APS的妇女中)妊娠丢失；补体介导的溶血病症诸如阵发性夜间血红蛋白尿(PNH)、aHUS和冷凝集素病(CAD)、缺血-再灌注损伤；中风、例如由创伤、败血症、休克和心肺分流(CPB)手术引起的心肌梗塞、由CPB心肺分流手术引起的疾患、过敏性哮喘、牙周炎、与异常补体活化相关的骨相关病症和骨损伤(例如通过过敏毒素对破骨细胞形成的影响)、急性期疾患，其中宿主面临损害相关分子样式和/或病原体相关分子样式的显著增加。
附图说明
图1含有显示克拉扎珠单抗对HLA-DR、CD54、IL-6和PDL-1的转录的影响的实验结果。
图2示意性显示在与同种异体PBMC共培养之前用克拉扎珠单抗对上皮细胞(EC)的预处理。
图3含有显示在克拉扎珠单抗的情况下共培养中IL-6分泌的实验结果。
图4含有显示将克拉扎珠单抗直接添加至EC-同种异体PBMC共培养物中的影响的实验结果。
图5含有显示克拉扎珠单抗对EC-PBMC共培养中IL-6、MCP-1和RANTES的水平的影响的实验结果。
图6含有显示克拉扎珠单抗对EC与同种异体PBMC的共培养中Tmem和Treg细胞的扩增的影响的实验结果。
图7含有显示克拉扎珠单抗对EC-PBMC共培养中T17和Th1细胞的扩增的影响的实验结果。
图8含有显示在EC刺激之后IL-6R分泌不变的实验。
图9示意性描绘显示克拉扎珠单抗对EC增殖和EC表型的影响的实验。
图10显示证明克拉扎珠单抗不改变EC增殖的实验。
图11显示证明克拉扎珠单抗对同种异体性介体的影响的实验。
图12示意性描绘显示克拉扎珠单抗对EC表型的影响的实验。
图13示意性描绘显示克拉扎珠单抗对IL-6ELISA的影响的实验。
图14描绘显示克拉扎珠单抗对由EC达成的IL-6分泌的影响的实验。
图15描绘显示克拉扎珠单抗在EC共培养的情况下对EC同种异体性的影响的实验。
图16描绘显示克拉扎珠单抗使EC-PMBC共培养中的CCL-2产生降低的实验。
图17描绘显示克拉扎珠单抗对CD4+T细胞活化的影响的实验。
图18描绘显示在克拉扎珠单抗存在下Th17和Th1细胞的扩增的实验。
图19描绘显示克拉扎珠单抗对同种异体CD4+T细胞的Th1应答的降低作用的实验。
图20描绘显示在“低剂量”克拉扎珠单抗存在下Th1细胞的扩增的实验。
图21描绘显示克拉扎珠单抗对由EC对补体调控蛋白的表达的影响的实验。
图22描绘显示克拉扎珠单抗对补体活化的影响的实验。
图23进一步描绘显示克拉扎珠单抗对补体活化的影响的实验。
具体实施方式
本领域中存在对使移植成功性改进，包括使移植前脱敏和移植后ABMR治疗和预防改进的方法的需要。白介素-6(IL-6)是一种对B细胞和浆细胞具有强力刺激作用的细胞因子，并且与其他细胞因子联合负责达成正常抗体产生。IL-6还对T细胞介导的炎症性过程具有强力刺激作用。本发明涉及特异性抗IL-6抗体或抗体片段用以在器官移植之前、并行或之后治疗器官移植的接受者的用途。特别地，本发明涉及使有需要的移植接受者的存活率和/或生活品质改进的方法，所述移植接受者特别是敏化移植前患者、例如由于输血史、妊娠或先前移植而处于变得对所移植供者组织或器官敏化的风险下的患者；显示ABMR或CAMBR的征象的移植前患者或移植后患者、或可处于显现ABMR或CAMBR的风险下的任何患者。
特别地，本发明提供了用于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗来治疗或预防有需要的患者中ABMR或CAMBR的新型治疗方案，所述患者特别是接受实体器官移植的那些。
此外，本发明提供了用于通过使用特异性抗IL-6抗体和抗体片段例如克拉扎珠单抗以及具有美国专利号9,452,227中公开的序列的其他特异性抗IL-6抗体和抗体片段来使等待同种异体移植物移植以及在同种异体移植物移植之后的高度敏化受试者脱敏的新型治疗方案，所述专利的包括序列表的内容以引用的方式整体并入本文。
更特别地，本发明提供了预防、稳定或减轻将接受或已接受实体器官移植的受试者中抗体介导的排斥(ABMR)或慢性抗体介导的排斥(CAMBR)的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽，例如其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽，或所述抗体包含分别与SEQ ID NO：704和702的多肽至少90、95、96、97、98或99％同一的重链多肽和轻链多肽，并且优选地，其中所述抗体是克拉扎珠单抗。在示例性实施方案中，实体器官选自肾、心脏、肝、肺、胰腺、皮肤、肠、胃或任何前述各物的组合，或优选地是肾。
此外，本发明提供了预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽，例如其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽，或所述抗体包含分别与SEQ ID NO：704和702的多肽至少90、95、96、97、98或99％同一的重链多肽和轻链多肽，并且优选地是克拉扎珠单抗。
在一些实施方案中，抗IL-6抗体含有如美国专利号9,452,227中所述的特异性CDR，所述专利的公开内容据此以引用的方式整体并入本文。在优选实施方案中，抗IL-6抗体是Ab1(参见例如美国专利号9,452,227的第46栏第8行至第47栏第12行)的人源化变体，例如克拉扎珠单抗，或特异性结合完整人IL-6多肽上的一个或多个与克拉扎珠单抗结合的表位相同的线性或构象性表位的抗体或抗体片段，或与这个抗体包含相同CDR的抗体或抗体片段。
示例性抗IL-6抗体和抗体片段包含：含有SEQ ID NO：4、5和6的CDR，以及与SEQ IDNO：709的可变轻链多肽具有至少90％同一性的可变轻链多肽，以及含有SEQ ID NO：7、8或120、以及9的CDR，以及与SEQ ID NO：657的可变重链多肽具有至少90％同一性的可变重链多肽，其中抗体或抗体片段特异性结合IL-6，并且拮抗一种或多种与IL-6相关的活性，并且特异性结合IL-6上的一个或多个与包含SEQ ID NO：709的可变轻链多肽和SEQ ID NO：657的可变重链多肽的抗IL-6抗体结合的表位相同的表位。(本文标识的所有序列都描述于美国专利号9,452,227中)。
在特别优选实施方案中，用于本发明方法中的抗IL-6抗体是克拉扎珠单抗。克拉扎珠单抗是一种结合并抑制IL-6的人源化单克隆抗体。这个抗体强力抑制或阻止IL1-6结合IL-6R以及结合gp130。克拉扎珠单抗已在评估患有类风湿性关节炎、牛皮癣性关节炎、癌症和恶病质的患者的临床和临床前试验中显示功效，并且具有用于治疗特征在于慢性炎症的众多疾病的潜在应用。
本发明涉及在移植前、在移植期间、在移植后或在它们的任何组合的情况下治疗患者的方法。移植物(移植体)可为一种或多种被/已被引入接受移植的患者(接受者)中/上的任何器官、组织或细胞。在一优选实施方案中，一种或多种移植物器官、组织或细胞是同种异体的，以致移植物是同种异体移植物。还优选的是肠(大肠和/或小肠)和实体器官(例如肾、心脏、肝、肺、胆囊、皮肤、胃和胰腺)。
用主题抗IL-6抗体例如克拉扎珠单抗进行的治疗可使在移植前在患者中的脱敏程序功效改进。特别地，抗体治疗可使脱敏失败的患者中的移植率改进或缩短这些敏化患者准备进行移植的时间。用抗IL-6抗体例如克拉扎珠单抗进行的移植前治疗还可使不是敏化的患者的移植成功性改进。用抗IL-6抗体例如克拉扎珠单抗进行的治疗还可通过预防、降低或改善由ABMR引起的损害来使在移植后在患者中的治疗功效改进。
如本文所用，“改进(improved/improvement)”以及其他语法变化形式包括由治疗所致的任何有益变化。有益变化是患者的状况好于在不存在治疗下将具有的状况所处的任何情形。“改进”包括预防非所需状况，减缓某一状况恶化所处的速率，延迟非所需状况的发展，以及使达到所需状况所处的速率增加。举例来说，敏化患者中的改进涵盖敏化的任何降低以及预防、移除或降低DSA所处的数量或速率的任何增加。再举例来说，移植接受者中的改进涵盖在抗体介导的对所移植器官的损害或功能丧失的速率或数量方面达成的任何阻止、降低、延迟或减缓。
抗IL-6抗体例如克拉扎珠单抗可与或不与一种或多种额外标准脱敏治疗(例如血浆除去或血浆交换、静脉内免疫球蛋白、抗B细胞剂诸如利妥昔单抗(抗CD20 mAb)以及浆细胞抑制剂诸如硼替佐米(蛋白体抑制剂))一起在移植前向患者施用。在一些实施方案中，抗IL-6抗体例如克拉扎珠单抗在静脉内(例如在0.01-5000mg，更通常在0.1-1000mg或1-500mg，以及在示例性实施方案中在5mg-50mg的范围内的剂量下)或通过皮下注射(例如在0.01-5000mg，更通常在0.1-1000mg或1-500mg的范围内的剂量下，以及在示例性实施方案中在10mg-50mg的剂量下)每4周加以施用，在移植之前数月(例如6个月)开始。
可在脱敏前以及在脱敏治疗过程期间在定期间隔下通过各种抗体检测方法(例如细胞毒性交叉配型、流式细胞计量交叉配型、Luminex抗体测试)评估所治疗患者的DSA水平。正性响应(例如阳性细胞毒性交叉配型转变成阴性细胞毒性交叉配型)使得患者能够以降低的移植后抗体介导的排斥风险进行移植。
用抗IL-6抗体例如克拉扎珠单抗进行的治疗可在移植后继续持续数月(例如一个月至36个月)以预防或治疗早期急性或晚期慢性排斥。早期急性排斥事件通常是T细胞介导的，而晚期慢性排斥事件通常是抗体介导的。排斥事件通常通过非特异性迹象(例如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低)和/或新的DSA(新生DSA)的产生来显现，并且可通过已知诊断血液测试和活检(例如器官活检)迹象(例如微血管炎症、间质性纤维化、移植肾小球病变、CD4沉积)确认。抗IL-6抗体可与或不与一种或多种额外免疫抑制剂(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司、抗CD20mAb诸如利妥昔单抗和皮质类固醇)一起施用。
此外，在经受抗体介导的排斥(ABMR)或慢性抗体介导的排斥(CABMR)或处于所述排斥的风险下的移植后患者中，IL-6的血浆水平显著升高，并且当排斥减退时，水平降低。因此，无论患者是否在移植前用抗IL-6抗体治疗，移植后施用抗IL-6抗体都可用于改善或降低ABMR患者中抗体介导的由HLA DSA和非HLA DSA引起的损害。
与以上类似，在ABMR患者中，抗IL-6抗体例如克拉扎珠单抗可与或不与一种或多种额外免疫抑制剂一起施用，并且抗体可在静脉内(例如在0.01-5000mg，更通常在0.1-1000mg或1-500mg的范围内的剂量下，以及在示例性实施方案中在5mg-50mg的剂量下)或通过皮下注射(例如在0.01-5000mg，更通常在0.1-1000mg或1-500mg的范围内的剂量下，以及在示例性实施方案中在10mg-50mg的剂量下)每4周加以施用，在移植之前、在移植时或当排斥迹象显现时开始。同样，最初排斥征象通常包括非特异性迹象诸如血清肌酸酐升高或显现蛋白尿，并且对ABMR的确认可使用已知诊断血液测试和活检实现。用抗IL-6抗体进行的治疗可继续持续数月(例如一个月至数年)以预防抗体介导的对同种异体移植物的损害以及所引起的功能丧失，此可最终导致所移植器官完全失功。
在一些实施方案中，本发明提供了一种适于预防或治疗ABMR或治疗或预防器官移植接受者的敏化的药物组合物。药物组合物包括克拉扎珠单抗和药学上可接受的载体或赋形剂，并且可任选地包括一种或多种其他免疫抑制剂。
用于本发明的方法中的药物组合物可含有任何药学上可接受的赋形剂。赋形剂的实例包括但不限于淀粉、糖、微晶纤维素、稀释剂、粒化剂、润滑剂、粘合剂、崩解剂、湿润剂、乳化剂、着色剂、释放剂、包覆剂、甜味剂、调味剂、芳香剂、防腐剂、抗氧化剂、塑化剂、胶凝剂、增稠剂、硬化剂、凝固剂、混悬剂、表面活性剂、保湿剂、载体、稳定剂、以及它们的组合。
在各种实施方案中，本发明的药物组合物可被配制以通过任何施用途径递送。这可包括例如气雾剂、经鼻、口服、经粘膜、经皮、胃肠外或经肠。
“胃肠外”是指通常与注射相关的施用途径，包括眶内、输注、动脉内、囊内、心内、真皮内、肌肉内、腹膜内、肺内、脊柱内、胸骨内、鞘内、子宫内、静脉内、蛛网膜下、囊下、皮下、经粘膜或经气管。通过胃肠外途径，组合物可呈用于输注或用于注射的溶液或混悬液形式，或呈冻干粉剂形式。通过胃肠外途径，组合物可呈用于输注或用于注射的溶液或混悬液形式。通过经肠途径，药物组合物可呈片剂、凝胶胶囊、糖包衣片剂、糖浆、混悬液、溶液、粉剂、颗粒剂、乳液、允许控制释放的微球体或纳米球体或脂质囊泡或聚合物囊泡形式。通常，组合物通过注射施用。用于这些施用的方法为本领域技术人员所知。
本发明的药物组合物可含有任何药学上可接受的载体。举例来说，载体可为液体或固体填充剂、稀释剂、赋形剂、溶剂、或囊封物质、或它们的组合。
为进一步描述本发明，提供了以下实施例。
实施例1
克拉扎珠单抗作为脱敏方案的一部分用于等待移植以及在同种异体移植物移植
之后的高度敏化受试者
对先前已变得敏化或处于变得对供者器官敏化的风险下(例如由于输血史、妊娠或先前移植)的等待肾移植的患者进行治疗性或防治性治疗以减轻或消除或预防对存在于供者器官中的抗原(例如HLA抗原和非HLA抗原)的敏化。举例来说，患者通过以下中的一者或多者来治疗：血浆除去、血浆交换，任选地与静脉内免疫球蛋白和抗B细胞剂诸如利妥昔单抗或浆细胞抑制剂诸如硼替佐米(蛋白体抑制剂)组合。这些程序根据需要加以重复，并且通常继续直至实行器官移植，并且可在器官移植之后继续。
另外，为使脱敏治疗方案的功效增强，还用抗IL-6抗体例如克拉扎珠单抗对患者进行治疗性或防治性治疗。这个抗IL-6抗体在静脉内在5mg-50mg的范围内的剂量下施用，或在皮下在10mg-50mg的范围内的剂量下施用。每4周或每月实行抗体给药，优选地在移植之前约一个月或数月开始，例如在移植之前约1-6个月开始。
此外，在脱敏前以及在整个这些脱敏程序中在定期间隔下，还通过一种或多种抗体检测方法(例如细胞毒性交叉配型、流式细胞计量交叉配型、Luminex抗体测试)评估患者以评估患者的DSA水平。
如果存在正性响应(例如阳性细胞毒性交叉配型转变成阴性细胞毒性交叉配型)，那么患者被确定适于器官移植，并且接着通过已知程序来用供者肾对患者进行移植。
并行地或在移植后，持续数月用克拉扎珠单抗治疗患者(例如在移植时开始，或在之后约一个月开始，并且继续持续移植之后数月或数年，例如移植之后6、12、18、24、30、36个月或甚至5、10、20年)以预防或治疗早期急性或晚期慢性排斥。早期急性排斥事件通常是T细胞介导的，而晚期慢性排斥事件通常是抗体介导的。
如果存在于移植接受者中，那么排斥事件可通过一种或多种临床征象(例如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低)、新的DSA(新生DSA)的产生来显现，所述排斥事件可通过活检迹象(例如微血管炎症、间质性纤维化、移植肾小球病变、CD4沉积)确认。
另外，患者还可通过使用其他护理标准免疫抑制方案(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司和皮质类固醇)来治疗。这些额外免疫抑制方案在移植前和移植后实行，例如在移植前约1-6个月实行，并且在移植后继续持续数月或甚至数年。在移植后定期评估患者的排斥反应的任何临床征象，诸如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低。如果观察到任何所述临床响应，那么可用免疫抑制剂更积极地治疗患者，例如可使免疫抑制剂剂量增加，或用免疫抑制剂更频繁地治疗患者，和/或可用其他免疫抑制剂治疗患者以使排斥反应稳定或消除。
实施例2：在等待肾移植的高度HLA敏化患者中使用克拉扎珠单抗
已遭受先前同种异体移植物衰竭的患者代表移植中心的主要问题，因为他们是高度人白细胞抗原(HLA)敏化的，并且不可能在不进行显著脱敏的情况下接受另一移植。根据本发明，合格的移植患者将通常在移植前每月一次接受多达6次25mg剂量的克拉扎珠单抗。如果患者在治疗期间接受HLAi移植，那么参与者可继续接受另外6次每月一次25mg剂量的克拉扎珠单抗，继之以6个月方案活检。如果在第6次剂量的克拉扎珠单抗之后观察到改进，那么患者将历经6个月接受另外6次剂量。显现持续同种异体移植物功能异常的迹象的患者可进行有因性非方案活检。在移植后接受12次剂量的克拉扎珠单抗的患者通常将接受12个月方案活检。
被考虑进行进一步治疗的患者可初始接受PLEX(5-7次)+IVIG，接着在IVIG后一周皮下接受25mg克拉扎珠单抗。如果在初始剂量之后未观察到安全性/可耐受性/功效问题，那么患者可接受5次额外注射(Q4W)。如果患者接受HLAi移植，那么在移植后持续6个月在25mg下继续皮下使用克拉扎珠单抗，共计6次剂量(Q4W)(在移植后第5天开始)。方案活检可在移植后6个月进行以使用Banff 2015准则评估同种异体移植物的ABMR或CAMBR的迹象，包括C4d染色和TG。如果在第6次剂量的克拉扎珠单抗之后观察到改进，那么患者将继续历经6个月接受另外6次剂量。显现持续同种异体移植物功能异常的迹象的患者可进行有因性非方案活检。在移植后接受12次剂量的克拉扎珠单抗的患者可接受12个月方案活检。在患者在接受6次剂量的克拉扎珠单抗之后不显示改进的情况下，通常将不再给与治疗。
通常将追踪所治疗受试者以确定在这个高风险移植群体中使用克拉扎珠单抗进行脱敏是否安全，并且不造成感染性风险。此外，将评估克拉扎珠单抗治疗对HLA抗体的影响。肾活检评估可在6个月时进行以及在12个月时(例如对于接受12次剂量的疗法的那些受试者)再次进行。将接着评估经移植患者以同时确定维持有活力和功能性肾同种异体移植物的数目。
通常，患者每月接受克拉扎珠单抗。患者将通常在移植前接受多达6次剂量。如果在IL-6抗体治疗期间对患者进行移植，那么他们可接着接受6次剂量的克拉扎珠单抗(每月)，并且可进行6个月方案活检。基于活检结果和临床实验室结果，确定PI以评估患者是否应继续每月剂量持续多达另外6次剂量。接受12次移植后剂量的克拉扎珠单抗的患者可接着经受12个月方案活检。
实施例3：使用克拉扎珠单抗治疗具有晚期AMBR的患者
在具有晚期抗体介导的排斥(ABMR)的患者中评估人源化抗IL-6单克隆抗体克拉扎珠单抗在肾移植接受者中的安全性、可耐受性、药物代谢动力学、药物效应动力学和功效(初步评估)。研究被设计为2期试验，并且具有两个后续子部分，即12周的随机化安慰剂对照试验(A部分)，其中接受者被分配来接受抗IL-6抗体克拉扎珠单抗(n＝10)或安慰剂(n＝10)，继之以开放标签前瞻性研究，其中所有20名研究患者都持续40周的时期接受克拉扎珠单抗。在A部分和B部分结束时进行研究方案活检。
A部分：
在两个中心地点的肾移植门诊服务处鉴定和招募了关于抗HLA供者特异性抗体(DSA)呈阳性，并且具有活检证明的晚期ABMR(根据Banff 2015分类的急性/活动性或慢性/活动性表型)的患者。将参与者随机化以持续12周的时期在皮下接受克拉扎珠单抗或安慰剂(关于ABMR类型加以分层的1∶1随机化)(在第0天，以及在4和8周之后施用克拉扎珠单抗/安慰剂)。在12周之后，患者通常将经受首次随访活检。试验的这个部分的主要目标在于评估短治疗过程的安全性、可耐受性、药物代谢动力学和药物效应动力学。此外，A部分提供对克拉扎珠单抗对在外周血液中以及在排斥器官同种异体移植物中检测到的ABMR相关炎症、对作为探针药物来研究IL-6阻断对细胞色素P450(CYP)依赖性药物代谢的影响(对CYP代谢的药物诸如泮托拉唑(pantoprazole)的半衰期的潜在影响)的泮托拉唑的药物代谢动力学、以及对DSA平均荧光强度(MFI)和肾同种异体移植物功能(eGFR、尿蛋白排泄)的短期过程的影响的第一初步评估。
B部分：
在12周之后完成A部分之后，研究患者可进入B部分，即研究的开放标签部分。受试者将通常以4周一次间隔接受皮下克拉扎珠单抗直至在52周之后的研究结束(EOS)访视，并且接着经受第二方案活检。B部分的主要目标在于评估用克拉扎珠单抗进行延长时期的治疗的安全性和可耐受性，以及历经12个月的时期这个抗体对ABMR的进展、排斥相关生物标志物以及肾同种异体移植物功能和存活的长期影响。
实施例4：克拉扎珠单抗用作具有移植后抗体介导的排斥(ABMR)的患者的治疗剂。
鉴定了已接受实体器官移植(例如肾、心脏、肝、肺、胰腺、皮肤、胆囊、胃、肠或前述各物的组合)，显示显现抗体介导的排斥(ABMR)的征象，或展现ABMR的患者。如本文所提及，这些患者不可用当前护理标准免疫抑制性药物治疗，此是不幸的，因为这是移植后同种异体移植物衰竭的最大单一原因。
特别地，在移植之后，通过允许对ABMR进行预测和早期诊断的诊断测试来监测患者。举例来说，患者可通过使用一种或多种检测预先形成和新生HLA DSA的测试(尤其是检测补体结合DSA的那些测试诸如C1q测试)和/或使用检测与ABMR相关的非HLA抗体的存在性的测定来评估。
此外，可检查所移植器官的ABMR介导的损害的组织学征象，所述组织学征象可通过使用肾同种异体移植物活检以及筛查活检样品的为ABMR介导的器官损害所特有的病理性症状来检测，所述病理性症状诸如微血管炎症、补体沉积(C4d)在肾小管周毛细血管中、肾小管周毛细血管炎、肾小球炎和移植肾小球病变(双重肾小球基底膜轮廓)。
所鉴定患者，即显示显现抗体介导的排斥(ABMR)或慢性抗体介导的排斥(CABMR)的临床或组织学征象或展现ABMR或CAMBR的个体，接着用克拉扎珠单抗进行防治性或治疗性治疗以预防、稳定或逆转ABMR的发生。这个治疗，即施用抗IL-6抗体，应会改善或降低由这些HLA DSA和非HLA DSA引起的ABM损害。
患者还可用护理标准移植后免疫抑制性药物(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司或抗CD20 mAb诸如利妥昔单抗和皮质类固醇)和克拉扎珠单抗的组合治疗，所述克拉扎珠单抗通常每4周以静脉内注射(在5mg-50mg的剂量下)形式或以皮下注射(在10mg-50mg的剂量下)形式给与，在移植时或当排斥迹象显现时开始。最初排斥征象通常包括非特异性迹象诸如血清肌酸酐升高或显现蛋白尿。对ABMR或CAMBR的确认通过如上所述的特定诊断血液测试和器官活检来实现。
用克拉扎珠单抗进行的治疗可继续持续数月(例如一个月至数年)以预防抗体介导的对同种异体移植物的损害以及所引起的功能丧失，此可最终导致所移植器官完全失功。
为进一步建立概念验证，进行实验以评估克拉扎珠单抗对包含同种异体细胞的共培养物、对特定免疫细胞的增殖、以及对排斥反应中涉及的细胞因子的表达的影响。
特别地，进行实验以评估克拉扎珠单抗对HLA-DR、CD54、IL-6和PDL-1的转录的影响。这些实验描述于以下实施例中。
实施例5：拮抗抗IL-6抗体(克拉扎珠单抗)对EC增殖的影响
已观察到在共培养物中存在内皮细胞会诱导由PBMC对IL-6R的分泌增加(参见图8)。相比之下，抗HLA-DR抗体与内皮细胞的结合不改变由PBMC对IL-6R的分泌。
基于此，推理出在与PBMC的共培养中，由EC达成的IL-6分泌可依赖于反式信号传导和自分泌EC应答。基于前述事项，进行实验以研究不同剂量的拮抗抗IL-6抗体(克拉扎珠单抗)对内皮细胞的增殖的影响。如图9中所示意性描绘，确定拮抗抗IL-6抗体(克拉扎珠单抗)对EC增殖和表型的影响。
特别地，使内皮细胞培养物与1μg/ml、20μg/ml和50μg/ml剂量的克拉扎珠单抗接触，以及不与克拉扎珠单抗接触。如图10中所示，不管IL-6拮抗抗体剂量如何，对内皮细胞增殖都不存在影响。
实施例7：克拉扎珠单抗对同种异体性的介体的影响
进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对牵涉于同种异体免疫应答中的基因的转录的影响。如图11中所示的实验所证实，已知涉及于同种异体免疫应答中的特定基因的转录未由克拉扎珠单抗改变。
特别地，在这些实验中，在用不同剂量的克拉扎珠单抗与或不与IFNγ一起处理3天之后，使用基于荧光的实时PCR来测定HLA-DR、CD54、IL-6、PDL-1和甘油醛-3-磷酸脱氢酶(GADPH)mRNA的水平，并且使用TRI试剂(Ambion，Applied Biosystems，Thermo FischerScientific)方案从内皮细胞(EC)分离总RNA。
使用分光光度计(ND-1000；Nanodrop)对RNA定量，并且使用用于RT-PCR的SuperScript III第一链合成系统(Invitrogen Life Technologies)，通过逆转录(RT)来转变成cDNA(1μg RNA/反应)。用ViiA 7实时PCR系统(Applied Biosystems，ThermoFischer Scientific)和TaqMan基因表达测定(Applied Biosystems，Thermo FischerScientific)进行实时PCR。
用于这个研究的引物和探针组是：IL-6(Hs00174131_m1)、CD54(Hs00164932_m1)、HLA-DR(Hs00219575_m1)、PDL1(Hs01125301_m1)和GAPDH(Hs027558991_g1)。
将阈值循环(Ct)确定为重复测定的平均值。将mRNA的相对丰度的差异计算为ΔCt(靶标基因-GAPDH‘持家’基因)，表示为对照条件(内皮细胞与IFNy一起孵育)的百分比。平均值±SEM值显示于图11中。
实施例8：克拉扎珠单抗对EC表型的影响
进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对EC表型的影响。如由图12中所示的实验所证实，在处理7天之后，EC表型不受抗IL-6抗体影响。
在这些实验中，使内皮细胞与20ng/ml的干扰素γ(IFN-γ)(Eurobio)一起在组织培养烧瓶中培养，并且如图12中所示与不同剂量的克拉扎珠单抗一起孵育3天。
对于内皮细胞的表型分析，使用以下抗体：HLA-DR APC(克隆L243，Biolegend)、CD54 PacBlue(克隆HCD54，Biolegend)、CD274PC7(克隆MIH1，BD Pharmingen)。
用0.05％胰蛋白酶EDTA(Gibco)对EC进行胰蛋白酶处理，随后用1ml具有0.5％牛血清白蛋白(BSA)的冷磷酸盐缓冲盐水(PBS)洗涤，并且在4℃下离心。添加单克隆抗体，并且在冰上孵育30分钟。然后，使用相同洗涤条件再次洗涤细胞，并且将细胞再混悬于0.5％BSA PBS中，随后在FACS Canto II(BD Biosciences)上分析。
如图12中所示，这些实验的结果表示为表达相关抗原的细胞的百分比，其中显示了平均值±SEM值。可见在处理7天之后，EC表型不受抗IL-6抗体影响。
实施例9：克拉扎珠单抗对ELISA检测IL-6的影响
还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对在ELISA测定中检测到的IL-6的量的影响。特别地，评估了当用来自Biolegend，根据制造商方案加以使用的酶联免疫吸附测定(ELISA)检测试剂盒对IL6定量时，克拉扎珠单抗是否干扰对IL-6的检测。
在这些实验中，测定向其中添加或不添加克拉扎珠单抗(20μg/ml)的具有已知浓度的IL-6的上清液中的IL6。包括了对照条件，其中不添加二级抗体，或不用检测抗体包被ELISA板。图13中的示意图代表不同测试条件。结果表示为吸光度单位。
基于图13中的结果，克拉扎珠单抗似乎不干扰使用酶联免疫吸附测定(ELISA)对IL-6的检测。
实施例10：克拉扎珠单抗对IL-6分泌的影响
如图14中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对由内皮细胞对IL-6的分泌的影响。在这些实验中，使内皮细胞与或不与20ng/ml的干扰素γ(IFN-γ)(Eurobio)一起在组织培养烧瓶中培养，并且如图14中所示与不同剂量的克拉扎珠单抗一起孵育。
在3天之后，使用来自Biolegend，根据制造商方案加以使用的酶联免疫吸附测定检测试剂盒对EC的上清液中的IL-6定量。如图14中所示的结果表示为分泌的IL-6的数量。在图中，显示了平均值±SEM值(*p＜0.05以及**p＜0.01，配对t检验)。
对在不同剂量浓度下的IL-6拮抗抗体(克拉扎珠单抗)检测的影响显示于图14中。
实施例11：克拉扎珠单抗对EC-PBMC共培养中CCL-2产生的影响
如图15中示意性所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对在EC共培养中观察到的同种异体性的影响。特别地，如图16中所示，进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对EC-PBMC共培养中CCL-2产生的影响。在这些实验中，通过IFNγ(20ng/ml(Eurobio))使EC活化3天，接着过夜进行IFNγ饥饿，随后与非HLA匹配PBMC一起共培养。洗涤EC，并且在20Gy下照射。
如图16中所示，照射步骤不阻止由EC在之后3天内进行细胞因子分泌。经羧基荧光素丁二酰亚胺基酯(CFSE)标记PBMC(2.5μM；Molecular Probes/Invitrogen)用经照射EC(1：1)在RPMI-10％人AB血清(EFS)中刺激7天。
在T0时，如图16中所示，将不同浓度的克拉扎珠单抗添加至EC/PBMC共培养物中。在72小时之后收集共培养物的上清液，并且通过来自Biolegend，再次根据制造商方案加以运用的酶联免疫吸附测定检测试剂盒来测定以检测IL-6、CCL2和RANTES的量。这些实验的显示于图16中的结果表示为分泌的细胞因子的数量。显示了平均值±SEM值(*p＜0.05，配对t检验)。结果指示IL-6拮抗抗体(克拉扎珠单抗)使EC-PBMC共培养中的CCL-2产生降低。
实施例12：IL-6拮抗抗体(克拉扎珠单抗)对由EC达成的T-CD4+活化的影响
如图17中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对由EC达成的T-CD4+活化的影响。在这些实验中，如先前所述获得EC/PBMC共培养物。在共培养七天之后，经羧基荧光素丁二酰亚胺基酯(CFSE)标记PBMC用于研究鉴定为(CD4+CD45RA-CD25高CD127低FoxP3明亮)的Treg子群体以及鉴定为(CD4+CD45RA-FoxP3低)的Tmem子群体的增殖。
对于流式细胞计量术，使用以下抗体：CD4 PB(克隆RPA-T4)、CD45RA PE/Cy7(克隆H100)、CD25 PE(克隆M-A251)、CD127 PerCP/Cy5.5(克隆A019D5)(Biolegend)。用抗人Foxp3染色套件APC(克隆236A/E7)(eBioscience)进行FoxP3的细胞内染色。在FACS CantoII(BD Biosciences)上进行流式细胞计量术。
结果表示为每个T细胞子组的百分比以及这些群体中增殖细胞的百分比。显示了中值(红线)。
实施例13：IL-6拮抗抗体(克拉扎珠单抗)对Th17和Th1细胞的内皮扩增的影响
如图18中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对Th17和Th1细胞的内皮扩增的影响。在这些实验中，如先前所述获得EC/PBMC共培养物。在共培养七天之后，在GolgiStop 1×(BD Biosciences)存在下用50ng/mL佛波醇12肉豆蔻酸酯13乙酸酯(PMA)和1μM离子霉素(Cell Signaling Technology)刺激PBMC 4小时，并且通过流式细胞计量术分析Th17(CD3+CD8-IL17+)和Th1(CD3+CD8-IFNγ+)子群体以检测细胞内细胞因子。
对于流式细胞计量术，使用以下抗体：IFN-γFITC(克隆B27)(BD Pharmingen；BDBiosciences)、CD4 PE(克隆RPA-T4)、CD3 PerCP(克隆SK7)、CD8 PB(克隆RPA-T8)(Biolegend)和IL-17efluor660(eBioscience)。在FACS Canto II(BD Biosciences)上进行流式细胞计量术。图18中的结果表示为每个T细胞子组的百分比。显示了中值(红线)(*p＜0.05，配对t检验)。
基于图18中的结果，可见在IL-6拮抗抗体存在下，IFNγ产生性细胞(Th1)扩增存在显著降低。
实施例14：IL-6拮抗抗体(克拉扎珠单抗)对同种异体CD4+T细胞的Th1应答的影响
如图19中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对同种异体CD4+T细胞的Th1应答的影响。这个图代表不同供者中Th1细胞的分布，并且将对照条件和如7天共培养中指示的使用不同剂量的克拉扎珠单抗的条件进行比较。如先前所述进行对Th1群体的分析。这些结果显示克拉扎珠单抗一致地使由同种异体CD4+T细胞引发的Th1应答降低。
实施例15：低剂量的IL-6拮抗抗体(克拉扎珠单抗)对Th1细胞的扩增的影响
如图20中所示，还进行实验以评估在‘低剂量’克拉扎珠单抗存在下，IL-6拮抗抗体(克拉扎珠单抗)对Th1细胞的扩增的影响。图20中的结果代表不同供者中Th1细胞的分布，并且将对照条件与如7天共培养中指示的涉及添加不同剂量的克拉扎珠单抗的条件进行比较。如先前所述进行对Th1群体的分析。
结果指示即使在低克拉扎珠单抗抗体剂量下，Th1细胞的分布也降低。
实施例16：IL-6拮抗抗体(克拉扎珠单抗)对由EC对补体调控蛋白的表达的影响
如图21中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对由EC对补体调控蛋白的表达的影响。在这些实验中，使内皮细胞与20ng/ml的干扰素γ(IFN-γ)(Eurobio)一起在组织培养烧瓶中培养，并且当指示时与不同剂量的克拉扎珠单抗(0.5；5；20；50μg/ml，持续3天)一起孵育。
使用以下抗体进行对内皮细胞的表型分析：CD55 FITC(克隆JS11)、CD46 PC7(克隆TRA-2-10)和CD59 PE(p282(H19))(Biolegend)。
用凡尔生(Versene)1X(Gibco)使EC脱离，并且于1ml具有0.5％牛血清白蛋白(BSA)的冷磷酸盐缓冲盐水(PBS)中洗涤，随后在4℃下离心。添加mAb，并且在冰上孵育30分钟。接着如先前所述再次洗涤细胞，并且再混悬于0.5％BSA PBS中。
图21显示在克拉扎珠单抗的所有测试浓度下，每种抗原的表达直方图的叠加。同种型对照由点线代表，并且无克拉扎珠单抗的对照以灰色表示。
实施例17：IL-6拮抗抗体(克拉扎珠单抗)对补体活化的影响
如图22中所示，还进行实验以评估IL-6拮抗抗体(克拉扎珠单抗)对补体活化的影响。在这些实验中，使内皮细胞与20ng/ml的干扰素γ(IFN-γ)(Eurobio)一起在组织培养烧瓶中培养3天。接着用0.05％胰蛋白酶EDTA(Gibco)使EC脱离，并且将来自3天培养物的上清液储存并对再接种的细胞再次使用。在18小时之后，将或不将10μg/ml克拉扎珠单抗添加至培养物中，在37℃下再持续45分钟。
在以上操作之后，添加人AB血清以制备最终10％的人AB血清，并且添加兔血清以制备最终5％的兔血清，并且添加5μg/ml针对HLA-DR或VE-钙粘着蛋白(cadherin)的mAb。使抗体在37℃下留置4小时以允许补体级联的活化。
为研究补体活化，通过流式细胞计量术来定量C5b9在EC上的固定。使用以下抗体：SC5b9生物素化抗体(Quidel，San Diego)和链霉亲和素A647(Invitrogen)。
用凡尔生1X(Gibco)使EC脱离，并且用1ml具有0.5％牛血清白蛋白(BSA)的冷磷酸盐缓冲盐水(PBS)洗涤，并且在4℃下离心。
添加C5b9生物素化mAb，并且在冰上孵育30分钟。接着如先前所述再次洗涤细胞，并且用链霉亲和素A647在4℃下染色15分钟。最后，用0.5％BSA PBS将EC洗涤两次，随后进行流式细胞计量术分析。
图23中的结果表示为关于C5b9的固定呈阳性的细胞的百分比。这些结果显示IL-6拮抗抗体(克拉扎珠单抗)使补体活化显著降低，并且应充分适合于治疗AMBR或CAMBR以及其中补体活性涉及于疾病病理学中的其他适应症。此外，在EC-PBMC共培养中获得的实验结果证明单独克拉扎珠单抗导致Treg降低，并且还使Th1促炎性淋巴细胞的扩增降低。
实施例18：克拉扎珠单抗作用于内皮细胞以限制抗体介导的损害
在炎症性条件下，在体外以及在体内，II类HLA抗原的人微血管内皮细胞表达均强烈增加。II类HLA抗体与内皮细胞的结合使IL-6分泌增强，并且由此使内皮细胞活化和分化促炎性Th17 CD4+淋巴细胞的能力增加，所述活化和分化由IL-6依赖性Stat-3活化介导(Taflin PNAS 2011，Lion AmJTrans.2016)。研究白介素-6特异性抗体克拉扎珠单抗以确定它作用于HLA II表达性内皮细胞的能力。
方法：
在与来自非相关个体的PBMC共培养之前以及期间，使内皮细胞与克拉扎珠单抗一起预孵育。另外，HLA-特异性抗体与内皮细胞的结合导致补体活化，并且导致C5b-C9沉积。这在克拉扎珠单抗存在下加以测试。CD4+T细胞子群体通过细胞内细胞因子染色来鉴定，并且C5b-C9通过多色流式细胞计量术来检测。
结果：
这个研究报告了内皮细胞与克拉扎珠单抗一起预孵育使由人内皮细胞达成的IL-6分泌降低。克拉扎珠单抗还使内皮细胞与同种异体PBMC的共培养中趋化性CCL2的水平降低。此外，促炎性Th17和Th1群体的由内皮细胞介导的扩增得以降低。C5b-C9的沉积在HLA抗体与内皮细胞的结合之后加以确定，并且当克拉扎珠单抗存在时，得以显著降低。
结论：
总之，这些数据支持克拉扎珠单抗直接作用于内皮细胞的理念。CCL2产生降低、促炎性CD4+T分化降低以及C5b-C9复合物的形成降低的组合结果应在与HLA特异性同种异体抗体相关的慢性体液排斥的情形下产生对同种异体移植物内皮的总体保护作用。
因此，这些结果显示测试的抗IL-6拮抗抗体(克拉扎珠单抗)使补体活化显著降低，并且应充分适合于治疗AMBR或CAMBR以及其中补体活性涉及于疾病病理学中的其他适应症。所述疾患包括年龄相关以及退变性疾病诸如年龄相关的黄斑变性(AMD)(湿性和干性)、阿尔茨海默氏病、肾小球疾病例如非典型溶血性尿毒综合征(aHUS)、由志贺(Shiga)毒素产生性大肠杆菌引起的溶血性尿毒综合征(STEC-HUS)、血栓性血小板减少性紫癜(TTP)、全身性红斑狼疮(SLE)、抗磷脂抗体综合征(APS)、抗嗜中性白细胞细胞质抗体(ANCA)诱发的血管炎、由针对嗜中性白细胞组分的自体抗体引起的炎症性小血管病症；涉及C5a介导的对胎盘血管生成的损害的抗体依赖性(即在具有APS的妇女中)妊娠丢失；补体介导的溶血病症诸如阵发性夜间血红蛋白尿(PNH)、aHUS和冷凝集素病(CAD)、缺血-再灌注损伤；中风、例如由创伤、败血症、休克和心肺分流(CPB)手术引起的心肌梗塞等。此外，可根据本发明治疗的补体介导的疾患包括移植相关并发症，尤其是当在供者循环骤停之后移植器官时，此可导致诱发IRI。在抗体介导的排斥(ABMR)中，同种异体抗体的产生(通过B细胞共刺激)与影响(通过CP/LP活化)两者均是补体驱动事件。在糖尿病患者中进行朗格汉斯胰岛(Langerhans islet)移植的情况下，被称为‘即时血液介导的炎症性反应’的血栓炎症性应答的发生由快速补体活化引起，并且由于胰岛破坏而限制移植效率。在移植的情形下，一个特别引起关注，但仍然不完全了解的现象是适应，其中移植细胞变得对补体介导的破坏‘具有抗性’。所述不相容性应答可影响CPB心肺分流手术的结果，在所述手术期间，循环物质、氧合器中的血液/空气界面、活化的血小板和鱼精蛋白复合物(被产生来在程序结束时中和可溶性肝素)可使补体活化，并且促进全身性炎症性应答综合征。
伴有补体影响的其他炎症性疾病包括过敏性哮喘和牙周炎。补体与哮喘之间的连系长久以来已得到认识，但牵连似乎是复杂的。在哮喘状况下，补体不仅经由通过过敏原-抗体复合物达成的CP来活化，而且C3和C5还可由源于某些过敏原(例如屋尘螨)的蛋白酶裂解。所得C3a和C5a以协同方式在创建促过敏性免疫环境方面起作用，然而，C5a还可起保护作用以在过敏原敏化期间免遭适应不良性Th2免疫性。还已将在哮喘中的一个重要又复杂的作用归因于C5L2。尽管先前治疗尝试集中于C5aR，但近来已将范围扩展以包括在C5和C3的水平上的抑制剂。相关地，C5a还已牵涉于慢性阻塞性肺病的恶化中。最后，已认定补体介导的过程对于骨相关病症和损伤至关重要(例如通过过敏毒素对破骨细胞形成的影响)，由此表明补体治疗剂的另一潜在适效领域。
也许，补体活化的最重度影响见于经常伴有SIRS的急性期疾患中，其中宿主面临损害相关分子样式和/或病原体相关分子样式的显著增加。在创伤中，举例来说，初始创伤性影响与创伤后IRI组合可触发伴有补体影响的毁灭性免疫炎症性反应级联，所述级联可维持SIRS。作为创伤的并发症，或作为独立事件，大规模感染可压倒补体和其他先天免疫性组分(例如TLR)的保护性功能，并且激起败血症，免疫细胞活化、细胞因子风暴和凝血病变可导致SIRS，并且甚至在病原体被清除之后持续存在；C5a依赖性信号传导似乎是那些毁灭性事件中的主要参与者。
这些实验结果进一步确证克拉扎珠单抗可用于持续延长持续时间来治疗或预防有需要的受试者中AMBR或CAMBR，所述受试者即为将接受、已接受或正接受所移植同种异体或异种异体细胞、组织或一种或多种器官的患者，所述细胞、组织或器官例如是用于基因或细胞疗法中的同种异体或异种异体细胞诸如免疫细胞、纤维母细胞、皮肤细胞、神经细胞、成体干细胞，或实体器官诸如肾、膀胱、肺、心脏、肝、皮肤、胰腺、胃、肠或前述各物的任何组合。
实施例19：用于治疗AMBR或CAMBR的克拉扎珠单抗临床方案
一般来说，在本AMBR或CAMBR临床方案中加以治疗的受试者将包含以下纳入准则：
1.年龄18-75岁；
2.从移植的时间开始，活体供者/死亡供者肾移植接受者≥6个月；
3.对CABMR进行诊断(根据Banff2015诊断准则)以包括以下中的全部：
i.活检证明的CABMR(即慢性肾小球病变(cg)＞0)，伴有/不伴有C4d染色
ii.在移植后存在HLA DSA(使用基于珠粒的单抗原测定)。
在主题临床方案中从治疗排除的患者包括满足以下排除准则中的全部的那些：
1.多器官移植接受者。
2.在筛选的3个月内针对ABMR(包括CABMR)或TCMR进行治疗。
3.在筛选的3个月内接受T细胞消减剂(例如阿来珠单抗、抗胸腺细胞球蛋白)。
4.活检显示单纯性TCMR或晚期间质性纤维化(ci3)、晚期肾小管萎缩(ct3)、血管纤维内膜增厚(cv3)或肾功能异常的其他重大原因(例如BKV肾病变、肾小球性肾炎)。
5.归因于所移植同种异体移植物中的病症(例如肾动脉狭窄、肾盂积水)的肾功能受损。
6.eGFR＜25mL/min/1.73m2或＞65mL/min/1.73m2。
7.规定为随机尿蛋白肌酸酐比率(UPCR)≥3,000mg/g(≥300mg/mmol)或随机尿白蛋白肌酸酐比率(UACR)≥2,200mg/g(≥220mg/mmol)的肾病范围蛋白尿。如果随机UPCR或UACR高于规定限度，那么在另一天重复测试(或收集24小时尿以确认肾病范围蛋白尿(≥3.0g/天))。
8.妊娠、哺乳、或不愿意在研究期间以及在末次剂量的克拉扎珠单抗之后持续5个月实施高度有效节育。
9.过敏症史。
10.LFT异常(丙氨酸转氨酶(ALT)/天冬氨酸转氨酶(AST)/胆红素＞1.5倍正常值上限)或其他重大肝病。
11.活动性结核(TB)史。
12.在不具有活动性TB史的情况下的潜伏性TB史(例如Quantiferon TB测试呈阳性)，除非受试者已完成防治性治疗的全过程。
13.人免疫缺陷病毒(HIV)感染史或关于HIV呈阳性。
14.关于乙型肝炎表面抗原(HBsAg)呈血清阳性。
15.丙型肝炎病毒(HCV)RNA阳性。
16.已知EBV不匹配：供者血清阳性，接受者血清阴性。
17.GI穿孔、憩室病或憩室炎、或炎症性肠病史。
18.嗜中性白细胞减少症(＜1,000/mm3)或血小板减少症(＜50,000/mm3)。
19.需要全身性抗微生物剂并且在筛选之前未消退的活动性感染。
20.历史或当前侵袭性真菌性感染或其他机会性感染，所述感染包括(但不限于)以下：非结核性分枝杆菌感染、曲霉病、肺囊虫病和弓形虫病。
21.基于聚合酶链式反应(PCR)测试，活动性病毒性感染诸如BKV、CMV或EBV。
22.当前或新近(在3个月内)参与克拉扎珠单抗试验。
23.在筛选的6周内施用活疫苗，包括但不限于以下：
i)腺病毒疫苗
ii)麻疹疫苗、腮腺炎疫苗和风疹疫苗
iii)口服脊髓灰质炎疫苗
iv)口服伤寒疫苗
v)轮状病毒疫苗
vi)水痘带状疱疹疫苗
vii)黄热病疫苗
24.酒精或非法物质(包括大麻)滥用史。
25.目前或先前(在3年内)恶性肿瘤，除基底细胞癌、完全切除的皮肤鳞状细胞癌、或非复发性(在5年内)原位宫颈癌之外。
26.存在在研究者看来将损害患者的安全性或预期寿命或数据的品质的状况或异常(即不受标准治疗控制的在临床上重大的内分泌、自体免疫、代谢、神经、精神病/心理、肾、GI、肝和血液或任何其他系统异常)。
27.甲氧苄啶和/或磺胺甲噁唑不耐受史。如果受试者已采用用于耶氏肺囊虫肺炎(PJP)防治的吸入型喷他脒或口服达普松，或如果受试者在第1天基线访视(访视2)之前至少1周正要开始采用这些药物中的任一者，那么这个准则不适用。
28.先前暴露于克拉扎珠单抗。
在出现选自以下的不可接受的不利事件(AE)后，受试者可被永久地停止抗IL-6抗体施用：
1.AST或ALT＞5.0倍正常值上限(ULN)
2.总胆红素＞3.0倍ULN
3.AST或ALT＞3.0至5.0倍ULN，以及总胆红素≥2.0倍ULN(或国际标准化比值(INR)＞1.5)
受试者可由于嗜中性白细胞减少症和/或血小板减少症而被永久地停止抗IL-6抗体施用。特别地，在治疗期间满足以下条件中的任一者的受试者可终止抗IL-6抗体施用治疗：
1.嗜中性白细胞计数＜1,000个细胞/mm3
2.血小板＜50,000/mm3
受试者可由于BKV、CMV或EBV病毒性感染而被永久地停止抗IL-6抗体施用。举例来说，在治疗期间的任何时间满足以下条件中的任一者的受试者可终止克拉扎珠单抗治疗：
1.BKV≥10,000个拷贝/mL(根据PCR)或活检证明的BKV肾病变
2.CMV终末器官疾病(例如肝炎、结肠炎、肺炎、视网膜炎)
3.EBV≥10,000个拷贝/mL(根据PCR)或移植后淋巴组织增生性病症或血清阴性接受者中原发性EBV感染
克拉扎珠单抗治疗方案
克拉扎珠单抗通常以25mg/mL和12.5mg/mL剂量制剂形式提供。赋形剂包括L-组氨酸、单盐酸L-组氨酸、山梨糖醇、聚山梨醇酯-80和注射用水。剂型包括适于注射的单次剂量小瓶剂(25mg/mL和12.5mg/mL)。
抗体在-20±5℃(-4±9°F)或更低温度下避光储存。
相伴甲氧苄啶/磺胺甲噁唑防治性疗法
在研究中心开具呈每日单强度丸剂(80mg，以甲氧苄啶计)或每周3次双强度丸剂(160mg，以甲氧苄啶计)形式的口服甲氧苄啶/磺胺甲噁唑用于PJP防治。甲氧苄啶/磺胺甲噁唑通常在第1天基线访视(访视2)之前至少1周开始(对于在进入研究中之前未已在采用甲氧苄啶/磺胺甲噁唑以及未已在接受吸入型喷他脒或口服达普松的受试者)。
相伴吸入型喷他脒和口服达普松防治性疗法
在筛选时已在接受用于PJP防治的吸入型喷他脒或口服达普松的受试者通常将保持采用这些药物，并且不开始采用甲氧苄啶/磺胺甲噁唑。对甲氧苄啶/磺胺甲噁唑不耐受以及未已在接受吸入型喷他脒或口服达普松的受试者通常将在第1天基线访视(访视2)之前至少1周开始采用这些药物中的任一者。
克拉扎珠单抗的剂量和施用
克拉扎珠单抗每4周(Q4W)通过皮下注射在25mg的靶标剂量下施用，或通过皮下注射在12.5mg的降低剂量下(Q4W)施用以支持由方案规定的安全性参数指导的潜在剂量降低。每个25mg/12.5mg剂量都以1mL克拉扎珠单抗注射液(25mg/mL/12.5mg/mL)形式施用。
克拉扎珠单抗通常被制备以及分配在相同经装填彩色注射器中。每个彩色注射器通常含有具有包括方案编号、受试者标识符、访视编号和分配日期的详情的标签。药剂师通常将在清点日志上记录分配给每个受试者的药盒/小瓶编号，包括分配日期和时间。准备好的注射器可在2℃至8℃(36°F至46°F)冰箱中储存多达24小时，并且24小时中多达4小时可在室温即15℃至25℃(59°F至77°F)下。准备好的注射器应避光。在施用之前，准备好的注射器必须通过在使用之前30至60分钟从冷藏移出来达到室温。
为确保患者安全性，通常在给药之前复审来自先前访视(预定的或另外的)的最新近LFT和CBC分析和病毒监测结果。通常在用克拉扎珠单抗给药之前完成给定访视的所有根据方案的评估。
包装
克拉扎珠单抗通常以单次剂量小瓶剂形式提供。小瓶是2mL燧石玻璃，含有最少1.1mL(25mg/mL或12.5mg/mL)克拉扎珠单抗以递送1mL(25mg或12.5mg)。
储存
克拉扎珠单抗优选地在-20±5℃或更低温度下避光储存。
克拉扎珠单抗剂量修改
在克拉扎珠单抗治疗期间，通常监测受试者的异常LFT、嗜中性白细胞和血小板计数、以及BKV、CMV和EBV病毒性感染。基于这些评估的结果，克拉扎珠单抗的剂量可降低至12.5mg SC Q4W，暂时地停用，或永久地停止。
一般来说，对于异常LFT所述的克拉扎珠单抗终止或药量降低根据治疗临床医师对任何实验室异常的判断来实行，所述判断取决于通用不利事件毒性准测(CTCAE)严重性(CTCAE等级1(轻度)、等级2(中度)、等级3(重度或医学上重大))和采取的修正行动。在嗜中性白细胞减少症或血小板减少症的情况下，可实行关于修改霉酚酸吗啉乙酯(MMF)/霉酚酸(MPA)/咪唑硫嘌呤(AZA)的指导方针。
此外，克拉扎珠单抗终止或剂量降低可由于任何其他临床重大感染而实行。一旦感染已得以治疗和消退，克拉扎珠单抗可能可在降低剂量下重新开始，或可根据临床医师的判断使剂量增加回到25mg SC Q4W。如果克拉扎珠单抗由于AE而停用≥3次剂量，临床医师通常可考虑永久地终止克拉扎珠单抗。
基于异常LFT、嗜中性白细胞减少症或血小板减少症修改克拉扎珠单抗和/或背景免疫抑制的剂量
在临床方案期间，在治疗开始时以及此后每4至12周进行对LFT异常、嗜中性白细胞减少症和血小板减少症的监测。在异常LFT(即AST/ALT)、嗜中性白细胞或血小板计数的情况下，可实行视CTCAE严重性分级而定的克拉扎珠单抗停止或剂量降低(至12.5mg SCQ4W)。克拉扎珠单抗可由于满足CTCAE等级≥3的任何LFT异常、嗜中性白细胞或血小板计数而停止。
下表1提供关于根据CTCAE严重性等级进行克拉扎珠单抗和/或背景免疫抑制的剂量调整的其他指导方针。关于剂量修改的决定应与临床医师商议来做出。
表1基于异常LFT、嗜中性白细胞减少症或血小板减少症修改克拉扎珠单抗和/或背景免疫抑制的剂量
注释：ALT＝丙氨酸转氨酶；AST＝天冬氨酸转氨酶；AZA＝咪唑硫嘌呤；CTCAE＝通用毒性准则；INR＝国际标准化比值；LFT＝肝功能测试；LLN＝正常值下限；MMF＝霉酚酸吗啉乙酯；MPA＝霉酚酸；Q4W＝每4周一次；SC＝皮下；ULN＝正常值上限。
此外，在整个临床方案中进行对CNI水平的监测。此外，在改变克拉扎珠单抗的剂量/停止克拉扎珠单抗(或改变CNI剂量)之后，每2周监测CNI直至实现目标CNI谷底水平。
对BKV、CMV和EBV感染的监测
在治疗期间，在筛选时以及此后每8至12周，通过PCR测试来进行对BKV、CMV和EBV感染的监测。如果PCR DNA试验变为阳性(即超过定量下限)或病毒载量增加，那么可实行克拉扎珠单抗停止或剂量降低(至12.5mg SC Q4W)。克拉扎珠单抗可由于满足准则的BKV、CMV或EBV感染而停止(参见表2)。表2提供关于根据如通过PCR测试检测的病毒载量进行克拉扎珠单抗和/或背景免疫抑制的剂量调整的其他指导方针。关于剂量修改的决定与治疗临床医师商议来做出。
表2基于对BKV、CMV和EBV感染的监测结果修改克拉扎珠单抗和/或背景免疫抑制的剂量
注释：AZA＝咪唑硫嘌呤；BKV＝多瘤BK病毒；CMV＝巨细胞病毒；CNI＝钙调神经磷酸酶抑制剂；EBV＝艾伯斯坦-巴尔病毒；IU＝国际单位；IV＝静脉内；LLOQ＝定量下限；MMF＝霉酚酸吗啉乙酯；MPA＝霉酚酸；PCR＝聚合酶链式反应；Q4W＝每4周一次；SC＝皮下。
一般来说，在其中使克拉扎珠单抗降低至12.5mg SC Q4W的情况下，它应在使克拉扎珠单抗剂量增加回到25mg SC Q4W之前在降低剂量下继续持续1或2次剂量，并且进行PCR测试监测。在重新开始/增加MMF/MPA/AZA或增加CNI水平之前，首先实行使克拉扎珠单抗剂量恢复回到25mg SC Q4W。此外，在整个治疗中进行对CNI水平的监测。此外，在改变CNI剂量或改变克拉扎珠单抗的剂量/停止克拉扎珠单抗之后，每2周监测CNI直至实现目标CNI谷底水平。
禁止的疗法和相伴治疗
在治疗期间不实行对ABMR(包括CABMR)和TCMR的其他治疗。对于在筛选前3个月时期之前的任何时间接受这些治疗的患者，这些受试者必须已在停止治疗之后进行肾活检以根据以下纳入准则确认合格性。
以下物质通常在治疗期间被排除：
1.利妥昔单抗
2.依库珠单抗
3.蛋白酶体抑制剂
4.IVIG，除治疗低γ球蛋白血症之外
5.PLEX
6.贝拉西普
7.其他克拉扎珠单抗/治疗
8.抗IL-6/IL-6R受体mAb(核准的和研究性的)
允许的相伴药物
在I1-6抗体治疗期间，以下相伴药物是容许的：
1.AZA，推荐的AZA剂量：1.0-2.0mg/kg/天(然而，在嗜中性白细胞减少症/血小板减少症或病毒性感染的情况下，AZA的剂量可如表1和表2中所指示加以降低)。
2.CNI
3.推荐的目标他克莫司血浆谷底水平：5-8ng/mL
4.推荐的目标环孢灵血浆谷底水平：50-150ng/mL
5.在病毒性感染的情况下，CNI目标水平可如表2中所指示加以修改。
6.在治疗期间，在第1天，以及在第一剂克拉扎珠单抗之后1周和4周；接着每4周直至第12周；接着此后每8周监测CNI谷底水平。还在改变CNI剂量或改变克拉扎珠单抗的剂量/停止克拉扎珠单抗之后每2周监测CNI直至实现目标CNI水平。
7.MMF/MPA(推荐的MMF剂量：1.0-2.0g/天)；推荐的MPA剂量：720-1,440mg/天；然而，在嗜中性白细胞减少症/血小板减少症或病毒性感染的情况下，可使MMF/MPA的剂量降低。
8.mTOR抑制剂(依维莫司、西罗莫司)。
9.低剂量皮质类固醇(泼尼松/泼尼松龙≤10mg/天)。
10.抗高血压剂(例如血管紧张素转化酶抑制剂(ACEI)、血管紧张素II受体阻断剂(ARB))(ACEI和ARB在筛选访视之前开始，并且使剂量稳定持续至少2个月)。
11.抗糖尿病剂。
12.允许的针对急性TCMR的治疗：脉冲类固醇(例如口服泼尼松，200mg/天)，并且历经2周逐渐缩减至基线水平。
13.用口服缬更昔洛韦或静脉内更昔洛韦对CMV感染进行治疗。
14.甲氧苄啶/磺胺甲噁唑或吸入型喷他脒或口服达普松
15.一般来说，不鼓励使用草本和顺势疗法药品(例如圣约翰草(St.John’sWort)、紫锥花、白毛茛、华中五味子(Schisandra sphenanthera)提取物)。
防治性疗法
受试者通常将采用针对PJP的防治性治疗。通常将开具口服甲氧苄啶/磺胺甲噁唑。如果受试者在治疗之前已采用甲氧苄啶/磺胺甲噁唑，那么在筛选访视之前，应使剂量稳定持续至少1周。如果受试者在治疗之前未采用甲氧苄啶/磺胺甲噁唑(以及未已在接受吸入型喷他脒或口服达普松)，那么甲氧苄啶/磺胺甲噁唑通常在第1天基线访视(访视2)之前至少1周开始。
如果受试者已在接受用于PJP防治的吸入型喷他脒或口服达普松，那么受试者应保持采用这些药物，并且不开始采用甲氧苄啶/磺胺甲噁唑。对甲氧苄啶/磺胺甲噁唑不耐受以及未已在接受吸入型喷他脒或口服达普松的受试者通常在开始治疗之前至少1周开始采用这些药物中的任一者。
感染
克拉扎珠单抗可使对感染的免疫应答降低，因此，通常不应向具有活动性细菌性、病毒性或真菌性感染的受试者，或满足可使受试者易受感染的某些实验室准则(例如低绝对嗜中性白细胞计数)的受试者施用克拉扎珠单抗。因此，临床医师在治疗期间应找寻任何感染征象或症状。应监测感染并根据护理标准加以治疗；对于严重和机会性感染，研究者应考虑停用和/或停止用克拉扎珠单抗治疗和/或使背景免疫抑制降低。关于剂量修改的决定应与治疗临床医师商议来做出。
病毒监测
在治疗期间，在初始筛选时以及此后每8-12周，通常将通过PCR测试来进行对BKV、CMV和EBV感染的常规监测。在阳性结果的情况下，可考虑修改克拉扎珠单抗和/或背景免疫抑制的剂量。对于任何其他临床重大感染，都可遵循这些指导方针。
肝功能
用克拉扎珠单抗进行的治疗可使转氨酶升高。因此，通常从克拉扎珠单抗治疗排除具有重大肝病迹象以及大量使用酒精或非法药物的受试者。在治疗期间，密切监测肝功能测试和肝胆AE。此外，在治疗期间，在筛选时以及此后每4-12周进行LFT的常规监测。在轻度至中度LFT异常的情况下，可修改克拉扎珠单抗的剂量，并且在重度LFT异常(CTCAE等级≥3)的情况下，通常停止用克拉扎珠单抗进行的治疗。为确保受试者安全性，通常在克拉扎珠单抗给药之前复审最新近的LFT。
血液学参数
用克拉扎珠单抗进行的治疗已与血小板和嗜中性白细胞的数目降低相关联，因此，在治疗期间监测血小板和嗜中性白细胞数目。在治疗期间，当开始治疗时以及此后每4-12周，进行CBC。在轻度至中度嗜中性白细胞减少症或血小板减少症的情况下，可修改克拉扎珠单抗和/或背景免疫抑制的剂量，并且在重度嗜中性白细胞减少症或血小板减少症(CTCAE等级≥3)的情况下，可停止用克拉扎珠单抗进行的治疗(参见表1)。为确保受试者安全性，通常在克拉扎珠单抗给药之前复审最新近的嗜中性白细胞和血小板结果。
血脂异常
用克拉扎珠单抗进行的治疗已与血脂异常相关联。因此，通常对用克拉扎珠单抗治疗的受试者进行脂质水平的常规监测。
胃肠穿孔
在对患有克罗恩氏病(Crohn’s Disease)的受试者进行的研究中观察到三例GI穿孔，所述受试者被给与高剂量的克拉扎珠单抗(即150mg IV、300mg IV/100mg SC、以及600mg IV)。基于此，患有炎症性肠病、憩室病或具有GI穿孔史的移植接受者患者将通常不用克拉扎珠单抗治疗。
恶性肿瘤
恶性肿瘤是与延长的免疫抑制相关的已知风险。恶性肿瘤被鉴定为调节免疫系统的疗法的潜在风险，并且通常应在克拉扎珠单抗治疗期间加以监测。
自体免疫性
某些自体免疫病症的显现已与针对RA的一些生物疗法相关联。因此，通常将在主题克拉扎珠单抗治疗期间监测自体免疫性的征象。
免疫原性
抗药物抗体(ADA)的产生与许多治疗性抗体相关联。所述抗体可导致功效降低，或具有安全性后果。迄今为止，尚未在用克拉扎珠单抗治疗的健康志愿者中检测到ADA。相比之下，已在用克拉扎珠单抗治疗的一些患有RA和PsA的受试者中检测到ADA。因此，通常将在本发明克拉扎珠单抗治疗期间监测抗克拉扎珠单抗抗体的存在性。
药物相互作用
尚未进行对克拉扎珠单抗的正式临床药物相互作用研究。然而，体外研究已显示克拉扎珠单抗在逆转IL-6对多种CYP酶的mRNA水平的下调的影响方面与TCZ具有类似作用。因此，用克拉扎珠单抗进行的治疗可恢复CYP酶介导的药物清除，从而导致由CYP酶代谢的药物的全身性暴露的潜在降低，如已用TCZ所观察。这个作用对于需要单独地调整剂量，具有狭窄治疗指数的CYP酶底物药物可为特别重要的。因此，当共同施用克拉扎珠单抗与有效性降低是不合需要的CYP3A4底物药物(例如口服避孕药、3-羟基-3-甲基-戊二酰基-辅酶A还原酶抑制剂)时，要小心谨慎。
此外，鉴于克拉扎珠单抗与CNI之间可能存在药物-药物相互作用，通常监测CNI谷底水平；例如在第1天，以及在第一剂克拉扎珠单抗之后1周和4周；接着每4周直至第12周；接着此后每8周，持续研究的剩余时间。还可在改变CNI剂量或改变克拉扎珠单抗的剂量/停止克拉扎珠单抗之后，每2周监测CNI直至实现目标CNI谷底水平。
剂量过度
在克拉扎珠单抗注射剂量过度的情况下，没有特定解毒剂或措施可采用。受试者应以适当支持性护理加以治疗。
注射部位事件和输注相关(过敏)反应
注射部位反应(ISR)已在皮下施用的情况下被报告，并且最频繁地报告为红斑。反应已是轻度的或中度的，并且已在不治疗的情况下消退。迄今为止，尚无输注反应与通过静脉内输注来施用克拉扎珠单抗相关联。
如同任何蛋白质治疗剂一样，存在严重过敏反应(输注反应)的风险。克拉扎珠单抗通常不应向已具有对mAb的任何先前过敏反应的受试者施用。过敏反应与ISR两者均应以护理标准加以治疗。通常不应对已显现对克拉扎珠单抗的重大过敏反应的受试者进行再激发。
临床实验室评估
通常使用标准经验证方法分析患者血液样品。用于以下功效和安全性评估的血液和尿样品通常将在第1-5年以及之后(如果适用)中的每一年获取。血液和尿样品通常将在门诊访视时在给药之前收集。所述实验室评估的概述提供于表3中。
表3实验室评估的概述
1需要禁食至少10小时。如果受试者未能禁食，那么应仍然收集和处理样品，同时在实验室申请书上记录未能禁食，并且作为方案偏差。
2 POCT尿妊娠测试在每剂克拉扎珠单抗之前。对于停止用克拉扎珠单抗/安慰剂治疗的受试者，可在末次剂量的克拉扎珠单抗之后再持续5个月进行这个评估。
注释：ALT＝丙氨酸转氨酶；AST＝天冬氨酸转氨酶；BKV＝多瘤BK病毒；BUN＝血液尿素氮；CBC＝全血细胞计数；CMV＝巨细胞病毒；CNI＝钙调神经磷酸酶抑制剂；DNA＝脱氧核糖核酸；DSA＝供者特异性抗体；EBV＝艾伯斯坦巴尔病毒；eGFR＝估计肾小球滤过率；EOS＝研究结束；GGT＝γ-谷氨酰基转移酶；Hb＝血红蛋白；HBsAg＝乙型肝炎表面抗原；HDL＝高密度脂蛋白；HIV＝人免疫缺陷病毒；HLA＝人白细胞抗原；hsCRP＝高敏感性C反应蛋白；INR＝国际标准化比值；IL-6＝白介素6；LDL＝低密度脂蛋白；MDRD4＝肾病膳食改进-4；MFI＝平均荧光强度；MPA＝霉酚酸；PCR＝聚合酶链式反应；POCT＝护理点测试；RNA＝核糖核酸；UACR＝尿白蛋白肌酸酐比率；UPCR＝尿蛋白肌酸酐比率；WOCBP＝具有生育潜力的妇女。
eGFR
估计肾小球滤过率通常将使用MDRD4方程确定：
eGFR＝175x(血清肌酸酐[mg/dL])-1.154x(年龄)-0.203x(0.742(如果是女性)；否则是1)x(1.212(如果是黑人)；否则是1)
通常在整个治疗3中，大致上在每次访视(Q4W)时都确定eGFR。
DSA效价和MFI评分
通常将使用基于珠粒的单抗原测定来测定DSA。
1.通常在访视1(筛选)、访视2(基线)、6、10、16、22、28、34、40、46、52、58、64和68时确定HLA DSA的MFI评分。
2.通常在访视1(筛选)、访视2(基线)、6、10、16、28、40、52、64和68(EOS)时测定DSA效价。
在筛选时，这些结果可用于确定DSA合格性准则。如果在筛选的6个月内确认了存在HLA DSA，那么不需要重复测试以确定合格性。
血浆IL-6
通常可使用经验证
测定来测量总IL-6(结合/未结合于可溶性IL-6受体以及结合/未结合于克拉扎珠单抗的配体)和游离IL-6(未结合于可溶性IL-6受体以及未结合于克拉扎珠单抗的配体)水平。
通常在访视2(基线)、6、9、15、21、27、33、39、45、51、57、63和68(EOS)时测量血浆IL-6水平(总体和游离)。
血浆克拉扎珠单抗
经验证酶联免疫吸附测定方法通常用于测量血清中克拉扎珠单抗的浓度。通常在访视2(基线)、6、9、15、21、27、33、39、45、51、57、63和68(EOS)时测量血浆克拉扎珠单抗水平。
抗克拉扎珠单抗抗体
经验证电化学发光免疫测定方法通常用于测量血清中克拉扎珠单抗抗体的效价。通常可在访视2(基线)、6、9、15、21、27、33、39、45、51、57、63和68(EOS)时测量血浆抗克拉扎珠单抗抗体水平。
MPA水平
可例如通过经验证定量液相色谱-串联质谱测定(LC-MS/MS)方法来测量血清/血浆中的MPA水平。一般来说，可在访视2(基线)、4、5、6、8、10、12、14、16、19、22、25、28、31、34、37、40、43、46、49、52、55、58、61、64、67和68(EOS)时测量MPA水平。在这些访视时，用MMF/MPA进行的防治性治疗通常被停用直至测定MPA水平。
CNI水平
可例如通过经验证定量LC-MS/MS方法来测量血清/血浆中的CNI(他克莫司和环孢灵)谷底水平。CNI谷底水平例如可在访视2(基线)、3至6、8、10、12、14、16、18、20、22、24、26、28、30、32、34、36、38、40、42、44、46、48、50、52、54、56、58、60、62、64、66和68(EOS)时测量。在这些访视时，用CNI进行的防治性治疗通常被停用直至测定CNI水平。
还可在改变CNI剂量或改变克拉扎珠单抗的剂量/停止克拉扎珠单抗之后，每2周监测CNI，例如直至实现目标CNI谷底水平。
身体检查
通常，在访视1(筛选)时，通常由医师进行根据护理标准进行的全面身体检查。还可进行额外简略身体检查；例如在访视2(基线)时以及在从访视4(第4周)至访视68(第260周)的每次访视时。通常，将在每次身体检查时记录受试者重量。
生命征象
通常在整个治疗中在约每次访视(Q4W)时测量生命征象。通常，在受试者已在静息5分钟之后处于坐位之后进行这些评估。为避免可变性，通常在整个治疗中使用相同的获得体温的方法。
通常测量以下生命征象：
1.血压(收缩和舒张)
2.心率
3.体温(℃或°F)，腋下或鼓膜
4.呼吸
标准12导联心电图
通常运用包含标准12导联描记的心电图(ECG)，所述心电图的结果通常由有资格的医师评估，并且通常作为源文件加以保留。在eCRF中记录包括任何异常的结果。
心电图通常将在受试者已处于静息仰卧位持续至少5分钟之后加以数字记录。应评估重大异常，包括可能促使克拉扎珠单抗的停止的观测数据。通常，在访视1(筛选)以及访视6、9、15、21、27、33、39、45、51、57、63和68(EOS)中的任一者或全部时运用心电图。
结核病筛查
对活动性和潜伏性TB的筛查通常为评估受试者关于克拉扎珠单抗治疗的合格性所需。通常需要以下程序：
1.全面身体检查和医学史以评估TB暴露以及具有潜伏性TB史(无活动性TB)的受试者是否完成了防治性治疗的全过程
2.胸部x射线程序
3.QuantiFERON-TB Gold干扰素-γ释放测定
通常不对干扰素-γ释放测定的阳性结果进行复测。不确定的结果可复测1次。如果第二测试是阳性或不确定，那么那个受试者的结果通常被视为阳性。通常不进行第三测试。患有新近诊断的TB的受试者通常应停止克拉扎珠单抗，或根据适当护理标准加以管理。
肾活检
在筛选的6个月内的活检证明的CABMR(根据Banff 2015诊断准则)通常为达成受试者关于治疗的合格性所需。如果先前活检不在筛选的6个月内，那么通常进行重复活检。如果受试者已接受针对ABMR(包括CABMR)或TCMR的治疗，那么通常进行重复活检(以显示CABMR的持续性)。
关于进入克拉扎珠单抗治疗的活检合格性通常基于病理学家诊断和Banff评分。可在访视16(第52周)时进行根据方案的重复活检。如果有临床指示，那么可在任何时间进行未预订的活检。如果已在第52周的2个月内进行有因性活检，那么通常不需要在第52周时的重复活检。
筛选访视(评估访视1)
筛选访视(访视1)通常可在访视2(基线，第1天)之前28天内进行。初始筛选评估可包括提供知情同意书；复审纳入/排除准则；全面身体检查；生命征象测量，包括重量和身高；医学史(包括关于病毒性感染的历史血清学)；尿妊娠测试(对于WOCBP)；TB筛查；12导联ECG；血液和尿样品收集以根据SOE进行中心实验室评估，确定eGFR，进行标准尿分析；随机尿收集(用于测定UPCR/UACR)；24小时尿收集(如果必要)；如果血清阴性或历史未知，那么进行关于HIV和HBsAg的血清学分析；针对BKV、CMV和EBV DNA以及针对HCV RNA进行PCR监测；以及复审先前和相伴药物以及进入准则。
最少10小时禁食通常为测定空腹葡萄糖和脂质/甘油三酯所需。在知情同意之后但在访视2之前发生的任何AE通常被记录为医学史。
用以确定关于进入治疗的合格性的活检诊断通常基于病理学家诊断和Banff评分。在筛选时，实验室结果可用于确定DSA合格性准则。如果在筛选的6个月内确认了存在HLA DSA，那么通常不需要重复测试。被确定为筛选失败的受试者通常可再评估一次。
治疗程序
在整个治疗时期(访视2直至68)中，一般来说，向受试者皮下施用25mg克拉扎珠单抗(Q4W)。在给药之前，在访视2以及访视4直至67时，通常进行以下评估：
1.AE和相伴药物(在进行任何其他研究评估之前收集和记录)。
2.简略身体检查(包括生命征象)。
3.针对WOCBP的妊娠测试。
4.血液收集以对eGFR进行中心实验室分析。
5.复审来自先前访视(预定的或另外的)的最新近LFT和CBC分析和病毒监测结果以根据这些准则的安全限度确认受试者对于接受克拉扎珠单抗是否合格，或是否需要/推荐对克拉扎珠单抗和/或背景免疫抑制的剂量进行修改(参见章节7.5)。
额外评估可每4至12周在给药之前进行，如SOE中所详述，并且可包括以下：
1.检查所有纳入/排除准则(仅访视2(基线，第1天))。
2.血液和尿样品收集以进行如表7中以及SOE中详述的额外中心实验室分析。最少10小时禁食为测定空腹葡萄糖和脂质/甘油三酯所需。在根据SOE的相关访视时，将停用CNI直至在收集血液样品以测定CNI谷底水平之后。
3.HRQoL问卷。在适用的访视时，这些问卷应在任何其他评估之前完成。
4.肾活检(访视16；如果有临床指示，那么可在更早访视时进行)。
在访视3时，通常，进行的唯一评估包括血液样品收集以监测CNI谷底水平。如上所指示，通常将停用CNI直至在收集血液样品以测定CNI谷底水平之后。
治疗结束程序
在完成治疗时，可实行以下评估：
1.AE和相伴药物(在进行其他研究评估之前收集)。
2.简略身体检查(包括生命征象)。
3.针对WOCBP的妊娠测试。
4.血液和尿样品收集以进行中心实验室分析。最少10小时禁食为测定空腹葡萄糖和脂质/甘油三酯所需。将停用CNI直至在收集血液样品以测定CNI谷底水平之后。
5.肾活检(如果受试者在第52周之前退出)。
随访程序
一般来说，所有经治疗受试者都将每月被评估以检测任何新的AE、SAE或妊娠。由于移植物失功而停止克拉扎珠单抗的受试者可经受EOS评估(访视68)，并且在末次剂量的克拉扎珠单抗之后持续5个月以每月TC加以追踪。
所有退出患者都通常将完成EOS评估(访视68)，并且如果可能，那么在末次剂量的克拉扎珠单抗之后持续5个月以每月TC加以追踪，并且可根据医师的判断加以召集以进行门诊访视。
未预订的访视
在治疗的过程期间，可出于安全性原因进行未预订的访视。此外，可见到停止克拉扎珠单抗的受试者在门诊进行未预订的访视。
不利事件的定义
AE定义为被施用克拉扎珠单抗的临床研究受试者中的任何不利医学事件或预先存在的医学状况的恶化，并且未必与这个治疗具有因果关系。因此，AE可为在时间上与克拉扎珠单抗的使用相关联，无论是否被视为与克拉扎珠单抗相关的任何不利和非意图征象(诸如异常实验室观测数据)、症状或疾病。
治疗中出现的AE(TEAE)定义为在暴露于克拉扎珠单抗之前不存在的任何事件，或在暴露于克拉扎珠单抗之后在强度或频率方面恶化的任何已存在事件。
不利药物反应的定义
在关于新医学产品或它的新用法的核准前临床体验中，特别是当一种或多种治疗剂量可未确立时，与任何剂量相关的对医学产品的所有有害和非意图响应都通常可被视为不利药物反应(ADR)。短语“对医学产品的响应”意指医学产品与不利事件之间的因果关系至少具有合理的可能性，即关系不能被排除。
出乎意料的不利事件/不利药物反应的定义
如果事件的性质、严重性或频率不与先前对于研究剂所述的风险信息一致，那么AE/ADR可被视为是出乎意料的。本文描述克拉扎珠单抗的鉴定的和潜在的风险。
严重不利事件的定义
SAE定义为一般来说导致以下结果中的任一者的任何AE或疑似不利反应：
1.死亡。
2.危急生命的AE。(应注意：SAE的术语危急生命的定义是指其中受试者在事件时处于死亡的风险下的事件；它不指假设如果它更加严重，那么可能已导致死亡的事件。)
3.住院或延长现有住院期。
4.持续或显著无能力执行正常生命功能或对执行正常生命功能的能力造成实质性破坏。
5.先天性异常/出生缺陷。
6.重要医学事件(参见下文)。
可不是危急生命的，也不需要住院，也不导致死亡的重要医学事件在以下情况下时可被视为是严重的：当基于适当医学判断时，它们可危害受试者，并且可需要医学或手术干预以预防这个定义中所列的结果中的一者。所述医学事件的实例包括需要在急诊室中或在家进行强化治疗的过敏性支气管痉挛，不导致住院的血质不调或惊厥，或产生药物依赖性或药物滥用。
以下住院通常在本文中不被视为SAE：
1.前往急诊室或其他医院部门就诊＜24小时，不导致入院(除非被视为是重要医学或危急生命的事件)。
2.在签署这个研究的知情同意书之前计划的择期手术。
3.根据计划的医学/手术程序(例如肾活检)的方案的入院。
4.需要入院的对健康状况的基线/趋势的常规健康评估(例如常规结肠镜检查)。
5.除医冶健康不佳的入院和在进入研究之前计划的入院以外的医学/手术入院。在这些情况下需要适当文件记载。
6.由于不涉及健康状况，并且不需要医学/手术干预的另一生活情况(例如缺乏住房、经济不足、护理者喘息、家庭情况、行政原因)而遭遇的入院。
疑似的出乎意料的严重不利反应的定义
SUSAR定义为是严重的且出乎意料的，以及被视为与克拉扎珠单抗具有合理的疑似因果关系的任何ADR。
特别关注的不利事件(AESI)的定义
特别关注的不利事件(AESI)是关于其进行持续监测和快速沟通是重要的受到科学或医学关注的AE。这些可包括为克拉扎珠单抗所特有的事件，或一般来说可对治疗具有临床重要性的事件。因此，AESI可或可不与克拉扎珠单抗相关。对于克拉扎珠单抗，已确定以下AESI：LFT异常、嗜中性白细胞减少症、血小板减少症、高脂质血症、GI穿孔、过敏性和过敏症、恶性肿瘤、机会性感染和妊娠。本文讨论这些AESI中的每一者。
LFT异常、嗜中性白细胞减少症、血小板减少症和高脂质血症
在整个克拉扎珠单抗治疗中，受试者通常将经受定期血液学和生物化学实验室测试以监测异常LFT、嗜中性白细胞减少症、血小板减少症和高脂质血症。一般来说，是等级3(重度)或更高等级的这些和任何其他异常测试结果应被视为AESI，并且可能应考虑终止克拉扎珠单抗治疗。
特别地，对于满足通常被视为AESI的以下准则中的任一者的受试者，可终止克拉扎珠单抗治疗：
1.AST/ALT＞5倍ULN
2.总胆红素＞3倍ULN
3.AST/ALT＞3至≤5倍ULN，以及总胆红素≥2倍ULN(或INR＞1.5)
4.嗜中性白细胞计数＜1,000个细胞/mm3
5.血小板＜50.000个细胞/mm3
此外，以下总胆固醇和甘油三酯水平被视为AESI：
1.总胆固醇＞400mg/dL或＞10.34mmol/L，不管基线水平如何
2.甘油三酯＞500mg/dL或＞5.7mmol/L，不管基线水平如何
胃肠穿孔
胃肠穿孔是鉴定的用抗IL-6抗体进行的治疗的风险，并且报告为AESI。
过敏性和过敏症
过敏性反应和过敏反应，例如满足关于过敏症的NIAID/FAAN第二界联合研讨会的定义的那些，通常被视为AESI：
1.涉及皮肤、粘膜组织或两者的急性病害发生(数分钟至数小时)(例如广泛性麻疹、瘙痒或发红、唇-舌-悬雍垂肿胀)以及以下中的至少一者
2.呼吸道损害(例如呼吸困难、喘息-支气管痉挛、喘鸣、呼气峰流量降低、低血氧症)
3.血压降低或相关的终末器官功能异常症状(例如张力减退(虚脱)、昏厥、失禁)
恶性肿瘤
任何新的恶性肿瘤或预先存在的恶性肿瘤的进展(排除非黑素瘤皮肤癌(鳞状细胞或基底细胞癌))通常被视为AESI。
机会性感染
在整个克拉扎珠单抗治疗中，通常将根据美国移植学会的推荐和/或KDIGO指导方针实行对潜在感染的监测。可在肾移植接受者中导致重大致病性的认定病毒包括BKV、CMV和EBV，并且通常将通过PCR例如在8至12周定期间隔下监测它们的存在性。
以下感染被视为AESI：
1.任何细菌性肺炎或支气管炎
2.任何革兰氏阴性细菌GI感染(包括沙门氏菌(肠道血清型鼠伤寒沙门氏菌(Typhimurium)和肠炎沙门氏菌(Enteritidis))、志贺氏菌(Shigella)、弯曲杆菌(Campylobacter)、大肠杆菌(Escherichia coli)和艰难梭菌(Clostridium difficile))
3.BKV肾病变
4.CMV感染/疾病
5.伴有隐孢子虫(Cryptosporidium)的隐孢子虫病
6.侵袭性念珠菌病
7.包括隐球菌病(cryptococcosis)、组织胞浆菌病(histoplasmosis)、曲霉病(aspergillosis)和球孢子菌病(coccidioidomycosis)的侵袭性霉菌病
8.JC病毒感染(进行性多灶性脑白质病)
9.乙型肝炎病毒(HBV)和HCV感染
10.人乳头状瘤病毒(HPV)疾病
11.HIV感染
12.伴有耶氏肺囊虫的肺囊虫性肺炎
13.结核分枝杆菌(Mycobacterium tuberculosis)感染和其他分枝杆菌感染(例如堪萨斯分枝杆菌(Mycobacterium kansasii)、鸟分枝杆菌(Mycobacterium avium))
14.非CMV疾病，包括单纯疱疹病毒1型(HSV-1)和2型(HSV-2)疾病、水痘-带状疱疹病毒疾病、人疱疹病毒-8(HHV-8)疾病
15.伴有刚地弓形虫(Toxoplasma gondii)的弓形虫病感染
以上清单不意图是完全的，并且还可监测通常不在肾移植群体中观察到的其他感染。
对于满足被视为AESI的以下准则和这些异常中的任一者的受试者，可终止克拉扎珠单抗治疗：
1.BKV＞10,000个拷贝/mL或活检证明的BKV肾病变
2.CMV终末器官疾病(例如肝炎、结肠炎、肺炎、视网膜炎)
3.EBV≥10,000个拷贝/mL或移植后淋巴组织增生性病症或血清阴性接受者中原发性EBV感染
妊娠
在治疗期间或在末次剂量的克拉扎珠单抗之后持续5个月，在女性受试者或男性受试者的女性伴侣中发生的妊娠应被视为AESI，并且在专门的妊娠表格上记录/报告。在妊娠的情况下，受试者通常应停止克拉扎珠单抗治疗。
不利事件的分类
强度/严重性分类
通常根据国立癌症研究所的5.0版CTCAE(参见表4)对所有AE的严重性进行评估和分级。
表4 AE严重性分级
注释：AE＝不利事件。
出处：国立癌症研究所的5.0版通用不利事件术语准则(CTCAE)[42]。
术语重度经常用于描述特定事件的强度(严重性)；然而，事件自身可具有相对较小的医学重要性(例如重度头痛)。这不与基于主题/事件结果或行动准则的“严重”相同。
与克拉扎珠单抗的关系
对于所有收集的AE，检查和评估患者的临床医师将通常基于时间关系以及他的/她的临床判断来确定AE的因果性。关于因果性的确定性程度通常使用如表5中所示的2个种类(相关/无关)来分级。
表5 AE与克拉扎珠单抗的关系
注释：AE＝不利事件。
结果分类
一般来说，AE的结果应如下分类：恢复/消退(即无后遗症)；恢复/消退，伴有后遗症；恢复中/消退中；未恢复/未消退；致命；或未知(如果不可能随访)。
预先存在的医学状况
预先存在的医学状况是在治疗之前存在的医学状况(除非事件是SAE)。预先存在的医学状况应仅当所述状况的频率、严重性或特性在研究期间恶化时被记录为AE。
所研究的疾病的症状
所研究的疾病(CAMBR或AMBR)的征象和症状通常不分类为AE，只要它们在疾病的正常日常波动内即可。然而，疾病症状的恶化可分类为AE。
临床实验室评估
安全性实验室研究的数值的变化可在以下情况下报告为AE：如果所述变化被视为临床相关，或如果在用克拉扎珠单抗治疗期间，观察到实验室参数从正常转变为病理性数值，或观察到已有病理性数值的进一步恶化。
身体检查和生命征象
如果变化被视为临床相关，或在生命征象的情况下，如果观察到从正常转变为病理性数值，那么任何身体检查观测数据或生命征象或任何新的身体检查观测数据的恶化可报告为AE。
不利事件的报告
如果报告任何AE，那么可记录发生日期、与克拉扎珠单抗的关系、采取的任何行动、消退日期(或它仍然在持续或已变为慢性的事实)、结果、强度(在事件期间的任何时刻的最不利强度)以及所述AE在事件期间的任何时间是否是严重的。为确定任何SAE的持续时间，可记录住院和出院的日期或满足其他SAE准则的日期。
AE报告时期通常将在由受试者签署知情同意书(ICF)时开始，并且持续直至治疗结束，或直至在末次剂量的克拉扎珠单抗之后5个月的随访时期。如果受试者报告AE，那么一般来说，临床医师将获取足够信息以评估因果性。这可能需要额外实验室测试、身体检查、电话联系等。
一般来说，追踪SAE直至令人满意的消退，或直至中心临床医师将事件视为是慢性的或稳定的，或丧失了对受试者的随访。SAE的发生日期通常规定为征象和症状/诊断变得严重的日期。SAE的消退日期规定为当症状消退，或事件被视为是慢性的或稳定的，和/或如果严重性准则不再适用时。
妊娠的报告
在研究期间或在末次剂量的克拉扎珠单抗之后持续5个月，在女性受试者中或男性受试者的女性伴侣中发生的任何妊娠应向临床医师报告。临床医师应对受试者(或在男性受试者的情况下，对受试者的伴侣)提供建议，并且讨论继续妊娠的风险以及对胎儿的任何可能影响。对女性受试者中妊娠的监测应持续直至妊娠结束。在治疗期间妊娠测试确认呈阳性的妇女通常应永久地停止克拉扎珠单抗。
妊娠本身不是SAE。然而，妊娠的并发症诸如流产(自发性或诱导性)、早产或先天性异常被视为SAE，并且通常应以文件记载。
数据分析
以下表6和表7提供样本量估计和预测的数据分析。
表6基于局限于活动性ABMR诊断后52周的eGFR数据的关于全因性移植物衰竭的样本量估计
1相对于平均eGFR情景的平均斜率变化，斜率＝-0.753，基于局限于ABMR诊断后前12个月的eGFR数据。
注释：ABMR＝抗体介导的排斥；eGFR＝估计肾小球滤过率。
出处：建模报告，章节10，表9-2-1b[36]。
当约200(每组100)名受试者已被随机化并接受至少52周的用克拉扎珠单抗进行的治疗时，可进行期中功效分析以评估治疗组之间的差异。如表6中所示，180名受试者(每组90名)的固定样本量将具有90％功效(双侧α是0.05)来检测治疗组之间在52周eGFR方面的最小差异4.515mL/min/1.73m2(假定在安慰剂治疗组中eGFR在0.75mL/min/1.73m2/月的速率下下降，并且克拉扎珠单抗使eGFR下降降低50％)。关于固定设计的样本量确定基于0.05的双侧α，以及从基线至第52周的平均eGFR变化的共同标准偏差9.252mL/min/1.73m2(效应大小＝4.515/9.252＝0.488)。计划样本量已增加至最少200名受试者以允许10％的受试者丧失随访或退出。
表7关于在活动性ABMR诊断后52周时eGFR(mL/min/1.73m2)变化的样本量估计
1当局限于0-12个月eGFR数据时，在ABMR诊断后12个月时从基线开始的eGFR差异的标准偏差＝9.252。
2相对于平均eGFR情景的平均斜率变化，斜率＝-0.753，基于局限于ABMR诊断后前12个月的eGFR数据。
注释：ABMR＝抗体介导的排斥；eGFR＝估计肾小球滤过率。
出处：建模报告，章节10，表9-2-1a[36]。
一旦至少100名受试者(每组50名)已持续至少52周接受克拉扎珠单抗，即可使用逆正态方法以预先指定的信息率(0.5556，1)来进行对200名受试者的计划样本量的再估计以控制I型错误率。样本量再估计确保当假定eGFR效应大小是0.488时，功效是95.9％。在这些假定下的平均样本量是202名可评估受试者(对应于约224名入组受试者，假定10％失访或退出)。当假定eGFR效应大小是0.368时，那么功效是79.6％，并且平均样本量是218名可评估受试者(约242名入组受试者)。关于期中功效分析替代终点的样本量通常将不超过总计250名可评估受试者(约280名入组受试者)。
治疗功效终点
本文主要功效终点通常包括达到全因性同种异体移植物失功的时间的复合临床终点，所述全因性同种异体移植物失功定义为恢复透析、同种异体移植物肾切除、再移植、eGFR＜15mL/min/1.73m2或由任何原因所致的死亡(包括在同种异体移植物具有功能性的情况下的死亡)。(通常排除归因于急性肾损伤(AKI)的暂时(≤60天))恢复透析)。
eGFR＜15mL/min/1.73m2通常通过在14天后至30天后之间进行重复测量来确认以满足移植物失功的主要终点定义。排除归因于AKI的暂时(≤60天)eGFR下降至＜15mL/min/1.73m2。
恢复透析或经确认eGFR下降(至＜15mL/min/1.73m2)＞60天的持续时间被视为是永久的，并且满足同种异体移植物失功的终点。
AKI被鉴定为一种或多种导致移植物功能急性恶化(包括但不限于急性肾小球肾炎、急性血栓形成事件、脱水、药物毒性或暴露于已知肾中毒剂、间质性肾炎、败血症、泌尿道梗阻、尿脓毒病、糖尿病的恶化以及心脏衰竭的恶化)的AE，所述急性恶化伴有以下中的一者或多者的存在：
1.在相关AE的开始日期的48小时内血清肌酸酐增加≥0.3mg/d1[49]
2.在相关AE的开始日期之前7天内已知或假定已发生血清肌酸酐增加至≥1.5倍[49]
3.组织学确认的急性排斥或通过移植物活检确认的任何其他急性状况
分层对数秩检验用于在每个治疗组别之间比较达到事件发生的中值时间。还呈现了发生率和危险比率。
为评估主要功效分析的稳健性，主要功效变量可在使用PP集的灵敏性分析中重复。可任选地进行另一灵敏性分析以阐明全因性同种异体移植物失功作为复发性事件的性质。
次要终点
还可分析以下次要功效终点：
1.删截了死亡的同种异体移植物失功(定义为恢复透析、同种异体移植物肾切除、再移植或eGFR＜15mL/min/1.73m2，但排除由任何原因所致的死亡)的发生和达到所述同种异体移植物失功的时间
2.从基线至EO的平均eGFR变化
3.从基线至EOS的随机UACR变化
4.从基线至EOS的DSA效价和MFI强度评分变化
5.从基线至EOS的急性排斥事件(TCMR和ABMR)的发生
6.治疗前肾活检体相对于治疗后(第52周)肾活检体的Banff病变分级评分(2015准则)变化
7.总体患者存活期
此外，可考查与健康护理利用和患者报告的结果相关的次要终点，诸如以下：
1.直至第52周以及直至EOS的与治疗ABMR相关的健康护理利用
2.患者报告的结果(包括HRQoL)从基线至第52周以及至EOS的变化
额外分析
可呈现IL-6(游离和总体)水平、抗克拉扎珠单抗抗体的存在性、以及其他评价/评估。
通常在整个治疗中测量CNI和MPA水平。可进行分析以分析这些药物的浓度。在克拉扎珠单抗组与对照组之间比较这些浓度可用于确定在启动克拉扎珠单抗之后是否已存在任何有意义的药物-药物PK相互作用。分析还研究和解释在克拉扎珠单抗组与对照组之间，这些药物在试验期间的剂量的任何显著差异。
安全性评估
可还评估和分析以下安全性终点：
1.TEAE、严重TEAE和AESI
2.通过PCR对BKV、CMV和EBV进行病毒性感染监测
3.实验室测试，包括LFT、CBC、血浆脂质、高敏感性CRP
4.生命征象、ECG和身体检查
期中分析
一旦约100名受试者已被随机化并接受克拉扎珠单抗，即可进行关于安全性的期中分析。还可制定其他安全性期中分析。
还可进行两个正式期中功效分析。
1.样本量再估计：在至少100名受试者已被随机化并持续至少52周接受克拉扎珠单抗之后，可由独立统计学家进行正式期中分析以评估用于52周eGFR终点的期中功效分析的样本量的充足性。
2.当约200名受试者(每组100名)已被随机化并接受至少52周的用克拉扎珠单抗进行的治疗时，可实行对52周eGFR终点(即从基线至第52周的平均eGFR变化)的期中功效分析。
使用混合模型重复测量方法分析期中功效终点。模型可包括治疗项目、分层因素、基线eGFR以及其他预定协变量。
灵敏性分析可包括以下：
1.使用在同一治疗组内在那个时间点的观察值的平均值插补遗漏值。
2.对于在已经受AE之后遗漏数值的受试者，遗漏值由在给定时间点在对照组中观察到的最糟(最低)eGFR值插补。对于由于除AE以外的原因而遗漏数值的受试者，数值由在同一治疗组内在那个时间点的观察值的平均值插补。
3.δ调整方法用于估计超过其之后积极治疗将具有不利影响的临界点。
4.基于秩次的非参数方法，其中受试者首先根据他们上一次提供数据的时间点，接着根据在那次访视时的eGFR值加以编秩。威尔卡森秩和检验(Wilcoxon rank sum test)可接着应用于使用秩次来比较治疗组。
可鉴于以上具体实施方式对本发明进行这些和其他变化。一般来说，在以下权利要求中，所用术语不应解释为将本发明限于说明书和权利要求中公开的特定实施方案。因此，本发明不受限于公开内容，而是本发明的范围将完全由以下权利要求确定。
参考文献
1.Keller ET，Wanagat J，Ershler WB.Molecular and cellular biology ofinterleukin-6and its receptor.Front Biosci.1996；1：d340-57.
2.Hirano T，Taga T，Nakano N，Yasukawa K，Kashiwamura S，Shimizu K，etal.PurifiGation to homogeneity and characterization of human B-celldifferentiation factor(BCDF or BSFp-2).Proc Natl Acad Sci USA.1985 Aug；82(16)：5490-4.
3.Kawano MM，Mihara K，Huang N，Tsujimoto T，Kuramoto A.Differentiationof early plasma cells on bone marrow stromal cells requires interleukin-6 forescaping from apoptosis.Blood.19g5 Jan 15；85(2)：487-94.
4.Muraguchi A，Hirano T，Tang B，Matsuda T，Horii Y，Nakajima K，et al.Theessential role of B cell stimulatory factor 2(BSF-2/IL-6)for the terminaldifferentiation of B cells.J Exp Med.1988Feb 1；167：332-44.
5.Lotz M，Jirik F，Kabouridis P，Tsoukas C，
T，Kishimoto T，et al. Bcellstimulating factor 2/interleukin 6is a costimulant for human thymocytesand T lymphocytes.J Exp Med.1988Mar 1；167(3)：1253-8.
6.Okada M，Kitahara M，Kishimoto S，Matsuda T，Hirano T，Kishimoto T.IL-6/BSF-2 functions as a killer helper factor in the in vitro induction ofcytotoxic T ce||s.J lmmunol.1988 Sep 1；141(5)：1543-9.
7.Jordan SC，Choi J，Kim l，Wu G，Toyoda M，Shin B，et al.Interleukin-6，acytokine critical to mediation of inflammation，autoimmunity and allograftrejection：therapeutic implications of IL-6 receptor blockade.Transplantation.2017Jan；101(1)：32-44.
8.Gaston RS，Cecka JM，Kasiske BL，Fieberg AM，Leduc R，Cosio FC，etal.Evidence for antibody-mediated injury as a major determinant of latekidney allograft failure.Transplantation.2010 Jul 15；90(1)：68-74.
9.Thomas KA，Valenzuela NM，Reed EF.The perfect storm：HLA antibodies，complement，FcγRs，and endothelium in transplant rejection.Trends MolMed.2015May；21(5)：319-29.
10.Wiebe C，Gibson IW，Blydt-Hansen TD，Karpinksi M，Ho J，Storsley LJ，etal.Evolution and clinical pathologic correlatlons of de novo donor-specificHLA antibody post kidney transplant.Am J Transplant.2012 May；12(5)：1157-67.
11.Wiebe C，Gibson IW，Blydt-Hansen TD；Pochinco D，Birk PE，Ho J，etal.Rates and determinants of progression to graft failure in kidney allograftrecipients with de novo donor-specific antibody.Am J Transplant.2015 Nov；15(11)：2921-30.
12.Hariharan S，McBride MA，Cherikh WS，Tolleris CB，Bresnahan BA，JohnsonCP.Post-transplant renal function in the first year predicts long-term kidneytransplant survival.Kidney Int.2002Jul；62(1)：311-8.
13.Kasiske BL，lsrani AK，Snyder JJ，Skeans MA.The relationship betweenkidney function and long-term graft survival after kidney transplant.Am JKidney Dis.2011 Mar；57(3)：466-75.
14.Clayton PA，Lim WH，Wong G，Chadban SJ.Relationship between eGFRdecline and hard outcomes after kidney.transplants.J Am Soc Nephrol.2016：27：3440-6.
15.Eskandary F，Bond G，Schwaiger E，Kikic Z，Winzer C，Wahrmann M，etal.Bortezomib in late antibody-mediated kidney transplant rejection(BORTEJECT Study)：study protocol for a randomized controlledtrial.Trials.2014 Apr 3；15：107.p.1-9.
16.Stegall MD，Gaston RS，Cosio FG，Matas A.Through a glass darkly：seeking clarity in preventing late kidney transplant failure.J Am SocNephrol.2015 Jan；26(1)：20-9.Epub 2014 Aug 5.
17.Kidney Disease：Improving Global Outcomes(KDIGO)Transplant WorkGroup.KDIGO clinical practice guideline for the care of kidney transplantrecipients.Am J Transplant.2009 Nov；9 Suppl 3：S1-155.
18.Roberts DM，Jiang SH，Chadban SJ.The treatment of acute antibody-mediated rejection in kidney transplant recipients-a systematicreview.Transplantation.2012 Oct；94(8)：775-83.
19.Wan SS，Ying TD，Wyburn K，Roberts DM，Wyld M，Chadban SJ.The treatmentof antibody-mediated rejection in kidney transplantation：an updatedsystematic review and meta-analysis.Transplantation.2018 Apr；102(4)：557-68.
20.Bailly E，Blancho G，Ville S，Morelon E，Bamoulid J，Caillard S，etal.Five-year outccmes after randomization treatment by rituximab in earlyacute antibody-mediated rejection in renal transplantation：long term outcomesof the RITUX ERAH Study.Am J Transplant.2017；17(Suppl 3).
21.Sautenet B，Blancho G，Büchler M，Morelon E，Toupance O，Barrou B，etal.One-year results of the effects of rituximab on acute antibody-mediatedreiection in renal transplantation：RITUX ERAH，a multicenter double-blindrandomized placebo-controlled trial.Transplantation.2016 Feb；100(2)：391-9.
22.Kulkarni S，Kirkiles-Smith NC，Deng YH，Formica RN，Moeckel G，BroeckerV，et al.Eculizumab therapy for chronic antibody-mediated injury in kidneytransplant recipients：a pilot randomized controlled trial.Am JTrahspjant.2017 Mar；17(3)：682-91.
23.EskandaryF，Regele H，Baumann L，Bond G，Kozakowski N，Wahrmann M，etal.A randomized trial of bortezomib in Iate antibody-mediated kidneytransplant rejection.J Am Soc Nephrol.2018；29：591-605.
24.Moreso F，Crespo M，Ruiz JC，Torres A，Gutierrez-Dalmau A，Osuna A，etal.Treatment of chronic antibody mediated rejection with intravenousimmunoglobulins and rituximab：a multicenter，prospective，randomized，double-blind clinical trial.Am J Transplant.2018；18：927-935.
25.
G，Rovira J，De Sousa-Amorim E，Villarreal J，Sole M，Revuelta I，et al.Treatment of active chronic antibody-mediated rejection with rituximab，IVIG and plasma exchange Am J Transplant.2017；17(Suppl 3).
26.Choi J，Aubert O，Vo A，Loupy A，Haas M，Puliyanda D，et al.Assessmentof tocilizumab(anti-interleukin-6 receptor monoclonal)as a potentialtreatmentfor chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients.Am J Transplant.2017；17：2381-9.
27.Choi J，Aubert O，Louie S，Ammerman N，Vo A，Peng A，et al.Extended experience using tocilizumab(anti-IL6R，TCZ)fbr the treatmant of chronic antibodymediated rejection(CABMR)Am J Transplant.2017；17(Suppl 3).
28.Puliyanda D，Kim l，Choi J，Haas M，ZhangX，Vo A，et al.Safety andefficacy of tocilizumab(anti-IL6R，TCZ)therapy in the treatment of chronicantibody mediated reiection(cABMR)in pediatric renal transplant recipients AmJ Transplant.2017；17(Suppl 3).
2g.Venkatachalam K，Reem D，Andrew M，Delos Santos R，A lhamad T.Efficacyand safety of tocilizumab in treatment of acute antibody mediatedreiection.Am J Transplant.2017；17(Suppl 3).
30.Chandran S，Leung J，Laszik Z，Tang Q，Hu C，Sarwal M，et al.IL-6inhibition with tocilizumab to promote tregs and control renal graftinflatmmation： a prospective randomized controlled trial.Am JTranspJant.2017；17(Suppl 3).
31.Patel S，Mohan S，Fernandez H，Batal l，Ratner L，Crew J.Tocilizumabstabilizes renal function in kdney transplant recipients with chronic activeantibody mediated rejection(CAAMR)Am J Transplant.2017；17(Suppl 3).
32.Vo AA，Choi J，Kim l，Louie S，Cisneros K，Kahwaji J，et al.A phase I/lltrial of the interleukin 6 receptor specific humanized monoclonal(tocilizumab)+intravenous immunoglobulin in difficult to desensitizepatients.Transplantation.2015；99(11)：2356-63.
33.Investigator’s Brochure Clazakizumab.Version 4.0.Finalreport.Victoria(BC)：Vitaeris Inc.；2018 May 1.
34.
(tocilizumab)injection，for intravenous or subcutaneoususe.Prescribing Information.Genentech，Inc.USA.2017 Aug.
35.RoActemra 20mg/ml concentrate for solution for infusion.Summary ofProduct Characteristics.Roche Products Limited，Garden City，Herfordshire，UK.2018 Apr 12.
36.Final report.Quantitative assessment of the relationship betweenchange in estimated glomerular filtration rate and risk of allograft failurein patients diagnosed with active antibody-mediated rejection followingkidney transplantation.Vancouver(BC)：Vitaeris Inc.；2018Jun 1.
37.Loupy A，Haas M，Solez K，Racusen L，Glotz D，Seron D，et al.The Banff2015 Kidney Meeting Report：current challenges：in rejection classificationandprospects for adopting molecular pathology.Am J Transplant.2017；17(1)：28-41.
38、Clinical study.redort IM1 33001.Phase.IIB，randomized，multi-center，double-blind，dose-ranging，placebo/active controlled study to evaluate theefficacy and safety of BMS-95429 subcutaneous iniection with or withoutmethotrexate in subjects with moderate to severe rheumatoid arthritis(RA)withinadequate response to methotrexate.Final report.Bristol-Myers SquibbCompany；2014Sep 12.Report No.：IM1 33001.
39.Hoffmann-La Roche Inc.Tocilizumab Arthritis AdvisoryCommittee.2008Jul 29.
40.Clinical trial results summary IM 133066.A Phase Ilb，randomized，multi-Center，double-blind，dose-Ranging Study to evaluate the efficacy andsafety of clazakizumab in subjects with moderate to severe active rheumatoidarthritis who have experienced an inadequate response to.TNFinhibitors.Report in preparation.Preliminary results available uponrequest.Report No.：lM133066.
41.Zhao Q，Pang J，Shuster D，Hung C，Baglino S，Dodge R，et al.Anti-IL-6antibody clazakizumab is more potent than tocilizumab in blocking in vitroand in vivo IL-6-induced functions.ACR/ARHP Annual Meeting；2013 Oct 25-30；SanDiego，CA.Poster 2385.
42.National Cancer Institute.Common Terminology Criteria for AdverseEvents(CTCAE).Versioh 5.0.2017Nov 27.
43.Bohmig GA，Budde K.Safety，tolerability and efficacy of anti-IL-6antibody clazakizumab in late antibody-mediated reiection after kidneytransplantation-a pilot trial.Medical University of Vienna；2018.
44.Kevzara(sarilumab)injection.Prescribing Information.RegeneronPharmaceuticals，Inc./sanofi-aventis U.S.LLC，USA.2017May.
45.Levey AS，Coresh J，Greene T，Stevens LA，Yaping Z，Hendriksen S，etal.Using standardized serum creatinine values in the modification of diet inrenal disease study equation for estimating glomerular filtration rate.Annlntern Med.2006Aug 15；145(4)：247-54.
46.Sampson HA，
-Furlong A，Campbell RL，Adkinson NF，Bock SA，BranumA，et al.Second symposium on the definition and management of anaphylaxis：summary report-Second National Institute of Allergy and lnfectious Disease/Food Allergy and Anaphylaxis Network Symposium.Ann Emerg Med.2006Apr；47(4)：373-80.
47.Humar A，Michaels M.American Society of Transplantationrecommendations for screening，monitoring and reporting of infectiouscomplications in immunosuppression trials in recipients of organtransplantation.Am J Transplant.2006；6：262-74.
48.Tong A，Sautenet B，Poggio ED，Lentine KL，Oberbauer R，Mannon R，etal.Establishing a core outcome measure for graft health：a standardizedoutcomes in Nephrology-Kidney Transplantation(SONG-Tx)Consensus WorkshopReport.Transplantation.2018Aug；102(8)：1358-66.
4g.Kidney International Supplements.Section 2：AKI Definition.KDIGOClinical praetice guideline for acute kidney injury.Kidney Int Suppl.2012；2：19-36.
50.World Medical Association.World Medical.Association Declaration ofHelsinki.Ethical principles for medical research involving humansubjects.JAMA.2013Nov；310(20)：2191-4.
51.ICH Harmonised Tripartite Guideline.Guideline for good clinicalpractice.E6(R1)1996 Jun 10.
52.Pharmaceutical Research and Manufacturers of America.Principles onconduct of clinical trials.Communication of Clinical Trial Results.Washington(DC)；2014Dec.Available from：http：//phrma-docs.phrma.org/sites/default/files/pdf/042009_clinical _trial_principles_final_0.pdf.
53.Intemational Comiittee of Medical Journal Edito rsCriteria.Defining the role of authors and contributors.C2018[accessed 2018Jul27].Available from：http：//www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors.html.
序列表
<110> 周, 凯文(Chow, Kevin)
庄, 爱德华(Chong, Edward)
慕尼, 诺阿拉(Mooney, Nuala)
莱昂, 朱利恩(Lion, Julien)
<120> 抗IL-6抗体例如克拉扎珠单抗(Clazakizumab)用于使实体器官移植接受者脱敏和/或用于预防、稳定或减轻抗体介导的排斥(ABMR)的用途
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Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
145 150 155 160
Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
165 170
<210> 22
<211> 167
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 22
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Lys Glu Ser Gly Gly Arg Leu Val Thr
20 25 30
Pro Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu
35 40 45
Asn Asp His Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Phe Ile Asn Ser Gly Gly Ser Ala Arg Tyr Ala Ser
65 70 75 80
Trp Ala Glu Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Val Arg Gly Gly Ala Val Trp Ser Ile His Ser Phe Asp Pro Trp Gly
115 120 125
Pro Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
145 150 155 160
Ala Leu Gly Cys Leu Val Lys
165
<210> 23
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 23
Gln Ala Ser Glu Thr Ile Tyr Ser Trp Leu Ser
1 5 10
<210> 24
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 24
Gln Ala Ser Asp Leu Ala Ser
1 5
<210> 25
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 25
Gln Gln Gly Tyr Ser Gly Ser Asn Val Asp Asn Val
1 5 10
<210> 26
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 26
Asp His Ala Met Gly
1 5
<210> 27
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 27
Phe Ile Asn Ser Gly Gly Ser Ala Arg Tyr Ala Ser Trp Ala Glu Gly
1 5 10 15
<210> 28
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 28
Gly Gly Ala Val Trp Ser Ile His Ser Phe Asp Pro
1 5 10
<210> 29
<211> 511
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 29
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtgagacc atttacagtt ggttatcctg gtatcagcag 180
aagccagggc agcctcccaa gctcctgatc taccaggcat ccgatctggc atctggggtc 240
ccatcgcgat tcagcggcag tggggctggg acagagtaca ctctcaccat cagcggcgtg 300
cagtgtgacg atgctgccac ttactactgt caacagggtt atagtggtag taatgttgat 360
aatgttttcg gcggagggac cgaggtggtg gtcaaacgta cggtagcggc cccatctgtc 420
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480
ctgaataact tctatcccag agaggccaaa g 511
<210> 30
<211> 501
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 30
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctga aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacacttacc 120
tgcacagcct ctggattctc cctcaatgac catgcaatgg gctgggtccg ccaggctcca 180
gggaaggggc tggaatacat cggattcatt aatagtggtg gtagcgcacg ctacgcgagc 240
tgggcagaag gccgattcac catctccaga acctcgacca cggtggatct gaaaatgacc 300
agtctgacaa ccgaggacac ggccacctat ttctgtgtca gagggggtgc tgtttggagt 360
attcatagtt ttgatccctg gggcccaggg accctggtca ccgtctcgag cgcctccacc 420
aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 480
gccctgggct gcctggtcaa g 501
<210> 31
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 31
caggccagtg agaccattta cagttggtta tcc 33
<210> 32
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 32
caggcatccg atctggcatc t 21
<210> 33
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 33
caacagggtt atagtggtag taatgttgat aatgtt 36
<210> 34
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 34
gaccatgcaa tgggc 15
<210> 35
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 35
ttcattaata gtggtggtag cgcacgctac gcgagctggg cagaaggc 48
<210> 36
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 36
gggggtgctg tttggagtat tcatagtttt gatccc 36
<210> 37
<211> 165
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 37
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Val Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Thr Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asn Ala Phe Gly Gly Gly Thr
115 120 125
Glu Val Val Val Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe
130 135 140
Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys
145 150 155 160
Leu Leu Asn Asn Phe
165
<210> 38
<211> 166
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 38
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Val Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Phe Ile Thr Met Ser Asp Asn Ile Asn Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Ser Arg Gly Trp Gly Thr Met Gly Arg Leu Asp Leu Trp Gly Pro
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys
165
<210> 39
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 39
Gln Ala Ser Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ser
1 5 10
<210> 40
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 40
Gly Ala Ser Thr Leu Ala Ser
1 5
<210> 41
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 41
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asn Ala
1 5 10
<210> 42
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 42
Val Tyr Tyr Met Asn
1 5
<210> 43
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 43
Phe Ile Thr Met Ser Asp Asn Ile Asn Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 44
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 44
Ser Arg Gly Trp Gly Thr Met Gly Arg Leu Asp Leu
1 5 10
<210> 45
<211> 496
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 45
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccg ccgtgctgac ccagactcca tctcccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttatgaca acaactactt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcatccac tctggcatct 240
ggggtcccat cgcggttcgt gggcagtgga tctgggacac agttcactct caccatcaca 300
gacgtgcagt gtgacgatgc tgccacttac tattgtgcag gcgtttatga tgatgatagt 360
gataatgcct tcggcggagg gaccgaggtg gtggtcaaac gtacggtagc ggccccatct 420
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 480
ctgctgaata acttct 496
<210> 46
<211> 499
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 46
atggagactg ggctgcgctg gcttctcctg gtggctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acccctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtgtctac tacatgaact gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg attcattaca atgagtgata atataaatta cgcgagctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagga gtcgtggctg gggtacaatg 360
ggtcggttgg atctctgggg cccaggcacc ctcgtcaccg tctcgagcgc ctccaccaag 420
ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480
ctgggctgcc tggtcaagg 499
<210> 47
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 47
caggccagtc agagtgttta tgacaacaac tacttatcc 39
<210> 48
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 48
ggtgcatcca ctctggcatc t 21
<210> 49
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 49
gcaggcgttt atgatgatga tagtgataat gcc 33
<210> 50
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 50
gtctactaca tgaac 15
<210> 51
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 51
ttcattacaa tgagtgataa tataaattac gcgagctggg cgaaaggc 48
<210> 52
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 52
agtcgtggct ggggtacaat gggtcggttg gatctc 36
<210> 53
<211> 164
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 53
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Ile Cys Asp Pro Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Pro Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Glu Asn Asn Tyr Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Leu Asp Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Thr Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asp Ala Phe Gly Gly Gly Thr
115 120 125
Glu Val Val Val Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe
130 135 140
Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys
145 150 155 160
Leu Leu Asn Asn
<210> 54
<211> 167
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 54
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Thr
20 25 30
Pro Gly Gly Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu
35 40 45
Asn Ala Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Gly Phe Ile Thr Leu Asn Asn Asn Val Ala Tyr Ala Asn
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Phe Ser Lys Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Pro Thr Pro Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Ser Arg Gly Trp Gly Ala Met Gly Arg Leu Asp Leu Trp Gly
115 120 125
His Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
130 135 140
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
145 150 155 160
Ala Leu Gly Cys Leu Val Lys
165
<210> 55
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 55
Gln Ala Ser Gln Ser Val Tyr Glu Asn Asn Tyr Leu Ser
1 5 10
<210> 56
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 56
Gly Ala Ser Thr Leu Asp Ser
1 5
<210> 57
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 57
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asp Ala
1 5 10
<210> 58
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 58
Ala Tyr Tyr Met Asn
1 5
<210> 59
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 59
Phe Ile Thr Leu Asn Asn Asn Val Ala Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 60
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 60
Ser Arg Gly Trp Gly Ala Met Gly Arg Leu Asp Leu
1 5 10
<210> 61
<211> 494
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 61
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
atatgtgacc ctgtgctgac ccagactcca tctcccgtat ctgcacctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttatgaga acaactattt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcatccac tctggattct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccattaca 300
gacgtgcagt gtgacgatgc tgccacttac tattgtgcag gcgtttatga tgatgatagt 360
gatgatgcct tcggcggagg gaccgaggtg gtggtcaaac gtacggtagc ggccccatct 420
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 480
ctgctgaata actt 494
<210> 62
<211> 502
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 62
atggagactg ggctgcgctg gcttctcctg gtggctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctga aggagtccgg aggaggcctg gtaacgcctg gaggaaccct gacactcacc 120
tgcacagcct ctggattctc cctcaatgcc tactacatga actgggtccg ccaggctcca 180
gggaaggggc tggaatggat cggattcatt actctgaata ataatgtagc ttacgcgaac 240
tgggcgaaag gccgattcac cttctccaaa acctcgacca cggtggatct gaaaatgacc 300
agtccgacac ccgaggacac ggccacctat ttctgtgcca ggagtcgtgg ctggggtgca 360
atgggtcggt tggatctctg gggccatggc accctggtca ccgtctcgag cgcctccacc 420
aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 480
gccctgggct gcctggtcaa gg 502
<210> 63
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 63
caggccagtc agagtgttta tgagaacaac tatttatcc 39
<210> 64
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 64
ggtgcatcca ctctggattc t 21
<210> 65
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 65
gcaggcgttt atgatgatga tagtgatgat gcc 33
<210> 66
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 66
gcctactaca tgaac 15
<210> 67
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 67
ttcattactc tgaataataa tgtagcttac gcgaactggg cgaaaggc 48
<210> 68
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 68
agtcgtggct ggggtgcaat gggtcggttg gatctc 36
<210> 69
<211> 164
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 69
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Val Asp Asp Asn Asn Trp Leu Gly Trp Tyr Gln Gln Lys Arg
50 55 60
Gly Gln Pro Pro Lys Tyr Leu Ile Tyr Ser Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Gly Phe Ser Gly Asn Ile Phe Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro
130 135 140
Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
145 150 155 160
Leu Asn Asn Phe
<210> 70
<211> 164
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 70
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Gly Gly Phe Gly Thr Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Arg Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Gly Gly Pro Gly Asn Gly Gly Asp Ile Trp Gly Gln Gly Thr Leu
115 120 125
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
130 135 140
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys
145 150 155 160
Leu Val Lys Asp
<210> 71
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 71
Gln Ala Ser Gln Ser Val Asp Asp Asn Asn Trp Leu Gly
1 5 10
<210> 72
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 72
Ser Ala Ser Thr Leu Ala Ser
1 5
<210> 73
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 73
Ala Gly Gly Phe Ser Gly Asn Ile Phe Ala
1 5 10
<210> 74
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 74
Ser Tyr Ala Met Ser
1 5
<210> 75
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 75
Ile Ile Gly Gly Phe Gly Thr Thr Tyr Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 76
<211> 9
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 76
Gly Gly Pro Gly Asn Gly Gly Asp Ile
1 5
<210> 77
<211> 493
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 77
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactcca tcgcctgtgt ctgcagctgt gggaggcaca 120
gtcaccatca actgccaggc cagtcagagt gttgatgata acaactggtt aggctggtat 180
cagcagaaac gagggcagcc tcccaagtac ctgatctatt ctgcatccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
gacctggagt gtgacgatgc tgccacttac tactgtgcag gcggttttag tggtaatatc 360
tttgctttcg gcggagggac cgaggtggtg gtcaaacgta cggtagcggc cccatctgtc 420
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480
ctgaataact tct 493
<210> 78
<211> 493
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 78
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gcttctccct cagtagctat gcaatgagct gggtccgcca ggctccagga 180
aaggggctgg agtggatcgg aatcattggt ggttttggta ccacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgag aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag gtggtcctgg taatggtggt 360
gacatctggg gccaagggac cctggtcacc gtctcgagcg cctccaccaa gggcccatcg 420
gtcttccccc tggcaccctc ctccaagagc acctctgggg gcacagcggc cctgggctgc 480
ctggtcaagg act 493
<210> 79
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 79
caggccagtc agagtgttga tgataacaac tggttaggc 39
<210> 80
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 80
tctgcatcca ctctggcatc t 21
<210> 81
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 81
gcaggcggtt ttagtggtaa tatctttgct 30
<210> 82
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 82
agctatgcaa tgagc 15
<210> 83
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 83
atcattggtg gttttggtac cacatactac gcgacctggg cgaaaggc 48
<210> 84
<211> 27
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 84
ggtggtcctg gtaatggtgg tgacatc 27
<210> 85
<211> 164
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 85
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Val Pro Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Phe Leu Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Gln Ala Ser Lys Leu Ala Ser Gly
65 70 75 80
Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu
85 90 95
Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Leu
100 105 110
Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro
130 135 140
Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
145 150 155 160
Leu Asn Asn Phe
<210> 86
<211> 170
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 86
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Asp Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Tyr Ala Gly Ser Gly Ser Thr Trp Tyr Ala Ser
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Asp Gly Tyr Asp Asp Tyr Gly Asp Phe Asp Arg Leu Asp Leu
115 120 125
Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
130 135 140
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
145 150 155 160
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
165 170
<210> 87
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 87
Gln Ser Ser Gln Ser Val Tyr Asn Asn Phe Leu Ser
1 5 10
<210> 88
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 88
Gln Ala Ser Lys Leu Ala Ser
1 5
<210> 89
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 89
Leu Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
1 5 10
<210> 90
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 90
Asp Tyr Ala Met Ser
1 5
<210> 91
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 91
Ile Ile Tyr Ala Gly Ser Gly Ser Thr Trp Tyr Ala Ser Trp Ala Lys
1 5 10 15
Gly
<210> 92
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 92
Asp Gly Tyr Asp Asp Tyr Gly Asp Phe Asp Arg Leu Asp Leu
1 5 10
<210> 93
<211> 492
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 93
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcgcccgtgt ctgtacctgt gggaggcaca 120
gtcaccatca agtgccagtc cagtcagagt gtttataata atttcttatc gtggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctaccagg catccaaact ggcatctggg 240
gtcccagata ggttcagcgg cagtggatct gggacacagt tcactctcac catcagcggc 300
gtgcagtgtg acgatgctgc cacttactac tgtctaggcg gttatgatga tgatgctgat 360
aatgctttcg gcggagggac cgaggtggtg gtcaaacgta cggtagcggc cccatctgtc 420
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480
ctgaataact tc 492
<210> 94
<211> 511
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 94
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac gctcacctgc 120
acagtctctg gaatcgacct cagtgactat gcaatgagct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcatttat gctggtagtg gtagcacatg gtacgcgagc 240
tgggcgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcacc 300
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gagatggata cgatgactat 360
ggtgatttcg atcgattgga tctctggggc ccaggcaccc tcgtcaccgt ctcgagcgcc 420
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 480
acagcggccc tgggctgcct ggtcaaggac t 511
<210> 95
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 95
cagtccagtc agagtgttta taataatttc ttatcg 36
<210> 96
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 96
caggcatcca aactggcatc t 21
<210> 97
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 97
ctaggcggtt atgatgatga tgctgataat gct 33
<210> 98
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 98
gactatgcaa tgagc 15
<210> 99
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 99
atcatttatg ctggtagtgg tagcacatgg tacgcgagct gggcgaaagg c 51
<210> 100
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 100
gatggatacg atgactatgg tgatttcgat cgattggatc tc 42
<210> 101
<211> 164
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 101
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Asn Asn Glu Leu Ser Trp Tyr Gln Gln Lys Ser Gly Gln
50 55 60
Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Leu Arg Asn Ile Asp Asn Ala Phe Gly Gly Gly Thr Glu
115 120 125
Val Val Val Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro
130 135 140
Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu
145 150 155 160
Leu Asn Asn Phe
<210> 102
<211> 166
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 102
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Ser Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Asn Tyr Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Trp
65 70 75 80
Ala Ile Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys
165
<210> 103
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 103
Gln Ala Ser Gln Ser Ile Asn Asn Glu Leu Ser
1 5 10
<210> 104
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 104
Arg Ala Ser Thr Leu Ala Ser
1 5
<210> 105
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 105
Gln Gln Gly Tyr Ser Leu Arg Asn Ile Asp Asn Ala
1 5 10
<210> 106
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 106
Asn Tyr Tyr Met Thr
1 5
<210> 107
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 107
Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Trp Ala Ile Gly
1 5 10 15
<210> 108
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 108
Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu
1 5 10
<210> 109
<211> 492
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 109
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctcggtgt ctgcagctgt gggaggcaca 120
gtcaccatca aatgccaggc cagtcagagc attaacaatg aattatcctg gtatcagcag 180
aaatcagggc agcgtcccaa gctcctgatc tatagggcat ccactctggc atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caacagggtt atagtctgag gaatattgat 360
aatgctttcg gcggagggac cgaggtggtg gtcaaacgta cggtagcggc cccatctgtc 420
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 480
ctgaataact tc 492
<210> 110
<211> 499
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 110
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tctcaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtaactac tacatgacct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatgatttat ggtagtgatg aaacagccta cgcgaactgg 240
gcgataggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ctgacagccg cggacacggc cacctatttc tgtgccagag atgatagtag tgactgggat 360
gcaaaattta acttgtgggg ccaagggacc ctcgtcaccg tctcgagcgc ctccaccaag 420
ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 480
ctgggctgcc tggtcaagg 499
<210> 111
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 111
caggccagtc agagcattaa caatgaatta tcc 33
<210> 112
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 112
agggcatcca ctctggcatc t 21
<210> 113
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 113
caacagggtt atagtctgag gaatattgat aatgct 36
<210> 114
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 114
aactactaca tgacc 15
<210> 115
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 115
atgatttatg gtagtgatga aacagcctac gcgaactggg cgataggc 48
<210> 116
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 116
gatgatagta gtgactggga tgcaaaattt aacttg 36
<210> 117
<211> 109
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 117
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Trp Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu
100 105
<210> 118
<211> 109
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 118
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu
100 105
<210> 119
<211> 100
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 119
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala
100
<210> 120
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 120
Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile Gly
1 5 10 15
<210> 121
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 121
Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Ser Ala Ile Gly
1 5 10 15
<210> 122
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 122
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Gly Asn Asn Gln Asp Leu Ser Trp Phe Gln Gln Arg Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Glu Ile Ser Lys Leu Glu Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr His Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
115 120
<210> 123
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 123
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys His Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Arg Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Tyr Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Leu Gly Asp Thr Gly Gly His Ala Tyr Ala Thr Arg Leu Asn Leu
115 120 125
<210> 124
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 124
Gln Ser Ser Gln Ser Val Gly Asn Asn Gln Asp Leu Ser
1 5 10
<210> 125
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 125
Glu Ile Ser Lys Leu Glu Ser
1 5
<210> 126
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 126
Leu Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
1 5 10
<210> 127
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 127
Ser Arg Thr Met Ser
1 5
<210> 128
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 128
Tyr Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 129
<211> 15
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 129
Leu Gly Asp Thr Gly Gly His Ala Tyr Ala Thr Arg Leu Asn Leu
1 5 10 15
<210> 130
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 130
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcacccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca gttgccagtc cagtcagagt gttggtaata accaggactt atcctggttt 180
cagcagagac cagggcagcc tcccaagctc ctgatctacg aaatatccaa actggaatct 240
ggggtcccat cgcggttcag cggcagtgga tctgggacac acttcactct caccatcagc 300
ggcgtacagt gtgacgatgc tgccacttac tactgtctag gcggttatga tgatgatgct 360
gataatgct 369
<210> 131
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 131
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcac 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct cagtagtcgt acaatgtcct gggtccgcca ggctccaggg 180
aaggggctgg agtggatcgg atacatttgg agtggtggta gcacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagat tgggcgatac tggtggtcac 360
gcttatgcta ctcgcttaaa tctc 384
<210> 132
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 132
cagtccagtc agagtgttgg taataaccag gacttatcc 39
<210> 133
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 133
gaaatatcca aactggaatc t 21
<210> 134
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 134
ctaggcggtt atgatgatga tgctgataat gct 33
<210> 135
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 135
agtcgtacaa tgtcc 15
<210> 136
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 136
tacatttgga gtggtggtag cacatactac gcgacctggg cgaaaggc 48
<210> 137
<211> 45
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 137
ttgggcgata ctggtggtca cgcttatgct actcgcttaa atctc 45
<210> 138
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 138
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Ser Asn Lys Tyr Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Thr Ser Lys Leu Ala Ser
65 70 75 80
Gly Ala Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Ala Tyr Asp Asp Asp Ala Asp Asn Ala
115 120
<210> 139
<211> 126
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 139
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Lys Pro
20 25 30
Asp Glu Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Glu
35 40 45
Gly Gly Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ser Tyr Asp Ser Gly Ser Thr Tyr Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Val Arg Ser Leu Lys Tyr Pro Thr Val Thr Ser Asp Asp Leu
115 120 125
<210> 140
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 140
Gln Ser Ser Gln Ser Val Tyr Ser Asn Lys Tyr Leu Ala
1 5 10
<210> 141
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 141
Trp Thr Ser Lys Leu Ala Ser
1 5
<210> 142
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 142
Leu Gly Ala Tyr Asp Asp Asp Ala Asp Asn Ala
1 5 10
<210> 143
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 143
Gly Gly Tyr Met Thr
1 5
<210> 144
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 144
Ile Ser Tyr Asp Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 145
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 145
Ser Leu Lys Tyr Pro Thr Val Thr Ser Asp Asp Leu
1 5 10
<210> 146
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 146
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcgtccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccagtc cagtcagagt gtttatagta ataagtacct agcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctact ggacatccaa actggcatct 240
ggggccccat cacggttcag cggcagtgga tctgggacac aattcactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgccacttac tactgtctag gcgcttatga tgatgatgct 360
gataatgct 369
<210> 147
<211> 378
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 147
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggaag agtccggggg tcgcctggtc aagcctgacg aaaccctgac actcacctgc 120
acagcctctg gattctccct ggagggcggc tacatgacct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcagttat gatagtggta gcacatacta cgcgagctgg 240
gcgaaaggcc gattcaccat ctccaagacc tcgtcgacca cggtggatct gaaaatgacc 300
agtctgacaa ccgaggacac ggccacctat ttctgcgtca gatcactaaa atatcctact 360
gttacttctg atgacttg 378
<210> 148
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 148
cagtccagtc agagtgttta tagtaataag tacctagcc 39
<210> 149
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 149
tggacatcca aactggcatc t 21
<210> 150
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 150
ctaggcgctt atgatgatga tgctgataat gct 33
<210> 151
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 151
ggcggctaca tgacc 15
<210> 152
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 152
atcagttatg atagtggtag cacatactac gcgagctggg cgaaaggc 48
<210> 153
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 153
tcactaaaat atcctactgt tacttctgat gacttg 36
<210> 154
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 154
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Asn Asp Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Ala Tyr Tyr Cys
100 105 110
Leu Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
115 120
<210> 155
<211> 129
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 155
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Leu Ser Leu Ser
35 40 45
Ser Asn Thr Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Tyr Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Ser Trp
65 70 75 80
Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Gly Gly Tyr Ala Ser Gly Gly Tyr Pro Tyr Ala Thr Arg Leu Asp
115 120 125
Leu
<210> 156
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 156
Gln Ser Ser Gln Ser Val Tyr Asn Asn Asn Asp Leu Ala
1 5 10
<210> 157
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 157
Tyr Ala Ser Thr Leu Ala Ser
1 5
<210> 158
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 158
Leu Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
1 5 10
<210> 159
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 159
Ser Asn Thr Ile Asn
1 5
<210> 160
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 160
Tyr Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Ser Trp Val Asn Gly
1 5 10 15
<210> 161
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 161
Gly Gly Tyr Ala Ser Gly Gly Tyr Pro Tyr Ala Thr Arg Leu Asp Leu
1 5 10 15
<210> 162
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 162
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcacccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca gttgccagtc cagtcagagt gtttataata ataacgactt agcctggtat 180
cagcagaaac cagggcagcc tcctaaactc ctgatctatt atgcatccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgccgcttac tactgtctag gcggttatga tgatgatgct 360
gataatgct 369
<210> 163
<211> 387
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 163
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtatctg gattatccct cagtagcaat acaataaact gggtccgcca ggctccaggg 180
aaggggctgg agtggatcgg atacatttgg agtggtggta gtacatacta cgcgagctgg 240
gtgaatggtc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag ggggttacgc tagtggtggt 360
tatccttatg ccactcggtt ggatctc 387
<210> 164
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 164
cagtccagtc agagtgttta taataataac gacttagcc 39
<210> 165
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 165
tatgcatcca ctctggcatc t 21
<210> 166
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 166
ctaggcggtt atgatgatga tgctgataat gct 33
<210> 167
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 167
agcaatacaa taaac 15
<210> 168
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 168
tacatttgga gtggtggtag tacatactac gcgagctggg tgaatggt 48
<210> 169
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 169
gggggttacg ctagtggtgg ttatccttat gccactcggt tggatctc 48
<210> 170
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 170
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Asp Tyr Leu Ser Trp Tyr Gln Gln Arg Pro
50 55 60
Gly Gln Arg Pro Lys Leu Leu Ile Tyr Gly Ala Ser Lys Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Lys Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Asp Tyr Asp Asp Asp Ala Asp Asn Thr
115 120
<210> 171
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 171
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Thr Leu Ser
35 40 45
Thr Asn Tyr Tyr Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Gly Ile Ile Tyr Pro Ser Gly Asn Thr Tyr Cys Ala Lys
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val
85 90 95
Asp Leu Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe
100 105 110
Cys Ala Arg Asn Tyr Gly Gly Asp Glu Ser Leu
115 120
<210> 172
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 172
Gln Ser Ser Gln Ser Val Tyr Asn Asn Asp Tyr Leu Ser
1 5 10
<210> 173
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 173
Gly Ala Ser Lys Leu Ala Ser
1 5
<210> 174
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 174
Leu Gly Asp Tyr Asp Asp Asp Ala Asp Asn Thr
1 5 10
<210> 175
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 175
Thr Asn Tyr Tyr Leu Ser
1 5
<210> 176
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 176
Ile Ile Tyr Pro Ser Gly Asn Thr Tyr Cys Ala Lys Trp Ala Lys Gly
1 5 10 15
<210> 177
<211> 8
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 177
Asn Tyr Gly Gly Asp Glu Ser Leu
1 5
<210> 178
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 178
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccagtc cagtcagagt gtttataata acgactactt atcctggtat 180
caacagaggc cagggcaacg tcccaagctc ctaatctatg gtgcttccaa actggcatct 240
ggggtcccgt cacggttcaa aggcagtgga tctgggaaac agtttactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgccacttac tactgtctgg gcgattatga tgatgatgct 360
gataatact 369
<210> 179
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 179
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacttgc 120
acagtctctg gattcaccct cagtaccaac tactacctga gctgggtccg ccaggctcca 180
gggaaggggc tagaatggat cggaatcatt tatcctagtg gtaacacata ttgcgcgaag 240
tgggcgaaag gccgattcac catctccaaa acctcgtcga ccacggtgga tctgaaaatg 300
accagtccga caaccgagga cacagccacg tatttctgtg ccagaaatta tggtggtgat 360
gaaagtttg 369
<210> 180
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 180
cagtccagtc agagtgttta taataacgac tacttatcc 39
<210> 181
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 181
ggtgcttcca aactggcatc t 21
<210> 182
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 182
ctgggcgatt atgatgatga tgctgataat act 33
<210> 183
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 183
accaactact acctgagc 18
<210> 184
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 184
atcatttatc ctagtggtaa cacatattgc gcgaagtggg cgaaaggc 48
<210> 185
<211> 24
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 185
aattatggtg gtgatgaaag tttg 24
<210> 186
<211> 119
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 186
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Glu Thr Ile Gly Asn Ala Leu Ala Trp Tyr Gln Gln Lys Ser Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Lys Ala Ser Lys Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Trp
100 105 110
Cys Tyr Phe Gly Asp Ser Val
115
<210> 187
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 187
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Thr Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
20 25 30
Pro Glu Gly Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Asp Phe
35 40 45
Ser Ser Gly Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Ala Cys Ile Phe Thr Ile Thr Thr Asn Thr Tyr Tyr
65 70 75 80
Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Leu Cys Ala Arg Gly Ile Tyr Ser Asp Asn Asn Tyr Tyr Ala Leu
115 120 125
<210> 188
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 188
Gln Ala Ser Glu Thr Ile Gly Asn Ala Leu Ala
1 5 10
<210> 189
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 189
Lys Ala Ser Lys Leu Ala Ser
1 5
<210> 190
<211> 9
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 190
Gln Trp Cys Tyr Phe Gly Asp Ser Val
1 5
<210> 191
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 191
Ser Gly Tyr Tyr Met Cys
1 5
<210> 192
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 192
Cys Ile Phe Thr Ile Thr Thr Asn Thr Tyr Tyr Ala Ser Trp Ala Lys
1 5 10 15
Gly
<210> 193
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 193
Gly Ile Tyr Ser Asp Asn Asn Tyr Tyr Ala Leu
1 5 10
<210> 194
<211> 357
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 194
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtgagacc attggcaatg cattagcctg gtatcagcag 180
aaatcagggc agcctcccaa gctcctgatc tacaaggcat ccaaactggc atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acagagtaca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caatggtgtt attttggtga tagtgtt 357
<210> 195
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 195
atggagactg ggctgcgctg gcttctcctg gtcactgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg tggagtccgg gggaggcctg gtccagcctg agggatccct gacactcacc 120
tgcacagcct ctggattcga cttcagtagc ggctactaca tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtg gatcgcgtgt attttcacta ttactactaa cacttactac 240
gcgagctggg cgaaaggccg attcaccatc tccaagacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatc tctgtgcgag agggatttat 360
tctgataata attattatgc cttg 384
<210> 196
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 196
caggccagtg agaccattgg caatgcatta gcc 33
<210> 197
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 197
aaggcatcca aactggcatc t 21
<210> 198
<211> 27
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 198
caatggtgtt attttggtga tagtgtt 27
<210> 199
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 199
agcggctact acatgtgc 18
<210> 200
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 200
tgtattttca ctattactac taacacttac tacgcgagct gggcgaaagg c 51
<210> 201
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 201
gggatttatt ctgataataa ttattatgcc ttg 33
<210> 202
<211> 119
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 202
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Glu Ser Ile Gly Asn Ala Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Lys Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Gly Val Gln Cys Ala Asp Ala Ala Ala Tyr Tyr Cys Gln Trp
100 105 110
Cys Tyr Phe Gly Asp Ser Val
115
<210> 203
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 203
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Gln Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys
20 25 30
Pro Gly Ala Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Phe Ser Phe
35 40 45
Ser Ser Gly Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly
50 55 60
Leu Glu Ser Ile Ala Cys Ile Phe Thr Ile Thr Asp Asn Thr Tyr Tyr
65 70 75 80
Ala Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Pro Ser Ser Pro
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Ile Tyr Ser Thr Asp Asn Tyr Tyr Ala Leu
115 120 125
<210> 204
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 204
Gln Ala Ser Glu Ser Ile Gly Asn Ala Leu Ala
1 5 10
<210> 205
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 205
Lys Ala Ser Thr Leu Ala Ser
1 5
<210> 206
<211> 9
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 206
Gln Trp Cys Tyr Phe Gly Asp Ser Val
1 5
<210> 207
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 207
Ser Gly Tyr Tyr Met Cys
1 5
<210> 208
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 208
Cys Ile Phe Thr Ile Thr Asp Asn Thr Tyr Tyr Ala Asn Trp Ala Lys
1 5 10 15
Gly
<210> 209
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 209
Gly Ile Tyr Ser Thr Asp Asn Tyr Tyr Ala Leu
1 5 10
<210> 210
<211> 357
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 210
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtgagagc attggcaatg cattagcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tacaaggcat ccactctggc atctggggtc 240
ccatcgcggt tcagcggcag tggatctggg acagagttca ctctcaccat cagcggcgtg 300
cagtgtgccg atgctgccgc ttactactgt caatggtgtt attttggtga tagtgtt 357
<210> 211
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 211
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
cagcagctgg tggagtccgg gggaggcctg gtcaagccgg gggcatccct gacactcacc 120
tgcaaagcct ctggattctc cttcagtagc ggctactaca tgtgctgggt ccgccaggct 180
ccagggaagg ggctggagtc gatcgcatgc atttttacta ttactgataa cacttactac 240
gcgaactggg cgaaaggccg attcaccatc tccaagccct cgtcgcccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgag ggggatttat 360
tctactgata attattatgc cttg 384
<210> 212
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 212
caggccagtg agagcattgg caatgcatta gcc 33
<210> 213
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 213
aaggcatcca ctctggcatc t 21
<210> 214
<211> 27
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 214
caatggtgtt attttggtga tagtgtt 27
<210> 215
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 215
agcggctact acatgtgc 18
<210> 216
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 216
tgcattttta ctattactga taacacttac tacgcgaact gggcgaaagg c 51
<210> 217
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 217
gggatttatt ctactgataa ttattatgcc ttg 33
<210> 218
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 218
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Val Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Glu Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys
100 105 110
Thr Tyr Gly Thr Ser Ser Ser Tyr Gly Ala Ala
115 120
<210> 219
<211> 133
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 219
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Ser Leu Ser
35 40 45
Ser Asn Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Ser Tyr Ser Gly Thr Thr Tyr Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Asp Asp Pro Thr Thr Val Met Val Met Leu Ile Pro Phe Gly
115 120 125
Ala Gly Met Asp Leu
130
<210> 220
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 220
Gln Ala Ser Gln Ser Val Ser Ser Tyr Leu Asn
1 5 10
<210> 221
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 221
Arg Ala Ser Thr Leu Glu Ser
1 5
<210> 222
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 222
Gln Cys Thr Tyr Gly Thr Ser Ser Ser Tyr Gly Ala Ala
1 5 10
<210> 223
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 223
Ser Asn Ala Ile Ser
1 5
<210> 224
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 224
Ile Ile Ser Tyr Ser Gly Thr Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 225
<211> 19
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 225
Asp Asp Pro Thr Thr Val Met Val Met Leu Ile Pro Phe Gly Ala Gly
1 5 10 15
Met Asp Leu
<210> 226
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 226
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc gttagtagct acttaaactg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tacagggcat ccactctgga atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caatgtactt atggtactag tagtagttat 360
ggtgctgct 369
<210> 227
<211> 399
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 227
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
accgtctctg gtatctccct cagtagcaat gcaataagct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcattagt tatagtggta ccacatacta cgcgagctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgtcgacca cggtggatct gaaaatcact 300
agtccgacaa ccgaggacac ggccacctac ttctgtgcca gagatgaccc tacgacagtt 360
atggttatgt tgataccttt tggagccggc atggacctc 399
<210> 228
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 228
caggccagtc agagcgttag tagctactta aac 33
<210> 229
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 229
agggcatcca ctctggaatc t 21
<210> 230
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 230
caatgtactt atggtactag tagtagttat ggtgctgct 39
<210> 231
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 231
agcaatgcaa taagc 15
<210> 232
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 232
atcattagtt atagtggtac cacatactac gcgagctggg cgaaaggc 48
<210> 233
<211> 57
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 233
gatgacccta cgacagttat ggttatgttg ataccttttg gagccggcat ggacctc 57
<210> 234
<211> 125
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 234
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Ala Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Lys Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Gly Leu Ile Tyr Ser Ala Ser Thr Leu Asp Ser
65 70 75 80
Gly Val Pro Leu Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Ser Tyr Asp Cys Ser Ser Gly Asp Cys Tyr Ala
115 120 125
<210> 235
<211> 119
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 235
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Glu Gly Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Ser
35 40 45
Ser Tyr Trp Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Ala Cys Ile Val Thr Gly Asn Gly Asn Thr Tyr Tyr Ala Asn
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val
85 90 95
Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe
100 105 110
Cys Ala Lys Ala Tyr Asp Leu
115
<210> 236
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 236
Gln Ala Ser Gln Ser Val Tyr Lys Asn Asn Tyr Leu Ser
1 5 10
<210> 237
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 237
Ser Ala Ser Thr Leu Asp Ser
1 5
<210> 238
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 238
Leu Gly Ser Tyr Asp Cys Ser Ser Gly Asp Cys Tyr Ala
1 5 10
<210> 239
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 239
Ser Tyr Trp Met Cys
1 5
<210> 240
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 240
Cys Ile Val Thr Gly Asn Gly Asn Thr Tyr Tyr Ala Asn Trp Ala Lys
1 5 10 15
Gly
<210> 241
<211> 4
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 241
Ala Tyr Asp Leu
1
<210> 242
<211> 375
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 242
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactgca tcgcccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca actgccaggc cagtcagagt gtttataaga acaactactt atcctggtat 180
cagcagaaac cagggcagcc tcccaaaggc ctgatctatt ctgcatcgac tctagattct 240
ggggtcccat tgcggttcag cggcagtgga tctgggacac agttcactct caccatcagc 300
gacgtgcagt gtgacgatgc tgccacttac tactgtctag gcagttatga ttgtagtagt 360
ggtgattgtt atgct 375
<210> 243
<211> 357
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 243
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgagg gatccctgac actcacctgc 120
acagcctctg gattctcctt cagtagctac tggatgtgct gggtccgcca ggctccaggg 180
aaggggctgg agtggatcgc atgcattgtt actggtaatg gtaacactta ctacgcgaac 240
tgggcgaaag gccgattcac catctccaaa acctcgtcga ccacggtgac tctgcaaatg 300
accagtctga cagccgcgga cacggccacc tatttttgtg cgaaagccta tgacttg 357
<210> 244
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 244
caggccagtc agagtgttta taagaacaac tacttatcc 39
<210> 245
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 245
tctgcatcga ctctagattc t 21
<210> 246
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 246
ctaggcagtt atgattgtag tagtggtgat tgttatgct 39
<210> 247
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 247
agctactgga tgtgc 15
<210> 248
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 248
tgcattgtta ctggtaatgg taacacttac tacgcgaact gggcgaaagg c 51
<210> 249
<211> 12
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 249
gcctatgact tg 12
<210> 250
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 250
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ser Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Thr Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Thr Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Val Phe Asn Asp Asp Ser Asp Asp Ala
115 120
<210> 251
<211> 125
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 251
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Pro Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Leu Ser Gly Phe Ser Leu Ser
35 40 45
Ala Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Phe Ile Thr Leu Ser Asp His Ile Ser Tyr Ala Arg Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Ser Arg Gly Trp Gly Ala Met Gly Arg Leu Asp Leu
115 120 125
<210> 252
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 252
Gln Ala Ser Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ser
1 5 10
<210> 253
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 253
Gly Ala Ser Thr Leu Ala Ser
1 5
<210> 254
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 254
Ala Gly Val Phe Asn Asp Asp Ser Asp Asp Ala
1 5 10
<210> 255
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 255
Ala Tyr Tyr Met Ser
1 5
<210> 256
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 256
Phe Ile Thr Leu Ser Asp His Ile Ser Tyr Ala Arg Trp Ala Lys Gly
1 5 10 15
<210> 257
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 257
Ser Arg Gly Trp Gly Ala Met Gly Arg Leu Asp Leu
1 5 10
<210> 258
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 258
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggttcc 60
acatttgccg ccgtgctgac ccagactcca tctcccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttatgaca acaactattt atcctggtat 180
cagcagaaac caggacagcc tcccaagctc ctgatctatg gtgcatccac tctggcatct 240
ggggtcccat cgcggttcaa aggcacggga tctgggacac agttcactct caccatcaca 300
gacgtgcagt gtgacgatgc tgccacttac tattgtgcag gcgtttttaa tgatgatagt 360
gatgatgcc 369
<210> 259
<211> 375
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 259
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc ccaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acactctctg gattctccct cagtgcatac tatatgagct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg attcattact ctgagtgatc atatatctta cgcgaggtgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagga gtcgtggctg gggtgcaatg 360
ggtcggttgg atctc 375
<210> 260
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 260
caggccagtc agagtgttta tgacaacaac tatttatcc 39
<210> 261
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 261
ggtgcatcca ctctggcatc t 21
<210> 262
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 262
gcaggcgttt ttaatgatga tagtgatgat gcc 33
<210> 263
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 263
gcatactata tgagc 15
<210> 264
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 264
ttcattactc tgagtgatca tatatcttac gcgaggtggg cgaaaggc 48
<210> 265
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 265
agtcgtggct ggggtgcaat gggtcggttg gatctc 36
<210> 266
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 266
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Asn Asn Lys Asn Leu Ala Trp Tyr Gln Gln Lys Ser
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Ser Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Val Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Val Phe Asp Asp Asp Ala Asp Asn Ala
115 120
<210> 267
<211> 121
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 267
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Ser Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Tyr Ile Gly Val Ile Gly Thr Ser Gly Ser Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Ala Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Val
100 105 110
Arg Ser Leu Ser Ser Ile Thr Phe Leu
115 120
<210> 268
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 268
Gln Ala Ser Gln Ser Val Tyr Asn Asn Lys Asn Leu Ala
1 5 10
<210> 269
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 269
Trp Ala Ser Thr Leu Ala Ser
1 5
<210> 270
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 270
Leu Gly Val Phe Asp Asp Asp Ala Asp Asn Ala
1 5 10
<210> 271
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 271
Ser Tyr Ser Met Thr
1 5
<210> 272
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 272
Val Ile Gly Thr Ser Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 273
<211> 8
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 273
Ser Leu Ser Ser Ile Thr Phe Leu
1 5
<210> 274
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 274
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acattcgcag ccgtgctgac ccagacacca tcgcccgtgt ctgcggctgt gggaggcaca 120
gtcaccatca gttgccaggc cagtcagagt gtttataaca acaaaaattt agcctggtat 180
cagcagaaat cagggcagcc tcccaagctc ctgatctact gggcatccac tctggcatct 240
ggggtctcat cgcggttcag cggcagtgga tctgggacac agttcactct caccgtcagc 300
ggcgtgcagt gtgacgatgc tgccacttac tactgtctag gcgtttttga tgatgatgct 360
gataatgct 369
<210> 275
<211> 363
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 275
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccaatgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtagctac tccatgacct gggtccgcca ggctccaggg 180
aaggggctgg aatatatcgg agtcattggt actagtggta gcacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctccagaacc tcgaccacgg tggctctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgtcagga gtctttcttc tattactttc 360
ttg 363
<210> 276
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 276
caggccagtc agagtgttta taacaacaaa aatttagcc 39
<210> 277
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 277
tgggcatcca ctctggcatc t 21
<210> 278
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 278
ctaggcgttt ttgatgatga tgctgataat gct 33
<210> 279
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 279
agctactcca tgacc 15
<210> 280
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 280
gtcattggta ctagtggtag cacatactac gcgacctggg cgaaaggc 48
<210> 281
<211> 24
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 281
agtctttctt ctattacttt cttg 24
<210> 282
<211> 120
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 282
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Phe Glu Leu Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Asn Ile Tyr Arg Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Phe Leu Ile Tyr Leu Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Ser
100 105 110
Tyr Tyr Ser Ser Asn Ser Val Ala
115 120
<210> 283
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 283
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Val Glu Ser Gly Gly Asp Leu Val Gln
20 25 30
Pro Glu Gly Ser Leu Thr Leu Thr Cys Thr Ala Ser Glu Leu Asp Phe
35 40 45
Ser Ser Gly Tyr Trp Ile Cys Trp Val Arg Gln Val Pro Gly Lys Gly
50 55 60
Leu Glu Trp Ile Gly Cys Ile Tyr Thr Gly Ser Ser Gly Ser Thr Phe
65 70 75 80
Tyr Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser
85 90 95
Thr Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala
100 105 110
Thr Tyr Phe Cys Ala Arg Gly Tyr Ser Gly Phe Gly Tyr Phe Lys Leu
115 120 125
<210> 284
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 284
Gln Ala Ser Gln Asn Ile Tyr Arg Tyr Leu Ala
1 5 10
<210> 285
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 285
Leu Ala Ser Thr Leu Ala Ser
1 5
<210> 286
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 286
Gln Ser Tyr Tyr Ser Ser Asn Ser Val Ala
1 5 10
<210> 287
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 287
Ser Gly Tyr Trp Ile Cys
1 5
<210> 288
<211> 18
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 288
Cys Ile Tyr Thr Gly Ser Ser Gly Ser Thr Phe Tyr Ala Ser Trp Ala
1 5 10 15
Lys Gly
<210> 289
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 289
Gly Tyr Ser Gly Phe Gly Tyr Phe Lys Leu
1 5 10
<210> 290
<211> 360
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 290
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcat tcgaattgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtcagaac atttatagat acttagcctg gtatcagcag 180
aaaccagggc agcctcccaa gttcctgatc tatctggcat ctactctggc atctggggtc 240
ccatcgcggt ttaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caaagttatt atagtagtaa tagtgtcgct 360
<210> 291
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 291
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctgg tggagtccgg gggagacctg gtccagcctg agggatccct gacactcacc 120
tgcacagctt ctgagttaga cttcagtagc ggctactgga tatgctgggt ccgccaggtt 180
ccagggaagg ggctggagtg gatcggatgc atttatactg gtagtagtgg tagcactttt 240
tacgcgagtt gggcgaaagg ccgattcacc atctccaaaa cctcgtcgac cacggtgact 300
ctgcaaatga ccagtctgac agccgcggac acggccacct atttctgtgc gagaggttat 360
agtggctttg gttactttaa gttg 384
<210> 292
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 292
caggccagtc agaacattta tagatactta gcc 33
<210> 293
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 293
ctggcatcta ctctggcatc t 21
<210> 294
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 294
caaagttatt atagtagtaa tagtgtcgct 30
<210> 295
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 295
agcggctact ggatatgc 18
<210> 296
<211> 54
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 296
tgcatttata ctggtagtag tggtagcact ttttacgcga gttgggcgaa aggc 54
<210> 297
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 297
ggttatagtg gctttggtta ctttaagttg 30
<210> 298
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 298
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Glu Asp Ile Tyr Arg Leu Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Asp Ser Ser Asp Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Ala
85 90 95
Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Ala Trp Ser Tyr Ser Asp Ile Asp Asn Ala
115 120
<210> 299
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 299
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Thr Thr Ser Gly Asn Thr Phe Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Leu Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Thr Ser Asp Ile Phe Tyr Tyr Arg Asn Leu
115 120
<210> 300
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 300
Gln Ala Ser Glu Asp Ile Tyr Arg Leu Leu Ala
1 5 10
<210> 301
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 301
Asp Ser Ser Asp Leu Ala Ser
1 5
<210> 302
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 302
Gln Gln Ala Trp Ser Tyr Ser Asp Ile Asp Asn Ala
1 5 10
<210> 303
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 303
Ser Tyr Tyr Met Ser
1 5
<210> 304
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 304
Ile Ile Thr Thr Ser Gly Asn Thr Phe Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 305
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 305
Thr Ser Asp Ile Phe Tyr Tyr Arg Asn Leu
1 5 10
<210> 306
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 306
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtgaggac atttataggt tattggcctg gtatcaacag 180
aaaccagggc agcctcccaa gctcctgatc tatgattcat ccgatctggc atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acagagttca ctctcgccat cagcggtgtg 300
cagtgtgacg atgctgccac ttactactgt caacaggctt ggagttatag tgatattgat 360
aatgct 366
<210> 307
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 307
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgccgggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtagctac tacatgagct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcattact actagtggta atacatttta cgcgagctgg 240
gcgaaaggcc ggctcaccat ctccagaacc tcgaccacgg tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagaa cttctgatat tttttattat 360
cgtaacttg 369
<210> 308
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 308
caggccagtg aggacattta taggttattg gcc 33
<210> 309
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 309
gattcatccg atctggcatc t 21
<210> 310
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 310
caacaggctt ggagttatag tgatattgat aatgct 36
<210> 311
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 311
agctactaca tgagc 15
<210> 312
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 312
atcattacta ctagtggtaa tacattttac gcgagctggg cgaaaggc 48
<210> 313
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 313
acttctgata ttttttatta tcgtaacttg 30
<210> 314
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 314
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Ala Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Ala Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asp Met Asp Leu Ala Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ser Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
85 90 95
Leu Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Leu Gly Ala Phe Asp Asp Asp Ala Asp Asn Thr
115 120
<210> 315
<211> 129
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 315
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Thr
35 40 45
Arg His Ala Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Cys Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Arg Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Val Ile Gly Asp Thr Ala Gly Tyr Ala Tyr Phe Thr Gly Leu Asp
115 120 125
Leu
<210> 316
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 316
Gln Ser Ser Gln Ser Val Tyr Asn Asp Met Asp Leu Ala
1 5 10
<210> 317
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 317
Ser Ala Ser Thr Leu Ala Ser
1 5
<210> 318
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 318
Leu Gly Ala Phe Asp Asp Asp Ala Asp Asn Thr
1 5 10
<210> 319
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 319
Arg His Ala Ile Thr
1 5
<210> 320
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 320
Cys Ile Trp Ser Gly Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 321
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 321
Val Ile Gly Asp Thr Ala Gly Tyr Ala Tyr Phe Thr Gly Leu Asp Leu
1 5 10 15
<210> 322
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 322
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acgtttgcag ccgtgctgac ccagactgca tcacccgtgt ctgccgctgt gggagccaca 120
gtcaccatca actgccagtc cagtcagagt gtttataatg acatggactt agcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatt ctgcatccac tctggcatct 240
ggggtcccat cgcggttcag cggcagtgga tctgggacag agttcactct caccatcagc 300
ggcgtgcagt gtgacgatgc tgccacttac tactgtctag gcgcttttga tgatgatgct 360
gataatact 369
<210> 323
<211> 387
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 323
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct cactaggcat gcaataacct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg atgcatttgg agtggtggta gcacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctcag aatcaccagt 300
ccgacaaccg aggacacggc cacctacttc tgtgccagag tcattggcga tactgctggt 360
tatgcttatt ttacggggct tgacttg 387
<210> 324
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 324
cagtccagtc agagtgttta taatgacatg gacttagcc 39
<210> 325
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 325
tctgcatcca ctctggcatc t 21
<210> 326
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 326
ctaggcgctt ttgatgatga tgctgataat act 33
<210> 327
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 327
aggcatgcaa taacc 15
<210> 328
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 328
tgcatttgga gtggtggtag cacatactac gcgacctggg cgaaaggc 48
<210> 329
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 329
gtcattggcg atactgctgg ttatgcttat tttacggggc ttgacttg 48
<210> 330
<211> 121
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 330
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Asn Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Thr Ala Ser Ser Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Gly Val Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Thr Ser Asp Val Asp Asn Val
115 120
<210> 331
<211> 130
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 331
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ala Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Ser Tyr Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Tyr Ile Gly Ile Ile Ser Ser Ser Gly Ser Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Gln Ala Ser Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Thr Glu Asp Ser Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Gly Gly Ala Gly Ser Gly Gly Val Trp Leu Leu Asp Gly Phe
115 120 125
Asp Pro
130
<210> 332
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 332
Gln Ala Ser Gln Ser Val Tyr Asn Trp Leu Ser
1 5 10
<210> 333
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 333
Thr Ala Ser Ser Leu Ala Ser
1 5
<210> 334
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 334
Gln Gln Gly Tyr Thr Ser Asp Val Asp Asn Val
1 5 10
<210> 335
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 335
Ser Tyr Ala Met Gly
1 5
<210> 336
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 336
Ile Ile Ser Ser Ser Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 337
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 337
Gly Gly Ala Gly Ser Gly Gly Val Trp Leu Leu Asp Gly Phe Asp Pro
1 5 10 15
<210> 338
<211> 363
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 338
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagt gtttataatt ggttatcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tatactgcat ccagtctggc atctggggtc 240
ccatcgcggt tcagtggcag tggatctggg acagagttca ctctcaccat cagcggcgtg 300
gagtgtgccg atgctgccac ttactactgt caacagggtt atactagtga tgttgataat 360
gtt 363
<210> 339
<211> 390
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 339
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg aggccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gaatcgacct cagtagctat gcaatgggct gggtccgcca ggctccaggg 180
aaggggctgg aatacatcgg aatcattagt agtagtggta gcacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctcacaagcc tcgtcgacca cggtggatct gaaaattacc 300
agtccgacaa ccgaggactc ggccacatat ttctgtgcca gagggggtgc tggtagtggt 360
ggtgtttggc tgcttgatgg ttttgatccc 390
<210> 340
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 340
caggccagtc agagtgttta taattggtta tcc 33
<210> 341
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 341
actgcatcca gtctggcatc t 21
<210> 342
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 342
caacagggtt atactagtga tgttgataat gtt 33
<210> 343
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 343
agctatgcaa tgggc 15
<210> 344
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 344
atcattagta gtagtggtag cacatactac gcgacctggg cgaaaggc 48
<210> 345
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 345
gggggtgctg gtagtggtgg tgtttggctg cttgatggtt ttgatccc 48
<210> 346
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 346
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Lys Cys Ala Asp Val Val Met Thr Gln Thr Pro Ala
20 25 30
Ser Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala
35 40 45
Ser Glu Asn Ile Tyr Asn Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Thr Val Gly Asp Leu Ala Ser Gly
65 70 75 80
Val Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu
85 90 95
Thr Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gln Gly Tyr Ser Ser Ser Tyr Val Asp Asn Val
115 120
<210> 347
<211> 130
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 347
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Lys Glu Ser Gly Gly Arg Leu Val Thr
20 25 30
Pro Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu
35 40 45
Asn Asp Tyr Ala Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Gly Tyr Ile Arg Ser Ser Gly Thr Thr Ala Tyr Ala Thr
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Ala Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Gly Gly Ala Gly Ser Ser Gly Val Trp Ile Leu Asp Gly Phe
115 120 125
Ala Pro
130
<210> 348
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 348
Gln Ala Ser Glu Asn Ile Tyr Asn Trp Leu Ala
1 5 10
<210> 349
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 349
Thr Val Gly Asp Leu Ala Ser
1 5
<210> 350
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 350
Gln Gln Gly Tyr Ser Ser Ser Tyr Val Asp Asn Val
1 5 10
<210> 351
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 351
Asp Tyr Ala Val Gly
1 5
<210> 352
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 352
Tyr Ile Arg Ser Ser Gly Thr Thr Ala Tyr Ala Thr Trp Ala Lys Gly
1 5 10 15
<210> 353
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 353
Gly Gly Ala Gly Ser Ser Gly Val Trp Ile Leu Asp Gly Phe Ala Pro
1 5 10 15
<210> 354
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 354
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
aaatgtgccg atgttgtgat gacccagact ccagcctccg tgtctgcagc tgtgggaggc 120
acagtcacca tcaattgcca ggccagtgag aacatttata attggttagc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctatactg taggcgatct ggcatctggg 240
gtctcatcgc ggttcaaagg cagtggatct gggacagagt tcactctcac catcagcgac 300
ctggagtgtg ccgatgctgc cacttactat tgtcaacagg gttatagtag tagttatgtt 360
gataatgtt 369
<210> 355
<211> 390
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 355
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctga aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 120
tgcacagtct ctggattctc cctcaatgac tatgcagtgg gctggttccg ccaggctcca 180
gggaaggggc tggaatggat cggatacatt cgtagtagtg gtaccacagc ctacgcgacc 240
tgggcgaaag gccgattcac catctccgct acctcgacca cggtggatct gaaaatcacc 300
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gagggggtgc tggtagtagt 360
ggtgtgtgga tccttgatgg ttttgctccc 390
<210> 356
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 356
caggccagtg agaacattta taattggtta gcc 33
<210> 357
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 357
actgtaggcg atctggcatc t 21
<210> 358
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 358
caacagggtt atagtagtag ttatgttgat aatgtt 36
<210> 359
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 359
gactatgcag tgggc 15
<210> 360
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 360
tacattcgta gtagtggtac cacagcctac gcgacctggg cgaaaggc 48
<210> 361
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 361
gggggtgctg gtagtagtgg tgtgtggatc cttgatggtt ttgctccc 48
<210> 362
<211> 121
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 362
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Gln Asn Asn Tyr Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ala Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Ala Tyr Arg Asp Val Asp Ser
115 120
<210> 363
<211> 130
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 363
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Thr
35 40 45
Ser Thr Tyr Tyr Ile Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Asp Ala Gly Ser Ser Gly Ser Thr Tyr Tyr
65 70 75 80
Ala Thr Trp Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Lys Trp Asp Tyr Gly Gly Asn Val Gly Trp Gly Tyr
115 120 125
Asp Leu
130
<210> 364
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 364
Gln Ala Ser Gln Ser Val Tyr Gln Asn Asn Tyr Leu Ser
1 5 10
<210> 365
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 365
Gly Ala Ala Thr Leu Ala Ser
1 5
<210> 366
<211> 9
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 366
Ala Gly Ala Tyr Arg Asp Val Asp Ser
1 5
<210> 367
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 367
Ser Thr Tyr Tyr Ile Tyr
1 5
<210> 368
<211> 18
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 368
Cys Ile Asp Ala Gly Ser Ser Gly Ser Thr Tyr Tyr Ala Thr Trp Val
1 5 10 15
Asn Gly
<210> 369
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 369
Trp Asp Tyr Gly Gly Asn Val Gly Trp Gly Tyr Asp Leu
1 5 10
<210> 370
<211> 363
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 370
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgctc aagtgctgac ccagactcca tcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtcagagt gtttatcaga acaactactt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcggccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
gacctggagt gtgacgatgc tgccacttac tactgtgcag gcgcttatag ggatgtggat 360
tct 363
<210> 371
<211> 390
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 371
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
acagcctctg gattctcctt tactagtacc tactacatct actgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgtatt gatgctggta gtagtggtag cacttactac 240
gcgacctggg tgaatggccg attcaccatc tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgaa atgggattat 360
ggtggtaatg ttggttgggg ttatgacttg 390
<210> 372
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 372
caggccagtc agagtgttta tcagaacaac tacttatcc 39
<210> 373
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 373
ggtgcggcca ctctggcatc t 21
<210> 374
<211> 27
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 374
gcaggcgctt atagggatgt ggattct 27
<210> 375
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 375
agtacctact acatctac 18
<210> 376
<211> 54
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 376
tgtattgatg ctggtagtag tggtagcact tactacgcga cctgggtgaa tggc 54
<210> 377
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 377
tgggattatg gtggtaatgt tggttggggt tatgacttg 39
<210> 378
<211> 120
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 378
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Phe Glu Leu Thr Gln Thr Pro Ser Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Phe Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Ser
100 105 110
Tyr Tyr Asp Ser Val Ser Asn Pro
115 120
<210> 379
<211> 127
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 379
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Glu Gly Ser Leu Thr Leu Thr Cys Lys Ala Ser Gly Leu Asp Leu Gly
35 40 45
Thr Tyr Trp Phe Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Tyr Thr Gly Ser Ser Gly Ser Thr Phe Tyr
65 70 75 80
Ala Ser Trp Val Asn Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr
85 90 95
Thr Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr
100 105 110
Tyr Phe Cys Ala Arg Gly Tyr Ser Gly Tyr Gly Tyr Phe Lys Leu
115 120 125
<210> 380
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 380
Gln Ala Ser Gln Ser Ile Ser Ser Tyr Leu Ala
1 5 10
<210> 381
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 381
Arg Ala Ser Thr Leu Ala Ser
1 5
<210> 382
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 382
Gln Ser Tyr Tyr Asp Ser Val Ser Asn Pro
1 5 10
<210> 383
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 383
Thr Tyr Trp Phe Met Cys
1 5
<210> 384
<211> 18
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 384
Cys Ile Tyr Thr Gly Ser Ser Gly Ser Thr Phe Tyr Ala Ser Trp Val
1 5 10 15
Asn Gly
<210> 385
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 385
Gly Tyr Ser Gly Tyr Gly Tyr Phe Lys Leu
1 5 10
<210> 386
<211> 360
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 386
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcat tcgaattgac ccagactcca tcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc attagtagtt acttagcctg gtatcagcag 180
aaaccagggc agcctcccaa gttcctgatc tacagggcgt ccactctggc atctggggtc 240
ccatcgcgat tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caaagctatt atgatagtgt ttcaaatcct 360
<210> 387
<211> 381
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 387
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgagg gatccctgac actcacctgc 120
aaagcctctg gactcgacct cggtacctac tggttcatgt gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcttgtatt tatactggta gtagtggttc cactttctac 240
gcgagctggg tgaatggccg attcaccatc tccaaaacct cgtcgaccac ggtgactctg 300
caaatgacca gtctgacagc cgcggacacg gccacttatt tttgtgcgag aggttatagt 360
ggttatggtt attttaagtt g 381
<210> 388
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 388
caggccagtc agagcattag tagttactta gcc 33
<210> 389
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 389
agggcgtcca ctctggcatc t 21
<210> 390
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 390
caaagctatt atgatagtgt ttcaaatcct 30
<210> 391
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 391
acctactggt tcatgtgc 18
<210> 392
<211> 54
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 392
tgtatttata ctggtagtag tggttccact ttctacgcga gctgggtgaa tggc 54
<210> 393
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 393
ggttatagtg gttatggtta ttttaagttg 30
<210> 394
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 394
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Val Thr Phe Ala Ile Glu Met Thr Gln Ser Pro Phe Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Lys Asn Asn Gln Leu Ser Trp Tyr Gln Gln Lys Ser
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Ala Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr
85 90 95
Leu Thr Ile Ser Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Ala Ile Thr Gly Ser Ile Asp Thr Asp Gly
115 120
<210> 395
<211> 130
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 395
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro
20 25 30
Gly Ala Ser Leu Thr Leu Thr Cys Thr Thr Ser Gly Phe Ser Phe Ser
35 40 45
Ser Ser Tyr Phe Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Ala Cys Ile Tyr Gly Gly Asp Gly Ser Thr Tyr Tyr Ala
65 70 75 80
Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr
85 90 95
Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr
100 105 110
Phe Cys Ala Arg Glu Trp Ala Tyr Ser Gln Gly Tyr Phe Gly Ala Phe
115 120 125
Asp Leu
130
<210> 396
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 396
Gln Ala Ser Gln Ser Val Tyr Lys Asn Asn Gln Leu Ser
1 5 10
<210> 397
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 397
Gly Ala Ser Ala Leu Ala Ser
1 5
<210> 398
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 398
Ala Gly Ala Ile Thr Gly Ser Ile Asp Thr Asp Gly
1 5 10
<210> 399
<211> 6
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 399
Ser Ser Tyr Phe Ile Cys
1 5
<210> 400
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 400
Cys Ile Tyr Gly Gly Asp Gly Ser Thr Tyr Tyr Ala Ser Trp Ala Lys
1 5 10 15
Gly
<210> 401
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 401
Glu Trp Ala Tyr Ser Gln Gly Tyr Phe Gly Ala Phe Asp Leu
1 5 10
<210> 402
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 402
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgtc 60
acatttgcca tcgaaatgac ccagagtcca ttctccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttataaga acaaccaatt atcctggtat 180
cagcagaaat cagggcagcc tcccaagctc ctgatctatg gtgcatcggc tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacag agttcactct caccatcagc 300
gacgtgcagt gtgacgatgc tgccacttac tactgtgcag gcgctattac tggtagtatt 360
gatacggatg gt 372
<210> 403
<211> 390
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 403
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgttggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc 120
acaacttctg gattctcctt cagtagcagc tacttcattt gctgggtccg ccaggctcca 180
gggaaggggc tggagtggat cgcatgcatt tatggtggtg atggcagcac atactacgcg 240
agctgggcga aaggccgatt caccatctcc aaaacctcgt cgaccacggt gacgctgcaa 300
atgaccagtc tgacagccgc ggacacggcc acctatttct gtgcgagaga atgggcatat 360
agtcaaggtt attttggtgc ttttgatctc 390
<210> 404
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 404
caggccagtc agagtgttta taagaacaac caattatcc 39
<210> 405
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 405
ggtgcatcgg ctctggcatc t 21
<210> 406
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 406
gcaggcgcta ttactggtag tattgatacg gatggt 36
<210> 407
<211> 18
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 407
agcagctact tcatttgc 18
<210> 408
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 408
tgcatttatg gtggtgatgg cagcacatac tacgcgagct gggcgaaagg c 51
<210> 409
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 409
gaatgggcat atagtcaagg ttattttggt gcttttgatc tc 42
<210> 410
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 410
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Glu Asp Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys
100 105 110
Thr Tyr Gly Thr Ile Ser Ile Ser Asp Gly Asn Ala
115 120
<210> 411
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 411
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Phe Met Thr Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Tyr Ile Gly Phe Ile Asn Pro Gly Gly Ser Ala Tyr Tyr Ala Ser Trp
65 70 75 80
Val Lys Gly Arg Phe Thr Ile Ser Lys Ser Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Val Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
115 120
<210> 412
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 412
Gln Ala Ser Glu Asp Ile Ser Ser Tyr Leu Ala
1 5 10
<210> 413
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 413
Ala Ala Ser Asn Leu Glu Ser
1 5
<210> 414
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 414
Gln Cys Thr Tyr Gly Thr Ile Ser Ile Ser Asp Gly Asn Ala
1 5 10
<210> 415
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 415
Ser Tyr Phe Met Thr
1 5
<210> 416
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 416
Phe Ile Asn Pro Gly Gly Ser Ala Tyr Tyr Ala Ser Trp Val Lys Gly
1 5 10 15
<210> 417
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 417
Val Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
1 5 10
<210> 418
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 418
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgg aggcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtgaggat attagtagct acttagcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tatgctgcat ccaatctgga atctggggtc 240
tcatcgcgat tcaaaggcag tggatctggg acagagtaca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ctattactgt caatgtactt atggtactat ttctattagt 360
gatggtaatg ct 372
<210> 419
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 419
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccaatgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct cagtagctac ttcatgacct gggtccgcca ggctccaggg 180
gaggggctgg aatacatcgg attcattaat cctggtggta gcgcttacta cgcgagctgg 240
gtgaaaggcc gattcaccat ctccaagtcc tcgaccacgg tagatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccaggg ttctgattgt ttcttatgga 360
gcctttacca tc 372
<210> 420
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 420
caggccagtg aggatattag tagctactta gcc 33
<210> 421
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 421
gctgcatcca atctggaatc t 21
<210> 422
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 422
caatgtactt atggtactat ttctattagt gatggtaatg ct 42
<210> 423
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 423
agctacttca tgacc 15
<210> 424
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 424
ttcattaatc ctggtggtag cgcttactac gcgagctggg tgaaaggc 48
<210> 425
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 425
gttctgattg tttcttatgg agcctttacc atc 33
<210> 426
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 426
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Asp Val Val Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Glu Asp Ile Glu Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Glu Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys
100 105 110
Thr Tyr Gly Ile Ile Ser Ile Ser Asp Gly Asn Ala
115 120
<210> 427
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 427
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Phe Met Thr Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Tyr Ile Gly Phe Met Asn Thr Gly Asp Asn Ala Tyr Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Val Leu Val Val Ala Tyr Gly Ala Phe Asn Ile
115 120
<210> 428
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 428
Gln Ala Ser Glu Asp Ile Glu Ser Tyr Leu Ala
1 5 10
<210> 429
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 429
Gly Ala Ser Asn Leu Glu Ser
1 5
<210> 430
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 430
Gln Cys Thr Tyr Gly Ile Ile Ser Ile Ser Asp Gly Asn Ala
1 5 10
<210> 431
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 431
Ser Tyr Phe Met Thr
1 5
<210> 432
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 432
Phe Met Asn Thr Gly Asp Asn Ala Tyr Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 433
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 433
Val Leu Val Val Ala Tyr Gly Ala Phe Asn Ile
1 5 10
<210> 434
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 434
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgatg ttgtgatgac ccagactcca gcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtgaggac attgaaagct atctagcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc tatggtgcat ccaatctgga atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactattgt caatgcactt atggtattat tagtattagt 360
gatggtaatg ct 372
<210> 435
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 435
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtgtctg gattctccct cagtagctac ttcatgacct gggtccgcca ggctccaggg 180
gaggggctgg aatacatcgg attcatgaat actggtgata acgcatacta cgcgagctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccaggg ttcttgttgt tgcttatgga 360
gcctttaaca tc 372
<210> 436
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 436
caggccagtg aggacattga aagctatcta gcc 33
<210> 437
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 437
ggtgcatcca atctggaatc t 21
<210> 438
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 438
caatgcactt atggtattat tagtattagt gatggtaatg ct 42
<210> 439
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 439
agctacttca tgacc 15
<210> 440
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 440
ttcatgaata ctggtgataa cgcatactac gcgagctggg cgaaaggc 48
<210> 441
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 441
gttcttgttg ttgcttatgg agcctttaac atc 33
<210> 442
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 442
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Glu Pro Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ser Ser
35 40 45
Lys Ser Val Met Asn Asn Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Gly Tyr Thr Gly Tyr Ser Asp His Gly Thr
115 120
<210> 443
<211> 127
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 443
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Lys Pro
20 25 30
Asp Glu Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Ser Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Phe Ile Asn Thr Gly Gly Thr Ile Val Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Gly Ser Tyr Val Ser Ser Gly Tyr Ala Tyr Tyr Phe Asn Val
115 120 125
<210> 444
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 444
Gln Ser Ser Lys Ser Val Met Asn Asn Asn Tyr Leu Ala
1 5 10
<210> 445
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 445
Gly Ala Ser Asn Leu Ala Ser
1 5
<210> 446
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 446
Gln Gly Gly Tyr Thr Gly Tyr Ser Asp His Gly Thr
1 5 10
<210> 447
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 447
Ser Tyr Pro Met Asn
1 5
<210> 448
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 448
Phe Ile Asn Thr Gly Gly Thr Ile Val Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 449
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 449
Gly Ser Tyr Val Ser Ser Gly Tyr Ala Tyr Tyr Phe Asn Val
1 5 10
<210> 450
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 450
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccg ccgtgctgac ccagactcca tctcccgtgt ctgaacctgt gggaggcaca 120
gtcagcatca gttgccagtc cagtaagagt gttatgaata acaactactt agcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcatccaa tctggcatct 240
ggggtcccat cacggttcag cggcagtgga tctgggacac agttcactct caccatcagc 300
gacgtgcagt gtgacgatgc tgccacttac tactgtcaag gcggttatac tggttatagt 360
gatcatggga ct 372
<210> 451
<211> 381
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 451
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc aagcctgacg aaaccctgac actcacctgc 120
acagtctctg gaatcgacct cagtagctat ccaatgaact gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg attcattaat actggtggta ccatagtcta cgcgagctgg 240
gcaaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag gcagttatgt ttcatctggt 360
tatgcctact attttaatgt c 381
<210> 452
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 452
cagtccagta agagtgttat gaataacaac tacttagcc 39
<210> 453
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 453
ggtgcatcca atctggcatc t 21
<210> 454
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 454
caaggcggtt atactggtta tagtgatcat gggact 36
<210> 455
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 455
agctatccaa tgaac 15
<210> 456
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 456
ttcattaata ctggtggtac catagtctac gcgagctggg caaaaggc 48
<210> 457
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 457
ggcagttatg tttcatctgg ttatgcctac tattttaatg tc 42
<210> 458
<211> 121
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 458
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Asn Trp Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Lys Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Val Gln Cys Asp Asp Val Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Gly Tyr Leu Asp Ser Val Ile
115 120
<210> 459
<211> 126
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 459
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Thr Tyr Ser Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Ala Asn Ser Gly Thr Thr Phe Tyr Ala Asn Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Val Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Glu Ser Gly Met Tyr Asn Glu Tyr Gly Lys Phe Asn Ile
115 120 125
<210> 460
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 460
Gln Ser Ser Gln Ser Val Tyr Asn Asn Asn Trp Leu Ser
1 5 10
<210> 461
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 461
Lys Ala Ser Thr Leu Ala Ser
1 5
<210> 462
<211> 9
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 462
Ala Gly Gly Tyr Leu Asp Ser Val Ile
1 5
<210> 463
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 463
Thr Tyr Ser Ile Asn
1 5
<210> 464
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 464
Ile Ile Ala Asn Ser Gly Thr Thr Phe Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 465
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 465
Glu Ser Gly Met Tyr Asn Glu Tyr Gly Lys Phe Asn Ile
1 5 10
<210> 466
<211> 363
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 466
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccg ccgtgctgac ccagactcca tctcccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccagtc cagtcagagt gtttataata acaactggtt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctaca aggcatccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
gacgtgcagt gtgacgatgt tgccacttac tactgtgcgg gcggttatct tgatagtgtt 360
att 363
<210> 467
<211> 378
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 467
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct cagtacctat tcaataaact gggtccgcca ggctccaggg 180
aagggcctgg aatggatcgg aatcattgct aatagtggta ccacattcta cgcgaactgg 240
gcgaaaggcc gattcaccgt ctccaaaacc tcgaccacgg tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag agagtggaat gtacaatgaa 360
tatggtaaat ttaacatc 378
<210> 468
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 468
cagtccagtc agagtgttta taataacaac tggttatcc 39
<210> 469
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 469
aaggcatcca ctctggcatc t 21
<210> 470
<211> 27
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 470
gcgggcggtt atcttgatag tgttatt 27
<210> 471
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 471
acctattcaa taaac 15
<210> 472
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 472
atcattgcta atagtggtac cacattctac gcgaactggg cgaaaggc 48
<210> 473
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 473
gagagtggaa tgtacaatga atatggtaaa tttaacatc 39
<210> 474
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 474
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Ser Asp Met Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Glu Asn Ile Tyr Ser Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Phe Lys Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Ala Thr Val Tyr Asp Ile Asp Asn Asn
115 120
<210> 475
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 475
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Ala Tyr Ala Met Ile Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Thr Ile Ile Tyr Pro Asn Gly Ile Thr Tyr Tyr Ala Asn Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Val Ser Lys Thr Ser Thr Ala Met Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Ala Glu Ser Ser Lys Asn Ala Tyr Trp Gly Tyr Phe Asn Val
115 120 125
<210> 476
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 476
Gln Ala Ser Glu Asn Ile Tyr Ser Phe Leu Ala
1 5 10
<210> 477
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 477
Lys Ala Ser Thr Leu Ala Ser
1 5
<210> 478
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 478
Gln Gln Gly Ala Thr Val Tyr Asp Ile Asp Asn Asn
1 5 10
<210> 479
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 479
Ala Tyr Ala Met Ile
1 5
<210> 480
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 480
Ile Ile Tyr Pro Asn Gly Ile Thr Tyr Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 481
<211> 15
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 481
Asp Ala Glu Ser Ser Lys Asn Ala Tyr Trp Gly Tyr Phe Asn Val
1 5 10 15
<210> 482
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 482
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct ctgatatgac ccagactcca tcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtgagaac atttatagct ttttggcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc ttcaaggctt ccactctggc atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acacagttca ctctcaccat cagcgacctg 300
gagtgtgacg atgctgccac ttactactgt caacagggtg ctactgtgta tgatattgat 360
aataat 366
<210> 483
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 483
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtttctg gaatcgacct cagtgcctat gcaatgatct gggtccgcca ggctccaggg 180
gaggggctgg aatggatcac aatcatttat cctaatggta tcacatacta cgcgaactgg 240
gcgaaaggcc gattcaccgt ctccaaaacc tcgaccgcga tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag atgcagaaag tagtaagaat 360
gcttattggg gctactttaa cgtc 384
<210> 484
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 484
caggccagtg agaacattta tagctttttg gcc 33
<210> 485
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 485
aaggcttcca ctctggcatc t 21
<210> 486
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 486
caacagggtg ctactgtgta tgatattgat aataat 36
<210> 487
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 487
gcctatgcaa tgatc 15
<210> 488
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 488
atcatttatc ctaatggtat cacatactac gcgaactggg cgaaaggc 48
<210> 489
<211> 45
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 489
gatgcagaaa gtagtaagaa tgcttattgg ggctacttta acgtc 45
<210> 490
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 490
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Ser Asp Met Thr Gln Thr Pro Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Glu Asn Ile Tyr Ser Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Phe Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Ala Thr Val Tyr Asp Ile Asp Asn Asn
115 120
<210> 491
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 491
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Ala Tyr Ala Met Ile Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Thr Ile Ile Tyr Pro Asn Gly Ile Thr Tyr Tyr Ala Asn Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Val Ser Lys Thr Ser Thr Ala Met Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Ala Glu Ser Ser Lys Asn Ala Tyr Trp Gly Tyr Phe Asn Val
115 120 125
<210> 492
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 492
Gln Ala Ser Glu Asn Ile Tyr Ser Phe Leu Ala
1 5 10
<210> 493
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 493
Arg Ala Ser Thr Leu Ala Ser
1 5
<210> 494
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 494
Gln Gln Gly Ala Thr Val Tyr Asp Ile Asp Asn Asn
1 5 10
<210> 495
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 495
Ala Tyr Ala Met Ile
1 5
<210> 496
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 496
Ile Ile Tyr Pro Asn Gly Ile Thr Tyr Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 497
<211> 15
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 497
Asp Ala Glu Ser Ser Lys Asn Ala Tyr Trp Gly Tyr Phe Asn Val
1 5 10 15
<210> 498
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 498
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct ctgatatgac ccagactcca tcctccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtgagaac atttatagct ttttggcctg gtatcagcag 180
aaaccagggc agcctcccaa gctcctgatc ttcagggctt ccactctggc atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acacagttca ctctcaccat cagcgacctg 300
gagtgtgacg atgctgccac ttactactgt caacagggtg ctactgtgta tgatattgat 360
aataat 366
<210> 499
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 499
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtttctg gaatcgacct cagtgcctat gcaatgatct gggtccgcca ggctccaggg 180
gaggggctgg aatggatcac aatcatttat cctaatggta tcacatacta cgcgaactgg 240
gcgaaaggcc gattcaccgt ctccaaaacc tcgaccgcga tggatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag atgcagaaag tagtaagaat 360
gcttattggg gctactttaa cgtc 384
<210> 500
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 500
caggccagtg agaacattta tagctttttg gcc 33
<210> 501
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 501
agggcttcca ctctggcatc t 21
<210> 502
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 502
caacagggtg ctactgtgta tgatattgat aataat 36
<210> 503
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 503
gcctatgcaa tgatc 15
<210> 504
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 504
atcatttatc ctaatggtat cacatactac gcgaactggg cgaaaggc 48
<210> 505
<211> 45
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 505
gatgcagaaa gtagtaagaa tgcttattgg ggctacttta acgtc 45
<210> 506
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 506
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ile Glu Met Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Glu Ser Val Phe Asn Asn Met Leu Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
His Ser Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asp Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu
85 90 95
Thr Ile Ser Gly Val Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Ala
100 105 110
Gly Tyr Lys Ser Asp Ser Asn Asp Gly Asp Asn Val
115 120
<210> 507
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 507
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn
35 40 45
Arg Asn Ser Ile Thr Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Thr Gly Ser Gly Arg Thr Tyr Tyr Ala Asn Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Gly His Pro Gly Leu Gly Ser Gly Asn Ile
115 120
<210> 508
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 508
Gln Ala Ser Glu Ser Val Phe Asn Asn Met Leu Ser
1 5 10
<210> 509
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 509
Asp Ala Ser Asp Leu Ala Ser
1 5
<210> 510
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 510
Ala Gly Tyr Lys Ser Asp Ser Asn Asp Gly Asp Asn Val
1 5 10
<210> 511
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 511
Arg Asn Ser Ile Thr
1 5
<210> 512
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 512
Ile Ile Thr Gly Ser Gly Arg Thr Tyr Tyr Ala Asn Trp Ala Lys Gly
1 5 10 15
<210> 513
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 513
Gly His Pro Gly Leu Gly Ser Gly Asn Ile
1 5 10
<210> 514
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 514
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcca ttgaaatgac ccagactcca tcccccgtgt ctgccgctgt gggaggcaca 120
gtcaccatca attgccaggc cagtgagagt gtttttaata atatgttatc ctggtatcag 180
cagaaaccag ggcactctcc taagctcctg atctatgatg catccgatct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacacagt tcactctcac catcagtggc 300
gtggagtgtg acgatgctgc cacttactat tgtgcagggt ataaaagtga tagtaatgat 360
ggcgataatg tt 372
<210> 515
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 515
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct caacaggaat tcaataacct gggtccgcca ggctccaggg 180
gaggggctgg aatggatcgg aatcattact ggtagtggta gaacgtacta cgcgaactgg 240
gcaaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag gccatcctgg tcttggtagt 360
ggtaacatc 369
<210> 516
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 516
caggccagtg agagtgtttt taataatatg ttatcc 36
<210> 517
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 517
gatgcatccg atctggcatc t 21
<210> 518
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 518
gcagggtata aaagtgatag taatgatggc gataatgtt 39
<210> 519
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 519
aggaattcaa taacc 15
<210> 520
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 520
atcattactg gtagtggtag aacgtactac gcgaactggg caaaaggc 48
<210> 521
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 521
ggccatcctg gtcttggtag tggtaacatc 30
<210> 522
<211> 121
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 522
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Ala Ser Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Thr Ala Ser Ser Leu Ala Ser Gly
65 70 75 80
Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu
85 90 95
Thr Ile Ser Glu Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln
100 105 110
Gly Tyr Tyr Ser Gly Pro Ile Ile Thr
115 120
<210> 523
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 523
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Asn
35 40 45
Asn Tyr Tyr Ile Gln Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Tyr Ala Gly Gly Ser Ala Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Asn Gly Arg Phe Thr Ile Ala Lys Thr Ser Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Gly Thr Phe Asp Gly Tyr Glu Leu
115 120
<210> 524
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 524
Gln Ser Ser Gln Ser Val Tyr Asn Asn Tyr Leu Ser
1 5 10
<210> 525
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 525
Thr Ala Ser Ser Leu Ala Ser
1 5
<210> 526
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 526
Gln Gly Tyr Tyr Ser Gly Pro Ile Ile Thr
1 5 10
<210> 527
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 527
Asn Tyr Tyr Ile Gln
1 5
<210> 528
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 528
Ile Ile Tyr Ala Gly Gly Ser Ala Tyr Tyr Ala Thr Trp Ala Asn Gly
1 5 10 15
<210> 529
<211> 8
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 529
Gly Thr Phe Asp Gly Tyr Glu Leu
1 5
<210> 530
<211> 363
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 530
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcgc aagtgctgac ccagactgca tcgtccgtgt ctgcagctgt gggaggcaca 120
gtcaccatca attgccagtc cagtcagagt gtttataata actacttatc ctggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctatactg catccagcct ggcatctggg 240
gtcccatcgc ggttcaaagg cagtggatct gggacacagt tcactctcac catcagcgaa 300
gtgcagtgtg acgatgctgc cacttactac tgtcaaggct attatagtgg tcctataatt 360
act 363
<210> 531
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 531
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct caataactac tacatacaat gggtccgcca ggctccaggg 180
gaggggctgg aatggatcgg gatcatttat gctggtggta gcgcatacta cgcgacctgg 240
gcaaacggcc gattcaccat cgccaaaacc tcgtcgacca cggtggatct gaagatgacc 300
agtctgacaa ccgaggacac ggccacctat ttctgtgcca gagggacatt tgatggttat 360
gagttg 366
<210> 532
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 532
cagtccagtc agagtgttta taataactac ttatcc 36
<210> 533
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 533
actgcatcca gcctggcatc t 21
<210> 534
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 534
caaggctatt atagtggtcc tataattact 30
<210> 535
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 535
aactactaca tacaa 15
<210> 536
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 536
atcatttatg ctggtggtag cgcatactac gcgacctggg caaacggc 48
<210> 537
<211> 24
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 537
gggacatttg atggttatga gttg 24
<210> 538
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 538
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Val Pro Val Gly Asp Thr Val Thr Ile Ser Cys Gln Ser Ser
35 40 45
Glu Ser Val Tyr Ser Asn Asn Leu Leu Ser Trp Tyr Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Gly Ala Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Gln Gly Tyr Tyr Ser Gly Val Ile Asn Ser
115 120
<210> 539
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 539
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Phe Met Ser Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu
50 55 60
Tyr Ile Gly Phe Ile Asn Pro Gly Gly Ser Ala Tyr Tyr Ala Ser Trp
65 70 75 80
Ala Ser Gly Arg Leu Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Ile Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
115 120
<210> 540
<211> 13
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 540
Gln Ser Ser Glu Ser Val Tyr Ser Asn Asn Leu Leu Ser
1 5 10
<210> 541
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 541
Arg Ala Ser Asn Leu Ala Ser
1 5
<210> 542
<211> 10
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 542
Gln Gly Tyr Tyr Ser Gly Val Ile Asn Ser
1 5 10
<210> 543
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 543
Ser Tyr Phe Met Ser
1 5
<210> 544
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 544
Phe Ile Asn Pro Gly Gly Ser Ala Tyr Tyr Ala Ser Trp Ala Ser Gly
1 5 10 15
<210> 545
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 545
Ile Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
1 5 10
<210> 546
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 546
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactcca tcccctgtgt ctgtccctgt gggagacaca 120
gtcaccatca gttgccagtc cagtgagagc gtttatagta ataacctctt atcctggtat 180
cagcagaaac cagggcagcc tcccaagctc ctgatctaca gggcatccaa tctggcatct 240
ggtgtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
ggcgcacagt gtgacgatgc tgccacttac tactgtcaag gctattatag tggtgtcatt 360
aatagt 366
<210> 547
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 547
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtgtctg gattctccct cagtagctac ttcatgagct gggtccgcca ggctccaggg 180
gaggggctgg aatacatcgg attcattaat cctggtggta gcgcatacta cgcgagctgg 240
gcgagtggcc gactcaccat ctccaaaacc tcgaccacgg tagatctgaa aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagga ttcttattgt ttcttatgga 360
gcctttacca tc 372
<210> 548
<211> 39
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 548
cagtccagtg agagcgttta tagtaataac ctcttatcc 39
<210> 549
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 549
agggcatcca atctggcatc t 21
<210> 550
<211> 30
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 550
caaggctatt atagtggtgt cattaatagt 30
<210> 551
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 551
agctacttca tgagc 15
<210> 552
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 552
ttcattaatc ctggtggtag cgcatactac gcgagctggg cgagtggc 48
<210> 553
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 553
attcttattg tttcttatgg agcctttacc atc 33
<210> 554
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 554
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Thr
35 40 45
Glu Ser Ile Gly Asn Glu Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Thr Gly Val Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Ser Ala Asn Ile Asp Asn Ala
115 120
<210> 555
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 555
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Lys Tyr Tyr Met Ser Trp Val Arg Gln Ala Pro Glu Lys Gly Leu Lys
50 55 60
Tyr Ile Gly Tyr Ile Asp Ser Thr Thr Val Asn Thr Tyr Tyr Ala Thr
65 70 75 80
Trp Ala Arg Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Gly Ser Thr Tyr Phe Thr Asp Gly Gly His Arg Leu Asp Leu
115 120 125
<210> 556
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 556
Gln Ala Thr Glu Ser Ile Gly Asn Glu Leu Ser
1 5 10
<210> 557
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 557
Ser Ala Ser Thr Leu Ala Ser
1 5
<210> 558
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 558
Gln Gln Gly Tyr Ser Ser Ala Asn Ile Asp Asn Ala
1 5 10
<210> 559
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 559
Lys Tyr Tyr Met Ser
1 5
<210> 560
<211> 17
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 560
Tyr Ile Asp Ser Thr Thr Val Asn Thr Tyr Tyr Ala Thr Trp Ala Arg
1 5 10 15
Gly
<210> 561
<211> 14
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 561
Gly Ser Thr Tyr Phe Thr Asp Gly Gly His Arg Leu Asp Leu
1 5 10
<210> 562
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 562
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca agtgccaggc cactgagagc attggcaatg agttatcctg gtatcagcag 180
aaaccagggc aggctcccaa gctcctgatc tattctgcat ccactctggc atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acacagttca ctctcaccat caccggcgtg 300
gagtgtgatg atgctgccac ttactactgt caacagggtt atagtagtgc taatattgat 360
aatgct 366
<210> 563
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 563
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
accgtctctg gattctccct cagtaagtac tacatgagct gggtccgcca ggctccagag 180
aaggggctga aatacatcgg atacattgat agtactactg ttaatacata ctacgcgacc 240
tgggcgagag gccgattcac catctccaaa acctcgacca cggtggatct gaagatcacc 300
agtccgacaa gtgaggacac ggccacctat ttctgtgcca gaggaagtac ttattttact 360
gatggaggcc atcggttgga tctc 384
<210> 564
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 564
caggccactg agagcattgg caatgagtta tcc 33
<210> 565
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 565
tctgcatcca ctctggcatc t 21
<210> 566
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 566
caacagggtt atagtagtgc taatattgat aatgct 36
<210> 567
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 567
aagtactaca tgagc 15
<210> 568
<211> 51
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 568
tacattgata gtactactgt taatacatac tacgcgacct gggcgagagg c 51
<210> 569
<211> 42
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 569
ggaagtactt attttactga tggaggccat cggttggatc tc 42
<210> 570
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 570
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Val Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Thr
35 40 45
Glu Ser Ile Gly Asn Glu Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr
85 90 95
Ile Thr Gly Val Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Ser Ala Asn Ile Asp Asn Ala
115 120
<210> 571
<211> 124
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 571
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Thr Tyr Asn Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ser Ile Thr Ile Asp Gly Arg Thr Tyr Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Val Ser Lys Ser Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Thr Gly Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Ile Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
115 120
<210> 572
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 572
Gln Ala Thr Glu Ser Ile Gly Asn Glu Leu Ser
1 5 10
<210> 573
<211> 7
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 573
Ser Ala Ser Thr Leu Ala Ser
1 5
<210> 574
<211> 12
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 574
Gln Gln Gly Tyr Ser Ser Ala Asn Ile Asp Asn Ala
1 5 10
<210> 575
<211> 5
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 575
Thr Tyr Asn Met Gly
1 5
<210> 576
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 576
Ser Ile Thr Ile Asp Gly Arg Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
1 5 10 15
<210> 577
<211> 11
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 577
Ile Leu Ile Val Ser Tyr Gly Ala Phe Thr Ile
1 5 10
<210> 578
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 578
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca agtgccaggc cactgagagc attggcaatg agttatcctg gtatcagcag 180
aaaccagggc aggctcccaa gctcctgatc tattctgcat ccactctggc atctggggtc 240
ccatcgcggt tcaaaggcag tggatctggg acacagttca ctctcaccat caccggcgtg 300
gagtgtgatg atgctgccac ttactactgt caacagggtt atagtagtgc taatattgat 360
aatgct 366
<210> 579
<211> 372
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 579
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggta acgcctggga cacccctgac actcacctgc 120
acagtctctg gattctccct cagtacctac aacatgggct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aagtattact attgatggtc gcacatacta cgcgagctgg 240
gcgaaaggcc gattcaccgt ctccaaaagc tcgaccacgg tggatctgaa aatgaccagt 300
ctgacaaccg gggacacggc cacctatttc tgtgccagga ttcttattgt ttcttatggg 360
gcctttacca tc 372
<210> 580
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 580
caggccactg agagcattgg caatgagtta tcc 33
<210> 581
<211> 21
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 581
tctgcatcca ctctggcatc t 21
<210> 582
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 582
caacagggtt atagtagtgc taatattgat aatgct 36
<210> 583
<211> 15
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 583
acctacaaca tgggc 15
<210> 584
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 584
agtattacta ttgatggtcg cacatactac gcgagctggg cgaaaggc 48
<210> 585
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 585
attcttattg tttcttatgg ggcctttacc atc 33
<210> 586
<211> 105
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> κ恒定结构域
<400> 586
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
1 5 10 15
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
20 25 30
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
35 40 45
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
50 55 60
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
65 70 75 80
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
85 90 95
Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 587
<211> 315
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> κ恒定结构域
<400> 587
gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact 60
gcctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtggaag 120
gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag 180
gacagcacct acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac 240
aaagtctacg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagcttc 300
aacaggggag agtgt 315
<210> 588
<211> 330
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> γ-1恒定结构域
<400> 588
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu
225 230 235 240
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 589
<211> 990
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> γ-1恒定结构域
<400> 589
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 240
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 300
aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 360
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 420
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 480
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgcc 540
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 600
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 660
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 720
atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 780
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 840
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 900
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 960
cagaagagcc tctccctgtc tccgggtaaa 990
<210> 590
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 590
Val Pro Pro Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg
1 5 10 15
<210> 591
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 591
Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu
1 5 10 15
<210> 592
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 592
Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr Ser Ser
1 5 10 15
<210> 593
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 593
Val Ala Ala Pro His Arg Gln Pro Leu Thr Ser Ser Glu Arg Ile
1 5 10 15
<210> 594
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 594
Pro His Arg Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys Gln
1 5 10 15
<210> 595
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 595
Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr
1 5 10 15
<210> 596
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 596
Thr Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp
1 5 10 15
<210> 597
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 597
Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile Ser
1 5 10 15
<210> 598
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 598
Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile Ser Ala Leu Arg
1 5 10 15
<210> 599
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 599
Ile Arg Tyr Ile Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu Thr
1 5 10 15
<210> 600
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 600
Ile Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys
1 5 10 15
<210> 601
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 601
Gly Ile Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met
1 5 10 15
<210> 602
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 602
Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser
1 5 10 15
<210> 603
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 603
Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser Ser Lys Glu
1 5 10 15
<210> 604
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 604
Cys Asn Lys Ser Asn Met Cys Glu Ser Ser Lys Glu Ala Leu Ala
1 5 10 15
<210> 605
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 605
Ser Asn Met Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn
1 5 10 15
<210> 606
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 606
Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu
1 5 10 15
<210> 607
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 607
Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met
1 5 10 15
<210> 608
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 608
Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala Glu Lys
1 5 10 15
<210> 609
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 609
Glu Asn Asn Leu Asn Leu Pro Lys Met Ala Glu Lys Asp Gly Cys
1 5 10 15
<210> 610
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 610
Leu Asn Leu Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser
1 5 10 15
<210> 611
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 611
Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn
1 5 10 15
<210> 612
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 612
Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr
1 5 10 15
<210> 613
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 613
Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu Val
1 5 10 15
<210> 614
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 614
Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu Val Lys Ile Ile
1 5 10 15
<210> 615
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 615
Gly Phe Asn Glu Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu
1 5 10 15
<210> 616
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 616
Glu Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe
1 5 10 15
<210> 617
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 617
Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr
1 5 10 15
<210> 618
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 618
Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr
1 5 10 15
<210> 619
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 619
Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln Asn
1 5 10 15
<210> 620
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 620
Leu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu
1 5 10 15
<210> 621
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 621
Glu Val Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu
1 5 10 15
<210> 622
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 622
Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala
1 5 10 15
<210> 623
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 623
Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val
1 5 10 15
<210> 624
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 624
Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln Met Ser
1 5 10 15
<210> 625
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 625
Ser Ser Glu Glu Gln Ala Arg Ala Val Gln Met Ser Thr Lys Val
1 5 10 15
<210> 626
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 626
Glu Gln Ala Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln
1 5 10 15
<210> 627
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 627
Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln
1 5 10 15
<210> 628
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 628
Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala
1 5 10 15
<210> 629
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 629
Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn Leu
1 5 10 15
<210> 630
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 630
Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn Leu Asp Ala Ile
1 5 10 15
<210> 631
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 631
Phe Leu Gln Lys Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro
1 5 10 15
<210> 632
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 632
Lys Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr
1 5 10 15
<210> 633
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 633
Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala
1 5 10 15
<210> 634
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 634
Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu
1 5 10 15
<210> 635
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 635
Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu Thr Lys Leu
1 5 10 15
<210> 636
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 636
Asp Pro Thr Thr Asn Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln
1 5 10 15
<210> 637
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 637
Thr Asn Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp
1 5 10 15
<210> 638
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 638
Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp
1 5 10 15
<210> 639
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 639
Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr
1 5 10 15
<210> 640
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 640
Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His Leu Ile
1 5 10 15
<210> 641
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 641
Asn Gln Trp Leu Gln Asp Met Thr Thr His Leu Ile Leu Arg Ser
1 5 10 15
<210> 642
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 642
Leu Gln Asp Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu
1 5 10 15
<210> 643
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 643
Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln
1 5 10 15
<210> 644
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 644
His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu
1 5 10 15
<210> 645
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 645
Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala Leu
1 5 10 15
<210> 646
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 646
Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala Leu Arg Gln Met
1 5 10 15
<210> 647
<211> 111
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 647
Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys Arg
100 105 110
<210> 648
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 648
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp
20 25 30
Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys
85
<210> 649
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 649
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys
85
<210> 650
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 650
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys
85
<210> 651
<211> 111
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 人源化抗体
<400> 651
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105 110
<210> 652
<211> 117
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 652
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser Asn Tyr Tyr
20 25 30
Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Trp Ala Ile Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Met Thr
65 70 75 80
Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Asp
85 90 95
Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 653
<211> 97
<212> PRT
<213> 智人(Homo sapiens)
<400> 653
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg
<210> 654
<211> 97
<212> PRT
<213> 智人(Homo sapiens)
<400> 654
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg
<210> 655
<211> 98
<212> PRT
<213> 智人(Homo sapiens)
<400> 655
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys
<210> 656
<211> 120
<212> PRT
<213> 人工序列(Artificial sequence)
<220>
<223> 人源化抗体
<400> 656
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Trp Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 657
<211> 120
<212> PRT
<213> 人工序列(Artificial sequence)
<220>
<223> 人源化抗体
<400> 657
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 658
<211> 166
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 658
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Asn Tyr Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser
65 70 75 80
Ala Ile Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
115 120 125
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
130 135 140
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
145 150 155 160
Leu Gly Cys Leu Val Lys
165
<210> 659
<211> 16
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 659
Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile Gly
1 5 10 15
<210> 660
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 660
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Asn Asn Glu Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Leu Arg Asn Ile Asp Asn Ala
115 120
<210> 661
<211> 125
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 661
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Asn Tyr Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Trp
65 70 75 80
Ala Ile Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu
115 120 125
<210> 662
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 662
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctcggtgt ctgcagctgt gggaggcaca 120
gtcaccatca agtgccaggc cagtcagagc attaacaatg aattatcctg gtatcagcag 180
aaaccagggc agcgtcccaa gctcctgatc tatagggcat ccactctggc atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caacagggtt atagtctgag gaatattgat 360
aatgct 366
<210> 663
<211> 375
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 663
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtaactac tacgtgacct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcatttat ggtagtgatg aaacggccta cgcgacctgg 240
gcgataggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ctgacagccg cggacacggc cacctatttc tgtgccagag atgatagtag tgactgggat 360
gcaaaattta acttg 375
<210> 664
<211> 450
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 664
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Trp Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 665
<211> 450
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 665
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 666
<211> 216
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 666
Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp
1 5 10 15
Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu Leu
20 25 30
Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn Ile
85 90 95
Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val
100 105 110
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
115 120 125
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
130 135 140
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
145 150 155 160
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
165 170 175
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
180 185 190
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
195 200 205
Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 667
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 667
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Glu Val Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Glu Thr Ile Tyr Ser Trp Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln
50 55 60
Pro Pro Lys Leu Leu Ile Tyr Gln Ala Ser Asp Leu Ala Ser Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ala Gly Thr Glu Tyr Thr Leu Thr
85 90 95
Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Gly Ser Asn Val Asp Asn Val
115 120
<210> 668
<211> 126
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 668
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Lys Glu Ser Gly Gly Arg Leu Val Thr
20 25 30
Pro Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu
35 40 45
Asn Asp His Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Tyr Ile Gly Phe Ile Asn Ser Gly Gly Ser Ala Arg Tyr Ala Ser
65 70 75 80
Trp Ala Glu Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Val Arg Gly Gly Ala Val Trp Ser Ile His Ser Phe Asp Pro
115 120 125
<210> 669
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 669
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctctgtgg aggtagctgt gggaggcaca 120
gtcaccatca attgccaggc cagtgagacc atttacagtt ggttatcctg gtatcagcag 180
aagccagggc agcctcccaa gctcctgatc taccaggcat ccgatctggc atctggggtc 240
ccatcgcgat tcagcggcag tggggctggg acagagtaca ctctcaccat cagcggcgtg 300
cagtgtgacg atgctgccac ttactactgt caacagggtt atagtggtag taatgttgat 360
aatgtt 366
<210> 670
<211> 378
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 670
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctga aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacacttacc 120
tgcacagcct ctggattctc cctcaatgac catgcaatgg gctgggtccg ccaggctcca 180
gggaaggggc tggaatacat cggattcatt aatagtggtg gtagcgcacg ctacgcgagc 240
tgggcagaag gccgattcac catctccaga acctcgacca cggtggatct gaaaatgacc 300
agtctgacaa ccgaggacac ggccacctat ttctgtgtca gagggggtgc tgtttggagt 360
attcatagtt ttgatccc 378
<210> 671
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 671
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Val Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Thr Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asn Ala
115 120
<210> 672
<211> 125
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 672
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Val Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Phe Ile Thr Met Ser Asp Asn Ile Asn Tyr Ala Ser Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Ser Arg Gly Trp Gly Thr Met Gly Arg Leu Asp Leu
115 120 125
<210> 673
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 673
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccg ccgtgctgac ccagactcca tctcccgtgt ctgcagctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttatgaca acaactactt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcatccac tctggcatct 240
ggggtcccat cgcggttcgt gggcagtgga tctgggacac agttcactct caccatcaca 300
gacgtgcagt gtgacgatgc tgccacttac tattgtgcag gcgtttatga tgatgatagt 360
gataatgcc 369
<210> 674
<211> 375
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 674
atggagactg ggctgcgctg gcttctcctg gtggctgtgc tcaaaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acccctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtgtctac tacatgaact gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg attcattaca atgagtgata atataaatta cgcgagctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagga gtcgtggctg gggtacaatg 360
ggtcggttgg atctc 375
<210> 675
<211> 123
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 675
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Ile Cys Asp Pro Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Pro Val Gly Gly Thr Val Ser Ile Ser Cys Gln Ala Ser
35 40 45
Gln Ser Val Tyr Glu Asn Asn Tyr Leu Ser Trp Phe Gln Gln Lys Pro
50 55 60
Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Leu Asp Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Thr Asp Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Val Tyr Asp Asp Asp Ser Asp Asp Ala
115 120
<210> 676
<211> 126
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 676
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Glu Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Thr
20 25 30
Pro Gly Gly Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu
35 40 45
Asn Ala Tyr Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Ile Gly Phe Ile Thr Leu Asn Asn Asn Val Ala Tyr Ala Asn
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Phe Ser Lys Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Met Thr Ser Pro Thr Pro Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Ser Arg Gly Trp Gly Ala Met Gly Arg Leu Asp Leu
115 120 125
<210> 677
<211> 369
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 677
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
atatgtgacc ctgtgctgac ccagactcca tctcccgtat ctgcacctgt gggaggcaca 120
gtcagcatca gttgccaggc cagtcagagt gtttatgaga acaactattt atcctggttt 180
cagcagaaac cagggcagcc tcccaagctc ctgatctatg gtgcatccac tctggattct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccattaca 300
gacgtgcagt gtgacgatgc tgccacttac tattgtgcag gcgtttatga tgatgatagt 360
gatgatgcc 369
<210> 678
<211> 378
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 678
atggagactg ggctgcgctg gcttctcctg gtggctgtgc tcaaaggtgt ccagtgtcag 60
gagcagctga aggagtccgg aggaggcctg gtaacgcctg gaggaaccct gacactcacc 120
tgcacagcct ctggattctc cctcaatgcc tactacatga actgggtccg ccaggctcca 180
gggaaggggc tggaatggat cggattcatt actctgaata ataatgtagc ttacgcgaac 240
tgggcgaaag gccgattcac cttctccaaa acctcgacca cggtggatct gaaaatgacc 300
agtccgacac ccgaggacac ggccacctat ttctgtgcca ggagtcgtgg ctggggtgca 360
atgggtcggt tggatctc 378
<210> 679
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 679
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Gln Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser
35 40 45
Gln Ser Val Asp Asp Asn Asn Trp Leu Gly Trp Tyr Gln Gln Lys Arg
50 55 60
Gly Gln Pro Pro Lys Tyr Leu Ile Tyr Ser Ala Ser Thr Leu Ala Ser
65 70 75 80
Gly Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr
85 90 95
Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys
100 105 110
Ala Gly Gly Phe Ser Gly Asn Ile Phe Ala
115 120
<210> 680
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 680
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser
35 40 45
Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Gly Gly Phe Gly Thr Thr Tyr Tyr Ala Thr Trp
65 70 75 80
Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Arg Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Gly Gly Pro Gly Asn Gly Gly Asp Ile
115 120
<210> 681
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 681
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgccc aagtgctgac ccagactcca tcgcctgtgt ctgcagctgt gggaggcaca 120
gtcaccatca actgccaggc cagtcagagt gttgatgata acaactggtt aggctggtat 180
cagcagaaac gagggcagcc tcccaagtac ctgatctatt ctgcatccac tctggcatct 240
ggggtcccat cgcggttcaa aggcagtgga tctgggacac agttcactct caccatcagc 300
gacctggagt gtgacgatgc tgccacttac tactgtgcag gcggttttag tggtaatatc 360
tttgct 366
<210> 682
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 682
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagtctctg gcttctccct cagtagctat gcaatgagct gggtccgcca ggctccagga 180
aaggggctgg agtggatcgg aatcattggt ggttttggta ccacatacta cgcgacctgg 240
gcgaaaggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgag aatcaccagt 300
ccgacaaccg aggacacggc cacctatttc tgtgccagag gtggtcctgg taatggtggt 360
gacatc 366
<210> 683
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 683
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Thr Phe Ala Ala Val Leu Thr Gln Thr Pro Ser Pro
20 25 30
Val Ser Val Pro Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ser Ser
35 40 45
Gln Ser Val Tyr Asn Asn Phe Leu Ser Trp Tyr Gln Gln Lys Pro Gly
50 55 60
Gln Pro Pro Lys Leu Leu Ile Tyr Gln Ala Ser Lys Leu Ala Ser Gly
65 70 75 80
Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu
85 90 95
Thr Ile Ser Gly Val Gln Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Leu
100 105 110
Gly Gly Tyr Asp Asp Asp Ala Asp Asn Ala
115 120
<210> 684
<211> 128
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 684
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly
1 5 10 15
Val Gln Cys Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser
35 40 45
Asp Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Ile Ile Tyr Ala Gly Ser Gly Ser Thr Trp Tyr Ala Ser
65 70 75 80
Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp
85 90 95
Leu Lys Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys
100 105 110
Ala Arg Asp Gly Tyr Asp Asp Tyr Gly Asp Phe Asp Arg Leu Asp Leu
115 120 125
<210> 685
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 685
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
acatttgcag ccgtgctgac ccagacacca tcgcccgtgt ctgtacctgt gggaggcaca 120
gtcaccatca agtgccagtc cagtcagagt gtttataata atttcttatc gtggtatcag 180
cagaaaccag ggcagcctcc caagctcctg atctaccagg catccaaact ggcatctggg 240
gtcccagata ggttcagcgg cagtggatct gggacacagt tcactctcac catcagcggc 300
gtgcagtgtg acgatgctgc cacttactac tgtctaggcg gttatgatga tgatgctgat 360
aatgct 366
<210> 686
<211> 384
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 686
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tcaaaggtgt ccagtgtcag 60
tcggtggagg agtccggggg tcgcctggtc acgcctggga cacccctgac gctcacctgc 120
acagtctctg gaatcgacct cagtgactat gcaatgagct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatcatttat gctggtagtg gtagcacatg gtacgcgagc 240
tgggcgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcacc 300
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gagatggata cgatgactat 360
ggtgatttcg atcgattgga tctc 384
<210> 687
<211> 122
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 687
Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Arg Cys Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser
20 25 30
Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Lys Cys Gln Ala Ser
35 40 45
Gln Ser Ile Asn Asn Glu Leu Ser Trp Tyr Gln Gln Lys Ser Gly Gln
50 55 60
Arg Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val
65 70 75 80
Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr
85 90 95
Ile Ser Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln
100 105 110
Gly Tyr Ser Leu Arg Asn Ile Asp Asn Ala
115 120
<210> 688
<211> 125
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 688
Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Ser Gly
1 5 10 15
Val Gln Cys Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro
20 25 30
Gly Thr Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser
35 40 45
Asn Tyr Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Ile Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Trp
65 70 75 80
Ala Ile Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu
85 90 95
Lys Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala
100 105 110
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu
115 120 125
<210> 689
<211> 366
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 689
atggacacga gggcccccac tcagctgctg gggctcctgc tgctctggct cccaggtgcc 60
agatgtgcct atgatatgac ccagactcca gcctcggtgt ctgcagctgt gggaggcaca 120
gtcaccatca aatgccaggc cagtcagagc attaacaatg aattatcctg gtatcagcag 180
aaatcagggc agcgtcccaa gctcctgatc tatagggcat ccactctggc atctggggtc 240
tcatcgcggt tcaaaggcag tggatctggg acagagttca ctctcaccat cagcgacctg 300
gagtgtgccg atgctgccac ttactactgt caacagggtt atagtctgag gaatattgat 360
aatgct 366
<210> 690
<211> 375
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 690
atggagactg ggctgcgctg gcttctcctg gtcgctgtgc tctcaggtgt ccagtgtcag 60
tcgctggagg agtccggggg tcgcctggtc acgcctggga cacccctgac actcacctgc 120
acagcctctg gattctccct cagtaactac tacatgacct gggtccgcca ggctccaggg 180
aaggggctgg aatggatcgg aatgatttat ggtagtgatg aaacagccta cgcgaactgg 240
gcgataggcc gattcaccat ctccaaaacc tcgaccacgg tggatctgaa aatgaccagt 300
ctgacagccg cggacacggc cacctatttc tgtgccagag atgatagtag tgactgggat 360
gcaaaattta acttg 375
<210> 691
<211> 450
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 691
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Trp Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 692
<211> 450
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 692
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Met Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Asn Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 693
<211> 217
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 693
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr
100 105 110
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
115 120 125
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
130 135 140
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
145 150 155 160
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
180 185 190
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
195 200 205
Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 694
<211> 33
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 694
caggccagtc agagcattaa caatgagtta tcc 33
<210> 695
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 695
caacagggtt atagtctgag gaacattgat aatgct 36
<210> 696
<211> 48
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 696
atcatctatg gtagtgatga aaccgcctac gctacctccg ctataggc 48
<210> 697
<211> 36
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 697
gatgatagta gtgactggga tgcaaagttc aacttg 36
<210> 698
<211> 336
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 698
gctatccaga tgacccagtc tccttcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattaac aatgagttat cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag ggttatagtc tgaggaacat tgataatgct 300
ttcggcggag ggaccaaggt ggaaatcaaa cgtacg 336
<210> 699
<211> 112
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 699
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr
100 105 110
<210> 700
<211> 360
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 700
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt aactactacg tgacctgggt ccgtcaggct 120
ccagggaagg ggctggagtg ggtcggcatc atctatggta gtgatgaaac cgcctacgct 180
acctccgcta taggccgatt caccatctcc agagacaatt ccaagaacac cctgtatctt 240
caaatgaaca gcctgagagc tgaggacact gctgtgtatt actgtgctag agatgatagt 300
agtgactggg atgcaaagtt caacttgtgg ggccaaggga ccctcgtcac cgtctcgagc 360
<210> 701
<211> 651
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 701
gctatccaga tgacccagtc tccttcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattaac aatgagttat cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag ggttatagtc tgaggaacat tgataatgct 300
ttcggcggag ggaccaaggt ggaaatcaaa cgtacggtgg ctgcaccatc tgtcttcatc 360
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651
<210> 702
<211> 217
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 702
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr
100 105 110
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
115 120 125
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
130 135 140
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
145 150 155 160
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
180 185 190
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
195 200 205
Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 703
<211> 1350
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 703
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt aactactacg tgacctgggt ccgtcaggct 120
ccagggaagg ggctggagtg ggtcggcatc atctatggta gtgatgaaac cgcctacgct 180
acctccgcta taggccgatt caccatctcc agagacaatt ccaagaacac cctgtatctt 240
caaatgaaca gcctgagagc tgaggacact gctgtgtatt actgtgctag agatgatagt 300
agtgactggg atgcaaagtt caacttgtgg ggccaaggga ccctcgtcac cgtctcgagc 360
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 660
aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgcc 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1080
atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggtaaa 1350
<210> 704
<211> 450
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 704
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 705
<211> 705
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 705
atgaagtggg taacctttat ttcccttctg tttctcttta gcagcgctta ttccgctatc 60
cagatgaccc agtctccttc ctccctgtct gcatctgtag gagacagagt caccatcact 120
tgccaggcca gtcagagcat taacaatgag ttatcctggt atcagcagaa accagggaaa 180
gcccctaagc tcctgatcta tagggcatcc actctggcat ctggggtccc atcaaggttc 240
agcggcagtg gatctgggac agacttcact ctcaccatca gcagcctgca gcctgatgat 300
tttgcaactt attactgcca acagggttat agtctgagga acattgataa tgctttcggc 360
ggagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg 420
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 660
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 705
<210> 706
<211> 235
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 706
Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala
1 5 10 15
Tyr Ser Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
20 25 30
Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn
35 40 45
Asn Glu Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
50 55 60
Leu Ile Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe
65 70 75 80
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
85 90 95
Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu
100 105 110
Arg Asn Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
115 120 125
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
130 135 140
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
145 150 155 160
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
165 170 175
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
180 185 190
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
195 200 205
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
210 215 220
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 707
<211> 1404
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 707
atgaagtggg taacctttat ttcccttctg tttctcttta gcagcgctta ttccgaggtg 60
cagctggtgg agtctggggg aggcttggtc cagcctgggg ggtccctgag actctcctgt 120
gcagcctctg gattctccct cagtaactac tacgtgacct gggtccgtca ggctccaggg 180
aaggggctgg agtgggtcgg catcatctat ggtagtgatg aaaccgccta cgctacctcc 240
gctataggcc gattcaccat ctccagagac aattccaaga acaccctgta tcttcaaatg 300
aacagcctga gagctgagga cactgctgtg tattactgtg ctagagatga tagtagtgac 360
tgggatgcaa agttcaactt gtggggccaa gggaccctcg tcaccgtctc gagcgcctcc 420
accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480
gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660
tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct 720
tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780
gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 900
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta cgccagcacg 960
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020
aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080
aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc 1140
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380
agcctctccc tgtctccggg taaa 1404
<210> 708
<211> 468
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 708
Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala
1 5 10 15
Tyr Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
20 25 30
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser
35 40 45
Asn Tyr Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
50 55 60
Trp Val Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser
65 70 75 80
Ala Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
85 90 95
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp
115 120 125
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
130 135 140
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
145 150 155 160
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
165 170 175
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
180 185 190
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
195 200 205
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
210 215 220
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
225 230 235 240
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
245 250 255
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
260 265 270
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
275 280 285
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
290 295 300
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr
305 310 315 320
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
325 330 335
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
340 345 350
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
355 360 365
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
370 375 380
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
385 390 395 400
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
405 410 415
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
420 425 430
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
435 440 445
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
450 455 460
Ser Pro Gly Lys
465
<210> 709
<211> 111
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 709
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105 110
<210> 710
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 710
Arg Ala Ser Gln Gly Ile Arg Asn Asp Leu Gly
1 5 10
<210> 711
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 711
Arg Ala Ser Gln Gly Ile Ser Asn Tyr Leu Ala
1 5 10
<210> 712
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 712
Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala
1 5 10
<210> 713
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 713
Ala Ala Ser Ser Leu Gln Ser
1 5
<210> 714
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 714
Ala Ala Ser Thr Leu Gln Ser
1 5
<210> 715
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<400> 715
Lys Ala Ser Ser Leu Glu Ser
1 5
<210> 716
<211> 5
<212> PRT
<213> 智人(Homo sapiens)
<400> 716
Ser Asn Tyr Met Ser
1 5
<210> 717
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 717
Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 718
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<400> 718
Val Ile Tyr Ser Gly Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 719
<211> 330
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> γ-1恒定结构域
<400> 719
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 720
<211> 297
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 720
atccagatga cccagtctcc ttcctccctg tctgcatctg taggagacag agtcaccatc 60
acttgccagg ccagtcagag cattaacaat gagttatcct ggtatcagca gaaaccaggg 120
aaagccccta agctcctgat ctatagggca tccactctgg catctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagacttc actctcacca tcagcagcct gcagcctgat 240
gattttgcaa cttattactg ccaacagggt tatagtctga ggaacattga taatgct 297
<210> 721
<211> 333
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 721
gcctatgata tgacccagac tccagcctcg gtgtctgcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagcattaac aatgaattat cctggtatca gcagaaacca 120
gggcagcgtc ccaagctcct gatctatagg gcatccactc tggcatctgg ggtctcatcg 180
cggttcaaag gcagtggatc tgggacagag ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ctgtcaacag ggttatagtc tgaggaatat tgataatgct 300
ttcggcggag ggaccgaggt ggtggtcaaa cgt 333
<210> 722
<211> 648
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 722
atccagatga cccagtctcc ttcctccctg tctgcatctg taggagacag agtcaccatc 60
acttgccagg ccagtcagag cattaacaat gagttatcct ggtatcagca gaaaccaggg 120
aaagccccta agctcctgat ctatagggca tccactctgg catctggggt cccatcaagg 180
ttcagcggca gtggatctgg gacagacttc actctcacca tcagcagcct gcagcctgat 240
gattttgcaa cttattactg ccaacagggt tatagtctga ggaacattga taatgctttc 300
ggcggaggga ccaaggtgga aatcaaacgt acggtggctg caccatctgt cttcatcttc 360
ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 420
ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 480
tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 540
ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 600
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgt 648
<210> 723
<211> 333
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 723
gctatccaga tgacccagtc tccttcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattaac aatgagttat cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaacag ggttatagtc tgaggaacat tgataatgct 300
ttcggcggag ggaccaaggt ggaaatcaaa cgt 333
<210> 724
<211> 327
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 724
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt aactactacg tgacctgggt ccgtcaggct 120
ccagggaagg ggctggagtg ggtcggcatc atctatggta gtgatgaaac cgcctacgct 180
acctccgcta taggccgatt caccatctcc agagacaatt ccaagaacac cctgtatctt 240
caaatgaaca gcctgagagc tgaggacact gctgtgtatt actgtgctag agatgatagt 300
agtgactggg atgcaaagtt caacttg 327
<210> 725
<211> 351
<212> DNA
<213> 穴兔(Oryctolagus cuniculus)
<400> 725
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctggattctc cctcagtaac tactacgtga cctgggtccg ccaggctcca 120
gggaaggggc tggaatggat cggaatcatt tatggtagtg atgaaacggc ctacgcgacc 180
tgggcgatag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatgacc 240
agtctgacag ccgcggacac ggccacctat ttctgtgcca gagatgatag tagtgactgg 300
gatgcaaaat ttaacttgtg gggccaaggc accctggtca ccgtctcgag c 351
<210> 726
<211> 224
<212> PRT
<213> 智人(Homo sapiens)
<400> 726
Met Glu Lys Leu Leu Cys Phe Leu Val Leu Thr Ser Leu Ser His Ala
1 5 10 15
Phe Gly Gln Thr Asp Met Ser Arg Lys Ala Phe Val Phe Pro Lys Glu
20 25 30
Ser Asp Thr Ser Tyr Val Ser Leu Lys Ala Pro Leu Thr Lys Pro Leu
35 40 45
Lys Ala Phe Thr Val Cys Leu His Phe Tyr Thr Glu Leu Ser Ser Thr
50 55 60
Arg Gly Tyr Ser Ile Phe Ser Tyr Ala Thr Lys Arg Gln Asp Asn Glu
65 70 75 80
Ile Leu Ile Phe Trp Ser Lys Asp Ile Gly Tyr Ser Phe Thr Val Gly
85 90 95
Gly Ser Glu Ile Leu Phe Glu Val Pro Glu Val Thr Val Ala Pro Val
100 105 110
His Ile Cys Thr Ser Trp Glu Ser Ala Ser Gly Ile Val Glu Phe Trp
115 120 125
Val Asp Gly Lys Pro Arg Val Arg Lys Ser Leu Lys Lys Gly Tyr Thr
130 135 140
Val Gly Ala Glu Ala Ser Ile Ile Leu Gly Gln Glu Gln Asp Ser Phe
145 150 155 160
Gly Gly Asn Phe Glu Gly Ser Gln Ser Leu Val Gly Asp Ile Gly Asn
165 170 175
Val Asn Met Trp Asp Phe Val Leu Ser Pro Asp Glu Ile Asn Thr Ile
180 185 190
Tyr Leu Gly Gly Pro Phe Ser Pro Asn Val Leu Asn Trp Arg Ala Leu
195 200 205
Lys Tyr Glu Val Gln Gly Glu Val Phe Thr Lys Pro Gln Leu Trp Pro
210 215 220
<210> 727
<211> 468
<212> PRT
<213> 智人(Homo sapiens)
<400> 727
Met Leu Ala Val Gly Cys Ala Leu Leu Ala Ala Leu Leu Ala Ala Pro
1 5 10 15
Gly Ala Ala Leu Ala Pro Arg Arg Cys Pro Ala Gln Glu Val Ala Arg
20 25 30
Gly Val Leu Thr Ser Leu Pro Gly Asp Ser Val Thr Leu Thr Cys Pro
35 40 45
Gly Val Glu Pro Glu Asp Asn Ala Thr Val His Trp Val Leu Arg Lys
50 55 60
Pro Ala Ala Gly Ser His Pro Ser Arg Trp Ala Gly Met Gly Arg Arg
65 70 75 80
Leu Leu Leu Arg Ser Val Gln Leu His Asp Ser Gly Asn Tyr Ser Cys
85 90 95
Tyr Arg Ala Gly Arg Pro Ala Gly Thr Val His Leu Leu Val Asp Val
100 105 110
Pro Pro Glu Glu Pro Gln Leu Ser Cys Phe Arg Lys Ser Pro Leu Ser
115 120 125
Asn Val Val Cys Glu Trp Gly Pro Arg Ser Thr Pro Ser Leu Thr Thr
130 135 140
Lys Ala Val Leu Leu Val Arg Lys Phe Gln Asn Ser Pro Ala Glu Asp
145 150 155 160
Phe Gln Glu Pro Cys Gln Tyr Ser Gln Glu Ser Gln Lys Phe Ser Cys
165 170 175
Gln Leu Ala Val Pro Glu Gly Asp Ser Ser Phe Tyr Ile Val Ser Met
180 185 190
Cys Val Ala Ser Ser Val Gly Ser Lys Phe Ser Lys Thr Gln Thr Phe
195 200 205
Gln Gly Cys Gly Ile Leu Gln Pro Asp Pro Pro Ala Asn Ile Thr Val
210 215 220
Thr Ala Val Ala Arg Asn Pro Arg Trp Leu Ser Val Thr Trp Gln Asp
225 230 235 240
Pro His Ser Trp Asn Ser Ser Phe Tyr Arg Leu Arg Phe Glu Leu Arg
245 250 255
Tyr Arg Ala Glu Arg Ser Lys Thr Phe Thr Thr Trp Met Val Lys Asp
260 265 270
Leu Gln His His Cys Val Ile His Asp Ala Trp Ser Gly Leu Arg His
275 280 285
Val Val Gln Leu Arg Ala Gln Glu Glu Phe Gly Gln Gly Glu Trp Ser
290 295 300
Glu Trp Ser Pro Glu Ala Met Gly Thr Pro Trp Thr Glu Ser Arg Ser
305 310 315 320
Pro Pro Ala Glu Asn Glu Val Ser Thr Pro Met Gln Ala Leu Thr Thr
325 330 335
Asn Lys Asp Asp Asp Asn Ile Leu Phe Arg Asp Ser Ala Asn Ala Thr
340 345 350
Ser Leu Pro Val Gln Asp Ser Ser Ser Val Pro Leu Pro Thr Phe Leu
355 360 365
Val Ala Gly Gly Ser Leu Ala Phe Gly Thr Leu Leu Cys Ile Ala Ile
370 375 380
Val Leu Arg Phe Lys Lys Thr Trp Lys Leu Arg Ala Leu Lys Glu Gly
385 390 395 400
Lys Thr Ser Met His Pro Pro Tyr Ser Leu Gly Gln Leu Val Pro Glu
405 410 415
Arg Pro Arg Pro Thr Pro Val Leu Val Pro Leu Ile Ser Pro Pro Val
420 425 430
Ser Pro Ser Ser Leu Gly Ser Asp Asn Thr Ser Ser His Asn Arg Pro
435 440 445
Asp Ala Arg Asp Pro Arg Ser Pro Tyr Asp Ile Ser Asn Thr Asp Tyr
450 455 460
Phe Phe Pro Arg
465
<210> 728
<211> 918
<212> PRT
<213> 智人(Homo sapiens)
<400> 728
Met Leu Thr Leu Gln Thr Trp Val Val Gln Ala Leu Phe Ile Phe Leu
1 5 10 15
Thr Thr Glu Ser Thr Gly Glu Leu Leu Asp Pro Cys Gly Tyr Ile Ser
20 25 30
Pro Glu Ser Pro Val Val Gln Leu His Ser Asn Phe Thr Ala Val Cys
35 40 45
Val Leu Lys Glu Lys Cys Met Asp Tyr Phe His Val Asn Ala Asn Tyr
50 55 60
Ile Val Trp Lys Thr Asn His Phe Thr Ile Pro Lys Glu Gln Tyr Thr
65 70 75 80
Ile Ile Asn Arg Thr Ala Ser Ser Val Thr Phe Thr Asp Ile Ala Ser
85 90 95
Leu Asn Ile Gln Leu Thr Cys Asn Ile Leu Thr Phe Gly Gln Leu Glu
100 105 110
Gln Asn Val Tyr Gly Ile Thr Ile Ile Ser Gly Leu Pro Pro Glu Lys
115 120 125
Pro Lys Asn Leu Ser Cys Ile Val Asn Glu Gly Lys Lys Met Arg Cys
130 135 140
Glu Trp Asp Gly Gly Arg Glu Thr His Leu Glu Thr Asn Phe Thr Leu
145 150 155 160
Lys Ser Glu Trp Ala Thr His Lys Phe Ala Asp Cys Lys Ala Lys Arg
165 170 175
Asp Thr Pro Thr Ser Cys Thr Val Asp Tyr Ser Thr Val Tyr Phe Val
180 185 190
Asn Ile Glu Val Trp Val Glu Ala Glu Asn Ala Leu Gly Lys Val Thr
195 200 205
Ser Asp His Ile Asn Phe Asp Pro Val Tyr Lys Val Lys Pro Asn Pro
210 215 220
Pro His Asn Leu Ser Val Ile Asn Ser Glu Glu Leu Ser Ser Ile Leu
225 230 235 240
Lys Leu Thr Trp Thr Asn Pro Ser Ile Lys Ser Val Ile Ile Leu Lys
245 250 255
Tyr Asn Ile Gln Tyr Arg Thr Lys Asp Ala Ser Thr Trp Ser Gln Ile
260 265 270
Pro Pro Glu Asp Thr Ala Ser Thr Arg Ser Ser Phe Thr Val Gln Asp
275 280 285
Leu Lys Pro Phe Thr Glu Tyr Val Phe Arg Ile Arg Cys Met Lys Glu
290 295 300
Asp Gly Lys Gly Tyr Trp Ser Asp Trp Ser Glu Glu Ala Ser Gly Ile
305 310 315 320
Thr Tyr Glu Asp Arg Pro Ser Lys Ala Pro Ser Phe Trp Tyr Lys Ile
325 330 335
Asp Pro Ser His Thr Gln Gly Tyr Arg Thr Val Gln Leu Val Trp Lys
340 345 350
Thr Leu Pro Pro Phe Glu Ala Asn Gly Lys Ile Leu Asp Tyr Glu Val
355 360 365
Thr Leu Thr Arg Trp Lys Ser His Leu Gln Asn Tyr Thr Val Asn Ala
370 375 380
Thr Lys Leu Thr Val Asn Leu Thr Asn Asp Arg Tyr Leu Ala Thr Leu
385 390 395 400
Thr Val Arg Asn Leu Val Gly Lys Ser Asp Ala Ala Val Leu Thr Ile
405 410 415
Pro Ala Cys Asp Phe Gln Ala Thr His Pro Val Met Asp Leu Lys Ala
420 425 430
Phe Pro Lys Asp Asn Met Leu Trp Val Glu Trp Thr Thr Pro Arg Glu
435 440 445
Ser Val Lys Lys Tyr Ile Leu Glu Trp Cys Val Leu Ser Asp Lys Ala
450 455 460
Pro Cys Ile Thr Asp Trp Gln Gln Glu Asp Gly Thr Val His Arg Thr
465 470 475 480
Tyr Leu Arg Gly Asn Leu Ala Glu Ser Lys Cys Tyr Leu Ile Thr Val
485 490 495
Thr Pro Val Tyr Ala Asp Gly Pro Gly Ser Pro Glu Ser Ile Lys Ala
500 505 510
Tyr Leu Lys Gln Ala Pro Pro Ser Lys Gly Pro Thr Val Arg Thr Lys
515 520 525
Lys Val Gly Lys Asn Glu Ala Val Leu Glu Trp Asp Gln Leu Pro Val
530 535 540
Asp Val Gln Asn Gly Phe Ile Arg Asn Tyr Thr Ile Phe Tyr Arg Thr
545 550 555 560
Ile Ile Gly Asn Glu Thr Ala Val Asn Val Asp Ser Ser His Thr Glu
565 570 575
Tyr Thr Leu Ser Ser Leu Thr Ser Asp Thr Leu Tyr Met Val Arg Met
580 585 590
Ala Ala Tyr Thr Asp Glu Gly Gly Lys Asp Gly Pro Glu Phe Thr Phe
595 600 605
Thr Thr Pro Lys Phe Ala Gln Gly Glu Ile Glu Ala Ile Val Val Pro
610 615 620
Val Cys Leu Ala Phe Leu Leu Thr Thr Leu Leu Gly Val Leu Phe Cys
625 630 635 640
Phe Asn Lys Arg Asp Leu Ile Lys Lys His Ile Trp Pro Asn Val Pro
645 650 655
Asp Pro Ser Lys Ser His Ile Ala Gln Trp Ser Pro His Thr Pro Pro
660 665 670
Arg His Asn Phe Asn Ser Lys Asp Gln Met Tyr Ser Asp Gly Asn Phe
675 680 685
Thr Asp Val Ser Val Val Glu Ile Glu Ala Asn Asp Lys Lys Pro Phe
690 695 700
Pro Glu Asp Leu Lys Ser Leu Asp Leu Phe Lys Lys Glu Lys Ile Asn
705 710 715 720
Thr Glu Gly His Ser Ser Gly Ile Gly Gly Ser Ser Cys Met Ser Ser
725 730 735
Ser Arg Pro Ser Ile Ser Ser Ser Asp Glu Asn Glu Ser Ser Gln Asn
740 745 750
Thr Ser Ser Thr Val Gln Tyr Ser Thr Val Val His Ser Gly Tyr Arg
755 760 765
His Gln Val Pro Ser Val Gln Val Phe Ser Arg Ser Glu Ser Thr Gln
770 775 780
Pro Leu Leu Asp Ser Glu Glu Arg Pro Glu Asp Leu Gln Leu Val Asp
785 790 795 800
His Val Asp Gly Gly Asp Gly Ile Leu Pro Arg Gln Gln Tyr Phe Lys
805 810 815
Gln Asn Cys Ser Gln His Glu Ser Ser Pro Asp Ile Ser His Phe Glu
820 825 830
Arg Ser Lys Gln Val Ser Ser Val Asn Glu Glu Asp Phe Val Arg Leu
835 840 845
Lys Gln Gln Ile Ser Asp His Ile Ser Gln Ser Cys Gly Ser Gly Gln
850 855 860
Met Lys Met Phe Gln Glu Val Ser Ala Ala Asp Ala Phe Gly Pro Gly
865 870 875 880
Thr Glu Gly Gln Val Glu Arg Phe Glu Thr Val Gly Met Glu Ala Ala
885 890 895
Thr Asp Glu Gly Met Pro Lys Ser Tyr Leu Pro Gln Thr Val Arg Gln
900 905 910
Gly Gly Tyr Met Pro Gln
915
<210> 729
<211> 111
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 729
Ala Tyr Asp Met Thr Gln Thr Pro Ala Ser Val Glu Val Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu Thr Ile Tyr Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Asp Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ala Gly Thr Glu Tyr Thr Leu Thr Ile Ser Gly Val Gln Cys
65 70 75 80
Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Gly Ser Asn
85 90 95
Val Asp Asn Val Phe Gly Gly Gly Thr Glu Val Val Val Lys Arg
100 105 110
<210> 730
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 730
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys
85
<210> 731
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 731
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys
85
<210> 732
<211> 88
<212> PRT
<213> 智人(Homo sapiens)
<400> 732
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys
85
<210> 733
<211> 111
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 人源化抗体
<400> 733
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Glu Thr Ile Tyr Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Asp Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Gly Ser Asn
85 90 95
Val Asp Asn Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105 110
<210> 734
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 734
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 735
<211> 118
<212> PRT
<213> 穴兔(Oryctolagus cuniculus)
<400> 735
Gln Glu Gln Leu Lys Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr
1 5 10 15
Pro Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Asn Asp His
20 25 30
Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Phe Ile Asn Ser Gly Gly Ser Ala Arg Tyr Ala Ser Trp Ala Glu
50 55 60
Gly Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Met
65 70 75 80
Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Val Arg Gly
85 90 95
Gly Ala Val Trp Ser Ile His Ser Phe Asp Pro Trp Gly Pro Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 736
<211> 98
<212> PRT
<213> 智人(Homo sapiens)
<400> 736
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ser Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Val
35 40 45
Ser Ala Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg
<210> 737
<211> 97
<212> PRT
<213> 智人(Homo sapiens)
<400> 737
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg
<210> 738
<211> 97
<212> PRT
<213> 智人(Homo sapiens)
<400> 738
Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg
<210> 739
<211> 120
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 人源化抗体
<400> 739
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ser Ala Ser Gly Phe Ser Leu Asn Asp His
20 25 30
Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Val
35 40 45
Gly Phe Ile Asn Ser Gly Gly Ser Ala Arg Tyr Ala Ser Ser Ala Glu
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Gly Gly Ala Val Trp Ser Ile His Ser Phe Asp Pro Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 740
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<400> 740
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 741
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> PCR引物
<400> 741
agcgcttatt ccgctatcca gatgacccag tc 32
<210> 742
<211> 22
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> PCR引物
<400> 742
cgtacgtttg atttccacct tg 22
<210> 743
<211> 32
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> PCR引物
<400> 743
agcgcttatt ccgaggtgca gctggtggag tc 32
<210> 744
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> PCR引物
<400> 744
ctcgagacgg tgacgagggt 20
<210> 745
<211> 450
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 重链
<400> 745
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 746
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 轻链
<400> 746
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn
85 90 95
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr
100 105 110
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
115 120 125
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
130 135 140
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
145 150 155 160
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
180 185 190
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
195 200 205
Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
Claims (103)
1.一种预防、稳定或减轻将接受，正接受，或已接受实体器官移植的受试者中抗体介导的排斥(ABMR)的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗人Il-6抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
2.一种逆转、稳定和/或减缓有需要的移植接受者中活动性抗体介导的排斥(AMBR)的进展的方法，所述方法包括施用有效量的抗IL-6抗体或抗体片段，任选地，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
3.如权利要求1或2所述的方法，其中所述抗人IL-6抗体包含SEQ ID NO：704或745的重链多肽，并且包含SEQ ID NO：702或746的轻链多肽。
4.如前述权利要求中任一项所述的方法，其中持续至少1年施用所述抗人IL-6抗体。
5.如前述权利要求中任一项所述的方法，其中持续至少2年施用所述抗人IL-6抗体。
6.如前述权利要求中任一项所述的方法，其中持续至少3年施用所述抗人IL-6抗体。
7.如前述权利要求中任一项所述的方法，其中持续至少4年施用所述抗人IL-6抗体。
8.如前述权利要求中任一项所述的方法，其中持续至少5年施用所述抗人IL-6抗体。
9.如前述权利要求中任一项所述的方法，其中持续超过5年施用所述抗人IL-6抗体。
10.如前述权利要求中任一项所述的方法，其中任选地，当开始治疗时，任选地，在跨越治疗之前1-6个月的时期内至少一次，所述移植接受者包含活动性抗体介导的排斥(AMBR)或慢性活动性抗体介导的排斥(CABMR)。
11.如前述权利要求中任一项所述的方法，其中所述移植接受者在抗IL-6抗体施用之前已被诊断为具有AMBR或CAMBR。
12.如前述权利要求中任一项所述的方法，其中用所述抗IL-6抗体进行的治疗使在治疗期间，任选地在整个治疗时期中的估计肾小球滤过率(eGFR)稳定或增加。
13.如前述权利要求中任一项所述的方法，其中用所述抗IL-6抗体进行的治疗使在治疗期间，任选地在整个治疗时期中的估计肾小球滤过率(eGFR)稳定或增加，并且此外，任选地，其中在治疗已结束之后，eGFR的所述稳定或增加维持至少3、6、9或12个月。
14.如前述权利要求中任一项所述的方法，其中当开始治疗时和/或在治疗方案期间，所治疗患者不包含嗜中性白细胞减少症(小于1,000mm3)或血小板减少症(小于50,000mm3)。
15.如前述权利要求中任一项所述的方法，其中在跨越治疗之前0-6个月的时期内，所治疗患者不-接受静脉内免疫球蛋白。
16.如前述权利要求中任一项所述的方法，其中所治疗患者在治疗之前包含人白细胞抗原(HLA)DSA，任选地，其中这已在跨越治疗之前0-6个月的时期内通过检测人白细胞抗原(HLA)DSA的测定加以确认。
17.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体在跨越移植之前0-3、1-3、1-4、1-5或1-6个月的时期中施用。
18.如前述权利要求中任一项所述的方法，其中所述治疗引发以下中的一者或多者：
(i)使供者特异性抗体(DSA)的数目降低或消除供者特异性抗体(DSA)，
(ii)使CCL2水平降低；
(iii)使补体活化降低和/或使检测到的C5b.C9和/或C5b/C9复合物的量降低；
(iv)使分泌DSA的浆细胞的数目降低；
(v)防止同种异体移植物失功；
(vi)防止恢复透析，
(vii)防止同种异体移植物肾切除，和/或
(viii)防止对再移植的需要，
(ix)维持或增加估计肾小球滤过率(eGFR)以使它是至少≥15mL/min/1.73m2。
19.如前述权利要求中任一项所述的方法，其中移植体包括实体器官。
20.如前述权利要求中任一项所述的方法，其中所述实体器官包括肾、心脏、肺、膀胱、胰腺、肝、胆囊、甲状腺、皮肤或前述各物的任何组合。
21.如前述权利要求中任一项所述的方法，其中所述实体器官包括肾或由肾组成。
22.如前述权利要求中任一项所述的方法，其中所述移植体来自活体或死亡供者。
23.如前述权利要求中任一项所述的方法，其中在治疗期间或之后的功效至少部分地通过检测eGFR值，任选地使用肾病膳食改进4(MDRD4)方程来评估。
24.如前述权利要求中任一项所述的方法，其中功效至少部分地通过根据Banff2015病变分级评分评估肾活检体的组织学来评估。
25.如前述权利要求中任一项所述的方法，其中功效至少部分地通过检测DSA效价和/或平均荧光强度(MFI)评分来评估。
26.如前述权利要求中任一项所述的方法，其中所述治疗是有效的，并且任选地，功效至少部分地通过评估急性排斥事件(TCMR和ABMR)的发生来评估。
27.如前述权利要求中任一项所述的方法，其中功效至少部分地通过评估治疗对白蛋白尿的影响来评估。
28.如前述权利要求中任一项所述的方法，其中功效至少部分地通过相较于对照和/或常规AMBR或CAMBR治疗评估存活率来评估。
29.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体包含人IgG1恒定区。
30.如权利要求29所述的方法，其中所述人IgG1恒定区包含SEQ ID NO：586的恒定轻多肽和SEQ ID NO：588的恒定重多肽。
31.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体包含SEQ ID NO：657的可变重链多肽和SEQ ID NO：709的可变轻链多肽。
32.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体包含SEQ ID NO：704或745的重链多肽和SEQ ID NO：702或746的轻链多肽。
33.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体每4周或每月在静脉内或在皮下给药。
34.如前述权利要求中任一项所述的方法，其中每4周或每月在静脉内或在皮下施用25mg或12.5mg剂量的所述抗IL-6抗体。
35.如前述权利要求中任一项所述的方法，其中每4周或每月在皮下施用25mg或12.5mg剂量的克拉扎珠单抗。
36.如前述权利要求中任一项所述的方法，其中持续至少1年、2年、3年、4年或5年实行所述治疗，而无选自恢复透析、同种异体移植物肾切除、再移植或eGFR≤15mL/min/1.73m2的不利事件。
37.如前述权利要求中任一项所述的方法，其中所述移植接受者任选地还用以下中的任一者治疗：
(i)咪唑硫嘌呤(例如1.0-2.0mg/kg/天)，
(ii)钙调神经磷酸酶抑制剂(CNI)，
(iii)霉酚酸吗啉乙酯(MMF)(例如1.0-2.0g/天)/霉酚酸(MPA)(例如720-1440mg/天)，
(iv)mTOR抑制剂(例如他克莫司、(例如目标谷底水平5-8ng/ml)依维莫司、西罗莫司)，
(v)低剂量皮质类固醇(例如泼尼松/泼尼松龙≤10mg/天)，
(vi)抗高血压剂(例如血管紧张素转化酶抑制剂(ACEI))，
(vii)血管紧张素II受体阻断剂(ARB)，
(viii)环孢灵(例如目标谷底水平50-150ng/ml)
(ix)抗糖尿病发生剂；
(x)或任何前述各物的组合。
38.如前述权利要求中任一项所述的方法，其中所述移植接受者任选地还用耶氏肺囊虫肺炎(PJP)防治剂治疗，所述防治剂例如是甲氧苄啶(例如80mg，每日，丸剂)，和/或磺胺甲噁唑(例如160mg，每周3次，丸剂)、吸入型喷他脒或口服达普松(任选地在治疗的至少1周内开始)。
39.如前述权利要求中任一项所述的方法，其中如果所述移植接受者经历急性TCMR，那么例如用脉冲类固醇诸如口服泼尼松(例如200mg/天)对所述急性TCMR进行治疗。
40.如前述权利要求中任一项所述的方法，其中在抗IL-6抗体治疗期间以及任选地在跨越开始治疗之前0、1、2、3、4、5或6个月的时期内，所述移植接受者不用以下中的任一者治疗：
(i)利妥昔单抗，
(ii)依库珠单抗，
(iii)蛋白酶体抑制剂，
(iv)静脉内免疫球蛋白(IVIG)(除治疗低γ球蛋白血症之外)，
(v)血浆交换(PLEX)、贝拉西普，
(vi)抗IL-6R抗体和/或
(vii)前述各物的任何组合。
41.如前述权利要求中任一项所述的方法，其中所述移植接受者包含以下中的任一者或全部：
(i)是18-75岁，
(ii)距离移植时间≥6个月开始治疗，
(iii)根据BANFF 2015诊断准则对CABMR的诊断，包括以下事项：活检证明的CABMR(即慢性肾小球病变(cg)＞0)，伴有/不伴有C4d染色(如果先前活检不在筛选的6个月内，那么进行重复活检)，
(iv)如果受试者已接受针对ABMR(包括CABMR)或TCMR的治疗，那么进行重复活检(以显示CABMR的持续性)，其中根据光学显微术不具有慢性组织损伤迹象，但根据电子显微术具有肾小球基底膜双重轮廓(cg1a)的受试者是合格的；
(v)在移植后存在人白细胞抗原(HLA)DSA(使用基于珠粒的单抗原测定)。
42.如前述权利要求中任一项所述的方法，其中所述移植接受者不包含以下中的一者或多者：
(i)尚未在跨越IL-6抗体治疗或筛选的0-3个月或0-6个月的时期内进行针对ABMR或CABMR或TCMR的治疗；
(ii)不正在接受任何T细胞消减剂，在筛选或治疗的3个月内未针对ABMR(包括CABMR)或TCMR进行治疗；
(iii)尚未在筛选或IL-6抗体治疗的3个月内接受T细胞消减剂(例如阿来珠单抗、抗胸腺细胞球蛋白)；
(iv)没有活检显示单纯性TCMR或晚期间质性纤维化(ci3)，
(v)无晚期肾小管萎缩(ct3)；
(vi)无血管纤维内膜增厚(cv3)或肾功能异常的其他重大原因(例如多瘤BK病毒(BKV)肾病变、肾小球性肾炎)；
(vii)无归因于所移植同种异体移植物中的病症(例如肾动脉狭窄、肾盂积水)的肾功能受损；
(viii)无eGFR＜25mL/min/1.73m2或＞65mL/min/1.73m2(MDRD4)，(viii)无规定为随机尿蛋白肌酸酐比率(UPCR)≥3,000mg/g(≥300mg/mmol)或随机尿白蛋白肌酸酐比率(UACR)≥2,200mg/g(≥220mg/mmol)的肾病范围蛋白尿；
(ix)不处于妊娠或哺乳中；
(x)无过敏症史；
(xi)肝功能测试(LFT)无异常(丙氨酸转氨酶(ALT)/天冬氨酸转氨酶(AST)/胆红素＞1.5倍正常值上限)或无其他重大肝病；
(xii)无活动性结核(TB)史；
(xiii)在不具有活动性TB史的情况下无潜伏性TB史(例如Quantiferon TB测试呈阳性)，除非受试者已完成防治性治疗的全过程，
(xiv)无人免疫缺陷病毒(HIV)感染史或关于HIV呈阳性；
(xv)关于乙型肝炎表面抗原(HBsAg)不呈血清阳性；
(xvi)不是丙型肝炎病毒(HCV)RNA阳性的；
(xvii)无已知艾伯斯坦-巴尔病毒(EBV)不匹配：供者血清阳性，接受者血清阴性；
(xviii)无胃肠穿孔、憩室病或憩室炎、或炎症性肠病史；
(xix)无嗜中性白细胞减少症(＜1,000/mm3)或血小板减少症(＜50,000/mm3)；
(xx)无需要全身性抗微生物剂并且在筛选之前未消退的活动性感染；
(xxi)无历史或当前侵袭性真菌性感染或其他机会性感染，所述感染包括(但不限于)以下：非结核性分枝杆菌感染、曲霉病、肺囊虫病和弓形虫病；(xxii)基于聚合酶链式反应(PCR)测试，无活动性病毒性感染诸如BKV、巨细胞病毒(CMV)或EBV；
(xxii)无当前或新近(在跨越治疗之前0-3或0-6个月的时期中)，
(xxiii)在筛选的6周内未施用活疫苗，包括但不限于以下：腺病毒疫苗、麻疹疫苗、腮腺炎疫苗和风疹疫苗、口服脊髓灰质炎疫苗、口服伤寒疫苗、轮状病毒疫苗、水痘带状疱疹疫苗、黄热病疫苗，无酒精或非法物质(包括大麻)滥用史；
(xxiv)无目前或先前(在3年内)恶性肿瘤，除基底细胞癌、完全切除的皮肤鳞状细胞癌、或非复发性(在5年内)原位宫颈癌之外；
(xxv)不存在可损害安全性或预期寿命的状况或异常(即不受标准治疗控制的在临床上重大的内分泌、自体免疫、代谢、神经、精神病/心理、肾、胃肠、肝和血液或任何其他系统异常)；
(xxvi)无甲氧苄啶和/或磺胺甲噁唑不耐受史，先前未用抗IL-6抗体治疗，和/或
(xxvii)前述事项的任何组合。
43.一种预防、稳定或降低有需要的受试者中的补体活性的方法，所述方法包括向所述受试者施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，例如以下抗体或抗体片段：其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
44.如前述权利要求中任一项所述的方法，其中在治疗之前、期间或之后测量所述受试者中的补体活性。
45.如前述权利要求中任一项所述的方法，其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽。
46.如前述权利要求中任一项所述的方法，其中所述抗体包含分别与SEQ ID NO：704或745以及702或746的多肽至少90、95、96、97、98或99％同一的重链多肽和轻多肽。
47.如前述权利要求中任一项所述的方法，其中所述抗体是克拉扎珠单抗。
48.如前述权利要求中任一项所述的方法，其中所述实体器官选自肾、心脏、肝、肺、胰腺、胆囊、皮肤、肠、胃或任何前述各物的组合。
49.如前述权利要求中任一项所述的方法，其中所述实体器官包括肾或由肾组成。
50.如前述权利要求中任一项所述的方法，其中所述患者在治疗之前被评估，并且已被诊断为具有ABMR或CAMBR。
51.如权利要求49所述的方法，其中所述评估包括以下中的一者或多者：检测预先形成和新生HLA DSA(尤其是检测补体结合DSA的那些评估诸如C1q评估)，检测与ABMR相关的非HLA抗体，和/或鉴定至少一种为抗体介导的器官损害所特有的组织学特征。
52.如权利要求49所述的方法，其中为抗体介导的器官损害所特有的所述组织学特征通过从所移植器官获得活检体来检测。
53.如权利要求49所述的方法，其中为抗体介导的器官损害所特有的所述组织学特征包括微血管炎症、补体沉积(C4d)和毛细血管炎中的任一者。
54.如权利要求49所述的方法，其中所移植器官是肾，并且为抗体介导的器官损害所特有的组织学特征包括微血管炎症、补体沉积(C4d)在肾小管周毛细血管中、肾小管周毛细血管炎、肾小球炎和移植肾小球病变(双重肾小球基底膜轮廓)中的任一者。
55.如先前权利要求中任一项所述的方法，其中所述治疗还包括施用至少一种其他免疫抑制剂。
56.如权利要求54所述的方法，其中所述至少一种其他免疫抑制剂是护理标准移植前或移植后免疫抑制性药物。
57.如权利要求54所述的方法，其中所述至少一种其他免疫抑制剂包括抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司、抗CD20 mAb诸如利妥昔单抗和皮质类固醇中的任一者。
58.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在静脉内或在皮下施用。
59.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在0.01-5000mg的范围内的剂量下施用。
60.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在0.1-1000mg的范围内的剂量下施用。
61.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在1-500mg的范围内的剂量下施用。
62.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在静脉内在约5mg-50mg的范围内的剂量下或在皮下在约10mg-50mg的范围内的剂量下施用。
63.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在约25mg的剂量下施用，所述剂量约每2周、4周、6周、8周、12周、16周、20周、24周、每月、每两月、每2个月、每3个月、每4个月、每5个月、每6个月、每年或以更小频率加以给药。
64.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体约每4周、8周、12周、16周、20周或24周加以施用。
65.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在25mg或12.5mg的剂量下每4周或每月在皮下施用。
66.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在检测ABMR或CAMBR的征象的约1、2或3个月内施用。
67.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体在移植之前持续数月以及在移植之后持续数月或数年加以施用以预防、稳定或降低抗体介导的对所移植器官的损害。
68.一种预防、稳定或减轻已接受或将接受实体器官移植的受试者中移植前或移植后敏化的方法，所述方法包括施用防治或治疗有效量的抗人白介素-6(IL-6)抗体或抗体片段，其中所述抗体或抗体片段包含：含有SEQ ID NO：4、5和6的CDR的可变轻链多肽以及含有SEQ ID NO：7、8或120、和9的CDR的可变重链多肽。
69.如权利要求68所述的方法，其中所述抗体包含分别与SEQ ID NO：657和709的多肽至少90、95、96、97、98或99％同一的VH多肽和VL多肽。
70.如权利要求68所述的方法，其中所述抗体包含与SEQ ID NO：657和709的多肽同一的VH多肽和VL多肽。
71.如权利要求68所述的方法，其中所述抗体包含分别与SEQ ID NO：702或746以及704或745的多肽同一的轻链多肽和重链多肽。
72.如前述权利要求中任一项所述的方法，其中所述患者已用实体器官移植，所述实体器官选自肾、心脏、肝、肺、胰腺、皮肤、肠、胃或任何前述各物的组合。
73.如前述权利要求中任一项所述的方法，其中所述实体器官包括肾或由肾组成。
74.如前述权利要求中任一项所述的方法，其中所述患者由于输血史、妊娠或先前移植而处于敏化的风险下或是敏化的。
75.如前述权利要求中任一项所述的方法，其中所述患者在抗IL-6抗体治疗之前和/或期间包含预先形成的针对供者器官的供者特异性抗体(DSA)。
76.如前述权利要求中任一项所述的方法，所述方法还包括移植前脱敏程序以移除或降低供者特异性同种异体抗体(DSA)。
77.如权利要求76所述的方法，其中所述脱敏治疗包括血浆除去或血浆交换，任选地与静脉内免疫球蛋白、抗B细胞剂诸如利妥昔单抗(抗CD20 mAb)以及浆细胞抑制剂诸如硼替佐米(蛋白体抑制剂)中的任一者组合。
78.如前述权利要求中任一项所述的方法，其中所述抗体在静脉内或在皮下施用。
79.如前述权利要求中任一项所述的方法，其中所述抗体在0.01-5000mg的范围内的剂量下施用。
80.如前述权利要求中任一项所述的方法，其中所述抗体在0.1-1000mg的范围内的剂量下施用。
81.如前述权利要求中任一项所述的方法，其中所述抗体在1-500mg的范围内的剂量下施用。
82.如前述权利要求中任一项所述的方法，其中所述抗体在约25mg的剂量下施用，所述剂量约每2周、4周、6周、8周、12周、16周、20周、24周、每月、每两月、每2个月、每3个月、每4个月、每5个月、每6个月、每年或以更小频率加以给药。
83.如前述权利要求中任一项所述的方法，其中所述抗体约每4或8周加以施用，在移植之前数月(例如在跨越0-6个月的时期内)开始。
84.如前述权利要求中任一项所述的方法，其中在脱敏前在治疗期间通过一种或多种抗体检测方法(例如细胞毒性交叉配型、流式细胞计量交叉配型、Luminex抗体测试)定期评估所述患者以检测在脱敏治疗过程期间DSA的水平。
85.如权利要求84所述的方法，其中正性响应(例如阳性细胞毒性交叉配型转变成阴性细胞毒性交叉配型)用于确定所述患者对于Il-6抗体治疗和/或移植来说是合格的。
86.如前述权利要求中任一项所述的方法，其中所述患者在移植后用所述抗IL-6抗体例如克拉扎珠单抗加以治疗。
87.如前述权利要求中任一项所述的方法，其中在移植后持续数月或数年继续所述抗IL-6抗体施用以预防或治疗早期急性或晚期慢性排斥。
88.如前述权利要求中任一项所述的方法，其中监测所述患者的临床排斥征象(诸如血清肌酸酐增加和/或蛋白尿、或肾移植中eGFR降低)或新的DSA(新生DSA)的产生。
89.如前述权利要求中任一项所述的方法，其中监测所述患者的组织学器官排斥征象。
90.如前述权利要求中任一项所述的方法，其中ABMR器官损害通过活检迹象(例如微血管炎症、间质性纤维化、移植肾小球病变、CD4沉积)确认。
91.如前述权利要求中任一项所述的方法，其中克拉扎珠单抗与通常在移植前和移植后向患者施用的护理标准免疫抑制方案(例如抗胸腺细胞球蛋白、巴利昔单抗、霉酚酸吗啉乙酯、他克莫司、皮质类固醇)组合使用。
92.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体或抗体片段含有已被修饰来改变效应功能、半衰期、蛋白水解和/或糖基化的Fc区。
93.如先前权利要求中任一项所述的方法，其中所述抗Il-6抗体选自人源化、单链或嵌合抗体，并且所述抗体片段选自Fab、Fab′、F(ab′)2、Fv或scFv。
94.如前述权利要求中任一项所述的方法，其中抗体剂量在每kg接受患者体重约0.001与100mg之间。
95.如前述权利要求中任一项所述的方法，其中抗IL-6抗体剂量在每kg接受患者体重约0.1与20mg之间，或包括约25mg。
96.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体或片段抑制IL-6与gp130和/或与IL-6R1的结合。
97.如前述权利要求中任一项所述的方法，其中所述抗IL-6抗体或抗体片段包含人恒定区。
98.如权利要求97所述的方法，其中所述人恒定区包括IgG1、IgG2、IgG3或IgG4恒定区。
99.如权利要求97所述的方法，其中所述人恒定区包括IgG1恒定区。
100.如先前权利要求中任一项所述的方法，其中所述抗IL-6抗体是克拉扎珠单抗。
101.如前述权利要求中任一项所述的方法，其中所治疗受试者具有晚期或后期AMBR(根据Banff 2015分类的急性/活动性或慢性/活动性表型)。
102.如前述权利要求中任一项所述的方法，其中施用的抗IL-6抗体是克拉扎珠单抗，并且所治疗受试者具有晚期或后期AMBR(根据Banff2015分类的急性/活动性或慢性/活动性表型)。
103.如前述权利要求中任一项所述的方法，其中所治疗受试者患有选自以下的补体相关疾患：年龄相关以及退变性疾病诸如年龄相关的黄斑变性(AMD)(湿性和干性)、阿尔茨海默氏病、肾小球疾病例如非典型溶血性尿毒综合征(aHUS)、由志贺毒素产生性大肠杆菌引起的溶血性尿毒综合征(STEC-HUS)、血栓性血小板减少性紫癜(TTP)、全身性红斑狼疮(SLE)、抗磷脂抗体综合征(APS)、抗嗜中性白细胞细胞质抗体(ANCA)诱发的血管炎、由针对嗜中性白细胞组分的自体抗体引起的炎症性小血管病症；涉及C5a介导的对胎盘血管生成的损害的抗体依赖性(即在具有APS的妇女中)妊娠丢失；补体介导的溶血病症诸如阵发性夜间血红蛋白尿(PNH)、aHUS和冷凝集素病(CAD)、缺血-再灌注损伤；中风、例如由创伤、败血症、休克和心肺分流(CPB)手术引起的心肌梗塞、由CPB心肺分流手术引起的疾患、过敏性哮喘、牙周炎、与异常补体活化相关的骨相关病症和骨损伤(例如通过过敏毒素对破骨细胞形成的影响)、急性期疾患，其中宿主面临损害相关分子样式和/或病原体相关分子样式的显著增加。
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| US62/773,630 | 2018-11-30 | ||
| PCT/US2019/012372 WO2019136266A1 (en) | 2018-01-04 | 2019-01-04 | Use of anti-il-6 antibody, e.g., clazakizumab for desensitization of solid organ transplant recipients and/or for preventing, stabilizing or reducing antibody mediated rejection (abmr) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113214393A (zh) * | 2021-05-25 | 2021-08-06 | 深圳市新产业生物医学工程股份有限公司 | Il-6抗体或其抗原结合片段及包含其的检测试剂盒 |
| CN116715763A (zh) * | 2022-11-22 | 2023-09-08 | 武汉爱博泰克生物科技有限公司 | Mouse IL-6兔单克隆抗体对及其制备方法和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US8062864B2 (en) | 2007-05-21 | 2011-11-22 | Alderbio Holdings Llc | Nucleic acids encoding antibodies to IL-6, and recombinant production of anti-IL-6 antibodies |
| CA3121934A1 (en) * | 2018-12-20 | 2020-06-25 | Cedars-Sinai Medical Center | Clazakizumab in the treatment of chronic antibody-mediated rejection of organ transplant |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008144763A2 (en) * | 2007-05-21 | 2008-11-27 | Alder Biopharmaceuticals, Inc. | Antibodies to il-6 and use thereof |
| US20100150829A1 (en) * | 2008-11-25 | 2010-06-17 | Leon Garcia-Martinez | Antibodies to IL-6 and use thereof |
| US20120142900A1 (en) * | 2007-05-21 | 2012-06-07 | Leon Garcia-Martinez | Antibodies to il-6 and use thereof |
| CN102740888A (zh) * | 2009-11-24 | 2012-10-17 | 奥尔德生物制药公司 | Il-6抗体及其用途 |
| US20170174760A1 (en) * | 2015-07-24 | 2017-06-22 | Cedars-Sinai Medical Center | Method for treating antibody-mediated rejection post-transplantation |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5859202B2 (ja) * | 2007-05-21 | 2016-02-10 | アルダーバイオ・ホールディングズ・エルエルシー | 新規のウサギ抗体ヒト化方法及びヒト化ウサギ抗体 |
| US7906117B2 (en) * | 2007-05-21 | 2011-03-15 | Alderbio Holdings Llc | Antagonists of IL-6 to prevent or treat cachexia, weakness, fatigue, and/or fever |
| AU2009323009B2 (en) * | 2008-11-25 | 2016-01-28 | Vitaeris Inc. | Antibodies to IL-6 and use thereof |
| US10227404B2 (en) * | 2008-11-25 | 2019-03-12 | Alderbio Holdings Llc | Antagonists of IL-6 to raise albumin and/or lower CRP |
| ES2847891T3 (es) * | 2010-11-23 | 2021-08-04 | Vitaeris Inc | Anticuerpos anti-IL-6 para el tratamiento de la mucositis oral |
| US20160130340A1 (en) * | 2013-10-07 | 2016-05-12 | Alderbio Holdings Llc | Dosing regimens using anti-il-6 antibodies for the treatment of rheumatoid and psoriatic arthritis |
| US10500260B2 (en) * | 2014-02-04 | 2019-12-10 | 3Dt Holdings, Llc | Substances, vaccines and methods for diagnosing and reducing incidences of transplant rejection |
| ES2845656T3 (es) * | 2014-09-18 | 2021-07-27 | Immucor Gti Diagnostics Inc | Kits y procedimientos para detectar anticuerpos anticélulas endoteliales en rechazo de aloinjertos |
| US20170022280A1 (en) * | 2015-07-24 | 2017-01-26 | Cedars-Sinai Medical Center | Method for treating antibody-mediated rejection post-transplantation |
-
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- 2019-01-04 KR KR1020207022447A patent/KR20200123779A/ko not_active Application Discontinuation
- 2019-01-04 CN CN201980010910.9A patent/CN111867627A/zh active Pending
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- 2019-01-04 WO PCT/US2019/012372 patent/WO2019136266A1/en unknown
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-
2023
- 2023-08-10 US US18/447,623 patent/US20240124573A1/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008144763A2 (en) * | 2007-05-21 | 2008-11-27 | Alder Biopharmaceuticals, Inc. | Antibodies to il-6 and use thereof |
| US20120142900A1 (en) * | 2007-05-21 | 2012-06-07 | Leon Garcia-Martinez | Antibodies to il-6 and use thereof |
| US20100150829A1 (en) * | 2008-11-25 | 2010-06-17 | Leon Garcia-Martinez | Antibodies to IL-6 and use thereof |
| CN102740888A (zh) * | 2009-11-24 | 2012-10-17 | 奥尔德生物制药公司 | Il-6抗体及其用途 |
| US20170174760A1 (en) * | 2015-07-24 | 2017-06-22 | Cedars-Sinai Medical Center | Method for treating antibody-mediated rejection post-transplantation |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113214393A (zh) * | 2021-05-25 | 2021-08-06 | 深圳市新产业生物医学工程股份有限公司 | Il-6抗体或其抗原结合片段及包含其的检测试剂盒 |
| CN116715763A (zh) * | 2022-11-22 | 2023-09-08 | 武汉爱博泰克生物科技有限公司 | Mouse IL-6兔单克隆抗体对及其制备方法和应用 |
| CN116715763B (zh) * | 2022-11-22 | 2023-11-24 | 武汉爱博泰克生物科技有限公司 | Mouse IL-6兔单克隆抗体对及其制备方法和应用 |
Also Published As
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| EP3737414A4 (en) | 2022-02-23 |
| KR20200123779A (ko) | 2020-10-30 |
| EP3737414A1 (en) | 2020-11-18 |
| JP2021509915A (ja) | 2021-04-08 |
| WO2019136266A1 (en) | 2019-07-11 |
| BR112020013531A2 (pt) | 2020-12-08 |
| US20240124573A1 (en) | 2024-04-18 |
| AU2019205488A1 (en) | 2020-07-23 |
| CA3088845A1 (en) | 2019-07-11 |
| US20210070853A1 (en) | 2021-03-11 |
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