CN111410691B - 结合至cd38和cd3的双特异性抗体 - Google Patents

Abstract

本发明涉及结合至CD38和CD3的双特异性抗体。本发明提供异二聚体蛋白质，所述异二聚体蛋白质包括结合至CD38和CD3的异二聚体抗体。本发明还涉及核酸组合物，包含所述核酸组合物的宿主细胞，制造所述异二聚体抗体的方法以及通过施用所述异二聚体抗体来治疗有需要的患者的方法。

Description

结合至CD38和CD3的双特异性抗体

本申请是申请日为2015年3月30日，申请号为201580016659.9， 发明名称为“结合至CD38和CD3的双特异性抗体”的发明专利的分案申请。

相关申请的交叉引用

本申请依据35U.S.C.§119要求2014年3月28日提交的美国临 时专利申请号61/972,172、2014年7月7日提交的62/025,974及2014 年7月17日提交的62/025,931的优先权，这些专利的全部内容在此 以引用的方式并入本文中用于所有目的，并且确切地说，用于本文略 述的附图、图例及数据。

技术领域

本发明描述了同时共接合抗原的新型免疫球蛋白组合物，其中两 种抗原都是单价结合的。所描述的新型免疫球蛋白优选利用异二聚体 Fc区。本文还描述了使用所述新型免疫球蛋白组合物，特别是用于 治疗目的的方法。

发明背景

基于抗体的治疗剂已经被成功地用于治疗多种疾病，包括癌症和 自身免疫性/炎症性病症。不过仍需要针对此类药物进行改良，特别 是增强其临床功效。所研究的一种方法是将另外的新型抗原结合位点 工程改造至基于抗体的药物中，由此使单一免疫球蛋白分子共接合两 种不同的抗原。此类接合两种不同抗原的非天然或替代性抗体形式通 常称为双特异性抗体。由于抗体可变区(Fv)相当大的多样性使得有可能产生识别实际上任何分子的Fv，故产生双特异性抗体的典型方法 是将新的可变区引入抗体中。

已经针对双特异性抗体靶向研究多种替代性抗体形式(Chames&，2009，mAbs 1[6]：1-9；Holliger&Hudson，2005，Nature Biotechnology 23[9]：1126-1136；及Kontermann，2012 MAbs 4(2)：182， 其全部以引用的方式明确地并入本文中)。起初，通过将分别产生单 一单克隆抗体的两个细胞系融合来制备双特异性抗体(Milstein等人，1983，Nature 305：537-540)。尽管由此得到的杂交的杂交瘤或四源杂交 瘤确实产生了双特异性抗体，但其只是极少的一群，而且需要充分纯 化以分离出期望的抗体。针对这一点的工程改造方法是使用抗体片段来产生双特异性抗体。由于这些片段缺乏全长抗体的复杂四级结构， 使得可变轻链和重链可以连接于单一基因构建体中。已经产生许多不 同形式的抗体片段，包括双功能抗体、串联scFv及Fab2双特异性抗 体(Chames&Baty，2009，mAbs 1[6]：1-9；Holliger&Hudson，2005， Nature Biotechnology 23[9]：1126-1136；以引用的方式明确地并入本文中)。尽管这些形式可以在细菌中高水平表达，并且可能由于尺寸较 小而具有有利的渗透益处，但其在体内迅速清除并且可能存在与其产 量和稳定性有关的制造难题。造成这些缺点的主要原因是，抗体片段 典型地缺乏抗体恒定区及其相关功能特性，包括较大的尺寸、高稳定 性，及与各种Fc受体和配体结合以维持较长的血清半衰期(即，新生 儿Fc受体FcRn)或用作纯化的结合位点(即，蛋白质A和蛋白质G)。

近期的研究尝试通过将双重结合工程改造至类全长抗体形式中 来解决基于片段的双特异性抗体的缺点(Wu等人，2007，Nature Biotechnology 25[11]：1290-1297；USSN12/477,711；Michaelson等人， 2009，mAbs 1[2]：128-141；PCT/US2008/074693；Zuo等人，2000，Protein Engineering 13[5]：361-367；USSN09/865，198；Shen等人，2006， JBiol Chem 281[16]：10706-10714；Lu等人，2005，J Biol Chem 280[20]：19665-19672；PCT/US2005/025472；及Kontermann，2012 MAbs 4(2)：182，全部以引用的方式明确地并入本文中)。这些形式主 要由于含有Fc区而克服了抗体片段双特异性抗体的一些问题。这些形式的一个重要缺点在于，由于其在同二聚体恒定链的顶部构造抗原 结合位点，使得与新抗原的结合通常是二价的。

对于在治疗性双特异性抗体形式中作为共同靶标而引起关注的 许多抗原来说，期望的结合是单价而非二价的。对于许多免疫受体， 细胞活化是通过单价结合相互作用的交联实现。交联机制典型地是由 抗体/抗原免疫复合体，或经由效应细胞靶向细胞接合来介导。举例来说，低亲和力Fcγ受体(FcγR)，如FcγRIIa、FcγRIIb及FcγRIIIa单 价结合至抗体Fc区。单价结合不能活化表达这些FcγR的细胞；不过， 在形成免疫复合体或细胞与细胞接触之后，受体发生交联并且群集在 细胞表面上，引起活化。对于负责介导细胞杀伤的受体，例如自然杀 伤(NK)细胞上的FcγRIIIa来说，当效应细胞以特别期望的方式接合靶 细胞时，发生受体交联和细胞活化(Bowles&Weiner，2005，J Immunol Methods 304：88-99，以引用的方式明确地并入本文中)。类似地，在B 细胞上，抑制性受体FcγRIIb只有在与细胞表面B细胞受体(BCR)接 合成免疫复合体时才下调B细胞活化，这一机制是由可溶性IgG与 BCR所识别的抗原形成免疫复合体所介导(Heyman 2003，Immunol Lett 88[2]：157-161；Smith和Clatworthy，2010，Nature Reviews Immunology 10：328-343；以引用的方式明确地并入本文中)。在另一 个实施例中，只有在T细胞相关T细胞受体(TCR)以特别期望的细胞 -细胞突触方式接合抗原呈递细胞上载有抗原的MHC时，才发生T 细胞的CD3活化(Kuhns等人，2006，Immunity 24：133-139)。实际上， 使用抗CD3抗体进行的CD3非特异性二价交联引起细胞因子风暴和 毒性(Perruche等人，2009，J Immunol 183[2]：953-61；Chatenoud&Bluestone，2007，Nature Reviews Immunology 7：622-632；以引用的方 式明确地并入本文中)。因此，对于实际临床应用来说，用于靶细胞 重定向杀伤的优选的CD3共接合模式是单价结合，该结合只有在与 共接合的靶接合后才引起活化。

CD38，又称环腺苷二磷酸核糖水解酶，是具有长C末端细胞外 结构域和短N末端细胞质结构域的II型跨膜糖蛋白。在造血细胞中， 功能作用的分类被认为是CD38介导的信号传导的结果，包括淋巴细 胞增殖、细胞因子释放、B细胞和骨髓细胞发育和存活的调控，以及 树突状细胞成熟的诱导。CD38在许多造血系统恶性疾病中以及来源 于各种造血系统恶性疾病的细胞系中失调，造血系统恶性疾病包括非霍奇金氏淋巴瘤(non-Hodgkin’slymphoma，NHL)、伯基特氏淋巴瘤 (Burkitt’s lymphoma，BL)、多发性骨髓瘤(MM)、B慢性淋巴细胞白 血病(B-CLL)、B和T急性礼拜那细胞白血病(ALL)、T细胞淋巴瘤 (TCL)、急性骨髓性白血病(AML)、毛细胞白血病(HCL)、霍奇金氏淋 巴瘤(HL)及慢性骨髓性白血病(CML)。另一方面，造血系统的最原始 的多能干细胞是CD38-。尽管近期在抗癌剂的发现和研发方面取得了 进展，但涉及CD38表达性肿瘤的许多癌症形式仍具有不良预后。因 此，需要改进治疗此类癌症形式的方法。

因此，尽管由抗体片段产生的双特异性抗体存在生物物理学和药 物动力学障碍，但利用类全长抗体形式构造的双特异性抗体的缺点在 于，其在无初级靶抗原存在下多价接合共同靶抗原，从而引起非特异 性活化和潜在毒性。本发明通过引入能够共接合不同靶抗原的新型双 特异性抗体形式解决了这一问题。

发明概述

因此，本发明提供了结合至CD3和CD38的异二聚体抗体。这 些异二聚体抗体包含第一重链，所述第一重链包含第一可变Fc结构 域及结合CD3的单链Fv区(scFv)。这些异二聚体抗体还包含第二重链，所述第二重链包含第二Fc可变Fc结构域和第一可变重链结构域。 这些异二聚体抗体另外包含第一轻链，所述第一轻链包含第一可变轻 链结构域和第二恒定轻链结构域，其中所述第一可变重链结构域和所 述第一可变轻链结构域结合至CD38。

在另一方面，本发明提供了选自由以下组成的组的异二聚体抗 体：XENP13243；XENP13545；XENP13546；XENP13547；XENP13548； XENP13549；XENP13550；XENP13551；XENP13544；XENP13752； XENP13753；XENP13754；XENP13756；XENP13757；及XENP13694。

在又一方面，所述scFv具有了包含以下的序列：具有序列 T-Y-A-M-Xaa1的vhCDR1，其中Xaa1是N、S或H(SEQ ID NO：435)； 具有序列R-I-R-S-K-Xaa1-N-Xaa2-Y-A-T-Xaa3-Y-Y-A-Xaa4-S-V-K-G 的vhCDR2，其中Xaa1是Y或A，Xaa2是N或S，Xaa3是Y或A 并且Xaa4是D或A(SEQ ID NO：436)；具有序列 H-G-N-F-G-Xaa1-S-Y-V-S-W-F-Xaa2-Y的vhCDR3，其中Xaa1是N、 D或Q并且Xaa2是A或D(SEQ ID NO：437)；具有序列 Xaa1-S-S-T-G-A-V-T-Xaa2-Xaa3-Xaa4-Y-A-N的vlCDR1，其中Xaa1 是G、R或K，Xaa2是T或S，Xaa3是S或G并且Xaa4是N或H(SEQ ID NO：438)；具有序列Xaa1-T-N-Xaa2-R-A-Xaa3的vlCDR2，其中 Xaa1是G或D，Xaa2是K或N，并且Xaa3是P或S(SEQ ID NO：439)； 及具有序列Xaa1-L-W-Y-S-N-Xaa2-W-V的vlCDR3，其中Xaa1是A 或L并且Xaa2是L或H(SEQ ID NO：440)。

在另一方面，scFv选自由H1.30_L1.47、H1.33_L1.47及 H1.31_L1.47组成的组。

在另一方面，抗CD3可变区具有选自由以下组成的组的序列：

a)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

b)包含了具有SEQ ID NO：412的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

c)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：414 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

d)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：417的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

e)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：418的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

f)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：421 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

g)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：422 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

h)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ lD NO：427的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

i)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：428的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

j)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：431 的vlCDR3的序列；

k)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

1)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：423 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：432 的vlCDR3的序列；

m)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：424 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：432 的vlCDR3的序列；

n)包含了具有SEQ ID NO：412的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：417的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

o)包含了具有SEQ ID NO：412的vhCDR1、具有SEQ ID NO：414 的vhCDR2、具有SEQID NO：419的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

p)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：415 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

q)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：415 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

r)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：417的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

s)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：419的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列；

t)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：417的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：433 的vlCDR3的序列；

u)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：413 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：433 的vlCDR3的序列；及

v)包含了具有SEQ ID NO：411的vhCDR1、具有SEQ ID NO：434 的vhCDR2、具有SEQID NO：416的vhCDR3、具有SEQ ID NO：420 的vlCDR1、具有SEQ ID NO：425的vlCDR2及具有SEQ ID NO：430 的vlCDR3的序列。

在另一方面，抗CD3可变区包含了选自由以下组成的组的可变 重链区和可变轻链区：

SEQ ID NO：5和6；SEQ ID NO：9和10；SEQ ID NO：13和14； SEQ ID NO：17和1 8；SEQ ID NO：21和22；SEQ ID NO：25和26； SEQ ID NO：29和30；SEQ ID NO：33和34；SEQ IDNO：37和38；SEQ ID NO：41和42；SEQ ID NO：45和46；SEQ ID NO：49和50； SEQ ID NO：53和54；SEQ ID NO：57和58；SEQ ID NO：61和62；SEQ ID NO：65和66；SEQ ID NO：69和70；SEQ IDNO：73和74； SEQ ID NO：77和78；SEQ ID NO：81和82；SEQ ID NO：85和86；SEQ ID NO：89和90；SEQ ID NO：93和94；SEQ ID NO：97和98； SEQ ID NO：101和102；SEQ ID NO：105和106；SEQ ID NO：109和 110；SEQ ID NO：113和114；SEQ ID NO：117和118；SEQ ID NO：121 和122；SEQ ID NO：125和126；SEQ ID NO：129和130；SEQ ID NO： 133和134；SEQ ID NO：137和138；SEQ ID NO：141和142；SEQ ID NO：145和146；SEQ ID NO：149和150；SEQ ID NO：153和154； SEQ ID NO：157和158；SEQ ID NO：161和162；SEQ ID NO：165和 166；SEQ ID NO：169和170；SEQ ID NO：173和174；SEQ ID NO：177 和178；SEQ ID NO：181和182；SEQ ID NO：185和186；SEQ ID NO： 189和190；SEQ ID NO：193和194；SEQ ID NO：197和198；SEQ ID NO：201和202；SEQ ID NO：205和206；SEQ ID NO：209和210； SEQ ID NO：213和214；SEQ ID NO：217和218；SEQ ID NO：221和 222；SEQ ID NO：225和226；SEQ ID NO：229和230；SEQ ID NO：233和234；SEQ ID NO：237和238；SEQ ID NO：241和242；SEQ ID NO： 245和246；SEQ ID NO：249和250；SEQ ID NO：253和254；SEQ ID NO：257和258；SEQ ID NO：261和262；SEQ ID NO：265和266； SEQ ID NO：269和270；SEQ ID NO：273和274；SEQ ID NO：277和 278；SEQ ID NO：281和282；SEQ ID NO：285和286；SEQ ID NO：289 和290；SEQ ID NO：293和294；SEQ ID NO：297和298；SEQ ID NO： 301和302；SEQ ID NO：305和306；SEQ ID NO：309和310；SEQ ID NO：313和314；SEQ ID NO：317和318；SEQ ID NO：321和322；SEQ ID NO：325和326；SEQ ID NO：329和330；SEQ ID NO：333和 334；SEQ ID NO：337和338；SEQ ID NO：34l和342；SEQ ID NO：345 和346；SEQ ID NO：349和350；SEQ ID NO：353和354；SEQ ID NO： 357和358；SEQ IDNO：361和362；SEQ ID NO：365和366；SEQ ID NO：369和370；SEQ ID NO：373和374；SEQ IDNO：377和378；SEQ ID NO：381和382；SEQ ID NO：385和386；SEQ ID NO：389和 390；SEQ IDNO：393和394；SEQ ID NO：397和398；SEQ ID NO：401 和402；SEQ ID NO：405和406；SEQ IDNO：409和410。

在另一方面，所述异二聚体抗体具有的第一可变重链结构域和第 一可变轻链结构域选自由以下组成的对：H1与L1；H1与L1.24；H1 与L1.96；H1.77与L1.96；H1.77与L1.97；H1.72与L1.97；H1.71 与L1.96；及H1.77与L1.24。

在另一方面，本发明提供了如以上所述的异二聚体抗体，其中 scFv具有带电的scFv连接子。所述带电的scFv连接子可以具有3至 8个正电荷，并且选自由SEQID NO：443至451组成的组。

在另一方面，scFv具有选自由以下组成的组的序列：SEQ ID NO： 4；SEQ ID NO：8；SEQ ID NO：12；SEQ ID NO：16；SEQ ID NO：20； SEQ ID NO：24；SEQ ID NO：28；SEQ ID NO：32；SEQ ID NO：36； SEQ ID NO：40；SEQ ID NO：44；SEQ ID NO：48；SEQ ID NO：52； SEQ IDNO：56；SEQ ID NO：60；SEQ ID NO：64；SEQ ID NO：68； SEQ ID NO：72；SEQ ID NO：76；SEQID NO：80；SEQ ID NO：84； SEQ ID NO：88；SEQ ID NO：92；SEQ ID NO：96；SEQ ID NO：100；SEQ ID NO：104；SEQ ID NO：108；SEQ ID NO：112；SEQ ID NO：116； SEQ ID NO：120；SEQ IDNO：124；SEQ ID NO：128；SEQ ID NO： 132；SEQ ID NO：136；SEQ ID NO：140；SEQ ID NO：144；SEQ ID NO： 148；SEQ ID NO：152；SEQ ID NO：156；SEQ ID NO：160；SEQ ID NO： 164；SEQ ID NO：168；SEQ ID NO：172；SEQ ID NO：176；SEQ ID NO： 180；SEQ ID NO：184；SEQ IDNO：188；SEQ ID NO：192；SEQ ID NO：196；SEQ ID NO：200；SEQ ID NO：204；SEQ ID NO：208；SEQ ID NO： 212；SEQ ID NO：216；SEQ ID NO：220；SEQ ID NO：224；SEQ ID NO： 228；SEQID NO：232；SEQ ID NO：236；SEQ ID NO：240；SEQ ID NO： 244；SEQ ID NO：248；SEQ ID NO：252；SEQ ID NO：256；SEQ ID NO： 260；SEQ ID NO：264；SEQ ID NO：268；SEQ ID NO：272；SEQ ID NO： 276；SEQ ID NO：280；SEQ ID NO：284；SEQ ID NO：288；SEQ ID NO： 292；SEQID NO：296；SEQ ID NO：300；SEQ ID NO：304；SEQ ID NO： 308；SEQ ID NO：312；SEQ ID NO：316；SEQ ID NO：320；SEQ ID NO： 324；SEQ ID NO：328；SEQ ID NO：332；SEQ ID NO：336；SEQ ID NO： 340；SEQ ID NO：344；SEQ ID NO：348；SEQ ID NO：352；SEQ ID NO： 356；SEQID NO：360；SEQ ID NO：364；SEQ ID NO：368；SEQ ID NO： 372；SEQ ID NO：376；SEQ ID NO：380；SEQ ID NO：384；SEQ ID NO： 388；SEQ ID NO：392；SEQ ID NO：396；SEQ ID NO：400；SEQ ID NO： 404；SEQ ID NO：408。

在另一方面，重链Fc区另外包含FcRn变体，包括但不限于， 428L/434S。

在另一方面，本发明提供核酸组合物，所述核酸组合物包含：编 码第一重链的第一核酸，该第一重链包含Fc区和结合至CD3的scFv； 编码第二重链的第二核酸，该第二重链包含恒定重链和可变重链；及 编码轻链的第三核酸，其中第二重链和轻链的Fv区结合CD38。这 些核酸可以在不同表达载体中，或在同一表达载体中。本发明提供了 包含所述核酸组合物的宿主细胞。

在另一方面，本发明提供了制造本发明的异二聚体抗体的方法， 这些方法包括：提供第一表达载体，该表达载体包含编码第一重链的 第一核酸，该第一重链包含第一Fc结构域和第一可变重链；提供第 二表达载体，该表达载体包含编码第二重链的第二核酸，该第二重链包含第一Fc结构域和结合CD3的单链Fv区(scFv)；及提供第三表达 载体，该表达载体包括含轻链的核酸；其中所述第一可变重链和所述 轻链的可变轻链结构域结合CD38。第一表达载体、第二表达载体及 第三表达载体以选自由以下组成的组的比率转染至宿主细胞中： 1∶1.5∶1.5、1∶2∶1.5、1∶0.667∶2、1∶1∶2、1∶1.5∶2及1∶2∶2。在宿主细胞中 表达第一表达载体、第二表达载体及第三表达载体，分别产生第一氨基酸序列、第二氨基酸序列及第三氨基酸序列，由此所述第一氨基酸 序列、所述第二氨基酸序列及所述第三氨基酸序列形成异二聚体抗 体。

在另一方面，本发明提供了通过施用根据本发明的异二聚体抗体 来治疗有需要的患者的方法。

附图简要说明

图1A和1B描绘了人类CD38的序列。图1A描绘全长序列，并 且图1B描绘细胞外结构域。

图2描绘人类CD3序列。

图3A至3YY描绘稳定性优化的人源化抗CD3变体scFv、可变 重链序列及可变轻链序列的氨基酸序列。(另外，应注意，为便于纯 化，第一序列是组氨酸标记形式)。CDR加下划线。应理解，优化的 可变链和优化的轻链(以及scFv链)的稳定性增加可以归于构架区以及CDR。因此，应理解，公开的完整可变区包括公开的构架区，不 过构架区未独立编号。此外，scFv连接子以灰色示出。每个scFv连 接子都可以用图5中所描绘的带电的scFv连接子替代。也就是说， 可以用任何带电的scFv连接子，无论是带正电或是带负电，包括图5 中描绘的那些，取代图3A至3YY中突出显示的区域。

图4A至4I描绘了可用于本发明中的所有CD3vhCDR1-3和 vlCDR1-3序列与共同CDR的组合。

图5描绘了适合的带正电和带负电的scFv连接子。带单一电荷 的单一现有技术scFv连接子被Whitlow等人，Protein Engineering 6(8)：989-995(1993)称为“Whitlow”。应注意，此连接子在scFv中用于 减少聚集及增强蛋白水解稳定性。

图6A、6B、6C及6D描绘新型空间变体。本领域技术人 员应理解，各表的第一栏表示“对应的”单体对；也就是说，单体1具 有405A并且对应的空间变体是394F。值得关注的是，在不对称三F 形式的情况下，任一单体可以具有任一变体。也就是说，scFv单体可 以是单体1或单体2。另外，这些集合可以任选并且独立地与其它空 间变体以及包括电荷对、同型变体、等排变体、pI变体等在内的其它 杂二聚化变体组合，只要保持某种“链型”即可。此外，“单体”是指Fc 结构域；也就是说，在三F形式中，一个单体是scFv构建体并且另一个单体是Fab构建体，不过实际上有两个氨基酸序列构成Fab构建 体(重链和轻链)的事实显示许多适合的空间或“偏向(skew)”变体适用 于本发明中。图a6描绘了多种空间变体，这些变体可以单独使用或与pI变体(实际上图6中的所有变体)组合使用；不过，本领域技术人 员应理解，如果存在pI变体，那么应保持pI变体和空间变体的“链型”。 也就是说，如果例如将pI变体S364K/E357Q(单体1)和L368D/K370S (单体2)与图29变体组合，那么空间变体的pI应当予以考虑并指定 给正确的单体。也就是说，例如，将改变电荷的空间变体(T411E)添加至“负值”单体中。

图7描绘了一系列工程改造的异二聚体偏向(例如“空间异二聚 化”)Fc变体以及异二聚体产率(通过HPLC-CIEX测定)和热稳定性(通 过DSC测定)。未测定的热稳定性以“n.d.”表示。

图8A至8C.示出“三F形式”的双特异性免疫球蛋白。图8A显 示scFv-Fc形式。图8C描绘了更标准的双特异性抗体形式，也利用 了本发明的pI变体(以及任选并且独立地其它异二聚化变体)。图8B 显示“三F”形式(有时也称为“开瓶器”构型；(以及任选并独立地其它异二聚化变体)。本文所列的许多实施方案具有双特异性抗体的抗 CD3组分作为scFv，以及抗CD38组分作为Fab片段，不过本领域 技术人员应理解，这些可以调换，其中抗CD38组分是scFv，任选地 具有带电的连接子，并且本文中的抗CD3序列scFv的Fv区被重新 工程改造成Fab片段。

图9描绘了用以减少与部分或全部FcγR受体的结合的多种适合 的“基因敲除”(“KO”)变体。本文的许多变体(如果不是全部变体的)是 KO变体，这些KO变体可以独立地并且任选地与图9中所描述的集 合组合，以及与包括空间变体和pI变体在内的本文所略述的任何异 二聚化变体组合。举例来说，E233P/L234V/L235A/G236del可以与清 单中的任何其它单一或双重变体组合。此外，尽管在一些实施方案中 优选两个单体含有相同的KO变体，但可能的情况是，在不同单体上组合不同的KO变体，并且仅有一个单体包含KO变体。另参看USSN 61/913,870的附图和图例，所有这些都以引用的方式整体明确地并入， 就如同其提及“基因敲除”或“切除”变体。

图10显示了一系列工程改造的异二聚体偏向Fc变体以及异二聚 体产率(通过HPLC-CIEX测定)和热稳定性(通过DSC测定)。未测定 的热稳定性以“n.d.”表示。

图11.显示抗CD38 x抗CD3双特异性分子的结构的示意图。

图12.亲和力/稳定性工程改造的变体抗CD38 x抗CD3双特异 性分子的表面等离子体共振(SPR)数据。

图13.荧光LDH重定向T细胞的细胞毒性(RTCC)检定，显示了 抗CD28 x抗CD3双特异性分子对RPMI8226多发性骨髓瘤细胞的 杀伤作用。

图14.RTCC检定(膜联蛋白(Annexin)V+)，显示了抗CD38 x抗 CD3双特异性分子对RPMI8226多发性骨髓瘤细胞的杀伤作用。T细 胞与RPMI8226细胞的比率及培育时间有所变化。

图15.列出亲和力/稳定性工程改造的变体抗CD38 x抗CD3双 特异性分子的特性的表格。编号是依据Kabat。

图16.抗CD38 x抗CD3双特异性分子与食蟹猴CD20+细胞的 结合。

图17.在移植huPBMC的SCID小鼠中抗CD38 x抗CD3双特 异性分子杀伤人浆细胞。观察到人IgG2和IgE同型显著减少。示出第22天的平均值±SEM。BLQ对于IgG2是＜1μg/mL，而对于IgE 是＜16ng/mL。低于BLQ的数据点指定为BLQ值。

图18.在移植huPBMC的SCID小鼠中抗CD38 x抗CD3双特 异性分子杀伤人浆细胞。观察到人IgM显著减少。示出第22天的平均值±SEM。IgM的BLQ是＜0.03μg/mL。低于BLQ的数据点指定 为BLQ值。

图19.抗CD38 x抗CD3双特异性抗体清除MM PBMC中的 CD38+CD138+细胞。

图20A至20Q显示了本发明的CD38 X CD3 scFv开瓶器的序列。

图21显示CD38 X CD3开瓶器的一些有用Fc结构域的变体。

图22A和22B描绘了抗CD38 x抗CD3双特异性抗体 XENP13243和XENP13551的氨基酸序列，其中CDR加下划线并且 存在带电连接子(连接子可以是不带电的或被任何其它带正电或带负 电的连接子取代，见图7)。

图23A、23B、23C及23D显示了编码抗CD38 x抗CD3双特异 性抗体XENP13243和XENP13551的DNA序列。

图24显示了用于产生XENP13243和XENP13551的稳定库的 DNA转柒比率表。列出了HC-Fab、HC-scFv及LC中转柒的DNA 的相对量。

图25A、25B、25C及25D描绘了通过蛋白质A从XENP13243 和XENP13551分批培养7天后收集的稳定库上清液中纯化的物质的 阳离子交换色谱图。DNA转柒比率如图24中所列。标出积分峰面积。

图26.由图25中所示的阳离子交换色谱图鉴别的稳定库所产生 的不同蛋白质种类的概述。DNA转染比率如图24中所列。

图27.在C57BL/6小鼠(n＝5只小鼠/组)中抗CD38 x抗CD3双 特异性抗体XENP13243和XENP13551的药物动力学。通过非房室分析计算的半衰期值在图例中注明。

图28.CD38+ RPMI8226细胞的重定向T细胞的细胞毒性。检定 由在37℃下10,000个RPMI8226细胞与400,000个纯化的人类T细 胞一起培育24小时组成。通过乳酸脱氢酶(LDH)读取细胞毒性。

图29.通过表面等离子体共振测定的人和食蟹猴CD38和CD3 与XENP13243和XENP13551的结合的动力学。检定方式如所述。

图30.XENP13243(上图)和XENP13551(下图)清除食蟹猴中的 CD20-CD38+细胞。

图31.XENP13243(上图)和XENP13551(下图)上调食蟹猴CD8+ T细胞中的CD69。

图32描绘了等排变体抗体恒定区及其对应取代的清单。pI_(-) 表示pI较低的变体，而pI_(+)表示pI较高的变体。这些变体可以任 选并且独立地与本发明的其它异二聚化变体组合。

图33显示了特定抗CD3 scFv的一些带电的连接子和数据。

图34描绘了与使用分离变体(本文中又称“pI变体”)及与异二聚 体组装变体(本文中又称为“偏向变体”)的组合有关的示意图。这些变 体可以按“即插即用(plug andplay)”形式使用，因为这些变体的作用易 于转移到具有不同Fv区的不同抗体中并且非常稳定。

图35描绘了共用抗CD3 scFv-Fc的优化。以多种方式增加稳定 性，包括置换稀有氨基酸；用不常见的接触残基置换氨基酸；进行连 接子工程改造(用于稳定性和增进纯化，例如带电scFv连接子)；及转 变成VL-VH取向。

图36描绘了使用保持野生型稳定性但去除所有FcγR结合的Fc 基因敲除(或切除变体)。

图37描绘了抗CD3X抗CD38开瓶器形式的体外杀伤和稳定性 数据。

图38描绘了人骨髓瘤细胞系的杀伤。XmAb13551对CD3具有 高亲和力，而XmAb13243具有较低亲和力。达雷木单抗(Daratumumab) 是抗CD38二价单特异性抗体。

图39显示了在小鼠中本发明的开瓶器双特异性抗体的长半衰期 活性及人Ig的相应抑制作用。

图40显示了XmAb13551和XmAb13243的抗CD38 X抗CD3 功能，包括在血液和骨髓中猴CD38+细胞的清除。

图41显示，CD38+细胞清除与T细胞再分布和活化相关。

图42显示了用于产生XmAb13551(高CD3亲和力)的稳定细胞系 的开发及其相应产率。

图43显示了用于改善产率进行的一些细胞培养优化，其中获得 的滴度≥3g/L，并且通过按比例放大未见到异二聚体/同二聚体比率的显著差异。

图44显示由三步制造工艺得到的分析结果。该工艺产生极纯异 二聚体双特异性分子的产率较高，超过55％，并且有效地去除同二聚 体、HMW及LMW污染物，以及HCP。

图45A至45U显示了多种另外的异二聚化形式，其中任一种可 以包括本发明的抗CD3和抗CD38序列。图45A至45U描绘了多种 多特异性(例如异二聚化)形式及可以用于本发明中的不同类型异二 聚化变体(这些在本文中有时称为“异二聚体支架”)的组合。此外，应注意，所有这些形式都可以包括在Fc区中的添加变体(如以下更完整 地论述)，包括“切除”或“基因敲除”变体(图7)、改变FcγR(FcγRIIb、 FcγRIIIa等)结合的Fc变体、改变与FcRn受体的结合的Fc变体等。 图45A显示了双scFv-Fc形式，与本文中的所有异二聚体化形式相同， 该形式可以包括异二聚化变体，如pI变体、钮与孔(KIH，在本文中 又称为空间变体或“偏向”变体)、电荷对(一小组空间变体)、等排变体， 及SEED体(“链交换工程改造结构域”；参见Klein等人，mAbs 4：6 653-663(2012)，及Davis等人，Protein Eng Des Sel 2010 23：195-202)， 此形式是基于人IgG和IgA的CH3结构域不彼此结合的事实。图45B描绘了双特异性IgG，以及多种异二聚化变体的选择。图45C描绘了 DVD-Ig的“单臂”形式，其利用了两个不同的可变重链结构域和可变 轻链结构域。图45D类似，不过可变重链和轻链在重链对面，而非“空 臂”。图45E一般称为“mAb-Fv”。图45F描绘了多scFv形式；本领 域技术人员应理解，类似于本文所论述的“A、B、C、D”形式，可能 存在许多相连的scFv(或就这一点来说，任何其它结合配体或功能性)。因此，图45F可以具有1、2、3或4个scFv(例如对于双特异性 抗体，scFv可以是“顺式”或“反式”的，或者都在分子的一“端”上)。图 45G描绘了异二聚体FabFc，其中Fab是由两个不同的重链形成，一 个含有重链Fab序列，而另一个含有轻链Fab序列。图45H描绘了“单 臂Fab-Fc”，其中一条重链包含Fab。图45I描绘了“单臂scFv-Fc”，其中一条重链Fc包含scFv，而另一条重链是“空的”。图45J显示了 scFv-CH3，其中仅使用重链CH3区，各自具有其自身的scFv。图45K描绘了mAb-scFv，其中该分子的一端二价接合抗原，并且在一条重 链上使用scFv单价接合。图45L描绘相同结构，但两条重链都包含 另外的scFv，这些scFv可以结合同一抗原或不同抗原。图45M显示 “CrossMab”结构，其中由两条不同轻链引起的复合体形成的问题通过 变换Fab部分中的序列而得到解决。图45N描绘scFv，图45O是以 本文略述的连接子连接的“BiTE”或scFv-scFv，图45P描绘DART， 图45Q描绘TandAb，并且图45R显示双功能抗体。图45S、45T及 45U描绘了用于本发明中的另外的替代性支架形式。

图46A、46B及46C描绘了稳定性优化的人源化抗CD3变体 scFv。取代是相对于H1.1_L1.4scFv序列给出。氨基酸编号是Kabat 编号。

图47A和47B.用于本发明中的抗CD3序列的可变重链和可变 轻链，包括“较强”和“较弱”结合序列。本领域技术人员应理解，这些 可以在Fab或scFv构建体中与任何靶肿瘤抗原结合结构域组合使用。

图48显示了在Biacore检定中的结合亲和力。

图49显示了在使用不同的轻链、Fab-Fc和scFv-Fc比率产生稳 定库期间的异二聚体纯度。

图50.在huPBMC小鼠模型中抗CD38 x抗CD3双特异性抗体 的人IgM和IgG2清除作用。

图51A和51B显示了针对CD38所设计的分别具有低亲和力和 高亲和力的XENP13243和XENP13551的纯化。

图52A、52B及52C显示了与人和猴CD38和CD3的结合，及 Kd。

图53显示了骨髓瘤细胞的杀伤。

图54显示，T细胞是连环杀伤细胞，即使在靶细胞数量较多时 也是如此。

图55显示，Fc结构域延长半衰期。

图56显示了图14实验的剂量。

图57显示相对于达雷木单抗更高的hIg清除率。

图58显示了图16实验的剂量。

图59A和59B双特异性抗体清除猴血液和淋巴系器官中的 CD38+细胞。

图60A、60B及60C。图60A(由血液再分布)，图60B(CD69 诱导)及图60C(细胞因子释放)显示，CD38+细胞清除与T细胞再分 布和活化有关。

图61描绘了本发明的具体应用的若干实施方案。

发明详述

I.综述

本发明针对能提供同时结合到CD3和CD38抗原的双特异性抗 体的新型构建体。抗体技术面临的一个问题是需要同时结合到两种 (或更多种)不同抗原的“双特异性”(和/或多特异性)抗体，由此大体上 使不同抗原能接近并产生新的功能和新的疗法。一般来说，这些抗体 是通过在宿主细胞中包括每一重链和轻链的基因来产生。由此一般会 形成期望的异二聚体(A-B)以及两个同二聚体(A-A和B-B)。然而，形 成多特异性抗体的一个主要难点在于，难以纯化分离异二聚体抗体与 同二聚体抗体，和/或相对于形成同二聚体，倾向于形成异二聚体。

本发明大体上针对产生异二聚体蛋白质，如能够基于恒定区中的 氨基酸变体以若干方式共接合抗原的抗体，所述恒定区的氨基酸变体 在每条链上不同，由此促进异二聚体形成和/或相对于同二聚体，能 够容易地纯化出异二聚体。

因此，本发明针对共接合至少第一抗原和第二抗原的新型免疫球 蛋白组合物。本发明的第一抗原和第二抗原在本文中分别称为抗原-1 和抗原-2。抗体的一条重链含有单链Fv(“scFv”，如下文所定义)，而 另一重链是“常规”Fab形式，包含可变重链和轻链。这一结构在本文 中有时称为“三F”形式(scFv-FAb-Fc)或“开瓶器”形式，因为看起来与 开瓶器大致类似(参见附图)。两条链通过使用恒定区(例如Fc结构域和/或铰链区)中的氨基酸变体连在一起，所述氨基酸变体促进异二聚 体抗体的形成，如以下更完整地描述。

本发明的“三F”形式具有若干不同益处。如本领域中所知，基于 两个scFv构建体的抗体类似物通常存在稳定性和聚集问题，这些问 题可以在本发明中通过添加“常规”重链和轻链配对得到缓解。此外，与基于两条重链和两条轻链的形式相对，不存在重链与轻链配对不正 确(例如重链1与轻链2配对等)的问题。

可以使用多种机制来产生本发明的异二聚体。此外，本领域技术 人员应理解并且如下文更完整地描述，这些机制可以组合以确保高度 异二聚化。

一种机制在本领域中一般称为“钮与孔(knobs and holes)”(“KIH”)，或在本文中有时称为“偏向”变体，还可以任选使用提 及的氨基酸工程改造以产生有利于异二聚体形成，而不利于同二聚体 形成的空间影响；这有时称为“钮与孔”，如USSN 61/596,846；Ridgway 等人，Protein Engineering 9(7)：617(1996)；Atwell等人，J.Mol.Biol. 1997270：26；美国专利号8,216,805中所描述，其全部以引用的方式 整体并入本文中。附图标识众多基于“钮与孔”的“单体A-单体B”对。 此外，如Merchant等人，Nature Biotech.16：677(1998)中所描述，这些“钮与孔”突变可以与二硫键组合以偏向形成异二聚化。

用于产生异二聚体的另一机制有时称为“静电镶饰(electrostatic steering)”，如Gunasekaran等人，J.Biol.Chem.285(25)：19637(2010) (以引用的方式整体并入本文中)所描述。这在本文中有时称为“电荷 对”。在这一实施方案中，使用了静电试剂来使形成偏向异二聚化。本 领域技术人员应理解，这些还可能影响pI，并由此影响纯化，因此在 一些情形中还可以视为pI变体。然而，由于这些静电试剂强迫异二聚化并且不被用作纯化工具，故其被归类为“空间变体”。这些包括但 不限于，D221E/P228E/L368E与D221R/P228R/K409R的配对(例如， 这些是“单体对应集合”)及C220E/P228E/368E与C220R/E224R/P228 R/K409R的配对。(应注意，重链和轻链二硫键的形成不再需要220突变去除半胱氨酸，以下将更完整地描述)。

在本发明中，有若干基本机制可以便利异二聚体蛋白质的纯化， 一种机制基于使用pI变体，以使每一单体具有不同pI，由此允许A-A、 A-B及B-B二聚体蛋白质的等电纯化。作为替代方案，“三F”形式还 允许基于尺寸进行分离。如下文进一步略述，相对于同二聚体，使形 成“偏向”异二聚体也是可能的(如下文大体上略述)。因此，空间异二 聚化变体与pI或电荷对变体的组合特别适用于本发明。另外，如以 下更完整地略述，三F形式的scFv单体可以包括带电的scFv连接子 (带正电或带负电)，由此进一步增进pI以达到纯化目的。本领域技术人员应理解，一些三F形式可以使用带电的scFv连接子，不必额外 的pI调整，而本发明也的确使用了含带电的scFv连接子的偏向变体 (及Fc、FcRn与KO变体的组合)。

在利用pI作为分离机制以产生异二聚体三F形式的本发明中， 可以将氨基酸变体引入一个或两个单体多肽中；也就是说，一个单体 (在本文中简称为“单体A”)的pI可以工程改造成与单体B不同，或单 体A与单体B都变为带电的，其中单体A的pI增加，而单体B的pI降低。如以下更完整地略述，任一单体或两个单体的pI变化可以 通过去除或添加带电残基(例如，中性氨基酸被带正电或带负电的氨 基酸残基置换，例如甘氨酸被谷氨酸置换)、将带电残基由带正电或 带负电变为带相反电荷(天冬氨酸变为赖氨酸)，或将带电残基变为中性残基(例如，失去电荷；赖氨酸变为丝氨酸)来进行。这些变体中有 许多显示于附图中。

因此，在本发明的这一实施方案中，提供在至少一个单体中引起 足够pI变化，以使得异二聚体可以与同二聚体分离。本领域技术人 员应理解，并且如以下进一步论述，这可以通过使用“野生型”重链恒 定区及工程改造成增加或降低其pI的变体区(wt A-+B或wtA--B)， 或通过增加一个区并降低另一区(A+-B-或A-B+)来进行。应注意， 在这一论述中，哪一单体包含scFv并且哪一单体包含Fab并不重要。

因此，一般说来，本发明的一种组分是在抗体恒定区中的氨基酸 变体，这些变体是针对通过在一个或两个单体中并入氨基酸取代(“pI 变体”或“pI取代”)来改变二聚体蛋白质的至少一个(如果不是两个)单 体的等电点(pI)，由此形成“pI异二聚体”(当蛋白质是抗体时，这些称 为“pI抗体”)。如本文所示，如果两个单体的pI相差低至0.1个pH单 位，就可以实现异二聚体与两个同二聚体的分离，并且0.2、0.3、0.4 及0.5或更高pH单位差异全部用于本发明中。

本领域技术人员应理解，为实现良好分离而在一个或两个单体上 包括的pI变体的数量将部分取决于所关注的scFv和Fab的起始pI。 也就是说，为了确定哪一单体经历工程改造或沿哪一“方向”(例如， 带更高正电或带更高负电)，对两个靶抗原的Fv序列进行计算并由此 作出决定。如本领域中所知，不同的Fv将具有不同的起始pI，这一 点被用于本发明中。一般来说，如本文所略述，pI被工程改造成使每 一单体的总pI差异是至少约0.1log，其中0.2至0.5是优选的(如本 文所略述)。

另外，本领域技术人员应理解并且如本文所略述，可以基于尺寸 来分离异二聚体与同二聚体。举例来说，如图8中所示，具有两个scFv 的异二聚体(图8A)可以与“三F”形式的异二聚体(图8B)和双特异性 mAb(图8C)分离。这可以进一步用于更高价态中，其中利用了另外 的抗原结合位点。举例来说，如另外显示，一个单体将具有两个Fab 片段，并且另一个将具有一个scFv，由此产生尺寸差异和分子量差异。

此外，本领域技术人员应理解并且如本文所略述，本文略述的形 式还可以扩展以提供三特异性和四特异性抗体。在这一实施方案(其 中一些变化描绘于附图中)中，应认识到，一些抗原可以是二价结合 的(例如，两个抗原结合位点针对单一抗原；例如，A和B可以是典 型二价缔合的一部分并且C和D可以任选地存在并且任选相同或不 同)。应理解，可以利用Fab与scFv的任何组合以实现期望的结果和 组合。

在使用pI变体实现异二聚化的情况下，通过使用重链恒定区， 又提供一种模块化方法来设计并纯化多特异性蛋白质，包括抗体。因 此，在一些实施方案中，异二聚化变体(包括偏向和纯化异二聚化变体)未包括在可变区中，因此，每一个别抗体必须经过工程改造。此 外，在一些实施方案中，通过输入来自不同IgG同型的pI变体来改 变pI，同时不会引入显著免疫原性，由此使得由pI变体产生免疫原 性的可能性显著降低。因此，另一有待解决的问题是说明具有高人类 序列含量的低pI恒定结构域，例如使任何特定位置处的非人类残基 最少或避免。

在一个实施方案中，异二聚体抗体使用scFv单价接合一个抗原， 并且使用FAb单价接合另一抗原。如以下所略述，这一形式也可以 变化；在一些实施方案中，三个抗原都是单价接合，有一个抗原是二价接合，而另一抗原是单价接合(例如，A和C接合相同抗原，而B接合不同抗原)等。

另外，可以利用这一pI工程改造得到的附带益处是延长血清半 衰期和增加FcRn结合。也就是说，如USSN 13/194,904(以引用的方式整体并入)中所描述，降低抗体恒定结构域(包括抗体和Fc融合物 中发现的那些)的pI可以延长体内血清保持。这些用于增加血清半衰 期的pI变体还有助于改变pI以实现纯化。

另外，如本文所略述，可以将另外的氨基酸变体引入本发明的双 特异性抗体中，以添加另外的功能。举例来说，可以添加(添加到一 个单体或两个单体中)Fc区内的氨基酸改变以促进ADCC或CDC的 增加(例如改变与Fcγ受体的结合)；允许或增加毒素和药物添加的产 率(例如对于ADC)；以及增加与FcRn的结合，和/或增加所得分子的 血清半衰期。如本文进一步描述并且本领域技术人员应理解，本文略 述的任何和所有变体都可以任选并且独立地与其它变体组合。

类似地，另一类功能变体是“Fcγ切除变体”或“Fc基因敲除(FcKO 或KO)变体”。在这些实施方案中，对于一些治疗应用，希望减少或 去除Fc结构域与一种或多种或者全部Fcγ受体(例如FcγR1、FcγRIIa、 FcγRIIb、FcγRIIIa等)的正常结合以避免另外的作用机制。也就是说， 例如，在许多实施方案中，一般希望切除FcγRIIIa结合以消除或显著 降低ADCC活性。

此外，本发明提供了新型人源化抗CD3序列，包括CDR集合、 完整可变轻链和重链，以及相连的scFv，这些scFv可以任选包括带 电的scFv连接子。使用的这些优化序列可以呈其它抗体形式。

本发明另外提供新型抗CD38序列，包括CDR集合、完整可变 轻链和重链，以及相连的scFv，这些scFv可以任选包括带电的scFv 连接子。使用的这些优化序列可以呈其它抗体形式。

因此，本发明提供了能产生同时结合至CD3和CD38的双特异 性、二价抗体的新型构建体。

此外，本发明提供了具有不同亲和力的抗原结合结构域。也就是 说，对于抗CD3和抗CD38序列，在一些情形中，可能优选较强亲 和力，而在其它情形中，可以使用较低亲和力。因此，在一些实施方 案中，本发明提供的抗体构建体包含“强”或“高亲和力”结合至CD3的抗CD3抗原结合结构域(例如，一个实例是描绘为H1.30_L1.47的 重链和轻链可变结构域(适当时，任选包括带电连接子))。在其它实施 方案中，本发明提供的抗体构建体包含“弱”或“低亲和力”结合至CD3 的抗CD3抗原结合结构域，如图47中所示。

II.定义

为了能更完全地了解本申请，以下陈述若干定义。这些定义意图 涵盖语法等效物。

“切除”在本文中意思指活性的降低或去除。因此，例如，“切除 FcγR结合”意思指相较于不含特定变体的Fc区，Fc区氨基酸变体具 有低于50％的起始结合，其中优选低于70％、80％、90％、95％、98％ 的活性损失，并且一般来说，在Biacore检定中，活性低于可检测的 结合水平。当使用切除变体(在本文中有时又称“FcγR切除变体”、“Fc 切除变体”、“Fc基因敲除”(“FcKO”)变体或“基因敲除”(“KO”)变体) 时，具有特定应用的变体是图35中描绘的那些。

如本文所使用，“ADCC”或“抗体依赖性细胞介导的细胞毒性”意 思指表达FcγR的非特异性细胞毒性细胞识别靶细胞上结合的抗体并且随后使靶细胞溶解的细胞介导的反应。ADCC与结合至FcγRIIIa 相关；增加与FcγRIIIa的结合引起ADCC活性的增加。

如本文所使用，“ADCP”或抗体依赖性细胞介导的吞噬作用意思 指表达FcγR的非特异性细胞毒性细胞识别靶细胞上结合的抗体并且随后吞噬靶细胞的细胞介导的反应。

“修饰”在本文中意思指多肽序列中的氨基酸取代、插入和/或缺 失，或针对以化学方式连接至蛋白质的部分的改变。举例来说，修饰 可以是附接至蛋白质的碳水化合物或PEG结构的改变。“氨基酸修饰”在本文中意思指多肽序列中的氨基酸取代、插入和/或缺失。为清楚 起见，除非另外说明，否则氨基酸修饰通常是针对DNA编码的氨基 酸，例如在DNA和RNA中具有密码子的20种氨基酸。

“氨基酸取代”或“取代”在本文中意思指亲本多肽序列中特定位 置处的氨基酸被不同氨基酸置换。确切地说，在一些实施方案中，取 代是针对特定位置处非天然存在的氨基酸，这些氨基酸不是生物体内 天然存在的或是任何生物体中的。举例来说，取代E272Y是指272 位的谷氨酸被酪氨酸置换的变体多肽，在此情形中是Fc变体。为清 楚起见，蛋白质被工程改造成改变核酸编码序列但不改变起始氨基酸 (例如CGG(编码精氨酸)变为CGA(仍编码精氨酸)，用以增加宿主生 物体表达水平)不是“氨基酸取代”；也就是说，尽管产生了编码同一 蛋白质的新基因，但如果该蛋白质在其起始的特定位置处具有相同氨 基酸，就不是氨基酸取代。

如本文所使用，“氨基酸插入”或“插入”意思指在亲本多肽序列中 的特定位置处添加氨基酸序列。举例来说，-233E或233E指示在233 位后并且在234位前插入谷氨酸。另外，-233ADE或A233ADE指示 在233位后并且在234位前插入AlaAspGlu。

如本文所使用，“氨基酸缺失”或“缺失”意思指去除亲本多肽序列 中特定位置处的氨基酸序列。举例来说，G236-或G236#或G236del 指示在236位处的甘氨酸缺失。另外，EDA233-或EDA233#表示自 233位开始缺失序列GluAspAla。类似地，一些异二聚化变体包括“K447del”，意思指缺失了447位的赖氨酸。

如本文所使用，“变体蛋白”或“蛋白质变体”或“变体”意思指由于 至少一个氨基酸修饰而不同于亲本蛋白质的一种蛋白质。蛋白质变体 可以指蛋白质本身、包含该蛋白质的组合物，或编码其的氨基酸序列。 优选蛋白质变体相较于亲本蛋白质具有至少一个氨基酸修饰，例如相 较于亲本，具有约一个至约七十个氨基酸修饰，并且优选具有约一个至约五个氨基酸修饰。如以下所描述，在一些实施方案中，亲本多肽， 例如Fc亲本多肽，是人类野生型序列，如来自IgGl、IgG2、IgG3 或IgG4的Fc区，，不过具有变体的人类序列也可以充当“亲本多肽”。 本文中的蛋白质变体序列优选与亲本蛋白质序列具有至少约80％一 致性，并且最优选具有至少约90％一致性，更优选具有至少约95％、98％、99％一致性。变体蛋白质可以指变体蛋白质本身、包含该蛋白 质变体的组合物，或编码其的DNA序列。因此，如本文所使用，“抗体变体”或“变体抗体”意思指由于至少一个氨基酸修饰而不同于亲本 抗体的抗体；如本文所使用，“IgG变体”或“变体IgG”意思指由于至 少一个氨基酸修饰而不同于亲本IgG(在许多情形中，也来自人类IgG 序列)的抗体，并且如本文所使用，“免疫球蛋白变体”或“变体免疫球 蛋白”意思指由于至少一个氨基酸修饰而不同于亲本免疫球蛋白序列 的免疫球蛋白序列。如本文所使用，“Fc变体”或“变体Fc”意思指在 Fc结构域中包含氨基酸修饰的蛋白质。本发明的Fc变体是根据构成 变体的氨基酸修饰定义。因此，例如，N434S或434S是相对于亲本 Fc多肽，在434位具有取代丝氨酸的Fc变体，其中编号是依据EU索引。同样，M428L/N434S定义相对于亲本Fc多肽，具有取代M428L 和N434S的Fc变体。野生型氨基酸的身份可能未指明，在此情形中， 以上提到的变体称为428L/434S。应注意，提供的取代的次序是任意的，也就是说，例如428L/434S与M428L/N434S是相同Fc变体，等 等。对于本发明中论述的有关抗体的所有位置，除非另外说明，否则 氨基酸位置编号是依据EU索引。EU索引或如在Kabat中的EU索引 或EU编号方案是指EU抗体的编号(Edelman等人，1969，Proc Natl Acad Sci USA 63：78-85，以引用的方式整体并入本文中)。修饰可以是 添加、缺失或取代。取代可以包括天然存在的氨基酸，并且在一些情 形中包括合成氨基酸。实例包括美国专利号6,586,207；WO 98/48032； WO 03/073238；US2004-0214988A1；WO 05/35727A2；WO 05/74524A2；J.W.Chin等人，(2002)，Journal of the American ChemicalSociety 124：9026-9027；J.W.Chin，&P.G.Schultz，(2002)， ChemBioChem 11：1135-1137；J.W.Chin等人，(2002)，PICAS United States of America 99：11020-11024；及L.Wang，&P.G.Schultz，(2002)， Chem.1-10，全部以引用的方式整体并入。

如本文所使用，“蛋白质”在本文中意思指至少两个共价附接的氨 基酸，包括蛋白质、多肽、寡肽及肽。肽基可以包含天然存在的氨基 酸和肽键，或合成拟肽结构，即“类似物”，如类肽(参见Simon等人， PNAS USA 89(20)：9367(1992)，以引用的方式整体并入)。本领域技 术人员应理解，氨基酸可以是天然存在的或合成的(例如，不是由D NA编码的氨基酸)。举例来说，出于本发明的目的，高苯丙氨酸、瓜氨酸、鸟氨酸及正亮氨酸被认为是合成氨基酸，并且可以利用D-和L -(R或S)构型的氨基酸。本发明的变体包含的修饰可以包括使用例如 Schultz和同事开发的技术，包括但不限于，Cropp&Shultz，2004， TrendsGenet.20(12)：625-30；Anderson等人，2004，ProcNatlAcadSci USA 101(2)：7566-71；Zhang等人，2003，303(5656)：371-3；及Chin 等人，2003，Science 301(5635)：964-7(全部以引用的方式整体并入)所 描述的方法并入的合成氨基酸的使用。此外，多肽可以包括一个或多个侧链或末端的合成衍生化、糖基化、PEG化、环式排列、环化、连 接至其它分子的连接子、与蛋白质或蛋白质结构域的融合物，及肽标 签或标记的添加。

如本文所使用，“残基”意思指蛋白质中的位置及其相关氨基酸的 身份。举例来说，天冬酰胺297(又称为Asn297或N297)是在人类抗 体IgG1中297位的残基。

如本文所使用，“Fab”或“Fab区”意思指包含VH、CH1、VL及 CL免疫球蛋白结构域的多肽。Fab可以指分离的这一区域，或处于 全长抗体环境中的这一区域、抗体片段或Fab融合蛋白。如本文所使 用，“Fv”或“Fv片段”或“Fv区”意思指包含单一抗体的VL和VH结构 域的多肽。

如本文所使用，“IgG子类修饰”或“同型修饰”意思指将一种IgG 同型的一个氨基酸转变成一种不同、对准的IgG同型中的相应氨基酸 的氨基酸修饰。举例来说，由于在EU位置296处，IgG1包含酪氨酸， 而IgG2包含苯丙氨酸，故IgG2中的F296Y取代被认为是IgG子类修饰。

如本文所使用，“非天然存在的修饰”意思指并非同型的氨基酸修 饰。举例来说，由于IgG在434位都不包含丝氨酸，故IgG1、IgG2、 IgG3或IgG4(或其混合物)中的取代434S被认为是非天然存在的修 饰。“同型”修饰是指在一个位置处的一个同型氨基酸输入不同的同型 的主链中；例如，IgG1氨基酸输入IgG2主链中的相同位置。

如本文所使用，“氨基酸”和“氨基酸身份”意思指由DNA和RNA 编码的20种天然存在的氨基酸之一。

如本文所使用，“效应功能”意思指由抗体Fc区与Fc受体或配体 相互作用引起的生物化学事件。效应功能包括但不限于，ADCC、 ADCP及CDC。

如本文所使用，“IgG Fc配体”意思指任何生物体中结合至IgG抗 体Fc区形成Fc/Fc配体复合体的分子，优选多肽。Fc配体包括但不 限于，FcγRI、FcγRII、FcγRIII、FcRn、C1q、C3、甘露糖结合凝集 素、甘露糖受体、葡萄球菌蛋白质A、链球菌蛋白质G及病毒FcγR。Fc配体还包括Fc受体同源物(FcRH)，其为与FcγR同源的一组Fc受 体(Davis等人，2002，Immunological Reviews 190：123-136，以引用的方 式整体并入)。Fc配体可以包括未发现的结合Fc的分子。特定IgG Fc 配体是FcRn和Fcγ受体。如本文所使用，“Fc配体”意思指任何生物 体中结合至抗体Fc区形成Fc/Fc配体复合体的分子，优选多肽。

如本文所使用，“Fcγ受体”或“FcγR”意思指结合IgG抗体Fc区并 且由FcγR基因编码的蛋白质家族的任何成员。在人体中，这一家族 包括但不限于，FcγRI(CD64)，包括同工型FcγRIa、FcγRIb及FcγRIc； FcγRII(CD32)，包括同工型FcγRIIa(包括异型H131和R131)、FcγRIIb (包括FcγRIIb-1和FcγRIIb-2)及FcγRIIc；及FcγRIII(CD16)，包括同工型FcγRIIIa(包括异型V158和F158)和FcγRIIIb(包括异型 FcγRIIb-NA1和FcγRIIb-NA2)(Jefferis等人，2002，Immunol Lett 82：57-65，以引用的方式整体并入)，以及任何未发现的人类FcγR或FcγR同工型或异型。FcγR可以来自任何生物体，包括但不限于，人类、小鼠、大鼠、兔及猴。小鼠FcγR包括但不限于，FcγRI(CD64)、 FcγRII(CD32)、FcγRIII(CD16)及FcγRIII-2(CD16-2)，以及任何未发现的小鼠FcγR或者FcγR同工型或异型。

如本文所使用，“FcRn”或“新生儿Fc受体”意思指结合IgG抗体 Fc区并且至少部分由FcRn基因编码的蛋白质。FcRn可以来自任何 生物体，包括但不限于，人类、小鼠、大鼠、兔及猴。如本领域中所 知，功能性FcRn蛋白质包含两个多肽，通常称为重链和轻链。轻链 是β-2-微球蛋白，而重链是由FcRn基因编码。除非本文另外说明， 否则FcRn或FcRn蛋白质是指FcRn重链与β-2-微球蛋白的复合体。多种FcRn变体被用于增加与FcRn受体的结合，并且在一些情形中， 增加血清半衰期。增加与FcRn受体的结合并相应地增加血清半衰期 的Fc变体包括但不限于，434A、434S、428L、308F、259I、428L/434S、 259I/308F、436I/428L、436I或V/434S、436V/428L、252Y、 252Y/254T/256E及259I/308F/428L。也就是说，图8B的三F形式可 以在任一个或两个单体序列上具有这些FcRn变体中的任一种。为清 楚起见，由于每个重链不同，FcRn变体(以及Fc变体)可以位于一个 或两个单体上。

如本文所使用，“亲本多肽”意思指起始多肽，该多肽随后经过修 饰以产生变体。亲本多肽可以是天然存在的多肽，或是天然存在的多肽的变体或工程改造形式。亲本多肽可以指多肽本身、包含亲本多肽 的组合物，或编码其的氨基酸序列。因此，如本文所使用，“亲本免 疫球蛋白”意思指未修饰的免疫球蛋白多肽，该多肽经过修饰以产生 变体，并且如本文所使用，“亲本抗体”意思指未修饰的抗体，该抗体 经过修饰以产生变体抗体。应注意，“亲本抗体”包括已知可商购的、 重组产生的抗体，如下文所略述。

“Fc融合蛋白”或“免疫粘附”在本文中意思指包含一般连接(任选 通过连接子部分，如本文所描述)至不同蛋白质的Fc区，如连接至靶 蛋白(如本文所描述)的结合部分的蛋白质。

如本文所使用，“位置”意思指在蛋白质序列中的定位。位置可以 依序编号，或依据公认的格式，例如用于抗体编号的EU索引进行编 号。

在本发明的异二聚体蛋白质的单体的情况下，“链型”在本文中意 思指，以“相配”的两条DNA链类似的方式，将异二聚化变体并入每 个单体中，由此保留“相配”以形成异二聚体的能力。举例来说，如果 一些pI变体被工程改造成单体A(例如使pI更高)，则可以利用的空 间变体(“电荷对”)不会干扰pI变体，例如，将使pI更高的电荷变体 放入相同“链”或“单体”上以保留两种功能。

如本文所使用，“靶抗原”意思指给定抗原的可变区特异性结合的 分子。靶抗原可以是蛋白质、碳水化合物、脂质或其它化合物。优选 本发明的靶抗原是CD3和CD38。

如本文所使用，“靶细胞”意思指表达靶抗原的细胞。

如本文所使用，“可变区”意思指免疫球蛋白中包含一个或多个Ig 结构域的区域，这些Ig结构域基本上由分别构成κ、λ及重链免疫球 蛋白基因座的Vκ、Vλ和/或VH基因编码。

“野生型或WT”在本文中意思指在自然界发现的氨基酸序列或核 苷酸序列，包括等位基因变体。WT蛋白具有并非有意修饰的氨基酸 序列或核苷酸序列。

如本领域中充分了解的，“单链可变片段”、“scFv”或“单链Fv”在 本文中意思指通常用连接子肽连接的抗体可变重链和轻链的融合蛋 白。典型的scFv连接子是本领域中众所周知的，一般是10至25个 氨基酸长并且包括甘氨酸和丝氨酸。

“带电scFv连接子”在本文中意思指利用带电氨基酸产生和纯化 包括至少一个scFv的异二聚体抗体的scFv连接子。适合的带电scFv 连接子示于附图中，不过也可以使用其它连接子。一般来说，相较于 标准的不带电scFv连接子，如通常使用的(GGGGS)_3-5序列，用于本 发明中的带电scFv连接子具有3至8(3、4、5、6、7或8都是可能 的)个电荷变化(带负电或带正电)。本领域技术人员应理解，利用两个 scFv的异二聚体抗体可以具有一个带电连接子和一个中性连接子(例 如带正电或带负电的scFv连接子)或两个带相反电荷的scFv连接子 (一个带正电并且一个带负电)。

异二聚体蛋白质

本发明是针对产生多特异性，特别是双特异性结合蛋白，并且确 切地说，一个单体包含scFv并且另一个单体包含Fv的多特异性抗体。 如本文所论述，公开的实施方案中有许多使用了结合CD3的scFv和 结合CD38的Fv(或Fab)。作为替代，本文中的vh和vl抗CD38序列可以用于scFv构建体中，其中抗CD3单体是Fab。

抗体

本发明涉及多特异性抗体(通常为治疗性抗体)的产生。如以下 所论述，术语“抗体”是常用的。可用于本发明中的抗体可以呈现如本 文所描述的多种形式，包括传统抗体以及下文所描述的抗体衍生物、 片段及模拟物。一般来说，术语“抗体”包括了含至少一个恒定结构域， 包括但不限于，CH1、CH2、CH3及CL的任何多肽。本文中特别优选的抗体是“三F”形式的抗体。

传统抗体结构单元典型地包含四聚体。每个四聚体典型地由两对 相同的多肽链构成，每一对具有一条“轻链”(典型地具有约25kDa的 分子量)和一条“重链”(典型地具有约50-70kDa的分子量)。人类轻链 被归类为κ轻链和λ轻链。本发明是针对IgG类别，该类别具有若干 子类，包括但不限于，IgG1、IgG2、IgG3及IgG4。因此，如本文所 使用，“同型”意思指根据恒定区的化学特征和抗原特征定义的免疫球 蛋白的任何子类。应理解，治疗性抗体还可以包含同型和/或子类的 混合物。举例来说，如美国公布2009/0163699(以引用的方式并入)中 所示，本发明涵盖IgG1/G2混合物的pI工程改造。

每条链的氨基末端部分包括主要负责抗原识别的具有约100至 110个或更多个氨基酸的可变区，一般在本领域中称为“Fv结构域” 或“Fv区”。在可变区中，重链和轻链的V结构域各自聚集三个环， 形成抗原结合位点。每个环称为互补决定区(下文称为“CDR”)，其中氨基酸序列的变化是最显著的。“可变”是指可变区某些区段的序列在 抗体间明显不同的事实。可变区内的变化不是均匀分布的。相反，V区由通过各自是9-15个氨基酸长或更长的称为“高变区”的变化极大 的较短区隔开的具有15-30个氨基酸的称为构架区(FR)的相对不变的 伸长区组成。

每个VH及VL是由从氨基末端至羧基末端按以下次序排列的三 个高变区(“互补决定区”，“CDR”)及四个FR构成：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。

高变区一般涵盖来自轻链可变区中大致氨基酸残基24-34 (LCDR1；“L”表示轻链)、50-56(LCDR2)和89-97(LCDR3)以及重链 可变区中大致31-35B(HCDR1；“H”表示重链)、50-65(HCDR2)及 95-102(HCDR3)的氨基酸残基；Kabat等人，SEQUENCES OF PROTEINS OFIMMUNOLOGICAL INTEREST，第5版，Public Health Service，National Institutes ofHealth，Bethesda，Md.(1991)；和/或形成 高变环的那些残基(例如，轻链可变区中的残基26-32(LCDR1)、50-52 (LCDR2)及91-96(LCDR3)，以及重链可变区中的26-32(HCDR1)、 53-55(HCDR2)和96-101(HCDR3)；Chothia和Lesk(1987)J.Mol.Biol. 196：901-917)。本发明的特定CDR描述于下。

贯穿本说明书，当提到可变结构域中的残基(近似地，轻链可变 区的残基1-107及重链可变区的残基1-113)时，一般使用Kabat编 号系统(例如Kabat等人，同上文(1991))。

CDR有助于形成抗体的抗原结合位点，或更确切地说，表位结 合位点。“表位”是指与抗体分子可变区中的特定抗原结合位点相互作 用的决定子，称为抗原决定簇。表位是通常具有特定结构特征以及特 定电荷特征的分子组，如氨基酸或糖侧链等。单一抗原可能具有超过 一个表位。

表位可以包含直接参与结合的氨基酸残基(又称表位的免疫优势 组分)及不直接参与结合的其它氨基酸残基，如被特定抗原结合肽有 效阻断的氨基酸残基；换句话说，氨基酸残基是在特定抗原结合肽的范围内。

表位可以是构象表位或线性表位。构象表位是通过空间并置来自 线性多肽链不同区段的氨基酸而产生。线性表位是由多肽链中的相邻氨基酸残基产生的表位。构象表位与非构象表位的区别在于，在变性 溶剂存在下与前者的结合丧失，而与后者的结合不然。

表位典型地在独特的空间构象中包括至少3个并且更通常，至少 5个或8-10个氨基酸。识别同一表位的抗体可以在简单的免疫检定中 验证，该免疫检定显示一种抗体阻断另一抗体与靶抗原的结合的能 力，例如“重新分级(binning)”。

每条链的羧基末端部分界定主要负责效应功能的恒定区。Kabat 等人收集了众多的重链和轻链可变区的初级序列。基于这些序列的保 守程度，其将个别初级序列分入CDR和构架中，并且列出其清单(参见SEQUENCES OF IMMUNOLOGICAL INTEREST，第5版，NIHpublication，No.91-3242，E.A.Kabat等人，以引用的方式整体并入)。

在免疫球蛋白的IgG子类中，在重链中存在若干免疫球蛋白结构 域。“免疫球蛋白(Ig)结构域”在本文中意思指具有截然不同的四级结 构的免疫球蛋白区域。在本发明中关注的是重链结构域，包括恒定重链(CH)结构域和铰链结构域。就IgG抗体来说，IgG同型各自具有三 个CH区。因此，就IgG来说，“CH”结构域如下：“CH1”是指如在 Kabat中，根据EU索引的位置118-220。“CH2”是指如在Kabat中， 根据EU索引的位置237-340，并且“CH3”是指如在Kabat中，根据 EU索引的位置341-447。如本文所示并且如下文所描述，pI变体可 以在一个或多个CH区，以及铰链区(如下文所论述)中。

应注意，本文所描绘的序列以CH1区118位起始；可变区不包 括在内，除非指明。举例来说，根据EU编号，SEQ ID NO：2的第一 个氨基酸，在序列表中指定为“1”位，对应于CH1区的118位。

另一类Ig重链结构域是铰链区。“铰链”或“铰链区”或“抗体铰链 区”或“免疫球蛋白铰链区”在本文中意思指包含在抗体第一恒定结构 域与第二恒定结构域之间的氨基酸的柔性多肽。IgG CH1结构域在结构上终止于EU位置220，并且IgG CH2结构域在残基EU位置237 处开始。因此，对于IgG，抗体铰链在本文中定义为包括位置221(IgG1 中的D221)至236(IgG1中的G236)，其中编号是依据Kabat中的EU 索引。在一些实施方案中，例如就Fc区来说，包括下铰链区，其中“下 铰链”一般是指226位或230位。如本文所示，也可以在铰链区中产 生pI变体。

轻链一般包含两个结构域，即可变轻链结构域(含有轻链CDR并 且与可变重链结构域一起形成Fv区)及恒定轻链区(通常称为CL或 Cκ)。

以下略述的用于另外的取代的另一关注区域是Fc区。如本文所 使用，“Fc”或“Fc区”或“Fc结构域”意思指包含抗体恒定区但不包括第 一恒定区免疫球蛋白结构域并且在一些情况下不包括部分铰链的多 肽。因此，Fc是指IgA、IgD及IgG的后两个恒定区免疫球蛋白结构 域、IgE和IgM的后三个恒定区免疫球蛋白结构域，以及这些结构域 N末端的柔性铰链。对于IgA和IgM，Fc可以包括J链。对于IgG，Fc结构域包含免疫球蛋白结构域Cγ2和Cγ3(Cγ2和Cγ3)以及在Cγ1 (Cγ1)与Cγ2(Cγ2)之间的下铰链区。尽管Fc区的边界可能变化，但人类IgG重链Fc区通常定义为包括残基C226或P230至其羧基末端， 其中编号是依据如在Kabat中的Eu索引。在一些实施方案中，如以 下更完整地描述，对Fc区进行氨基酸修饰，例如以改变与一个或多 个FcγR受体或与FcRn受体的结合。

在一些实施方案中，这些抗体是全长的。“全长抗体”在本文中意 思指构成抗体的天然生物形式的结构，包括可变区和恒定区，包括如 本文略述的一个或多个修饰。

作为替代，抗体可以包括多种结构，分别包括但不限于，抗体片 段、单克隆抗体、双特异性抗体、微型抗体、结构域抗体、合成抗体 (在本文中有时称为“抗体模拟物”)、嵌合抗体、人源化抗体、抗体融 合物(有时称为“抗体缀合物”)及各自的片段。

在一个实施方案中，抗体是抗体片段，只要其含有至少一个能够 工程改造以产生异二聚体(如pI工程改造)的恒定结构域即可。可以使 用的其它抗体片段包括了含有经过pI工程改造的本发明的CH1、 CH2、CH3、铰链及CL结构域中的一个或多个的片段。举例来说，Fc融合物是Fc区(CH2和CH3，任选地带有铰链区)与另一蛋白质融 合的融合物。本领域中已知多种Fc融合物，并且其可以通过添加本 发明的异二聚化变体加以改进。在本发明的情形中，可以利用本文所 描述的异二聚化变体的任何组合制备出包含CH1；CH1、CH2及CH3；CH2；CH3；CH2和CH3；CH1和CH3的抗体融合物，其中任一个 或全部可以任选地具有铰链区。

在本发明的一些实施方案中，一个单体包括了包含连接至Fc结 构域的scFV的重链，而另一单体包括了包含连接至Fc结构域的Fab 的重链(例如“典型”重链)，及轻链。如本文所使用，“Fab”或“Fab区” 意思指包含VH、CH1、VL及CL免疫球蛋白结构域的多肽。Fab可以指分离的这一区域，或处于全长抗体环境中的这一区域、抗体片段 或Fab融合蛋白。如本文所使用，“Fv”或“Fv片段”或“Fv区”意思指 包含单一抗体的VL和VH结构域的多肽。

嵌合抗体及人源化抗体

在一些实施方案中，抗体可以是来自例如嵌合抗体和/或人源化 抗体不同物种的混合物。一般来说，“嵌合抗体”和“人源化抗体”是指 组合来自超过一种物种的区域的抗体。举例来说，“嵌合抗体”传统上 包含来自小鼠(或在一些情形中，大鼠)的可变区和来自人类的恒定 区。“人源化抗体”一般是指可变结构域构架区与人类抗体中所见序列交换的非人类抗体。一般来说，在人源化抗体中，除CDR外的整个 抗体是由人类来源的多核苷酸编码或除在其CDR内外，与此类抗体 的一致。这些CDR的一部分或全部是由源于非人类生物体的核酸编 码，将其移植到人类抗体可变区的β-折叠构架中以产生抗体，该抗体 的特异性是由移植的CDR决定。此类抗体的产生描述于例如WO 92/11018；Jones，1986，Nature 321：522-525；Verhoeyen等人，1988， Science 239：1534-1536中，全部以引用的方式整体并入。通常需要所选受体构架残基“回复突变”成相应的供体残基以重新得到最初移植 的构建体中丧失的亲和力(US 5530101；US 5585089；US 5693761； US 5693762；US 6180370；US5859205；US 5821337；US 6054297； US 6407213，全部以引用的方式整体并入)。人源化抗体还任选包含 免疫球蛋白恒定区的至少一部分，典型地包含人类免疫球蛋白恒定区 的至少一部分，并因此典型地包含人类Fc区。人源化抗体也可以使 用免疫系统经过遗传工程改造的小鼠产生。Roque等人，2004， Biotechnol.Prog.20：639-654，以引用的方式整体并入。本领域众所周 知使非人类抗体人源化和重构的多种技术和方法(参见Tsurushita&Vasquez，2004，Humanization of Monoclonal Antibodies，Molecular Biology of BCells，533-545，Elsevier Science(USA)，及其中引用的参 考文献，全部以引用的方式整体并入)。人源化方法包括但不限于以 下文献中所描述的方法：Jones等人，1986，Nature321：522-525；Riechmann等人，1988；Nature 332：323-329；Verhoeyen等人，1988，Science，239：1534-1536；Queen等人，1989，Proc Natl Acad Sci，USA 86：10029-33；He等人，1998，J.Immunol.160：1029-1035；Carter等人， 1992，Proc Natl Acad Sci USA 89：4285-9；Presta等人，1997，Cancer Res. 57(20)：4593-9；Gorman等人，1991，Proc.Natl.Acad.Sci.USA 88：4181-4185；O’Connor等人，1998，Protein Eng 11：321-8，全部以引 用的方式整体并入。人源化或降低非人类抗体可变区免疫原性的其它 方法可以包括表面重塑法，如例如Roguska等人，1994，Proc.Natl. Acad.Sci.USA 91：969-973(以引用的方式整体并入)中所描述。在一个 实施方案中，如本领域中所知，亲本抗体经历亲和力成熟。可以采用 基于结构的方法进行人源化和亲和力成熟，如例如USSN 11/004,590 中所描述。可以采用基于选择的方法使抗体可变区人源化和/或亲和 力成熟，包括但不限于以下文献中所描述的方法：Wu等人，1999，J. Mol.Biol.294：151-162；Baca等人，1997，J.Biol.Chem. 272(16)：10678-10684；Rosok等人，1996，J.Biol.Chem.271(37)： 22611-22618；Rader等人，1998，Proc.Natl.Acad.Sci.USA 95： 8910-8915；Krauss等人，2003，Protein Engineering 16(10)：753-759，全部以引用的方式整体并入。其它人源化方法可以涉及仅部分CDR的 移植，包括但不限于USSN 09/810,510；Tan等人，2002，J.Immunol.169：1119-1125；De Pascalis等人，2002，J.Immunol.169：3076-3084中所 描述的方法，全部以引用的方式整体并入。

多特异性抗体构建体

本领域技术人员应理解并且如以下更完整地论述，本发明的异二聚体融合蛋白呈多种构型，其中图8B中所示的优选实施方案为“三F”构建体。

异二聚体重链恒定区

因此，本发明基于使用含有变体重链恒定区作为第一结构域的单 体提供异二聚体蛋白质。“单体”在本文中意思指异二聚体蛋白质的一 半。应注意，传统的抗体实际上是四聚体(两条重链和两条轻链)。在本发明的上下文中，一个重链-轻链对(如果适用，例如，如果单体包 含Fab)被视为“单体”。类似地，包含scFv的重链区被视为单体。基本上，每个单体包含足够的重链恒定区以允许异二聚化工程改造，不 管是全部恒定区，例如Ch1-铰链-CH2-CH3；Fc区(CH2-CH3)；还是 仅仅CH3结构域。

变体重链恒定区可以包含重链恒定区的全部或一部分，包括全长 构建体、CH1-铰链-CH2-CH3，或其部分，包括例如CH2-CH3或单 独CH3。此外，每个单体的重链区可以是相同主链(CH1-铰链 -CH2-CH3或CH2-CH3)或不同主链。该定义内还包括N末端和C末 端截短和添加；例如，一些pI变体包括在重链结构域的C末端添加 带电氨基酸。

因此，一般说来，本发明的“三F”构建体的一个单体是(scFv区- 铰链-Fc结构域)，并且另一个是(VH-CH1-铰链-CH2-CH3加相连的轻 链)，及异二聚化变体，包括空间变体和pI变体、Fc和FcRn变体， 以及这些区域中包括的另外的抗原结合结构域(任选带有连接子)。

除本文略述的异二聚化变体(例如空间变体和pI变体)外，重链区 还可以含有另外的氨基酸取代，包括如下文所论述的改变FcγR和 FcRn结合的变化。

此外，一些单体可以利用连接子用于“开瓶器”的scFv部分。在 三F形式中，使用了一个带电scFv连接子。如本文所述，取决于针对靶抗原的scFv的固有pI以及针对另一靶抗原的Fab的固有pI，带 电scFv连接子可以是带正电或带负电的。在双scFv形式中，在一个单体(带正电或带负电的)或两个单体(一个带正电并且一个带负电)上 使用单一带电scFv连接子。在这一实施方案中，两个连接子各自的 电荷无需相同(例如，一个是+3，而另一个是-4等)。

在一个实施方案中，抗CD3抗原结合位点是scFv，并且包括带 正电的scFv连接子。作为替代，抗CD38抗原结合位点可以是“开瓶 器”构建体的scFv。

异二聚化变体包括多种不同类型的变体，包括但不限于，空间变 体(包括带电变体)和pI变体，这些变体可以任选并且独立地与任何其 它变体组合。在这些实施方案中，“单体A”与“单体B”相配很重要； 也就是说，如果异二聚体蛋白质基于空间变体和pI变体，那么这些 需要与每个单体正确地相配：例如，起作用的空间变体集合(单体A 上的1个集合，单体B上的1个集合)与pI变体集合(单体A上的1 个集合，单体B上的1个集合)组合，由此使每个单体上的变体被设 计用于实现期望的功能。在例如空间变体也可以改变电荷的情况下， 正确集合需与正确单体相配。

值得注意的是，本文略述的异二聚化变体(例如，包括但不限于 附图中所示的那些变体)可以任选并且独立地与任何其它变体并且在 任何其它单体上组合。因此，例如，来自一个附图的单体1的pI变 体可以添加至不同附图中的单体1或来自单体2的其它异二聚化变体 上。也就是说，对于异二聚化很重要的是，存在变体“集合”，一个集 合是针对一个单体，并且一个集合是针对另一单体。这些集合是来自图1与1(例如，单体1清单可以相配)还是变换(单体1的pI变体与单 体2的空间变体)的组合并无关系。然而，如本文所述，当如以上所 略述进行组合时，“链型”应得到保留，由此有利于异二聚化；例如， 增加pI的带电变体应与增加的pI变体和/或具有增加的pI的scFv连 接子一起使用等。另外，对于另外的Fc变体(如对于FcγR结合、FcRn 结合、切除变体等)来说，任一单体或两个单体可以任选并独立地包 括所列变体中的任一种。在一些情形中，两个单体都具有另外的变体并且在一些情形中，仅一个单体具有另外的变体，或这些变体可以组 合。

异二聚化变体

本发明例如在如图8B中所描绘的“三F”或“开瓶器”支架上提供 多特异性抗体形式。

空间变体

在一些实施方案中，通过添加空间变体可以促进异二聚体的形 成。也就是说，通过改变每个重链中的氨基酸，不同重链缔合形成异 二聚体结构的可能性高于形成具有相同Fc氨基酸序列的同二聚体。 适合空间变体示于附图中。

一种机制一般在本领域中称为“钮与孔”，还可以任选使用提到的 氨基酸工程改造以产生有利于异二聚体形成，而不利于同二聚体形成 的空间影响；这有时称为“钮与孔”，如USSN 61/596,846；Ridgway 等人，Protein Engineering 9(7)：617(1996)；Atwell等人，J.Mol.Biol.1997 270：26；美国专利号8,216,805中所描述，其全部以引用的方式 整体并入本文中。图4和5(下文进一步描述)标识众多基于“钮与孔” 的“单体A-单体B”对。此外，如Merchant等人，Nature Biotech.16：677 (1998)中所描述，这些“钮与孔”突变可以与二硫键组合以偏向形成异 二聚化。

用于产生异二聚体的另一机制有时称为静电镶饰，如 Gunasekaran等人，J.Biol.Chem.285(25)：19637(2010)(以引用的方式 整体并入本文中)所描述。这在本文中有时称为“电荷对”。在这一实施方案中，使用了静电试剂来使形成偏向异二聚化。本领域技术人员 应理解，这些还可能影响pI，并由此影响纯化，因此在一些情形中也可以视为pI变体。然而，由于这些静电试剂强迫异二聚化并且不被 用作纯化工具，故其被归类为“空间变体”。这些包括但不限于，附图 中产生超过75％异二聚化的变体，如D221E/P228E/L368E与D221R/P228R/K409R的配对(例如，这些是“单体对应集合”)及 C220E/P228E/368E与C220R/E224R/P228R/K409R的配对。

另外的单体A和单体B变体可以任选并且独立地以任何量与其 它变体组合，如本文略述的pI变体，或US 2012/0149876的图37中 所示的其它空间变体，该案的附图和图例以引用的方式明确地并入本 文中。

在一些实施方案中，本文略述的空间变体可以任选并且独立地与 包括pI变体(或其它变体，如Fc变体、FcRn变体、切除变体等)在内 的任何异二聚化变体一起并入一个或两个单体中。

异二聚体的pI(等电点)变体

一般来说，本领域技术人员应理解，存在两个通用类别的pI变 体：增加蛋白质pI(碱性变化)的变体及降低蛋白质pI(酸性变化)的变 体。如本文所描述，这些变体的所有组合都可以进行：一个单体可以是野生型，或是pI与野生型无显著不同的变体，并且另一单体可以 是偏碱性或偏酸性的。作为替代，每个单体是变化的，一个偏碱性并 且一个偏酸性。

优选的pI变体组合示于附图中。

重链酸性pI变化

因此，当使包含变体重链恒定结构域的一个单体正值更大(例如， 降低pI)时，可以进行以下取代中的一个或多个：S119E、K133E、 K133Q、T164E、K205E、K205Q、N208D、K210E、K210Q、K274E、 K320E、K322E、K326E、K334E、R355E、K392E、K447缺失、在 c末端添加肽DEDE、G137E、N203D、K274Q、R355Q、K392N及 Q419E。如本文所略述并且如附图中所示，这些变化是相对于IgG1 显示，但所有同型以及同型混合物可以按此方式改变。

在重链恒定结构域来自IgG2-4的情况下，还可以使用R133E和 R133Q。

碱性pI变化

因此，当使包含变体重链恒定结构域的一个单体负值更大(例如， 增加pI)时，可以进行以下取代中的一个或多个：Q196K、P217R、 P228R、N276K及H435R。如本文所略述并且如附图中所示，这些变 化是相对于IgG1显示，但所有同型以及同型混合物可以按此方式改变。

抗体异二聚体轻链变体

就基于抗体的异二聚体来说，例如在至少一个单体除重链结构域 外还包含轻链的情况下，也可以在轻链中产生pI变体。降低轻链pI 的氨基酸取代包括但不限于，K126E、K126Q、K145E、K145Q、N152D、 S156E、K169E、S202E、K207E及在轻链c末端添加肽DEDE。在这一类别中基于恒定λ轻链的变化包括R108Q、Q124E、K126Q、N138D、 K145T及Q199E中的一个或多个取代。此外，还可以增加轻链的pI。

同型变体

此外，本发明的许多实施方案是基于一种IgG同型中特定位置处 的pI氨基酸“输入”另一同型中，由此减小或消除不想要的免疫原性 被引入变体中的可能性。也就是说，出于多种原因，包括高效应功能， IgG1是治疗性抗体的常见同型。然而，IgG1的重链恒定区的pI高于 IgG2(8.10对7.31)。通过将IgG2在特定位置处的残基引入IgG1主链 中，使所得单体的pI降低(或增加)并且另外展现较长的血清半衰期。举例来说，IgG1在137位具有甘氨酸(pI 5.97)，而IgG2具有谷氨酸 (pI 3.22)；输入谷氨酸将影响所得蛋白质的pI。如以下所描述，一般 需要多个氨基酸取代来显著影响变体抗体的pI。然而，应注意，如以 下所论述，甚至IgG2分子的变化也能够增加血清半衰期。

在其它实施方案中，进行非同型氨基酸变化，以降低所得蛋白质 的总体电荷状态(例如通过将pI较高的氨基酸变为pI较低的氨基酸)， 或实现结构适应性以得到稳定性等，下文将更进一步描述。

此外，通过对重链和轻链恒定结构域进行pI工程改造，可以见 到异二聚体每个单体的显著变化。如本文所论述，两个单体的pI相 差至少0.5可以允许通过离子交换色谱法或等电聚焦，或对等电点敏感的其它方法进行分离。

等排变体

此外，如图47中所示，可以制备等排pI变体，例如尺寸与亲本 氨基酸大致相同的电荷变体。

计算pI

每个单体的pI可以取决于变体重链恒定结构域的pI及包括变体 重链恒定结构域和融合搭配物在内的总单体的pI。因此，在一些实施 方案中，基于变体重链恒定结构域，使用附图中的表计算pI的变化。 作为替代，可以比较每个单体的pI。类似地，计算“起始”可变区(例 如scFv或Fab)的pI以了解哪个单体将在哪一方向上工程改造。

另外赋予更佳FcRn体内结合的pI变体

在pI变体降低单体的pI的情况下，其可以具有改善体内血清保 持的附加益处。

尽管仍有待检验，但相信Fc区在体内具有较长半衰期，因为在 pH 6下与FcRn在核内体中的结合隔离Fc(Ghetie和Ward，1997 Immunol Today.18(12)：592-598，以引用的方式整体并入)。核内体区 室接着使Fc再循环至细胞表面。一旦该区室向细胞外空间开放，则较高的pH值，约7.4，诱导Fc释放回血液中。在小鼠中，Dall’Acqua 等人显示，在pH 6和pH7.4下FcRn结合增加的Fc突变体实际上具 有降低的血清浓度以及与野生型Fc相同的半衰期(Dall’Acqua等人， 2002，J.Immunol.169：5171-5180，以引用的方式整体并入)。在pH7.4 下Fc对FcRn的亲和力增加被认为禁止Fc释放回血液中。因此，增 加Fc体内半衰期的Fc突变理想地将增加在较低pH值下FcRn的结 合，同时仍允许在较高pH值下释放Fc。氨基酸组氨酸在6.0至7.4 的pH值范围内改变其电荷状态。因此，在Fc/FcRn复合体的重要位 置处发现His残基在意料之中。

近来，已提出可变区具有较低等电点的抗体也可能具有较长的血 清半衰期(Igawa等人，2010PEDS.23(5)：385-392，以引用的方式整体 并入)。不过，这一机制仍有待了解。此外，可变区随抗体而不同。 具有较低pI和较长半衰期的恒定区变体将提供一种改善抗体的药物 动力学特性的更具模块化的方法，如本文所论述。

用于本实施方案中的pI变体以及其在纯化优化方面的用途公开 于附图中。

变体的组合

本领域技术人员应理解，所阐述的所有异二聚化变体可以任选并 且独立地以任何方式组合，只要其保持其“链型”或“单体区分”即可。 此外，所有这些变体都可以组合成任何异二聚化形式。

就pI变体来说，尽管附图中显示了特别适用的实施方案，但遵 循改变两个单体之间的pI差异以促进纯化的基本原则，也可以产生 其它实施方案。

本发明的抗体一般是分离的或重组的。“分离的”当用于描述本文 所公开的各种多肽时，意思指多肽经过鉴别并且从表达多肽的细胞或细胞培养物分离和/或回收。通常，分离的多肽是通过至少一个纯化 步骤制备。“分离的抗体”是指抗体基本上不含具有不同抗原特异性的 其它抗体。

“特异性结合”或“特异性结合至”特定抗原或表位，或对特定抗原 或表位“具有特异性”意思指与非特异性相互作用明显不同的结合。特 异性结合可以例如通过测定一个分子的结合与对照分子的结合的差 异来测量，对照分子一般是结构类似但不具有结合活性的分子。举例 来说，特异性结合可以通过与类似于靶标的对照分子竞争来测定。

针对特定抗原或表位的特异性结合可以例如通过抗体针对抗原 或表位的至少约10-4M、至少约10-5M、至少约10-6M、至少约10-7 M、至少约10-8M、至少约10-9M，或至少约10-10M、至少约10-11 M、至少约10-12M或更高的KD来展现，其中KD是指特定抗体- 抗原相互作用的解离速率。典型地，特异性结合抗原的抗体的KD是 对照分子相对于该抗原或表位的KD的20、50、100、500、1000、 5,000、10,000或更高倍数。

另外，针对特定抗原或表位的特异性结合可以例如通过抗体针对 抗原或表位的KA或Ka是该表位相对于对照物的KA或Ka的至少 20、50、100、500、1000、5,000、10,000或更高倍数来展现，其中 KA或Ka是指特定抗体-抗原相互作用的缔合速率。

修饰的抗体

除以上略述的修饰外，还可以进行其它修饰。举例来说，可以通 过并入二硫桥连接VH和VL结构域来使分子稳定(Reiter等人，1996， Nature Biotech.14：1239-1245，以引用的方式整体并入)。此外，如下 文所略述，可以对抗体进行多种共价修饰。

抗体的共价修饰包括在本发明的范围内，并且一般(但不总是)在 翻译后进行。举例来说，通过使抗体的特定氨基酸残基与有机衍生化 试剂反应，将若干类型的抗体共价修饰引入分子中，该衍生化试剂能 够与所选侧链或者N末端或C末端残基反应。

半胱氨酰基残基最常与α-卤代乙酸酯(及相应胺)，如氯代乙酸或 氯代乙酰胺反应，得到羧甲基或羧酰胺基甲基衍生物。半胱氨酰基残 基还可以通过与溴代三氟丙酮、α-溴代-β-(5-咪唑基)丙酸、氯乙酰基 磷酸酯、N-烷基k丁烯二酰亚胺、3-硝基-2-吡啶基二硫化物、甲基 2-吡啶基二硫化物、对氯苯甲酸汞、2-氯汞-4-硝基苯酚或氯代-7-硝基 苯并-2-氧杂-1，3-二唑等反应来进行衍生化。

此外，在半胱氨酸处的修饰特别适用于抗体-药物缀合物(ADC) 应用(下文进一步描述)。在一些实施方案中，抗体恒定区可以工程改 造成含有一个或多个特别具有“硫醇反应性”的半胱氨酸，由此使药物 部分更具特异性以及控制性放置。参见例如美国专利号7,521,541，以引用的方式整体并入本文中。

组氨酰基残基通过与焦碳酸二乙酯在pH 5.5-7.0下反应进行衍生 化，因为这一试剂对组氨酰基侧链具有相对较高特异性。对溴苯甲酰 甲基溴也是有用的；反应优选在pH6.0下于0.1M二甲胂酸钠中进行。

赖氨酰基和氨基末端残基与琥珀酸酐或其它羧酸酐反应。用这些 试剂进行衍生化具有逆转赖氨酰基残基的电荷的作用。用于使含α- 氨基的残基衍生化的其它适合试剂包括酰亚胺酯，如甲基吡啶亚胺甲 酯；磷酸吡哆醛；吡哆醛；氯代硼氢化物；三硝基苯磺酸；O-甲基异 脲；2，4-戊二酮；及转氨酶催化的与乙醛酸的反应。

精氨酰基残基通过与一种或若干常规试剂反应进行修饰，这些试 剂中有苯甲酰甲醛、2，3-丁二酮、1，2-环己二酮及茚三酮。使精氨酸 残基衍生化需要反应在碱性条件下进行，因为胍官能团的pKa较高。 此外，这些试剂可以与赖氨酸的基团以及精氨酸ε-氨基反应。

可以对酪氨酰基残基进行特殊修饰，其中特别值得关注的是，通 过与芳香族重氮盐化合物或四硝基甲烷反应将光谱标记引入酪氨酰 基残基中。最常见的是，使用N-乙酰咪唑和四硝基甲烷分别形成O- 乙酰基酪氨酰基物质和3-硝基衍生物。使用125I或131I使酪氨酰基残基碘化以制备标记的蛋白质用于放射免疫检定中，以上描述的氯胺 T法是适合的。

羧基侧基(天冬氨酰基或谷氨酰基)通过与碳化二亚胺 (R’-N＝C＝N--R’)反应进行选择性修饰，其中R和R’是任选不同的烷 基，如1-环己基-3-(2-吗啉基-4-乙基)碳化二亚胺或1-乙基-3-(4-氮-4，4- 二甲基戊基)碳化二亚胺。此外，天冬氨酰基和谷氨酰基通过与铵离 子反应而转化成天冬酰胺酰基和谷氨酰胺酰基残基。

用双官能试剂进行衍生化适用于使抗体与不溶于水的载体基质 或表面交联以用于包括以下所描述的方法在内的多种方法中。常用交 联剂包括例如1，1-双(重氮乙酰基)-2-苯基乙烷、戊二醛、N-羟基琥珀 酰亚胺酯，例如与4-叠氮基水杨酸形成的酯、同双官能酰亚胺酯，包 括二琥珀酰亚胺基酯，如3，3’-二硫代双(琥珀酰亚胺基丙酸酯)，及双 官能顺丁烯二酰亚胺，如双-N-顺丁烯二酰亚胺基-1，8-辛烷。衍生化 试剂，如甲基-3-[(对叠氮基苯基)二硫基]亚胺丙酸酯得到能够在光存 在下形成交联的可光活化的中间体。作为替代，采用了不溶于水的反 应性基质，如cynomolgusogen bromide活化的碳水化合物及美国专利 号3,969,287、3,691,016、4,195,128、4,247,642、4,229,537及4,330,440(全部以引用的方式整体并入)中描述的反应性基质进行蛋 白质固定。

谷氨酰胺酰基和天冬酰胺酰基残基常常分别脱去酰胺基，得到相 应的谷氨酰基和天冬氨酰基残基。作为替代，这些残基在微酸性条件 下脱去酰胺基。这些残基的任一形式都在本发明的范围内。

其它修饰包括脯氨酸和赖氨酸的羟基化；丝氨酰基或苏氨酰基残 基的羟基的磷酸化；赖氨酸、精氨酸及组氨酸侧链的α-氨基的甲基化 (T.E.Creighton，Proteins：Structure and Molecular Properties，W.H. Freeman&Co.，San Francisco，第79-86页[1983]，以引用的方式整体 并入)；N末端胺的乙酰化；及任何C末端羧基的酰胺化。

此外，本领域技术人员应理解，标记(包括荧光标记、酶标记、 磁性标记、放射性标记等)都可以添加至抗体(以及本发明的其它组合物)中。

糖基化

另一类共价修饰是糖基化的改变。在另一实施方案中，本文所公 开的抗体可以被修饰成包括一个或多个工程改造的糖型。如本文所使 用，“工程改造的糖型”意思指共价附接到抗体的碳水化合物组合物， 其中所述碳水化合物组合物在化学上不同于亲本抗体。工程改造的糖 型可以用于多种目的，包括但不限于，增强或减弱效应功能。工程改造的糖型的一种优选形式是脱岩藻糖基化，经显示，其可能通过与 FcγRIIIa受体更紧密结合而与ADCC功能增加相关。在这一情形中， “脱岩藻糖基化”意思指，宿主细胞中产生的大部分抗体基本上不含岩 藻糖，例如产生的抗体中有90％、95％、98％不具有明显的岩藻糖作为抗体碳水化合物部分的组分(一般附接在Fc区中的N297位)。在功 能上定义，脱岩藻糖基化的抗体一般对FcγRIIIa受体展现至少50％ 或更高亲和力。

工程改造的糖型可以通过本领域中已知的多种方法产生(等人，1999，NatBiotechnol17：176-180；Davies等人，2001，Biotechnol Bioeng 74：288-294；Shields等人，2002，J Biol Chem 277：26733-26740； Shinkawa等人，2003，J Biol Chem 278：3466-3473；US 6,602,684；USSN 10/277,370；USSN 10/113,929；PCT WO 00/61739A1；PCT WO01/29246A1；PCT WO 02/31140A1；PCT WO 02/30954A1，全部以引 用的方式整体并入；(技术[Biowa，Inc.，Princeton，NJ]；/>糖基化工程改造技术[Glycart Biotechnology AG， Zürich， Switzerland])。这些技术中有许多是基于例如通过在工程改造或其它方式处理的各种生物体或细胞株(例如Lec-13 CHO细胞或大鼠杂交瘤YB2/0细胞)中表达IgG，通过调控糖基化路径中所涉及的酶(例如， FUT8[α1，6-岩藻糖基转移酶]和/或(β1-4-N-乙酰葡糖胺基转移酶III [GnTIll])，或通过在表达IgG之后对碳水化合物进行修饰来控制岩藻 糖化程度和/或对分共价附接至Fc区的寡糖。举例来说，Seattle Genetics的“糖工程改造的抗体”或“SEA技术”通过添加在制造期间抑 制岩藻糖基化的经修饰糖来起作用；参见例如20090317869，以引用 的方式整体并入本文中。工程改造的糖型典型地是指不同碳水化合物或寡糖；由此，抗体可以包括工程改造的糖型。

作为替代，工程改造的糖型可以指包含不同碳水化合物或寡糖的 IgG变体。如本领域中所知，糖基化模式可以取决于蛋白质的序列(例 如存在或不存在特定糖基化氨基酸残基，如下文所论述)，或产生该 蛋白质的宿主细胞或生物体。特定表达系统论述于下。

多肽的糖基化典型地是N-连接或O-连接的。N-连接是指碳水化 合物部分附接至天冬酰胺残基的侧链。三肽序列天冬酰胺-X-丝氨酸 和天冬酰胺-X-苏氨酸(其中X是除脯氨酸外的任何氨基酸)是将碳水 化合物部分酶促附接至天冬酰胺侧链的识别序列。因此，在多肽中这 些三肽序列中任一种的存在产生了潜在的糖基化位点。O-连接的糖基 化是指糖N-乙酰半乳糖胺、半乳糖或木糖之一附接至羟基氨基酸，最常见是丝氨酸或苏氨酸，不过也可以使用5-羟基脯氨酸或5-羟基 赖氨酸。

在抗体中添加糖基化位点通常是通过改变氨基酸序列，以使其含 有上述三肽序列中的一个或多个来实现(对于N-连接的糖基化位点)。 还可以通过起始序列中一个或多个丝氨酸或苏氨酸残基的添加或取 代来进行改变(对于O-连接的糖基化位点)。为便利起见，优选通过在 DNA水平上的变化，特别是通过使编码靶多肽的DNA在预先选择的 碱基处突变，由此产生会翻译成期望的氨基酸的密码子，来改变抗体氨基酸序列。

增加抗体上碳水化合物部分的数量的另一种方式是糖苷与蛋白 质的化学或酶促偶合。这些工序的优势在于，其不需要在具有进行 N-连接和O-连接糖基化的糖基化能力的宿主细胞中产生蛋白质。取 决于所用偶合模式，糖可以附接至(a)精氨酸和组氨酸；(b)游离羧基； (c)游离硫氢基，如半胱氨酸的硫氢基；(d)游离羟基，如丝氨酸、苏 氨酸或羟基脯氨酸的羟基；(e)芳香族残基，如苯丙氨酸、酪氨酸或色 氨酸的芳香族残基；或(f)谷氨酰胺的酰胺基团。这些方法描述于WO 87/05330及Aplin和Wriston，1981，CRCCrit.Rev.Biochem.，第 259-306页中，二者以引用的方式整体并入。

去除起始抗体上存在的碳水化合物部分(例如翻译后)可以通过 化学方式或酶促方式实现。化学脱糖基化需要使蛋白质暴露于化合物 三氟甲烷磺酸，或等效化合物。这一处理使得除连接糖(N-乙酰葡糖 胺或N-乙酰半乳糖胺)外的大部分或所有糖裂解，而多肽保持完整。 化学脱糖基化描述于Hakimuddin等人，1987，Arch.Biochem.Biophys. 259：52及Edge等人，1981，Anal.Biochem.118：131(都以引用的方式整 体并入)中。可以通过使用Thotakura等人，1987，Meth.Enzymol.138：350(以引用的方式整体并入)所描述的多种内切和外切糖苷酶来 酶促裂解多肽上的碳水化合物部分。如Duskin等人，1982，J.Biol.Chem.257：3105(以引用的方式整体并入)所描述，使用化合物衣霉素 可以防止在潜在的糖基化位点处发生糖基化。衣霉素阻止蛋白质-N-糖苷键联的形成。

另一类抗体共价修饰包含以例如2005-2006 PEG Catalog from NektarTherapeutics(可见于Nektar网站)；美国专利4,640,835、4,496,689、4,301,144、4,670,417、4,791,192或4,179,337(全部以引用 的方式整体并入)中陈述的方式，将抗体连接至各种非蛋白质聚合物， 包括但不限于，各种多元醇，如聚乙二醇、聚丙二醇或聚氧化烯。此外，如本领域中所知，可以在抗体内的各种位置进行氨基酸取代以促 进如PEG等聚合物的添加。参见例如，美国公布号2005/0114037A1，以引用的方式整体并入。

用于另外的功能的另外的Fc变体

除pI氨基酸变体外，出于多种原因，包括但不限于，改变与一 种或多种FcγR受体的结合、改变与FcRn受体的结合等，还可以进 行众多有用的Fc氨基酸修饰。

因此，本发明的蛋白质可以包括氨基酸修饰，包括本文略述的异 二聚化变体，这些变体包括pI变体。

FcγR变体

因此，可以进行众多有用的Fc取代以改变与一种或多种FcγR受 体的结合。使结合增加以及使结合减少的取代可以是有用的。举例来 说，已知增加与Fc RIIIa的结合一般引起ADCC(抗体依赖性细胞介 导的细胞毒性；在这种细胞介导的反应中，表达FcγR的非特异性细 胞毒性细胞识别靶细胞上结合的抗体，随后引起靶细胞的溶解)增加。 类似地，在一些情况下，降低与FcγRIIb(抑制性受体)的结合也是有 益的。用于本发明中的氨基酸取代包括USSN 11/124,620(特别是图 41)、11/174,287、11/396,495、11/538,406中所列的取代，全部以引用 的方式以其全文并且特别是关于本文公开的变体明确地并入本文中。 所用特定变体包括但不限于，236A、239D、239E、332E、332D、 239D/332E、267D、267E、328F、267E/328F、236A/332E、 239D/332E/330Y、239D、332E/330L及299T。

此外，如USSN 12/341,769(以引用的方式整体并入本文中)中特 别公开的，有另外的Fc取代可用于增加与FcRn受体的结合并增加 血清半衰期，包括但不限于，434S、428L、308F、259I、428L/434S、 259I/308F、436I/428L、436I或V/434S、436V/428L及259I/308F/428L。

Fc切除变体

用于本发明中的另外的变体是切除(例如减少或除去)与Fcγ受体 的结合的变体。这将是减少本发明的异二聚体抗体的潜在作用机制 (例如降低ADCC活性)所希望的。众多适合的Fc切除变体描绘于图 35中，并且可以任选并独立地包括或不包括与任何其它异二聚化变体(包括pI变体和空间变体)的组合。

在一些实施方案中，特别使用含有pI变体N208D/Q295E/N384D /Q418E/N421D、偏向变体368D/370S及切除变体E233P/L234V/L235 A/G236del/S267K的第一单体(“负侧”)与不包含pI变体、偏向变体S 364K/E357Q及切除变体E233P/L234V/L235A/G236del/S267K的正侧 的配对(任选两个单体都含有FcRn变体428L/434S)，其中正侧是scF v单体并含有带电scFv连接子(特别是在scFv是抗CD3时)。第二个 实施方案利用了包含I199T/N203D/K274Q/R355Q/Q419E/K447del、偏向变体S364K/E357Q及切除变体E233P/L234V/L235A/G236del/S267 K的第一负侧单体(任选两个单体都含有FcRn变体428L/434S)与包含 pI变体Q196K/I199T/P271R/P228R/N276K、偏向变体S364K/E357Q 及切除变体E233P/L234V/L235A/G236del/S267K的正侧(任选两个单 体都含有FcRn变体428L/434S)的配对，其中正侧是scFv单体并含有 带电scFv连接子(特别是在scFv是抗CD3时)。第三个实施方案利用了包含I199T/N203D/K274Q/R355Q/N384S/K392N/V397M/Q419E/K4 47del、偏向变体S364K/E357Q及切除变体E233P/L234V/L235A/G23 6del/S267K的第一负侧单体(任选两个单体都含有FcRn变体428L/43 4S)与不具有pI变体、偏向变体S364K/E357Q及切除变体E233P/L234V/L235A/G236del/S267K的正侧单体(任选两个单体都含有FcRn变 体428L/434S)的配对，其中正侧是scFv单体并含有带电scFv连接子 (特别是在scFv是抗CD3时)。第四个实施方案利用了含有pI变体N 208D/Q295E/N384D/Q418E/N421D、偏向变体368D/370S及切除变体 E233P/L234V/L235A/G236del/S239K的第一单体(“负侧”)与不包含pI 变体、偏向变体S364K/E357Q及切除变体E233P/L234V/L235A/G23 6del/S239K的正侧(任选两个单体都含有FcRn变体428L/434S)的配 对。第五个实施方案利用了包含I199T/N203D/K274Q/R355Q/Q419E/K447del、偏向变体S364K/E357Q及切除变体E233P/L234V/L235A/ G236del/S239K的第一负侧单体(任选两个单体都含有FcRn变体428 L/434S)与包含pI变体Q196K/I199T/P271R/P228R/N276K、偏向变体 S364K/E357Q及切除变体E233P/L234V/L235A/G236del/S239K的正侧(任选两个单体都含有FcRn变体428L/434S)的配对。第六个实施方 案利用了包含1199T/N203D/K274Q/R355Q/N384S/K392N/V397M/Q4 19E/K447del、偏向变体S364K/E357Q及切除变体E233P/L234V/L23 5A/G236del/S267K的第一负侧单体(任选两个单体都含有FcRn变体428L/434S)与包含偏向变体S364K/E357Q及切除变体E233P/L234V/L 235A/G236del/S239K的正侧单体(任选两个单体都含有FcRn变体42 8L/434S)的配对，其中正侧是scFv单体并含有带电scFv连接子(特别 是在scFv是抗CD3时)。第七个实施方案利用了含有pI变体N208D/ Q295E/N384D/Q418E/N421D、偏向变体368D/370S及切除变体S239 K/S267K的第一单体(“负侧”)与不包含pI变体、偏向变体S364K/E35 7Q及切除变体S239K/S267K的正侧的配对(任选两个单体都含有Fc Rn变体428L/434S)，其中正侧是scFv单体并含有带电scFv连接子(特别是在scFv是抗CD3时)。第八个实施方案利用了包含I199T/N203D/K274Q/R355Q/Q419E/K447del、偏向变体S364K/E357Q及切除变 体S239K/S267K的第一负侧单体(任选两个单体都含有FcRn变体42 8L/434S)与包含pI变体Q196K/I199T/P271R/P228R/N276K、偏向变 体S364K/E357Q及切除变体S239K/S267K的正侧(任选两个单体都含有FcRn变体428L/434S)的配对，其中正侧是scFv单体并含有带电s cFv连接子(特别是在scFv是抗CD3时)。第九个实施方案利用了包含I199T/N203D/K274Q/R355Q/N384S/K392N/V397M/Q419E/K447de l、偏向变体S364K/E357Q及切除变体S239K/S267K的第一负侧单体(任选两个单体都含有FcRn变体428L/434S)与不具有pT变体、偏向 变体S364K/E357Q及切除变体S239K/S267K的正侧单体(任选两个单 体都含有FcRn变体428L/434S)的配对，其中正侧是scFv单体并含有 带电scFv连接子(特别是在scFv是抗CD3时)。第十个实施方案利用了含有pI变体N208D/Q295E/N384D/Q418E/N421D、偏向变体368D /370S及切除变体S267K/P329K的第一单体(“负侧”)与不包含pI变体、偏向变体S364K/E357Q及切除变体S267K/P329K的正侧的配对 (任选两个单体都含有FcRn变体428L/434S)，其中正侧是scFv单体 并含有带电scFv连接子(特别是在scFv是抗CD3时)。第十一个实施 方案利用了包含I199T/N203D/K274Q/R355Q/Q419E/K447del、偏向变体S364K/E357Q及切除变体S267K/P329K的第一负侧单体(任选两个 单体都含有FcRn变体428L/434S)与包含pI变体Q196K/I199T/P271R/P228R/N276K、偏向变体S364K/E357Q及切除变体S267K/P329K 的正侧(任选两个单体都含有FcRn变体428L/434S)的配对，其中正侧 是scFv单体并含有带电scFv连接子(特别是在scFv是抗CD3时)。 第12个实施方案利用了包含I199T/N203D/K274Q/R355Q/N384S/K392N/V397M/Q419E/K447del、偏向变体S364K/E357Q及切除变体S26 7K/P329K的第一负侧单体(任选两个单体都含有FcRn变体428L/434 S)与不具有pI变体、偏向变体S364K/E357Q及切除变体S267K/P32 9K的正侧单体(任选两个单体都含有FcRn变体428L/434S)的配对， 其中正侧是scFv单体并含有带电scFv连接子(特别是在scFv是抗C D3时)。

连接子

必要时，本发明还任选提供连接子，以例如增加另外的抗原结合 位点，如例如图11、12及13中所描绘，其中分子的“另一端”含有另 外的抗原结合组分。此外，如以下所略述，连接子还任选用于抗体药 物缀合物(ADC)系统中。当用于接合中心mAb-Fv构建体的组分时， 连接子一般是包含通过肽键接合的两个或更多个氨基酸残基的多肽 并且用于连接一种或多种本发明组分。此类连接子多肽是本领域中众所周知的(参见例如，Holliger，P.等人(1993)Proc.Natl.Acad.Sci.USA 90：6444-6448；Poljak，R.J.等人(1994)Structure2：1121-1123)。多种连 接子可以用于本文所描述的一些实施方案中。本领域技术人员应理解，本发明中使用至少三种不同的连接子类型。

“连接子”在本文中又称为“连接子序列”、“间隔子”、“系栓序列” 或其语法等效词。众所周知同双官能连接子或异双官能连接子(参见 1994 Pierce Chemical Companycatalog，有关交联剂的技术章节，第 155-200页，以引用的方式整体并入)。(注意“连接子”与“scFv连接子” 和“带电scFv连接子”之间的区别)。可以使用多种策略将分子共价连 接在一起。这些包括但不限于，蛋白质或蛋白质结构域的N末端与C 末端之间的多肽键联、经由二硫键进行的键联，及经由化学交联试剂 进行的键联。在本实施方案的一个方面，连接子是通过重组技术或肽 合成而产生的肽键。连接子肽主要可以包括以下氨基酸残基：Gly、Ser、Ala或Thr。连接子肽的长度应适于以一定方式连接两个分子使 得这些分子相对彼此呈现正确的构象，由此其保持期望的活性。在一 个实施方案中，连接子是约1至50个氨基酸长度，优选是约1至30 个氨基酸长度。在一个实施方案中，可以使用1至20个氨基酸长度 的连接子。有用的连接子包括甘氨酸-丝氨酸聚合物，包括例如(GS)n、 (GSGGS)n、(GGGGS)n及(GGGS)n，其中n是至少一的整数；甘氨 酸-丙氨酸聚合物；丙氨酸-丝氨酸聚合物；及其它柔性连接子。作为 替代，多种非蛋白质聚合物，包括但不限于，聚乙二醇(PEG)、聚丙 二醇、聚氧化烯，或聚乙二醇和聚丙二醇的共聚物，可以用作连接子， 也就是说，可以作为连接子使用。

其它连接子序列可以包括CL/CH1结构域的任何长度的任何序列，但非CL/CH1结构域的所有残基；例如CL/CH1结构域的前5-12 个氨基酸残基。连接子可以来源于免疫球蛋白轻链，例如Cκ或Cλ。 连接子可以来源于任何同型的免疫球蛋白重链，包括例如Cγ1、Cγ2、Cγ3、Cγ4、Cα1、Cα2、C8、Cε及Cμ。连接子序列还可以来源于其 它蛋白质，如类Ig蛋白质(例如TCR、FcR、KIR)、铰链区来源的序 列及来自其它蛋白质的其它天然序列。

抗体-药物缀合物

在一些实施方案中，本发明的多特异性抗体与药物缀合，形成抗 体-药物缀合物(ADC)。一般来说，ADC被用于肿瘤学应用中，其中 使用抗体-药物缀合物局部递送细胞毒性剂或细胞抑制剂允许将药物 部分靶向递送至肿瘤，由此实现更高功效、更低毒性等。有关此技术 的评述提供于Ducry等人，Bioconjugate Chem.，21：5-13(2010)；Carter 等人，Cancer J.14(3)：154(2008)；及Senter，Current Opin.Chem.Biol. 13：235-244(2009)中，全部以引用的方式整体并入本文中。

因此，本发明提供多特异性抗体与药物的缀合物。一般来说，缀 合是通过共价附接至抗体进行(如以下进一步描述)，并且一般依赖于 连接子，通常依赖于肽键联(如下文所描述，该键联可以设计成对蛋 白酶在靶位点处裂解敏感或不敏感)。此外，如以上所描述，连接子- 药物单元(LU-D)的键联可以通过附接至抗体内的半胱氨酸实现。本领 域技术人员应理解，每个抗体的药物部分数量可以取决于反应条件而 变化，并且可以在1∶1至10∶1的药物：抗体间变化。本领域技术人员 应理解，实际数量是平均值。

因此，本发明提供多特异性抗体与药物的缀合物。如以下所描述， ADC中的药物可以是多种药剂，包括但不限于，细胞毒性剂，如化 学治疗剂、生长抑制剂、毒素(例如细菌、真菌、植物或动物来源的 酶活性毒素，或其片段)或放射性同位素(即，放射性缀合物)。在其它实施方案中，本发明另外提供了使用ADC的方法。

用于本发明中的药物包括细胞毒性药物，特别是用于癌症疗法中 的那些。此类药物一般包括DNA损伤剂、抗代谢物、天然产物及其 类似物。细胞毒性剂的示例性类别包括酶抑制剂，如二氢叶酸还原酶 抑制剂及胸苷酸合成酶抑制剂；DNA嵌入剂；DNA裂解剂；拓扑异构酶抑制剂；蒽环霉素家族药物；长春碱类药物；丝裂霉素类；博莱 霉素类；细胞毒性核苷；蝶啶家族类药物；烯二炔类；鬼臼毒素类； 多拉司他汀类(dolastatins)；美登素类；分化诱导剂；及紫杉醇类。

这些类别的成员包括例如甲氨蝶呤、甲蝶呤、二氯甲氨蝶呤、5- 氟尿嘧啶、6-巯基嘌呤、胞嘧啶阿拉伯糖苷(cytosine arabinoside)、美 法仑、白诺生(leurosine)、鲁拉西酮(1eurosideine)、放射菌素、道诺霉素、阿霉素、丝裂霉素C、丝裂霉素A、洋红霉素(caminomycin)、氨 蝶呤、太利苏霉素(tallysomycin)、鬼臼毒素及鬼臼毒素衍生物如依托泊苷或磷酸依托泊苷、长春花碱、长春新碱、长春地辛、紫杉烷(包 括紫杉醇、泰诺帝(taxotere))、视黄酸、丁酸、N8-乙酰亚精胺、喜树 碱、卡里奇霉素(calicheamicin)、埃斯培拉霉素(esperamicin)、烯-二炔、 倍癌霉素A(duocarmycin A)、倍癌霉素SA、卡里奇霉素、喜树碱、 类美登素(maytansinoid)(包括DM1)、单甲基奥瑞他汀 E(monomethylauristatin E，MMAE)、单甲基奥瑞他汀F(MMAF)及类 美登素(DM4)，及其类似物。

所用毒素可以呈抗体-毒素缀合物形式并且包括细菌毒素如白喉 毒素、植物毒素如蓖麻毒素、小分子毒素如格尔德霉素(Mandler等 人(2000)J.Nat.Cancer Inst.92(19)：1573-1581；Mandler等人(2000)Bioorganic&Med.Chem.Letters 10：1025-1028；Mandler等人(2002) Bioconjugate Chem.13：786-791)、类美登素(EP 1391213；Liu等人(1996)Proc.Natl.Acad.Sci.USA 93：8618-8623)及卡里奇霉素(Lode等人 (1998)CancerRes.58：2928；Hinman等人(1993)Cancer Res. 53：3336-3342)。毒素可以通过包括微管蛋白结合、DNA结合或拓扑 异构酶抑制在内的机制发挥其细胞毒性和细胞抑制作用。

涵盖多特异性抗体与一种或多种小分子毒素的缀合物，这些小分 子毒素如类美登素、多拉司他汀、奥瑞他汀、单端孢霉烯、卡里奇霉 素及CC1065，以及这些毒素的具有毒素活性的衍生物。

类美登素

适合用作类美登素药物部分的美登素化合物是本领域中众所周 知的，并且可以根据已知方法从天然来源分离，使用基因工程改造技 术制备(参见Yu等人(2002)PNAS 99：7968-7973)或根据已知方法合成 制备美登醇和美登醇类似物。如以下所描述，可以通过并入功能活性 基团，如硫醇或胺基用于缀合抗体，来修饰药物。

示例性类美登素药物部分包括具有修饰的芳香族环的那些，如： C-19-脱氯(美国专利号4,256,746)(通过氢化锂铝还原安丝菌素 (ansamytocin)P2制备)；C-20-羟基(或C-20～脱甲基)+/-C-19-脱氯(美国 专利号4,361,650和4,307,016)(通过使用链球菌或放线菌脱甲基化， 或使用LAH脱氯来制备)；及C-20-脱甲氧基、C-20-酰氧基(--OCOR)+/-脱氯(美国专利号4,294,757)(通过使用酰氯进行酰基化来 制备)，以及在其它位置处具有修饰的那些。

示例性类美登素药物部分还包括具有如以下修饰的那些：C-9-SH (美国专利号4,424,219)(通过美登醇与H2S或P2S5反应来制备)； C-14-烷氧基甲基(脱甲氧基/CH2OR)(美国专利号4,331,598)；C-14- 羟甲基或酰氧甲基(CH2OH或CH2OAc)(美国专利号4,450,254)(由 Nocardia制备)；C-15-羟基/酰氧基(美国专利号4,364,866)(通过用链 球菌转化美登醇来制备)；C-15-甲氧基(美国专利号4,313,946和4,315,929)(从滑桃树(Trewianudlflora)分离)；C-18-N-脱甲基(美国专 利号4,362,663和4,322,348)(通过用链球菌使美登醇脱甲基化来制备)；及4，5-脱氧(美国专利号4,371,533)(通过用三氯化钛/LAH还原美登醇来制备)。

特别有用的是DM1(公开于美国专利号5,208,020中，以引用的 方式并入)和DM4(公开于美国专利号7,276,497中，以引用的方式并 入)。另参见5,416,064、WO/01/24763、7,303,749、7,601,354、USSN 12/631,508、WO02/098883、6,441,163、7,368,565、WO02/16368及 WO04/1033272(全部以引用的方式整体明确地并入)中的其它类美登素衍生物及方法。

含有类美登素的ADC、其制备方法及其治疗应用公开于例如美 国专利号5,208,020、5,416,064、6,441,163以及欧洲专利EP 0 425 235 B1中，其公开内容以引用的方式明确地并入本文中。Liu等人，Proc. Natl.Acad.Sci.USA 93：8618-8623(1996)描述了包含称为DM1的类美 登素连接至针对人结肠直肠癌的单克隆抗体C242的ADC。已发现， 该缀合物针对培养的结肠癌细胞具有高细胞毒性，并且在体内肿瘤生 长检定中显示出抗肿瘤活性。

Chari等人，Cancer Research 52：127-131(1992)描述了一类ADC， 其中类美登素经由二硫化物连接子与结合至人结肠癌细胞系上的抗 原的鼠类抗体A7缀合，或与结合HER-2/neu癌基因的另一鼠类单克隆抗体TA.1缀合。在体外测试TA.1-类美登素缀合物针对人乳癌细胞 系SK-BR-3的细胞毒性，该细胞系每个细胞表达3×105个HER-2表面抗原。该药物缀合物得到的细胞毒性程度类似于游离类美登素药 物，通过增加每个抗体分子的类美登素分子数量可以增加该细胞毒性 程度。A7-类美登素缀合物在小鼠中显示较低的全身细胞毒性。

奥瑞他汀和多拉司他汀

在一些实施方案中，ADC包含多特异性抗体与多拉司他汀或多 拉司他汀肽类似物及衍生物奥瑞他汀的缀合物(美国专利号 5,635,483、5,780,588)。经显示，多拉司他汀和奥瑞他汀可干扰微管 动力学、GTP水解以及核和细胞分裂(Woyke等人(2001)Antimicrob.Agents and Chemother.45(12)：3580-3584)，并具有抗癌(美国专利号 5,663,149)和抗真菌活性(Pettit等人(1998)Antimicrob.Agents Chemother.42：2961-2965)。多拉司他汀或奥瑞他汀药物部分可以通过 肽药物部分的N(氨基)末端或C(羧基)末端附接至抗体(WO 02/088172)。

示例性奥瑞他汀实施方案包括Senter等人于2004年3月28日提 交的Proceedingsof the American Association for Cancer Research，第 45卷，Abstract Number 623中所公开及美国专利公布号 2005/0238648(其公开内容以引用的方式整体明确地并入)中所描述的 N末端连接的单甲基奥瑞他汀药物部分DE和DF。

示例性奥瑞他汀实施方案是MMAE(参见美国专利号6,884,869， 以引用的方式整体明确地并入)。

另一示例性奥瑞他汀实施方案是MMAF(参见US 2005/0238649、5,767,237及6,124,431，以引用的方式整体明确地并 入)。

包含MMAE或MMAF和各种连接子组分(如本文进一步描述) 的其它示例性实施方案具有以下结构和缩写(其中Ab是指抗体并且p 是1至约8)：

典型地，基于肽的药物部分可以通过在两个或更多个氨基酸和/ 或肽片段之间形成肽键来制备。此类肽键可以例如根据肽化学领域中 众所周知的液相合成法(参见E.Schroder和K.Lubke，“The Peptides”， 第1卷，第76-136页，1965，Academic Press)制备。奥瑞他汀/多拉司他 汀药物部分可以根据以下中的方法制备：美国专利号5,635,483；美 国专利号5,780,588；Pettit等人(1989)J.Am.Chem.Soc. 111：5463-5465；Pettit等人(1998)Anti-Cancer Drug Design 13：243-277； Pettit，G.R.等人，Synthesis，1996，719-725；Pettit等人(1996)J.Chem.Soc.Perkin Trans.1 5：859-863；及Doronina(2003)NatBiotechnol 21(7)：778-784。

卡里奇霉素

在其它实施方案中，ADC包含本发明的抗体与一个或多个卡里 奇霉素分子的缀合物。举例来说，Mylotarg是第一种市售ADC药物并且利用了卡里奇霉素γ1作为有效负荷(参见美国专利号4,970,198， 以引用的方式整体并入)。其它卡里奇霉素衍生物描述于美国专利号 5,264,586、5,384,412、5,550,246、5,739,116、5,773,001、5,767,285 及5,877,296中，全部以引用的方式明确地并入。抗生素卡里奇霉素 家族能够以亚皮摩尔浓度产生双链DNA断裂。对于卡里奇霉素家族 缀合物的制备，参见美国专利号5,712,374、5,714,586、5,739,116、 5,767,285、5,770,701、5,770,710、5,773,001、5,877,296(都属于AmericanCyanamid Company)。可以使用的卡里奇霉素的结构类似物包括但不 限于γ1I、α2I、α2I、N-乙酰基-γ1I、PSAG及θI1(Hinman等人，Cancer Research 53：3336-3342(1993)；Lode等人，Cancer Research 58：2925-2928(1998)；及以上提到的属于American Cyanamid的美国专利)。可以缀合抗体的另一抗肿瘤药物是QFA，即，抗叶酸剂。卡里奇霉素和QFA都具有细胞内作用位点并且不易于跨过质膜。因此， 这些药剂通过抗体介导的内化作用被细胞吸收使其细胞毒性作用大 幅增加。

倍癌霉素

CC-1065(参见4,169,888，以引用的方式并入)和倍癌霉素是ADC 中所利用的抗肿瘤抗生素家族的成员。这些抗生素看来是通过在 DNA小沟中的腺嘌呤N3位进行序列选择性烷基化来起作用，由此起 始了引起细胞凋亡的一系列事件。

倍癌霉素的重要成员包括倍癌霉素A(美国专利号4,923,990，以 引用的方式并入)和倍癌霉素SA(美国专利号5,101,038，以引用的方 式并入)，以及如美国专利号7,517,903、7,691,962、5,101,038、 5,641,780、5,187,186、5,070,092、5,070,092、5,641,780、5,101,038、 5,084,468、5,475,092、5,585,499、5,846,545、WO2007/089149、 WO2009/017394A1、5,703,080、6,989,452、7,087,600、7,129,261、 7,498,302及7,507,420(全部以引用的方式明确地并入)中所描述的大 量类似物。

其它细胞毒性剂

可以与本发明的抗体缀合的其它抗肿瘤剂包括BCNU、链脲霉素(streptozoicin)、长春新碱及5-氟尿嘧啶、美国专利号5,053,394、 5,770,710中所描述的统称为LL-E33288复合体的药剂家族，以及埃 斯培拉霉素(美国专利号5,877,296)。

可以使用的酶活性酶活性毒素及其片段包括白喉A链、白喉毒 素的非结合活性片段、外毒素A链(来自绿脓杆菌(Pseudomonas aeruginosa))、篦麻毒素A链、相思子毒素(abrin)A链、莫迪素(modeccin) A链、α-帚曲菌素(alpha-sarcin)、油桐(Aleuritesfordii)蛋白、石竹素 (dianthin)蛋白、洋商陆(Phytolaca americana)蛋白(PAPI、PAPII及PAP-S)、苦瓜抑制剂、麻疯树毒蛋白(curcin)、巴豆毒素(crotin)、肥皂 草(sapaonariaofficinalis)抑制剂、白树素(gelonin)、有丝分裂素 (mitogellin)、局限曲菌素(restrictocin)、酚霉素(phenomycin)、伊诺霉 素(enomycin)及霉菌毒素(tricothecene)。参见例如，1993年10月28 日公布的WO 93/21232。

本发明另外涵盖在抗体与具有核溶解活性的化合物(例如核糖核 酸酶或DNA内切核酸酶，如脱氧核糖核酸酶；DNA酶)之间形成的 ADC。

为了选择性破坏肿瘤，抗体可以包含高放射性原子。多种放射性 同位素可用于产生放射性缀合的抗体。实例包括At211、I131、1125、 Y90、Re186、Re188、Sm153、Bi212、P32、Pb212及Lu的放射性 同位素。

放射性标记或其它标记可以通过已知方式并入缀合物中。举例来 说，肽可以是生物合成的，或可以通过使用涉及例如氟-19替代氢的 适合氨基酸前驱物进行化学氨基酸合成进行合成。标记，如Tc99m 或I123、Re186、Re188及In111，可以经由肽中的半胱氨酸残基附接。 钇-90可以经由赖氨酸残基附接。IODOGEN法(Fraker等人(1978)Biochem.Biophys.Res.Commun.80：49-57)可以用于并入碘-123。 “MonoclonalAntibodies in Immunoscintigraphy”(Chatal，CRC Press 1989)详细描述了其它方法。

对于包含多种抗体的组合物来说，载药量由p表示，p是每个抗 体中药物分子的平均数量。载药量可以在每个抗体1至20个药物(D) 的范围内。在缀合反应的制备中每个抗体的药物平均数量可以通过常 规方式，如质谱法、ELISA检定及HPLC来表征。关于p的抗体-药物缀合物的定量分布也可以得到测定。

在一些情形中，可以通过如反相HPLC或电泳法等方式实现均匀 抗体-药物缀合物(其中p是某一值)自具有其它载药量的抗体-药物缀 合物的分离、纯化及表征。在示例性实施方案中，p是2、3、4、5、 6、7或8，或其分数。

抗体-药物缀合复合物可以通过熟练技术人员已知的任何技术产 生。简单地说，抗体-药物缀合复合物可以包括作为抗体单元的多特 异性抗体、药物，及任选存在的接合药物与结合剂的连接子。

多种不同反应可用于将药物和/或连接子共价附接至结合剂。这 可以通过结合剂(例如抗体分子)的氨基酸残基的反应来实现，包括赖氨酸的胺基、谷氨酸和天冬氨酸的游离羧酸基团、半胱氨酸的硫氢基 及芳香族氨基酸的各种部分。常用的非特异性共价附接方法是将化合 物的羧基(或氨基)连接到抗体的氨基(或羧基)的碳化二亚胺反应。另 外，使用了如二醛或酰亚胺酯等双官能试剂来连接化合物的氨基与抗 体分子的氨基。

此外，可用于附接药物与结合剂的是席夫碱反应。这一方法涉及 含有二醇或羟基的药物的高碘酸盐氧化，由此形成一种醛，该醛然后 与结合剂反应。附接经由与结合剂的氨基形成席夫碱来发生。还可以 使用异硫氰酸酯作为偶合剂用于共价地附接药物与结合剂。熟练技术 人员已知其它技术并且这些技术在本发明的范围内。

在一些实施方案中，使中间体，即连接子前驱物与药物在适当条 件下反应。在其它实施方案中，使用了药物和/或中间体上的反应性 基团。药物与中间体之间的反应产物，或衍生化的药物，随后与本发 明的多特异性抗体在适当条件下反应。

应理解，出于制备本发明的缀合物的目的，还可以对期望的化合 物进行化学修饰以便使所述化合物更易于反应。举例来说，可以将官 能团，例如胺、羟基或硫氢基，附加至药物中对该药物的活性或其它 特性具有最小或可接受的影响的位置。

连接子单元

典型地，抗体-药物缀合复合物在药物单元与抗体单元之间包含 连接子单元。在一些实施方案中，连接子在细胞内或细胞外条件下是 可裂解的，因此该连接子在适当环境中裂解而使药物单元从该抗体释 放。举例来说，分泌某些蛋白酶的实体肿瘤可以用作可裂解连接子的靶；在其它实施方案中，利用的是细胞内蛋白酶。在又其它实施方案 中，连接子单元是不可裂解的，并且药物是例如通过抗体在溶酶体中 降解而释放。

在一些实施方案中，连接子可以在细胞内环境中(例如，在溶酶 体或核内体或细胞膜穴样内陷内)存在的裂解剂作用下裂解。连接子 可以例如是一种肽基连接子，它被细胞内肽酶或蛋白酶(包括但不限 于，溶酶体或核内体蛋白酶)裂解。在一些实施方案中，肽基连接子是至少两个氨基酸长或至少三个氨基酸长或更长。

裂解剂可以包括但不限于，组织蛋白酶B和D，及纤溶酶，已知 其都水解二肽药物衍生物，引起活性药物在靶细胞内部释放(参见例 如，Dubowchik和Walker，1999，Pharm.Therapeutics 83：67-123)。可以 被酶裂解的肽基连接子存在于CD38表达细胞中。举例来说，可以使用能被癌组织中高水平表达的硫醇依赖性蛋白酶，即组织蛋白酶-B 裂解的肽基连接子(例如，Phe-Leu或Gly-Phe-Leu-Gly连接子(SEQ ID NO：X))。此类连接子的其它实例描述于例如美国专利号6,214,345中， 以引用的方式整体并入本文中并用于所有目的。

在一些实施方案中，可以被细胞内蛋白酶裂解的肽基连接子是 Val-Cit连接子或Phe-Lys连接子(参见例如，美国专利号6,214,345， 该案描述了在val-cit连接子存在下阿霉素的合成)。

在其它实施方案中，可裂解连接子具有pH敏感性，即，对在某 些pH值下进行的水解敏感。典型地，pH敏感性连接子在酸性条件 下可水解。举例来说，可以使用在溶酶体中可水解的酸不稳定性连接子(例如，腙、缩氨基脲、缩氨基硫脲、顺-乌头酰胺、原酸酯、乙缩醛、缩酮等)。(参见例如，美国专利号5,122,368、5,824,805、5,622,929； Dubowchik和Walker，1999，Pharm.Therapeutics 83：67-123；Neville等 人，1989，Biol.Chem.264：14653-14661。)此类连接子在中性pH条件 (如在血液中的那些)下相对稳定，但在低于pH5.5或5.0(溶酶体的近 似pH值)下不稳定。在某些实施方案中，可水解连接子是硫醚连接子(如例如，经由酰基腙键附接至治疗剂的硫醚；参见例如美国专利号 5,622,929)。

在又其它实施方案中，连接子可以在还原条件下裂解(例如，二 硫化物连接子)。本领域中已知多种二硫化物连接子，包括例如，可 以使用SATA(N-琥珀酰亚胺基-5-乙酰基硫代乙酸酯)、SPDP(N-琥珀酰亚胺基-3-(2-吡啶基二硫代)丙酸酯)、SPDB(N-琥珀酰亚胺基-3-(2- 吡啶基二硫代)丁酸酯)及SMPT(N-琥珀酰亚胺基-氧基羰基-α-甲基 -α-(2-吡啶基-二硫代)甲苯)、SPDB及SMPT形成的那些。(参见例如， Thorpe等人，1987，CancerRes.47：5924-5931；Wawrzynczak等人，In Immunoconjugates：Antibody Conjugates inRadioimagery and Therapy of Cancer(C.W.Vogel编，Oxford U.Press，1987。另参见美国专利号 4,880,935。)

在其它实施方案中，连接子是丙二酸酯连接子(Johnson等人， 1995，AnticancerRes.15：1387-93)、顺丁烯二酰亚胺基苯甲酰基连接子 (Lau等人，1995，Bioorg-Med-Chem.3(10)：1299-1304)或3’-N-酰胺类似 物(Lau等人，1995，Bioorg-Med-Chem.3(10)：1305-12)。

在又其它实施方案中，连接子单元是不可裂解的，并且药物是通 过抗体降解来释放。(参见美国公布号2005/0238649，以引用的方式 整体并入本文中并用于所有目的)。

在许多实施方案中，连接子是自降解的。如本文所使用，术语“自 降解性间隔子”是指能够将两个隔开的化学部分共价连接在一起成为 分三部分的稳定分子的双官能化学部分。如果其与第一部分的键裂 解，那么其将自发与第二化学部分分离。参见例如，WO2007059404A2、WO06110476A2、WO05112919A2、WO2010/062171、 WO09/017394、WO07/089149、WO 07/018431、WO04/043493及 WO02/083180，这些专利是针对药物-可裂解基质缀合物，其中药物 和可裂解基质任选通过自降解性连接子连接，并且全部都以引用的方式明确地并入。

通常，连接子对于细胞外环境基本上不敏感。如本文所使用，就 连接子来说，“对于细胞外环境基本上不敏感”意味着，当抗体-药物 缀合复合物存在于细胞外环境(例如，血浆)中时，抗体-药物缀合复合 物样品中不超过约20％、15％、10％、5％、3％或不超过约1％的连接 子裂解。

可以例如通过将抗体-药物缀合复合物与血浆一起温育预定时间 段(例如2、4、8、16或24小时)，然后对血浆中存在的游离药物的 量进行定量，来确定连接子是否对于细胞外环境基本上不敏感。

在其它不相互排斥的实施方案中，连接子促进细胞内化。在某些 实施方案中，连接子当与治疗剂缀合(也就是说，在如本文所描述的 抗体-药物缀合复合物的连接子-治疗剂部分的环境下)时促进细胞内 化。在又其它实施方案中，连接子当与奥瑞他汀化合物和本发明的多 特异性抗体缀合时促进细胞内化。

可以用于本发明的组合物和方法的多种示例性连接子描述于 WO 2004-010957、美国公布号2006/0074008、美国公布号 20050238649及美国公布号2006/0024317中(其各自以引用的方式并 入本文中并用于所有目的)。

载药量

载药量是以p表示并且是分子中每个抗体的药物部分的平均数 量。载药量(“p”)可以是每个抗体1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20或更多个部分(D)，不过 平均数量常常是分数或小数。一般来说，载药量为1至4常常是有用 的，并且1至2也是有用的。本发明的ADC包括抗体与一系列药物 部分(1至20个)的缀合物的集合。在由缀合反应制备的ADC中每个 抗体的药物部分的平均数量可以通过常规方式，如质谱法和ELISA 检定来表征。

就p来说，ADC的定量分布也可以得到测定。在一些情形中， 可以通过如或电泳法等方式实现均匀ADC(其中p是某一值)自具有 其它载药量的ADC的分离、纯化及表征。

对于一些抗体-药物缀合物，p可能受抗体上附接位点的数量限 制。举例来说，当附接点是半胱氨酸硫醇时，如在以上示例性实施方 案中，抗体可以仅具有一个或若干个半胱氨酸硫醇基，或可能仅具有 一个或若干个可以附接连接子的具有足够反应性的硫醇基。在某些实 施方案中，较高的载药量，例如p＞5，可能引起某些抗体-药物缀合物 聚集、不溶解、毒性或是细胞渗透性损失。在某些实施方案中，本发明的ADC的载药量范围是1至约8；约2至约6；约3至约5；约3 至约4；约3.1至约3.9；约3.2至约3.8；约3.2至约3.7；约3.2至 约3.6；约3.3至约3.8；或约3.3至约3.7。实际上，经显示，对于某 些ADC，每个抗体的最佳药物部分比率可以低于8，并且可以是约2 至约5。参见US 2005-0238649 A1(以引用的方式整体并入本文中)。

在某些实施方案中，低于理论最大量的药物部分在缀合反应期间 与抗体缀合。抗体可以含有例如不与药物-连接子中间体或连接子试 剂(如以下所论述)反应的赖氨酸残基。一般来说，抗体包含许多游离 的反应性半胱氨酸硫醇基，这些基团可以连接至药物部分；实际上， 抗体中大部分的半胱氨酸硫醇残基是以二硫桥形式存在。在某些实施 方案中，抗体可以在部分或总体还原条件下被如二硫苏糖醇(DTT)或 三羰基乙基膦(TCEP)等还原剂还原，产生反应性半胱氨酸硫醇基。在 某些实施方案中，抗体经历变性条件，由此展现反应性亲核基团，如 赖氨酸或半胱氨酸。

ADC的负荷(药物/抗体比)可以通过不同方式控制，例如：(i)限 制药物-连接子中间体或连接子试剂相对于抗体的摩尔过量；(ii)限制 缀合反应时间或温度；(iii)针对半胱氨酸硫醇修饰的部分或限制性还 原条件；(iv)通过重组技术对抗体的氨基酸序列进行工程改造，由此 修饰半胱氨酸残基的数量和位置以控制连接子-药物附接的数量和/或位置(如本文及WO2006/034488(以引用的方式整体并入本文中)中所 公开而制备的硫代Mab或硫代Fab)。

应理解，在超过一个亲核基团与药物-连接子中间体或连接子试 剂，随后药物部分试剂反应的情况下，所得产物是分布有附接至抗体 的一个或多个药物部分的ADC复合物的混合物。每个抗体的平均药物数量可以由该混合物，通过双重ELISA抗体检定来计算，该检定 对于抗体具有特异性并且对于药物具有特异性。可以通过质谱法鉴别 出该混合物中的个别ADC分子，并通过HPLC，例如疏水相互作用色谱法进行分离。

在一些实施方案中，具有单一负荷值的均匀ADC可以通过电泳 或色谱法从缀合混合物分离。

测定ADC的细胞毒性作用的方法

已知确定药物或抗体-药物缀合物是否对细胞发挥细胞抑制作用 和/或细胞毒性作用的方法。一般来说，抗体药物缀合物的细胞毒性 或细胞抑制活性可以通过以下方式测量：使表达抗体药物缀合物的靶蛋白的哺乳动物细胞暴露于细胞培养基中；培养细胞约6小时至约5 天的时间；及测量细胞活力。可以使用基于细胞的体外检定来测量抗 体药物缀合物的活力(增殖)、细胞毒性及细胞凋亡诱导作用(胱天蛋白 酶活化)。

为了确定抗体药物缀合物是否发挥细胞抑制作用，可以使用胸苷 并入检定。举例来说，可以将以5,000个细胞/孔的密度接种于96孔 板中的表达靶抗原的癌细胞培养72小时时间，并使其在该72小时时间的最后8小时里暴露于0.5μCi的3H-胸苷。在存在和不存在抗体 药物缀合物情况下测量培养的细胞中3H-胸苷的并入。

为测定细胞毒性，可以测量坏死或细胞凋亡(程序式细胞死亡)。 坏死典型地伴随质膜渗透性的增加；细胞膨胀；及质膜的破裂。细胞 凋亡典型地以膜起泡、细胞质浓缩及内源性内切核酸酶活化为特征。 这些针对癌细胞的作用的任一种的测定表明，抗体药物缀合物可用于 治疗癌症。

细胞活力可以通过测定细胞中如中性红、台盼蓝或ALAMARTM 蓝等染料的吸收情况来测量(参见例如，Page等人，1993，Intl.J. Oncology 3：473-476)。在此类检定中，在含有染料的培养基中培育细 胞，洗涤细胞，并通过分光光度法测量残留的染料，由此反映染料的 细胞吸收。还可以使用蛋白质结合染料磺基若丹明B(sulforhodamine B，SRB)来测量细胞毒性(Skehan等人，1990，J.Natl.Cancer Inst. 82：1107-12)。

作为替代，在通过检测活细胞而非死细胞进行的有关哺乳动物细 胞存活和增殖情况的定量比色检定中使用四唑盐，如MTT(参见例 如，Mosmann，1983，J.Immunol.Methods65：55-63)。

细胞凋亡可以通过测量例如DNA片段化进行定量。可用商业上 的光度测定法在体外定量测定DNA片段化。此类检定的实例，包括 TUNEL(用于检测片段化DNA中并入的标记的核苷酸)和基于ELISA的检定，描述于Biochemica，1999，第2期，第34-37页(RocheMolecular Biochemicals)中。

还可以通过测量细胞形态的变化来确定细胞凋亡。举例来说，与 坏死相同，可以通过测量某些染料(例如荧光染料，如例如吖啶橙或 溴乙锭)的吸收情况来确定质膜完整性的丧失。用于测量凋亡细胞数 量的方法描述于Duke和Cohen，Current Protocols inImmunology (Coligan等人编，1992，第3.17.1-3.17.16页)中。细胞也可以用DNA 染料(例如吖啶橙、溴乙锭或碘丙锭)标记，并观察细胞的染色质缩合 和边集情况以及内核膜。可以经过测量以测定细胞凋亡的其它形态变 化包括例如，细胞质浓缩、膜起泡增加及细胞收缩。

凋亡细胞的存在可以在培养物的附着部分和“漂浮”部分中测量。 举例来说，可以通过去除上清液，使附着的细胞胰蛋白酶化，合并在 离心洗涤步骤(例如，2000rpm下10分钟)之后得到的标本，并检测 细胞凋亡情况(例如，通过测量DNA片段化)来收集两个部分。(参见 例如，Piazza等人，1995，Cancer Research 55：3110-16)。

在体外，可以在适合动物模型中评价本发明的多特异性抗体的治 疗性组合物的作用。举例来说，可以使用异体癌症模型，其中将癌症 外植体或传代的异种移植组织引入免疫功能低下的动物，如裸小鼠或 SCID小鼠中(Klein等人，1997，Nature Medicine 3：402-408)。可以使用 测量肿瘤形成、肿瘤消退或转移抑制等的检定来测量功效。

用于实行前述方法的治疗性组合物可以配制成包含适于期望的 递送方法的载剂的药物组合物。适合载剂包括当与治疗性组合物组合 时保持治疗性组合物的抗肿瘤功能并且一般不与患者的免疫系统反 应的任何物质。实例包括但不限于，多种标准药物载剂，如无菌磷酸 盐缓冲生理盐水溶液、抑菌水等(一般参见，Remington’s PharmaceuticalSciences第16版，A.Osal.编，1980)。

供体外施用的抗体组合物

根据本发明使用的抗体的配制物是通过将具有期望的纯度的抗 体与可选的药学上可接受的载剂、赋形剂或稳定剂(Remington’s Pharmaceutical Sciences，第16版，Osol，A.编[1980])混合来制备，这些 配制物是呈冻干的配制物或水溶液形式。可接受的载剂、赋形剂或稳 定剂在所用剂量和浓度下对接受者无毒，并且包括：缓冲剂，如磷酸 盐、柠檬酸盐及其它有机酸；抗氧化剂，包括抗坏血酸和甲硫氨酸；防腐剂(如十八烷基二甲基苯甲基氯化铵；氯化己烷双胺；氯化苯甲 烃铵(benzalkonium chloride)；苄索氯铵(benzethonium chloride)；苯酚； 丁醇或苯甲醇；对羟基苯甲酸烷酯，如对羟基苯甲酸甲酯或对羟基苯 甲酸丙酯；儿茶酚；间苯二酚；环己醇；3-戊醇；及间甲酚)；低分子量(少于约10个残基)多肽；蛋白质，如血清白蛋白、明胶或免疫 球蛋白；亲水性聚合物，如聚乙烯吡咯烷酮；氨基酸，如甘氨酸、谷 氨酰胺、天冬酰胺、组氨酸、精氨酸或赖氨酸；单糖、双糖及其它碳 水化合物，包括葡萄糖、甘露糖或糊精；螯合剂，如EDTA；糖，如 蔗糖、甘露糖醇、海藻糖或山梨糖醇；成盐平衡离子，如钠；金属络 合物(例如Zn-蛋白质络合物)；及/或非离子型表面活性剂，如 TWEENTM、PLURONICSTM或聚乙二醇(PEG)。

本文中的配制物根据所治疗的特定适应症的需要，还可以含有超 过一种活性化合物，优选具有不会彼此不利地影响的互补活性的那些 活性化合物。举例来说，可能期望提供具有其它特异性的抗体。作为 替代，或除此之外，组合物可以包含细胞毒性剂、细胞因子、生长抑 制剂和/或小分子拮抗剂。此类分子宜以有效达成预定目的的量组合 存在。

活性成分还可以覆埋在例如通过凝聚技术或通过界面聚合所制 备的微囊中，例如分别覆埋在胶状药物递送系统(例如脂质体、白蛋 白微球体、微乳液、纳米粒子及纳米胶囊)中或在巨乳液中的羟甲基 纤维素或明胶微囊及聚(甲基丙烯酸甲酯)微囊。这些技术公开于 Remington’s Pharmaceutical Sciences，第16版，Osol，A.编(1980)中。

打算用于体内施用的配制物应当是无菌或近似无菌的。这易于通 过滤过无菌过滤膜来实现。

可以制备持续释放制剂。持续释放制剂的适合实例包括含有抗体 的固体疏水聚合物的半渗透性基质，这些基质呈成形物品，例如薄膜 或微囊的形式。持续释放基质的实例包括聚酯、水凝胶(例如聚(甲基 丙烯酸2-羟乙酯)或聚(乙烯醇))、聚丙交酯(美国专利号3,773,919)、 L-谷氨酸与L-谷氨酸γ乙酯的共聚物、不可降解的乙烯-乙酸乙烯酯、 可降解的乳酸-乙醇酸共聚物(如LUPRON DEPOTTM(由乳酸-乙醇酸 共聚物与乙酸亮丙瑞林(leuprolide acetate)构成的可注射微球体))及聚 -D-(-)-3-羟基丁酸。聚合物，如乙烯-乙酸乙烯酯和乳酸-乙醇酸能够 在100天内释放分子，而某些水凝胶在更短时间段内释放蛋白质。

当囊封的抗体在体内保持较长时间时，其可能由于在37℃下暴 露于水分而变性或聚集，由此导致生物活性丧失及可能的免疫原性变 化。取决于所涉及的机制，可以设计合理的策略实现稳定。举例来说， 如果发现聚集机制是通过硫醇-二硫化物交换而形成分子间S-S键， 那么可以通过修饰硫氢基残基、自酸性溶液冻干、控制水分含量、使用适当添加剂及产生特定聚合物基质组合物来实现稳定。

施用方法

本发明的抗体和化学治疗剂是根据已知方法，如以推注或通过经 一段时间连续输注进行静脉内施用、通过肌肉内、腹膜内、脑脊髓内、 皮下、关节内、滑膜内、鞘内、口服、外敷或吸入途径施用给受试者。 优选静脉内或皮下施用所述抗体。

治疗方法

在本发明的方法中，使用了疗法来提供针对疾病或病症的阳性治 疗反应。“阳性治疗反应”意图指疾病或病症的改善，和/或与该疾病 或病症有关的症状的改善。举例来说，阳性治疗反应是指以下疾病改 善中的一种或多种：(1)赘生细胞的数量减少；(2)赘生细胞死亡增加； (3)赘生细胞存活受抑制；(5)肿瘤生长抑制(即，在某种程度上减慢， 优选停止)；(6)患者存活率增加；及(7)与疾病或病症相关的一种或多 种症状的一定程度减轻。

在任何给定疾病或病症中的阳性治疗反应可以通过该疾病或病 症特有的标准化反应标准来确定。肿瘤反应可以使用筛查技术，如磁 共振成像(MRI)扫描、x线放射成像、计算机断层摄影(CT)扫描、骨 扫描成像、内窥镜检查，及肿瘤活检取样，包括骨髓穿刺(BMA)和循环中肿瘤细胞计数等，通过肿瘤形态的变化(即，总肿瘤负荷、肿瘤 尺寸等)来评估肿瘤反应。

除这些阳性治疗反应外，经历疗法的受试者还可能经历疾病相关 症状改善的有益作用。

因此，对于B细胞肿瘤来说，受试者可能经历所谓的B症状， 即，盗汗、发热、体重减轻和/或风疹的减少。对于恶变前病症，利 用多特异性治疗剂的疗法可以阻止相关恶性病症的发展和/或延长相 关恶性病症发展前的时间，例如，罹患意义未明单克隆丙球蛋白病(MGUS)的受试者的多发性骨髓瘤的发展。

疾病的改善可以通过完全反应表征。“完全反应”意图指不存在临 床上可检测的疾病以及任何先前异常的放射成像研究(就骨髓瘤来 说，骨髓和脑脊髓液(CSF)或异常单克隆蛋白质)的正常化。

此类反应可以在根据本发明的方法进行治疗之后持续至少4至8 周，或有时是6至8周。作为替代，疾病的改善可以归类为部分反应。 “部分反应”意图指在无新病变存在下，所有可测量的肿瘤负荷(即， 受试者体内存在的恶性细胞的数量，或测量的肿块体积，或异常单克隆蛋白质的量)的至少50％降低，该反应可以持续4至8周，或6至 8周。

根据本发明的治疗包括“治疗有效量”的所用药剂。“治疗有效量” 是指以所需剂量并且在所需时间段内有效达成期望的治疗结果的量。

治疗有效量可以根据多种因素而变化，如疾病状态；个体的年龄、 性别及体重；以及药物在个体中引起期望的反应的能力。治疗有效量 还是抗体或抗体部分的治疗有益作用超过其任何有毒或有害作用的 量。

肿瘤疗法的“治疗有效量”还可以通过其使疾病进展稳定的能力 来测量。一种化合物抑制癌症的能力可以在预测在人类肿瘤中的功效的动物模型系统中评价。

作为替代，组合物的这种特性可以通过用熟练从业人员已知的体 外检定检查化合物抑制细胞生长或诱导细胞凋亡的能力来评价。治疗 化合物的治疗有效量可以减小肿瘤大小，或以其它方式改善受试者的 症状。本领域普通技术人员将能够基于如受试者的体格、受试者症状 的严重程度及所选特定组合物或施用途径等因素确定此类量。

剂量方案经调整以提供最佳的期望反应(例如治疗反应)。举例来 说，可以施用单次推注；可以随时间投与若干分次剂量；或可以按治 疗情况的紧急性指示按比例减小或增加剂量。不经肠组合物可以配制 成单位剂型以便剂量的施用和均一性。如本文中所使用，单位剂型是 指适合作为单一剂量用于待治疗的受试者的物理离散单元；每一单元 含有经计算以产生期望的治疗作用的预定量的活性化合物与所需药物载剂的组合。

本发明的单位剂型的规格是由以下因素规定并且直接取决于以 下因素：(a)活性化合物的独特特征及有待实现的特定治疗作用，及(b) 本领域中混配此类活性化合物用于治疗个体的敏感性所固有的局限。

用于本发明中的多特异性抗体的有效剂量和剂量方案取决于有 待治疗的疾病或病症，并且可以由本领域技术人员确定。

用于本发明中的多特异性抗体的治疗有效量的示例性、非限制性 范围是约0.1-100mg/kg，如约0.1-50mg/kg，例如约0.1-20mg/kg， 如约0.1-10mg/kg，例如约0.5mg/kg，如约0.3mg/kg、约1mg/kg 或约3mg/kg。在另一实施方案中，施用的抗体剂量是1mg/kg或更高，如1至20mg/kg剂量，例如5至20mg/kg剂量，例如8mg/kg 剂量。

具有本领域普通技术的医疗从业人员能容易地确定所需药物组 合物的有效量并开具处方。举例来说，医师或兽医可以低于获得所期 望的治疗作用所需剂量的剂量的以药物组合物形式使用的药物开始， 并逐步增加剂量直到达到所期望的作用。

在一个实施方案中，多特异性抗体是以10至500mg/kg，如200 至400mg/kg的周剂量通过输注施用。此类施用可以重复例如1至8 次，如3至5次。施用可以通过经2至24小时，如2至12小时时间 连续输注来进行。

在一个实施方案中，多特异性抗体是经一段较长时间，必要时超 过24小时，通过缓慢连续输注施用，以降低副作用，包括毒性。

在一个实施方案中，多特异性抗体是以250mg至2000mg，如 例如300mg、500mg、700mg、1000mg、1500mg或2000mg周剂 量施用，达8次，如4至6次。施用可以通过经2至24小时，如2 至12小时时间连续输注来进行。必要时，此方案可以在例如6个月 或12个月后重复一次或多次。可以通过在施用后，例如取出生物样 品测量血液中本发明化合物的量，并使用靶向多特异性抗体的抗原结 合区的抗独特性抗体来测定或调整剂量。

在另一实施方案中，每周施用一次多特异性抗体，持续2至12 周，如3至10周，如4至8周。

在一个实施方案中，根据维持疗法施用多特异性抗体，例如一周 一次，持续6个月或更长时间。

在一个实施方案中，根据包括输注一次多特异性抗体，随后输注 多特异性抗体与放射性同位素的缀合物的方案，施用多特异性抗体。 该方案可以例如在7至9天后重复进行。

在非限制性实施例中，根据本发明的治疗可以按抗体的日剂量， 在起始治疗后第1天、2天、第3天、第4天、第5天、第6天、第 7天、第8天、第9天、第10天、第11天、第12天、第13天、第 14天、第15天、第16天、第17天、第18天、第19天、第20天、 第21天、第22天、第23天、第24天、第25天、第26天、第27 天、第28天、第29天、第30天、第31天、第32天、第33天、第 34天、第35天、第36天、第37天、第38天、第39天或第40天 中至少一天，或者第1周、第2周、第3周、第4周、第5周、第6 周、第7周、第8周、第9周、第10周、第11周、第12周、第13 周、第14周、第15周、第16周、第17周、第18周、第19周或第 20周中至少一周，或其任何组合，使用单次剂量，或每24小时、12 小时、8小时、6小时、4小时或2小时，或其任何组合以分次剂量 以每天约0.1-100mg/kg，如0.5mg/kg、0.9mg/kg、1.0mg/kg、1.1mg/kg、1.5mg/kg、2mg/kg、3mg/kg、4mg/kg、5mg/kg、6mg/kg、 7mg/kg、8mg/kg、9mg/kg、10mg/kg、11mg/kg、12mg/kg、13mg/kg、14mg/kg、15mg/kg、16mg/kg、17mg/kg、18mg/kg、19mg/kg、20 mg/kg、21mg/kg、22mg/kg、23mg/kg、24mg/kg、25mg/kg、26mg/kg、 27mg/kg、28mg/kg、29mg/kg、30mg/kg、40mg/kg、45mg/kg、50 mg/kg、60mg/kg、70mg/kg、80mg/kg、90mg/kg或100mg/kg的量 提供。

在一些实施方案中，其多特异性抗体分子是与一种或多种另外的 治疗剂，例如化学治疗剂组合使用。DNA损伤性化学治疗剂的非限 制性实例包括拓扑异构酶I抑制剂(例如伊立替康、拓扑替康、喜树 碱及其类似物或代谢物，以及阿霉素)；拓扑异构酶II抑制剂(例如， 依托泊苷、替尼泊苷及道诺霉素)；烷化剂(例如，美法仑、苯丁酸氮 芥、白消安、噻替哌、异环磷酰胺、卡莫司汀、洛莫司汀、司莫司汀、 链佐星、达卡巴嗪(decarbazine)、甲氨蝶呤、丝裂霉素C及环磷酰胺)； DNA嵌入剂(例如，顺铂、奥沙利铂及卡铂)；DNA嵌入剂和自由基 产生剂如博莱霉素；及核苷模拟物(例如5-氟尿嘧啶、卡培他滨(capecitibine)、吉西他滨、氟达拉滨、阿糖胞苷、巯基嘌呤、硫鸟嘌 呤、喷司他丁及羟基脲)。

破坏细胞复制的化学治疗剂包括：太平洋紫杉醇(paclitaxel)、多 西他赛及相关类似物；长春新碱、长春花碱及相关类似物；沙立度胺、 来那度胺及相关类似物(例如CC-5013和CC-4047)；蛋白质酪氨酸激 酶抑制剂(例如甲磺酸伊马替尼和吉非替尼)；蛋白酶体抑制剂(例如硼 替佐米)；NF-κB抑制剂，包括IκB激酶抑制剂；结合至癌症中过表达的蛋白质并由此下调细胞复制的抗体(例如曲妥珠单抗、利妥昔单 抗、西妥昔单抗及贝伐单抗)；及其它已知在癌症中上调、过表达或 活化的蛋白质或酶的抑制剂，这些蛋白质或酶的抑制使细胞复制下 调。

在一些实施方案中，本发明的抗体可以在用(硼替佐米) 治疗之前、同时或之后使用。

所有引用的参考文献都以引用的方式整体明确地并入本文中。

尽管以上出于说明的目的描述了本发明的特定实施方案，但本领 域技术人员应理解，在不背离所附权利要求书中所描述的本发明的情 况下，可以对细节进行多种变更。

实施例

以下提供实施例以说明本发明。这些实施例不打算将本发明局限 于任何特定应用或操作理论。对于本发明中论述的所有恒定区，编号 是根据Kabat中的EU索引(Kabat等人，1991，Sequences of Proteins of Immunological Interest，第5版，United StatesPublic Health Service， National Institutes of Health，Bethesda，以引用的方式整体并入)。抗体 领域的技术人员应理解，这一惯例由免疫球蛋白序列特定区域中的非顺次编号组成，由此能够归一化提及免疫球蛋白家族中的保守位置。 因此，通过EU索引定义的任何给定免疫球蛋白的位置不必对应于其 顺次序列。

实施例1.原型“三F”双特异性抗体。

本发明描述了共接合第一抗原和第二抗原的新型免疫球蛋白组 合物。抗体的一条重链含有单链Fv(“scFv”，如本文所定义)，而另一 重链是“常规”Fab形式，包含可变重链和轻链(参见图1)。这一结构在 本文中有时称为“三F”形式(scFv-Fab-Fc)。两条链通过二聚体Fc区连 在一起(参见图2)。Fc区可以通过氨基酸取代进行修饰以便能有效纯化“三F”异二聚体。另外，Fc区可以通过氨基酸取代进行修饰以促进 “三F”异二聚体的形成。以下更完整地描述Fc取代的实例。

“三F”形式中可以包括Fc取代以便能相对于不希望的双scFv-Fc 和mAb同二聚体，有效地纯化出所希望的“三F”异二聚体。此情形 的一个实例是纳入改变每个单体的等电点(pI)，以使每个单体具有不 同pI的Fc取代。在这一情形中，所期望的“三F”异二聚体的pI将不 同于不希望的双scFv-Fc和mAb同二聚体，由此促进“三F”异二聚体 的等电纯化(例如，阴离子交换色谱柱、阳离子交换色谱柱)。这些取 代还有助于纯化后(例如IEF凝胶、cIEF及分析型IEX柱)任何污染性 双scFv-Fc和mAb同二聚体的测定和监测。有关可以在Fc单体1和Fc单体2中进行以便能有效纯化所期望的“三F”异二聚体的取代的清 单，参见图3。

“三F”形式中可以包括Fc取代以便相对于不希望的双scFv-Fc和 mAb同二聚体，使形成“偏向”于所期望的“三F”异二聚体。举例来说， 有关可以在Fc单体1和Fc单体2中进行以使制造“偏向”于“三F”异 二聚体的取代的清单，参见图4。图3和图4中所列的氨基酸取代可 以组合，以增加可以与任何污染性双scFv-Fc和mAb同二聚体纯化分离的“三F”异二聚体的产率。

在优化“三F”形式中所包括的scFv结构域之后，可以通过一种便 利的方式将优化的scFv结构域与多条标准抗体重链偶合。举例来说， 用于募集T细胞的细胞毒性的抗CD3scFv可以与多条抗肿瘤抗原抗体重链(例如，结合CD5、CD20、CD30、CD40、CD33、CD38、EGFR、EpCAM、Her2、HM1.24或其它肿瘤抗原的那些)偶合。宜与标准抗 体重链偶合的优化的scFv结构域的其它实例包括有关自然杀伤细胞 的细胞毒性的抗CD16scFv；有关抑制活性的抗CD32b scFv(此处，偶合的抗体重链将结合例如CD19、CD40、CD79a、CD79b或其它免 疫受体)；及有关跨血脑屏障转运的抗转铁蛋白受体scFv、抗胰岛素 受体或抗LRP1。

实施例2.来源于“三F”形式的多特异性抗体。

可以通过将结合第三抗原的另外的scFv或Fab结构域附接至“三 F”重链之一的C末端来构建多特异性抗体。参看例如图5。作为替代， C末端scFv或Fab可以结合第一抗原或第二抗原，由此赋予二价并 增加对该抗原的总体结合亲和力。

还可以通过将“三F”形式的scFv-Fc重链与重排的抗体重链偶合 来构建多特异性抗体，如图6中所描绘。此类重排抗体重链可以包括 结合第三抗原的另外的Fv区，或者结合第一抗原或第二抗原的另外 的Fv区，由此赋予二价并增加对该抗原的总体结合亲和力。

实施例3.抗CD19 Fab x抗CD3 scFv“三F”双特异性抗体。

抗CD19 Fab x抗CD3 scFv“三F”双特异性抗体的氨基酸序列列 于附图中。能够相对于不希望的双scFv-Fc和mAb同二聚体有效纯 化出所希望的“三F”异二聚体的氨基酸取代加下划线。优选的人源化 抗CD3可变区的氨基酸序列列于图2和图6中(其中CDR加下划线)。 以下给出表达和纯化所希望的“三F”物质及其生物活性的一些实施 例。

图9中略述了XENP11874的产生，其为具有抗CD19 Fab 和抗CD3 scFv的“三F”双特异性抗体。在图9中，显示出通过离子 交换从不希望的双scFv-Fc和mAb同二聚体纯化出希望的“三F”异二 聚体。通过IEF凝胶检查“三F”部分的纯度(数据示于USSN 61/818,410 的图9B中，该案所有附图和图例以引用的方式明确地并入)。最后， 使用SEC确定“三F”产物的均匀尺寸(数据示于USSN 61/818,410的 图9C中，该案所有附图和图例以引用的方式明确地并入)。

经显示，XENP11874，即抗CD19 Fab x抗CD3 scFv“三F”双特 异性抗体具有有效生物活性。XENP11874有效募集T细胞以清除B 细胞的能力显示于USSN 61/818,410的图10中，该案以引用的方式 明确地并入。

USSN 61/818,410的图11(以引用的方式明确地并入)中略述了 XENP11924的产生，其为具有抗CD19 Fab和抗CD3 scFv的“三F” 双特异性抗体。在USSN 61/818,410的图11A中，显示出通过离子交 换从不希望的双scFv-Fc和mAb同二聚体纯化出希望的“三F”异二聚 体。如图11B(USSN 61/818,410)中所示，通过IEF凝胶检查“三F”部 分的纯度。最后，使用SEC确定“三F”产物的均匀尺寸(参见例如 USSN 61/818,410的图11C中)。

经显示，XENP11924，即抗CD19 Fab x抗CD3 scFv“三F”双特 异性抗体具有有效生物活性。XENP11924有效募集T细胞以杀伤Raji 肿瘤细胞系的能力显示于USSN 61/818,410的图12中。

实施例4.抗CD38 Fab x抗CD3 scFv“三F”双特异性抗体。

抗CD38 Fab x抗CD3 scFv“三F”双特异性抗体的氨基酸序列列 于USSN 61/818,410的图13中。能够相对于不希望的双scFv-Fc和 mAb同二聚体有效纯化出所希望的“三F”异二聚体的氨基酸取代加 下划线。以下给出表达和纯化所希望的“三F”物质及其生物活性的一 些实施例。

USSN 61/818,410的图14中略述了XENP11925的产生，其为具 有抗CD38 Fab和抗CD3 scFv的“三F”双特异性抗体。在USSN 61/818,410的图14A中，显示出通过离子交换从不希望的双scFv-Fc 和mAb同二聚体纯化出希望的“三F”异二聚体。如USSN 61/818,410 的图14B中所示，通过IEF凝胶检查“三F”部分的纯度。最后，使用 SEC确定“三F”产物的均匀尺寸(参见例如USSN 61/818,410的图14C 中)。

经显示，XENP11925，即抗CD38 Fab x抗CD3 scFv“三F”双特 异性抗体具有有效生物活性。XENP11925有效募集T细胞以杀伤 RPMI8226肿瘤细胞系的能力显示于USSN 61/818,410的图15中。

实施例5.使pI改变的同型恒定区变体不稳定的鉴别和修复。

如以上所描述，可以尝试通过利用IgG子类(IgG1、IgG2、IgG3 及IgG4)之间的同型差异使增加或降低pI的取代引起免疫原性的风险 降到最低。基于这一原理，设计出一组新的新型同型。这些新变体称 为ISO(-)、ISO(+)及ISO(+RR)。在铰链-CH2-CH3(H-CH2-CH3)系统 (仅Fc区)中确定这些新型同型的热稳定性。如以上所描述，表达并纯化蛋白质。这一概念验证系统的序列列于图16中。

利用差示扫描量热法(DSC)测定的热稳定性测量值(图17)揭示，ISO(-)/ISO(+RR)异二聚体(XENP12488，其序列参看图16)不如野生型 IgG1(XENP8156，其序列参看图16)稳定。随后的工程改造尝试鉴别 出ISO(-)重链中的取代N384S/K392N/M397V为不稳定的来源。因此， 设计出称为ISO(-NKV)的变体并进行测试(参看图16)。在这一变体 中，384位、392位及397位被复原成野生型IgG1(S384N/N392K/ M397V)。通过DSC测量ISO(-NKV)/ISO(+RR)异二聚体(XENP12757， 其序列参看图16)的热稳定性并发现与野生型IgG1的热稳定性相当 (图17)。这一结果强调了选择或不选择改变pI的特定同型取代以避 免引起不稳定的因素的重要性。

实施例6.另外的异二聚体偏向Fc变体。

如以上所描述，可以制备异二聚体偏向Fc变体以相对于不希望 的同二聚体，倾向于形成希望的异二聚体。在铰链-CH2-CH3系统(仅 Fc区)中设计出另外的异二聚体偏向Fc变体L368D/K370S-S364K/E3 57Q(XENP12760，其序列参看图18)并进行测试。如以上所描述，表达并纯化蛋白质。

使用阳离子交换(CIEX)色谱柱，通过高效液相色谱法(HPLC)检 查仅在单链蛋白质A纯化步骤后存在的蛋白质(参看图19)。此允许相 对于不希望的同二聚体测定希望的异二聚体的产率。 L368D/K370S-S364K/E357Q变体(XENP12760，图19下图)的存在相 对于不存在这一变体(XENP12757，图19顶图)的情形引入了对于所 希望的异二聚体的形成的极强偏好。应注意，具有 L368D/K370S-S364K/E357Q变体的异二聚体的产率是95.8％，而不 具有该变体的异二聚体的产率仅52.7％。

此外，设计出另外的异二聚体偏向Fc变体并进行测试。图36显 示了一系列工程改造的异二聚体偏向Fc变体以及异二聚体产率(通过 HPLC-CIEX测定)和热稳定性(通过DSC测定)。特别优选具有较高异 二聚体产率和较高热稳定性的L368D/K370S-S364K/E357Q变体。

实施例7.在Fab-scFv-Fc背景下的另外的异二聚体偏向Fc变体。

将异二聚体偏向Fc变体L368D/K370S-S364K/E357Q工程改造成 抗CD19 x抗CD3Fab-scFv-Fc(有关氨基酸序列，参看图15)。对照 Fab-scFv-Fc XENP13228缺乏这些异二聚体偏向Fc变体。利用等电 聚焦(IEF)凝胶检查仅在单链蛋白质A纯化步骤后存在的蛋白质。此允许相对于不希望的同二聚体测定希望的异二聚体的产率。 L368D/K370S-S364K/E357Q变体(XENP13122，图22右图)的存在相 对于不存在这一变体(XENP13228，图22左图)的情形引入了对于所 希望的异二聚体的形成的极强偏好。

实施例7.构建抗CD38 x抗CD3双特异性抗体

通过优化人类链含量使抗CD38抗体OKT10人源化(Lazar等人， Mol.Immunol.，(2007)，44：1986-1998)，并产生含有人源化抗CD38 Fv 和抗CD3结构域的双特异性分子(图37)。通过Blue Heron Biotechnologies(Bothell，WA)，由利用自动基因合成得到的合成寡核 苷酸和PCR产物合成希望的基因区段。在293E细胞中表达在pTT5 载体中的抗体构建体，并依序通过标准蛋白质A和使用GE HiTrap SP 阳离子交换色谱柱进行的IEX色谱法进行纯化，以分离出希望的异 二聚体双特异性抗体。抗体Fc结构域含有工程改造的异二聚体Fc区以便有效纯化双特异性分子。通过使用Biacore 3000在SPR上筛选 Fv区文库来改善双特异性分子对CD38的亲和力(图38)。

实施例8.抗CD38 x抗CD3双特异性抗体的体外特性

在LDH重定向T细胞的细胞毒性(RTCC)检定(图39)中及在利用 不同T细胞：RPMI8226比率的膜联蛋白V+RTCC检定(图40)中针对 杀伤RPMI8226多发性骨髓瘤(MM)细胞系的能力筛选优化的双特异性分子。另外，使用直接结合检定评估优化的分子与食蟹猴抗CD38 的交叉反应(图41)。概述优化的抗CD38 x抗CD3双特异性分子的 各种特性的表格显示于图42中。

实施例8.在移植huPBMC的SCID小鼠中抗CD38 x抗CD3双 特异性分子杀伤人浆细胞

在移植huPBMC的SCID小鼠模型中针对杀伤人浆细胞的能力筛 选优化的双特异性分子。第0天，用α-ASGM1处理每组各10只的 数组小鼠以清除SCIDNK细胞，随后在第1天，移植3×107个人 PBMC。第4天，基于总IgG含量随机分组。在移植PBMC之后第7 天和第15天，给予抗CD38 x抗CD3双特异性分子或对照物。在第 14天和第21天测定IgG2、IgE及IgM滴度。包括5mg/kg剂量的达 雷木单抗(一种抗CD38 IgG1抗体)作为对照物。观察到相较于达雷木单抗，在抗CDCD38 x抗CD3双特异性分子存在下，人Ig同型显著 减少。(图43和图44)。

实施例4.抗CD38 x抗CD3双特异性抗体清除多发性骨髓瘤患 者PBMC中的CD38+CD138+细胞

将来自两个MM供体的PBMC与1μg/mL抗CD38 x抗CD3双 特异性分子一起培育24小时，并进行细胞计数。对来自预先门控的 活细胞(通过FSC相对SSC分选)的CD38+CD138+细胞进行技术，并 针对PBS处理的对照物对事件进行归一化。结果显示于图45中。双 特异性抗体能够在此浓度下有效清除MM细胞。

实施例5.抗CD38 x抗CD3双特异性抗体的氨基酸和DNA序 列。

抗CD38 x抗CD3双特异性抗体XENP13243和XENP13551的 氨基酸和DNA序列分别列于图50和图51中。

实施例6.在中国仓鼠卵巢(CHO)中产生抗CD38 x抗CD3双特 异性抗体的稳定库。

使用Selexis专有的SURE Technology PlatformTM，根据图3中所 列的比率，用编码XENP13243和XENP13551的DNA转染中国仓鼠 卵巢(CHO)细胞，以产生平行稳定库。转染的DNA由含有图52中所 列DNA的单顺反子载体组成。稳定库细胞在10mL离心管中培养7 天，并在第7天，提取出5mL培养物上清液，通过蛋白质A亲和色 谱法纯化，并利用阳离子交换色谱法进行分析。由于产生的可能蛋白质被设计成具有不同的等电点，故阳离子交换色谱法能够分析CHO 细胞随不同DNA比率而分泌的蛋白质种类。图4列出XENP13243 和XENP13551在图3中所列每一指定DNA比率下的阳离子交换色 谱图。在用于阳离子交换色谱分析的条件下，HC-Fab同二聚体在约 15分钟时洗脱；所期望的异二聚体双特异性抗体在约22分钟时洗脱； HC-scFv单体在约26分钟时洗脱；并且HC-scFv同二聚体在约29分 钟时洗脱。不同蛋白质种类的量的概述列于图54中。

意外的是，宿主细胞中三种核酸(HC-scFv、HC及LC)的转染比 率可以驱使异二聚体的形成。若干DNA转染比率形成占总蛋白质A 纯化的物质超过80％的量的优选的双特异性异二聚体。形成超过80％ 的异二聚体的优选比率是1∶1.5∶1.5、1∶2∶1.5、1∶0.667∶2、1∶1∶2、1∶1.5∶2 及1∶2∶2(全部以HC-Fab∶HC-scFv∶LC列出)。一些DNA比率形成超过 90％的量的优选的双特异性异二聚体。形成超过90％的异二聚体的优 选比率是1∶1.5∶1.5、1∶2∶1.5、1∶1∶2及1∶2∶2(全部以HC-Fab∶HC-scFv∶LC 列出)。一种DNA比率形成超过95％的量的优选的双特异性异二聚 体。形成超过95％的异二聚体的特别优选的比率是1∶2∶2(以 HC-Fab∶HC-scFv∶LC列出)。

实施例7.抗CD38 x抗CD3双特异性抗体在C57BL/6小鼠中的 药物动力学。

静脉内给予C57BL/6小鼠(n＝5只/组)2mg/kg单次剂量的抗 CD38 x抗CD3双特异性抗体XENP13243和XENP13551。在施用测试物后1小时以及1天、3天、6天、10天、14天、17天及21天， 经由眶窦穿刺(OSP)对小鼠抽血，并将血液处理成血清以测定测试物 含量。通过免疫检定测定血清浓度并绘制于图6中。使用Phoenix WinNonlin 6.3的非房室分析模块测定测试物的半衰期。半衰期列于 图55中。应注意，在双特异性抗体的设计中包括Fc区使得半衰期与 典型单克隆抗体相当。典型的不合Fc的双特异性抗体，如BiTE或 DART形式，具有短得多的半衰期，为约数小时。

实施例8.由抗CD38 x抗CD3双特异性抗体介导的CD38+ RPMI8226细胞的重定向T细胞的细胞毒性。

使用抗CD38 x抗CD3双特异性抗体XENP13243和XENP13551 介导CD38+ RPMI 8226细胞的重定向T细胞的细胞毒性。该检定由 在37℃下10,000个RPMI8226细胞与400,000个纯化的人类T细胞 一起培育24小时组成。通过乳酸脱氢酶(LDH)读取细胞毒性。结果 示于附图中。.

实施例9.抗CD38 x抗CD3双特异性抗体的结合亲和力。

经由Biacore 3000通过表面等离子体共振测量XENP13243和 XENP13551对人和食蟹猴CD38和CD3的亲和力。使用标准方法， 并使用BIAevaluation软件测定动力学参数。结果列于附图中。

实施例10.利用抗CD38 x抗CD3双特异性抗体清除食蟹猴的 CD38+细胞。

经由静脉内输注对六组食蟹猴(n＝2只/组)施用XENP13243或 XENP13551。间隔3周对每只猴施用两次剂量。初始剂量是5ng/kg、 50ng/kg及500ng/kg，并且第二次剂量是2μg/kg、5μg/kg及20μg/kg。 观察到CD20-CD38+细胞以剂量依赖性方式清除(参看附图)。观察到 CD8+ T细胞上CD69上调证实T细胞的募集(参看附图)。

序列表

<110> XENCOR公司

Bernettt, Matthew

Bernett, Matthew

Chu, Seung

Moore, Gregory

Desjarlais, John

<120> 结合至CD38和CD3的双特异性抗体

<130> 067461-5172-WO

<140> PCT/US15/23411

<141> 2015-03-30

<150> US 61/972,172

<151> 2014-03-28

<150> US 62/025,931

<151> 2014-07-17

<150> US 62/025,974

<151> 2014-07-17

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Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 13

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11795 H1.4_L1.4

<400> 13

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 14

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11795 H1.4_L1.4

<400> 14

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 15

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11796 H1.5_L1.4

<400> 15

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 16

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11796 H1.5_L1.4, cont.

<400> 16

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 17

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11796 H1.5_L1.4, cont.

<400> 17

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 18

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11796 H1.5_L1.4, cont.

<400> 18

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 19

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11801 H1.6_L1.4

<400> 19

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Ser Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 20

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11801 H1.6_L1.4

<400> 20

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Ser Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 21

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11801 H1.6_L1.4

<400> 21

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Ser Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 22

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11801 H1.6_L1.4

<400> 22

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 23

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11802 H1.7_L1.4

<400> 23

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 24

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11802 H1.7_L1.4

<400> 24

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 25

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11802 H1.7_L1.4

<400> 25

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 26

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11802 H1.7_L1.4

<400> 26

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 27

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11803 H1.8_L1.4

<400> 27

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 28

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11803 H1.8_L1.4

<400> 28

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 29

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11803 H1.8_L1.4

<400> 29

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 30

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11803 H1.8_L1.4

<400> 30

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 31

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11804 H1.9_L1.4

<400> 31

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 Phe Asn Thr Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 32

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11804 H1.9_L1.4

<400> 32

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 Phe Asn Thr Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 33

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11804 H1.9_L1.4

<400> 33

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 Phe Asn Thr Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 34

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11804 H1.9_L1.4

<400> 34

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 35

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11805 H1.10_L1.4

<400> 35

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 Phe Asn Thr Tyr

20 25 30

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

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 36

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11805 H1.10_L1.4

<400> 36

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 Phe Asn Thr Tyr

20 25 30

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

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 37

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11805 H1.10_L1.4

<400> 37

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 Phe Asn Thr Tyr

20 25 30

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

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 38

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11805 H1.10_L1.4

<400> 38

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 39

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11806 H1.11_L1.4

<400> 39

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Ser Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 40

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11806 H1.11_L1.4

<400> 40

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Ser Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 41

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11806 H1.11_L1.4

<400> 41

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Ser Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 42

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11806 H1.11_L1.4

<400> 42

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 43

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11807 H1.12_L1.4

<400> 43

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 44

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11807 H1.12_L1.4

<400> 44

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 45

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11807 H1.12_L1.4

<400> 45

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 46

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11807 H1.12_L1.4

<400> 46

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 47

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11808 H1.13_L1.4

<400> 47

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 48

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11808 H1.13_L1.4

<400> 48

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 49

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11808 H1.13_L1.4

<400> 49

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 50

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11808 H1.13_L1.4

<400> 50

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 51

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11809 H1.14_L1.4

<400> 51

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 52

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11809 H1.14_L1.4

<400> 52

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 53

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11809 H1.14_L1.4

<400> 53

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 54

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11809 H1.14_L1.4

<400> 54

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 55

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11810 H1.15_L1.4

<400> 55

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Ala

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 56

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11810 H1.15_L1.4

<400> 56

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Ala

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 57

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11810 H1.15_L1.4

<400> 57

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Ala

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 58

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11810 H1.15_L1.4

<400> 58

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 59

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11811 H1.16_L1.4

<400> 59

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 60

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11811 H1.16_L1.4

<400> 60

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 61

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11811 H1.16_L1.4

<400> 61

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 62

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11811 H1.16_L1.4

<400> 62

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 63

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11812 H1.17_L1.4

<400> 63

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 64

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11812 H1.17_L1.4

<400> 64

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 65

<211> 123

<212> PRT

<213> 人工序列

<220>

<223> XENP11812 H1.17_L1.4

<400> 65

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115 120

<210> 66

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11812 H1.17_L1.4

<400> 66

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 67

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11813 H1.18_L1.4

<400> 67

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 68

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11813 H1.18_L1.4

<400> 68

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 69

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11813 H1.18_L1.4

<400> 69

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 70

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11813 H1.18_L1.4

<400> 70

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 71

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11814 H1.19_L1.4

<400> 71

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 72

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11814 H1.19_L1.4

<400> 72

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 73

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11814 H1.19_L1.4

<400> 73

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 74

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11814 H1.19_L1.4

<400> 74

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 75

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11815 H1.20_L1.4

<400> 75

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Lys Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 76

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11815 H1.20_L1.4

<400> 76

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Lys Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 77

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11815 H1.20_L1.4

<400> 77

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Lys Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 78

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11815 H1.20_L1.4

<400> 78

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 79

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11816 H1.21_L1.4

<400> 79

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 80

<400> 80

000

<210> 81

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11816 H1.21_L1.4

<400> 81

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 82

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11816 H1.21_L1.4

<400> 82

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 83

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11817 H1.22_L1.4

<400> 83

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 84

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11817 H1.22_L1.4

<400> 84

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 85

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11817 H1.22_L1.4

<400> 85

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 86

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11817 H1.22_L1.4

<400> 86

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 87

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11818 H1.23_L1.4

<400> 87

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Thr Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 88

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11818 H1.23_L1.4

<400> 88

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Thr Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 89

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11818 H1.23_L1.4

<400> 89

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Thr Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 90

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11818 H1.23_L1.4

<400> 90

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 91

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11819 H1.24_L1.4

<400> 91

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 92

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11819 H1.24_L1.4

<400> 92

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 93

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11819 H1.24_L1.4

<400> 93

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 94

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11819 H1.24_L1.4

<400> 94

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 95

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11820 H1.25_L1.4

<400> 95

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 96

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11820 H1.25_L1.4

<400> 96

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 97

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11820 H1.25_L1.4

<400> 97

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 98

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11820 H1.25_L1.4

<400> 98

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 99

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11821 H1.26_L1.4

<400> 99

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Thr Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 100

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11821 H1.26_L1.4

<400> 100

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Thr Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 101

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11821 H1.26_L1.4

<400> 101

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Thr Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 102

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11821 H1.26_L1.4

<400> 102

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 103

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11822 H1.27_L1.4

<400> 103

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 104

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11822 H1.27_L1.4

<400> 104

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 105

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11822 H1.27_L1.4

<400> 105

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 106

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11822 H1.27_L1.4

<400> 106

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 107

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11823 H1.28_L1.4

<400> 107

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 108

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11823 H1.28_L1.4

<400> 108

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 109

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11823 H1.28_L1.4

<400> 109

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 110

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11823 H1.28_L1.4

<400> 110

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 111

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11824 H1.29_L1.30

<400> 111

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 112

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11824 H1.29_L1.30

<400> 112

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 113

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11824 H1.29_L1.30

<400> 113

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Ser Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 114

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11824 H1.29_L1.30

<400> 114

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 115

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11825 H1_L1.10

<400> 115

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 116

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11825 H1_L1.10

<400> 116

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 117

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11825 H1_L1.10

<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 Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 118

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11825 H1_L1.10

<400> 118

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 119

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11826 H1_L1.11

<400> 119

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 120

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11826 H1_L1.11

<400> 120

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 121

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11826 H1_L1.11

<400> 121

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 122

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11826 H1_L1.11

<400> 122

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 123

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11827 H1_L1.12

<400> 123

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 124

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11827 H1_L1.12

<400> 124

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 125

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11827 H1_L1.12

<400> 125

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 126

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11827 H1_L1.12

<400> 126

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 127

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11828 H1_L1.13

<400> 127

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 128

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11828 H1_L1.13

<400> 128

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 129

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11828 H1_L1.13

<400> 129

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 130

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11828 H1_L1.13

<400> 130

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 131

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11829 H1_L1.14

<400> 131

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 132

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11829 H1_L1.14

<400> 132

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 133

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11829 H1_L1.14

<400> 133

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 134

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11829 H1_L1.14

<400> 134

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 135

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11830 H1_L1.15

<400> 135

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 136

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11830 H1_L1.15

<400> 136

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 137

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11830 H1_L1.15

<400> 137

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 138

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11830 H1_L1.15

<400> 138

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly

20 25 30

His Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 139

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11831 H1_L1.16

<400> 139

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Tyr Asp

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 140

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11831 H1_L1.16

<400> 140

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Tyr Asp

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 141

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11831 H1_L1.16

<400> 141

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 142

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11831 H1_L1.16

<400> 142

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Tyr Asp Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 143

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11832 H1_L1.17

<400> 143

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 144

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11832 H1_L1.17

<400> 144

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 145

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11832 H1_L1.17

<400> 145

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 146

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11832 H1_L1.17

<400> 146

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 147

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11833 H1_L1.18

<400> 147

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 148

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11833 H1_L1.18

<400> 148

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 149

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11833 H1_L1.18

<400> 149

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 150

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11833 H1_L1.18

<400> 150

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 151

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11834 H1_L1.19

<400> 151

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Ser Asn Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 152

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11834 H1_L1.19

<400> 152

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Ser Asn Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 153

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11834 H1_L1.19

<400> 153

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 154

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11834 H1_L1.19

<400> 154

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Ser Asn Lys His Ser Trp Thr Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 155

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11835 H1_L1.20

<400> 155

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 156

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11835 H1_L1.20

<400> 156

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 157

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11835 H1_L1.20

<400> 157

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 158

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11835 H1_L1.20

<400> 158

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 159

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11836 H1_L1.21

<400> 159

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 160

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11836 H1_L1.21

<400> 160

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 161

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11836 H1_L1.21

<400> 161

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 162

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11836 H1_L1.21

<400> 162

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Lys Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 163

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11837 H1_L1.22

<400> 163

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 164

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11837 H1_L1.22

<400> 164

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 165

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11837 H1_L1.22

<400> 165

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 166

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11837 H1_L1.22

<400> 166

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Ser Ser Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 167

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11838 H1_L1.23

<400> 167

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 168

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11838 H1_L1.23

<400> 168

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 169

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11838 H1_L1.23

<400> 169

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 170

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11838 H1_L1.23

<400> 170

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 171

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11839 H1_L1.24

<400> 171

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 172

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11839 H1_L1.24

<400> 172

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 173

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11839 H1_L1.24

<400> 173

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 174

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11839 H1_L1.24

<400> 174

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

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

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 175

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11840 H1_L1.25

<400> 175

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 176

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11840 H1_L1.25

<400> 176

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 177

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11840 H1_L1.25

<400> 177

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 178

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11840 H1_L1.25

<400> 178

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

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

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 179

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11841 H1_L1.26

<400> 179

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 180

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11841 H1_L1.26

<400> 180

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 181

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11841 H1_L1.26

<400> 181

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 182

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11841 H1_L1.26

<400> 182

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 183

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11842 H1_L1.27

<400> 183

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Leu Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 184

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11842 H1_L1.27

<400> 184

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Leu Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 185

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11842 H1_L1.27

<400> 185

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 186

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11842 H1_L1.27

<400> 186

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Leu Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 187

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11843 H1_L1.28

<400> 187

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 188

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11843 H1_L1.28

<400> 188

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 189

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11843 H1_L1.28

<400> 189

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 190

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11843 H1_L1.28

<400> 190

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 191

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11844 H1_L1.29

<400> 191

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Ser His His His His His

245 250 255

His

<210> 192

<211> 251

<212> PRT

<213> 人工序列

<220>

<223> XENP11844 H1_L1.29

<400> 192

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Ser

245 250

<210> 193

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11844 H1_L1.29

<400> 193

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 194

<211> 111

<212> PRT

<213> 人工序列

<220>

<223> XENP11844 H1_L1.29

<400> 194

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Ser

100 105 110

<210> 195

<211> 258

<212> PRT

<213> 人工序列

<220>

<223> XENP11920 H1_L3.1

<400> 195

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

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

145 150 155 160

Leu Ser Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

165 170 175

Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly

180 185 190

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

195 200 205

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

210 215 220

Asp Phe Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val

225 230 235 240

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser His His His His

245 250 255

His His

<210> 196

<211> 252

<212> PRT

<213> 人工序列

<220>

<223> XENP11920 H1_L3.1

<400> 196

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

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

145 150 155 160

Leu Ser Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

165 170 175

Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly

180 185 190

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

195 200 205

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

210 215 220

Asp Phe Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val

225 230 235 240

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser

245 250

<210> 197

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11920 H1_L3.1

<400> 197

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 198

<211> 112

<212> PRT

<213> 人工序列

<220>

<223> XENP11920 H1_L3.1

<400> 198

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ser Ser Thr Gly Ala Val Thr Thr

20 25 30

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg

35 40 45

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

50 55 60

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

65 70 75 80

Leu Gln Pro Glu Asp Phe Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser

85 90 95

Asn Leu Trp Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser

100 105 110

<210> 199

<211> 258

<212> PRT

<213> 人工序列

<220>

<223> XENP11921 H1_L5.1

<400> 199

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met

130 135 140

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

145 150 155 160

Ile Asn Cys Lys Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

165 170 175

Asn Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Lys Gly Leu Ile Gly

180 185 190

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

195 200 205

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu

210 215 220

Asp Val Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val

225 230 235 240

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser His His His His

245 250 255

His His

<210> 200

<211> 252

<212> PRT

<213> 人工序列

<220>

<223> XENP11921 H1_L5.1

<400> 200

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met

130 135 140

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

145 150 155 160

Ile Asn Cys Lys Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

165 170 175

Asn Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Lys Gly Leu Ile Gly

180 185 190

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

195 200 205

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu

210 215 220

Asp Val Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val

225 230 235 240

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser

245 250

<210> 201

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11921 H1_L5.1

<400> 201

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 202

<211> 112

<212> PRT

<213> 人工序列

<220>

<223> XENP11921 H1_L5.1

<400> 202

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

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Thr Gly Ala Val Thr Thr

20 25 30

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Lys

35 40 45

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

50 55 60

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

65 70 75 80

Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser

85 90 95

Asn Leu Trp Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Ser

100 105 110

<210> 203

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11922 H1_L1.31

<400> 203

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 204

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11922 H1_L1.31

<400> 204

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 205

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11922 H1_L1.31

<400> 205

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 206

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11922 H1_L1.31

<400> 206

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Asp Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 207

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP11923 H1_L1.32

<400> 207

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 208

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP11923 H1_L1.32

<400> 208

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 209

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP11923 H1_L1.32

<400> 209

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 210

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP11923 H1_L1.32

<400> 210

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 211

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12107 H1.38_L1.4

<400> 211

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 212

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12107 H1.38_L1.4

<400> 212

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 213

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12107 H1.38_L1.4

<400> 213

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 214

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12107 H1.38_L1.4

<400> 214

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 215

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12108 H1_L1.33

<400> 215

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 216

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12108 H1_L1.33

<400> 216

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 217

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12108 H1_L1.33

<400> 217

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 218

<211> 107

<212> PRT

<213> 人工序列

<220>

<223> XENP12108 H1_L1.33

<400> 218

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr

100 105

<210> 219

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12109 H1_L1.34

<400> 219

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Thr Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 220

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12109 H1_L1.34

<400> 220

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Thr Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 221

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12109 H1_L1.34

<400> 221

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 222

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12109 H1_L1.34

<400> 222

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Thr Ala Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 223

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12110 H1_L1.35

<400> 223

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Ser Pro Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 224

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12110 H1_L1.35

<400> 224

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Ser Pro Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 225

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12110 H1_L1.35

<400> 225

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 226

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12110 H1_L1.35

<400> 226

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Ser Pro Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 227

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12111 H1_L1.36

<400> 227

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 228

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12111 H1_L1.36

<400> 228

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 229

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12111 H1_L1.36

<400> 229

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 230

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12111 H1_L1.36

<400> 230

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Pro Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 231

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12112 H1_L1.37

<400> 231

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Gly Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 232

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12112 H1_L1.37

<400> 232

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Gly Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 233

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12112 H1_L1.37

<400> 233

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 234

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12112 H1_L1.37

<400> 234

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Gly Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 235

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12113 H1_L1.38

<400> 235

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 236

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12113 H1_L1.38

<400> 236

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 237

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12113 H1_L1.38

<400> 237

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 238

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12113 H1_L1.38

<400> 238

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 239

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12114 H1_L1.39

<400> 239

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Asp Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 240

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12114 H1_L1.39

<400> 240

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

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

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Asp Pro Arg Gly Leu Ile Gly Gly

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 241

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12114 H1_L1.39

<400> 241

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

<210> 242

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12114 H1_L1.39

<400> 242

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

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Asp Pro Arg Gly

35 40 45

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

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 243

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12131 H1.30_L1.4

<400> 243

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

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

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

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

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 244

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12131 H1.30_L1.4

<400> 244

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 245

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12131 H1.30_L1.4

<400> 245

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 246

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12131 H1.30_L1.4

<400> 246

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 247

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12132 H1.31_L1.4

<400> 247

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 248

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12132 H1.31_L1.4

<400> 248

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 249

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12132 H1.31_L1.4

<400> 249

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 250

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12132 H1.31_L1.4

<400> 250

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 251

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12133 H1.32_L1.4

<400> 251

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 252

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12133 H1.32_L1.4

<400> 252

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 253

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12133 H1.32_L1.4

<400> 253

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 254

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12133 H1.32_L1.4

<400> 254

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 255

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12134 H1.33_L1.4

<400> 255

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 256

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12134 H1.33_L1.4

<400> 256

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 257

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12134 H1.33_L1.4

<400> 257

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 258

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12134 H1.33_L1.4

<400> 258

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 259

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12135 H1.34_L1.4

<400> 259

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 260

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12135 H1.34_L1.4

<400> 260

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 261

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12135 H1.34_L1.4

<400> 261

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 262

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12135 H1.34_L1.4

<400> 262

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 263

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12136 H1.35_L1.4

<400> 263

Glu Val Gln Leu Val Glu Ser Gly Gly Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 264

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12136 H1.35_L1.4

<400> 264

Glu Val Gln Leu Val Glu Ser Gly Gly Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 265

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12136 H1.35_L1.4

<400> 265

Glu Val Gln Leu Val Glu Ser Gly Gly Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 266

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12136 H1.35_L1.4

<400> 266

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 267

<211> 255

<212> PRT

<213> 人工序列

<220>

<223> XENP12137 H1.36_L1.4

<400> 267

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp 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

Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln

130 135 140

Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys

145 150 155 160

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Asn

180 185 190

Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly

195 200 205

Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala

210 215 220

Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly

225 230 235 240

Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His His

245 250 255

<210> 268

<211> 247

<212> PRT

<213> 人工序列

<220>

<223> XENP12137 H1.36_L1.4

<400> 268

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp 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

Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln

130 135 140

Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys

145 150 155 160

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Asn

180 185 190

Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly

195 200 205

Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala

210 215 220

Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly

225 230 235 240

Gly Thr Lys Leu Thr Val Leu

245

<210> 269

<211> 123

<212> PRT

<213> 人工序列

<220>

<223> XENP12137 H1.36_L1.4

<400> 269

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp 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

Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 270

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12137 H1.36_L1.4

<400> 270

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 271

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12138 H1.37_L1.4

<400> 271

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 272

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12138 H1.37_L1.4

<400> 272

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 273

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12138 H1.37_L1.4

<400> 273

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 274

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12138 H1.37_L1.4

<400> 274

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 275

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12139 H1.37_L1.32

<400> 275

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 276

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12139 H1.37_L1.32

<400> 276

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 277

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12139 H1.37_L1.32

<400> 277

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 278

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12139 H1.37_L1.32

<400> 278

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 279

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12149 H1_L1.40

<400> 279

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 280

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12149 H1_L1.40

<400> 280

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 281

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12149 H1_L1.40

<400> 281

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 Phe Asn Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 282

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12149 H1_L1.40

<400> 282

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 283

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12213 H1.30_L1.40

<400> 283

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 284

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12213 H1.30_L1.40

<400> 284

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 285

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12213 H1.30_L1.40

<400> 285

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 286

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12213 H1.30_L1.40

<400> 286

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 287

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12214 H1.8_L1.40

<400> 287

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 288

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12214 H1.8_L1.40

<400> 288

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 289

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12214 H1.8_L1.40

<400> 289

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 290

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12214 H1.8_L1.40

<400> 290

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 291

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12215 H1.39_L1.40

<400> 291

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 292

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12215 H1.39_L1.40

<400> 292

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 293

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12215 H1.39_L1.40

<400> 293

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 294

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12215 H1.39_L1.40

<400> 294

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 295

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12216 H1.40_L1.40

<400> 295

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 296

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12216 H1.40_L1.40

<400> 296

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 297

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12216 H1.40_L1.40

<400> 297

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 298

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12216 H1.40_L1.40

<400> 298

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 299

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12217 H1.30_L1.41

<400> 299

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 300

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12217 H1.30_L1.41

<400> 300

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 301

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12217 H1.30_L1.41

<400> 301

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 302

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12217 H1.30_L1.41

<400> 302

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 303

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12218 H1.8_L1.41

<400> 303

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 304

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12218 H1.8_L1.41

<400> 304

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 305

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12218 H1.8_L1.41

<400> 305

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 306

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12218 H1.8_L1.41

<400> 306

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 307

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12219 H1.39_L1.41

<400> 307

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 308

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12219 H1.39_L1.41

<400> 308

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 309

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12219 H1.39_L1.41

<400> 309

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 310

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12219 H1.39_L1.41

<400> 310

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 311

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12220 H1.40_L1.41

<400> 311

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 312

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12220 H1.40_L1.41

<400> 312

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 313

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12220 H1.40_L1.41

<400> 313

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 314

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12220 H1.40_L1.41

<400> 314

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 315

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12221 H1.30_L1.42

<400> 315

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 316

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12221 H1.30_L1.42

<400> 316

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 317

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12221 H1.30_L1.42

<400> 317

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 318

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12221 H1.30_L1.42

<400> 318

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 319

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12222 H1.8_L1.42

<400> 319

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 320

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12222 H1.8_L1.42

<400> 320

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 321

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12222 H1.8_L1.42

<400> 321

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 322

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12222 H1.8_L1.42

<400> 322

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 323

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12223 H1.39_L1.42

<400> 323

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 324

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12223 H1.39_L1.42

<400> 324

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 325

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12223 H1.39_L1.42

<400> 325

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 326

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12223 H1.39_L1.42

<400> 326

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 327

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12224 H1.40_L1.42

<400> 327

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 328

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12224 H1.40_L1.42

<400> 328

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 329

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12224 H1.40_L1.42

<400> 329

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 330

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12224 H1.40_L1.42

<400> 330

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 331

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12225 H1.30_L1.43

<400> 331

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 332

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12225 H1.30_L1.43

<400> 332

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 333

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12225 H1.30_L1.43

<400> 333

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 334

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12225 H1.30_L1.43

<400> 334

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 335

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12226 H1.8_L1.43

<400> 335

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 336

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12226 H1.8_L1.43

<400> 336

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 337

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12226 H1.8_L1.43

<400> 337

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 338

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12226 H1.8_L1.43

<400> 338

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 339

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12227 H1.39_L1.43

<400> 339

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 340

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12227 H1.39_L1.43

<400> 340

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 341

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12227 H1.39_L1.43

<400> 341

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 342

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12227 H1.39_L1.43

<400> 342

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 343

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12228 H1.40_L1.43

<400> 343

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 344

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12228 H1.40_L1.43

<400> 344

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 345

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12228 H1.40_L1.43

<400> 345

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 346

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12228 H1.40_L1.43

<400> 346

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 347

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12229 H1.30_L1.44

<400> 347

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 348

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12229 H1.30_L1.44

<400> 348

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 349

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12229 H1.30_L1.44

<400> 349

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 350

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12229 H1.30_L1.44

<400> 350

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 351

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12230 H1.8_L1.44

<400> 351

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 352

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12230 H1.8_L1.44

<400> 352

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 353

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12230 H1.8_L1.44

<400> 353

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 354

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12230 H1.8_L1.44

<400> 354

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 355

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12231 H1.39_L1.44

<400> 355

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 356

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12231 H1.39_L1.44

<400> 356

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 357

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12231 H1.39_L1.44

<400> 357

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 358

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12231 H1.39_L1.44

<400> 358

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 359

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12232 H1.40_L1.44

<400> 359

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 360

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12232 H1.40_L1.44

<400> 360

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 361

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12232 H1.40_L1.44

<400> 361

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 362

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12232 H1.40_L1.44

<400> 362

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 363

<211> 256

<212> PRT

<213> 人工序列

<220>

<223> XENP12233 H1.30_L1.45

<400> 363

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

<210> 364

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12233 H1.30_L1.45

<400> 364

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 365

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12233 H1.30_L1.45

<400> 365

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 366

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12233 H1.30_L1.45

<400> 366

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 367

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12234 H1.8_L1.45

<400> 367

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 368

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12234 H1.8_L1.45

<400> 368

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 369

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12234 H1.8_L1.45

<400> 369

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 370

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12234 H1.8_L1.45

<400> 370

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 371

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12235 H1.39_L1.45

<400> 371

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 372

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12235 H1.39_L1.45

<400> 372

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 373

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12235 H1.39_L1.45

<400> 373

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 374

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12235 H1.39_L1.45

<400> 374

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 375

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12236 H1.40_L1.45

<400> 375

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 376

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12236 H1.40_L1.45

<400> 376

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 377

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12236 H1.40_L1.45

<400> 377

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 378

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12236 H1.40_L1.45

<400> 378

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ala Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 379

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12237 H1.30_L1.46

<400> 379

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 380

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12237 H1.30_L1.46

<400> 380

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 381

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12237 H1.30_L1.46

<400> 381

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 382

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12237 H1.30_L1.46

<400> 382

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 383

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12238 H1.8_L1.46

<400> 383

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 384

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12238 H1.8_L1.46

<400> 384

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 385

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12238 H1.8_L1.46

<400> 385

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 386

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12238 H1.8_L1.46

<400> 386

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 387

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12239 H1.39_L1.46

<400> 387

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 388

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12239 H1.39_L1.46

<400> 388

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 389

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12239 H1.39_L1.46

<400> 389

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 390

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12239 H1.39_L1.46

<400> 390

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 391

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12240 H1.40_L1.46

<400> 391

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 392

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12240 H1.40_L1.46

<400> 392

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 393

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12240 H1.40_L1.46

<400> 393

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 394

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12240 H1.40_L1.46

<400> 394

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 395

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12241 H1.30_L1.47

<400> 395

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 396

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12241 H1.30_L1.47

<400> 396

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 397

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12241 H1.30_L1.47

<400> 397

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 398

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12241 H1.30_L1.47

<400> 398

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 399

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12242 H1.8_L1.47

<400> 399

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 400

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12242 H1.8_L1.47

<400> 400

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 401

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12242 H1.8_L1.47

<400> 401

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 402

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12242 H1.8_L1.47

<400> 402

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 403

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12243 H1.39_L1.47

<400> 403

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 404

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12243 H1.39_L1.47

<400> 404

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 405

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12243 H1.39_L1.47

<400> 405

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 406

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12243 H1.39_L1.47

<400> 406

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 407

<211> 257

<212> PRT

<213> 人工序列

<220>

<223> XENP12244 H1.40_L1.47

<400> 407

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser His His His His His

245 250 255

His

<210> 408

<211> 249

<212> PRT

<213> 人工序列

<220>

<223> XENP12244 H1.40_L1.47

<400> 408

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val

130 135 140

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu

145 150 155 160

Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

165 170 175

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly

180 185 190

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu

195 200 205

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp

210 215 220

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val Phe

225 230 235 240

Gly Gly Gly Thr Lys Leu Thr Val Leu

245

<210> 409

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> XENP12244 H1.40_L1.47

<400> 409

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Lys Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 410

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> XENP12244 H1.40_L1.47

<400> 410

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 411

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> vhCDR1

<400> 411

Thr Tyr Ala Met Asn

1 5

<210> 412

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> vhCDR1

<400> 412

Thr Tyr Ala Met Ser

1 5

<210> 413

<211> 19

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<400> 413

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

1 5 10 15

Val Lys Gly

<210> 414

<211> 19

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<400> 414

Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

1 5 10 15

Val Lys Gly

<210> 415

<211> 17

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<400> 415

Arg Ile Arg Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 416

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vhCD3

<400> 416

His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr

1 5 10

<210> 417

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vhCDR3

<400> 417

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr

1 5 10

<210> 418

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vhCDR3

<400> 418

His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe Ala Tyr

1 5 10

<210> 419

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vhCDR3

<400> 419

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Asp Tyr

1 5 10

<210> 420

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<400> 420

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

1 5 10

<210> 421

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<400> 421

Gly Ser Ser Thr Gly Ala Val Thr Ser Ser Asn Tyr Ala Asn

1 5 10

<210> 422

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<400> 422

Gly Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Ala Asn

1 5 10

<210> 423

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<400> 423

Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

1 5 10

<210> 424

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<400> 424

Lys Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

1 5 10

<210> 425

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> vlCDR2

<400> 425

Gly Thr Asn Lys Arg Ala Pro

1 5

<210> 426

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> vlCDR2

<400> 426

Asp Thr Asn Lys Arg Ala Pro

1 5

<210> 427

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> vlCDR2

<400> 427

Gly Thr Asn Asn Arg Ala Pro

1 5

<210> 428

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> vlCDR2

<400> 428

Gly Thr Asn Lys Arg Ala Ser

1 5

<210> 429

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> uncharged ScFv linker

<400> 429

Gly Gly Gly Gly Ser

1 5

<210> 430

<211> 9

<212> PRT

<213> 人工序列

<220>

<223> vlCDR3

<400> 430

Ala Leu Trp Tyr Ser Asn Leu Trp Val

1 5

<210> 431

<211> 4

<212> PRT

<213> 人工序列

<220>

<223> sequence linker

<400> 431

Gly Phe Leu Gly

1

<210> 432

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> vhCDR1

<400> 432

Thr Tyr Ala Met His

1 5

<210> 433

<211> 9

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<400> 433

Ala Leu Trp Tyr Ser Asn His Trp Val

1 5

<210> 434

<211> 19

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<400> 434

Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser

1 5 10 15

Val Lys Gly

<210> 435

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> vhCDR1

<220>

<221> MISC_FEATURE

<222> (5)..(5)

<223> Xaa可为Asn, Ser或His

<400> 435

Thr Tyr Ala Met Xaa

1 5

<210> 436

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> vhCDR2

<220>

<221> MISC_FEATURE

<222> (6)..(6)

<223> Xaa可为Tyr或Ala

<220>

<221> MISC_FEATURE

<222> (8)..(8)

<223> Xaa可为Asn或Ser

<220>

<221> MISC_FEATURE

<222> (12)..(12)

<223> Xaa可为Tyr或Ala

<220>

<221> MISC_FEATURE

<222> (16)..(16)

<223> Xaa可为Asp或Ala

<400> 436

Arg Ile Arg Ser Lys Xaa Asn Xaa Tyr Ala Thr Xaa Tyr Tyr Ala Xaa

1 5 10 15

Ser Val Lys Gly

20

<210> 437

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vhCDR3

<220>

<221> MISC_FEATURE

<222> (6)..(6)

<223> Xaa可为Asn, Asp或Gln

<220>

<221> MISC_FEATURE

<222> (13)..(13)

<223> Xaa可为Ala或Asp

<400> 437

His Gly Asn Phe Gly Xaa Ser Tyr Val Ser Trp Phe Xaa Tyr

1 5 10

<210> 438

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> vlCDR1

<220>

<221> MISC_FEATURE

<222> (1)..(1)

<223> Xaa可为Gly, Arg或Lys

<220>

<221> MISC_FEATURE

<222> (9)..(9)

<223> Xaa可为Thr或Ser

<220>

<221> MISC_FEATURE

<222> (10)..(10)

<223> Xaa可为Ser或Gly

<220>

<221> MISC_FEATURE

<222> (11)..(11)

<223> Xaa可为Asn或His

<400> 438

Xaa Ser Ser Thr Gly Ala Val Thr Xaa Xaa Xaa Tyr Ala Asn

1 5 10

<210> 439

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> vlCDR2

<220>

<221> MISC_FEATURE

<222> (1)..(1)

<223> Xaa可为Gly或Asp

<220>

<221> MISC_FEATURE

<222> (4)..(4)

<223> Xaa可为Lys或Asn

<220>

<221> MISC_FEATURE

<222> (7)..(7)

<223> Xaa可为Pro或Ser

<400> 439

Xaa Thr Asn Xaa Arg Ala Xaa

1 5

<210> 440

<211> 9

<212> PRT

<213> 人工序列

<220>

<223> vlCDR3

<220>

<221> MISC_FEATURE

<222> (1)..(1)

<223> Xaa可为Ala或Leu

<220>

<221> MISC_FEATURE

<222> (7)..(7)

<223> Xaa可为Leu或His

<400> 440

Xaa Leu Trp Tyr Ser Asn Xaa Trp Val

1 5

<210> 441

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Gly-Ser 15

<400> 441

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10 15

<210> 442

<211> 18

<212> PRT

<213> 人工序列

<220>

<223> Whitlow linker

<400> 442

Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr

1 5 10 15

Lys Gly

<210> 443

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> 6paxA_1 (+A)

<400> 443

Ile Arg Pro Arg Ala Ile Gly Gly Ser Lys Pro Arg Val Ala

1 5 10

<210> 444

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +B

<400> 444

Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser

1 5 10 15

<210> 445

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> GKGGSGKGGSGKGGS +C

<400> 445

Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser

1 5 10 15

<210> 446

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +D

<400> 446

Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser

1 5 10 15

<210> 447

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +E

<400> 447

Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser

1 5 10 15

<210> 448

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +F

<400> 448

Gly Gly Gly Lys Ser Gly Gly Lys Gly Ser Gly Lys Gly Gly Ser

1 5 10 15

<210> 449

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +G

<400> 449

Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser

1 5 10 15

<210> 450

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +H

<400> 450

Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly

1 5 10 15

Lys Pro Gly Ser

20

<210> 451

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> Positive charged scFv linkers +I

<400> 451

Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly

1 5 10 15

Lys Gly Lys Ser

20

<210> 452

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> Negative Gly-Ser 15

<400> 452

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

1 5 10 15

Gly Gly Gly Ser

20

<210> 453

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> 3hsc_2 (-A)

<400> 453

Ser Thr Ala Gly Asp Thr His Leu Gly Gly Glu Asp Phe Asp

1 5 10

<210> 454

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -B

<400> 454

Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser

1 5 10 15

<210> 455

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -C

<400> 455

Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser

1 5 10 15

<210> 456

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -D

<400> 456

Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser

1 5 10 15

<210> 457

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -E

<400> 457

Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser

1 5 10 15

<210> 458

<211> 15

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -F

<400> 458

Gly Gly Gly Glu Ser Gly Gly Glu Gly Ser Gly Glu Gly Gly Ser

1 5 10 15

<210> 459

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> Negative charged scFv linkers -G

<400> 459

Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly

1 5 10 15

Glu Gly Glu Ser

20

<210> 460

<211> 300

<212> PRT

<213> 人工序列

<220>

<223> CD38 (Full Sequence)

<400> 460

Met Ala Asn Cys Glu Phe Ser Pro Val Ser Gly Asp Lys Pro Cys Cys

1 5 10 15

Arg Leu Ser Arg Arg Ala Gln Leu Cys Leu Gly Val Ser Ile Leu Val

20 25 30

Leu Ile Leu Val Val Val Leu Ala Val Val Val Pro Arg Trp Arg Gln

35 40 45

Gln Trp Ser Gly Pro Gly Thr Thr Lys Arg Phe Pro Glu Thr Val Leu

50 55 60

Ala Arg Cys Val Lys Tyr Thr Glu Ile His Pro Glu Met Arg His Val

65 70 75 80

Asp Cys Gln Ser Val Trp Asp Ala Phe Lys Gly Ala Phe Ile Ser Lys

85 90 95

His Pro Cys Asn Ile Thr Glu Glu Asp Tyr Gln Pro Leu Met Lys Leu

100 105 110

Gly Thr Gln Thr Val Pro Cys Asn Lys Ile Leu Leu Trp Ser Arg Ile

115 120 125

Lys Asp Leu Ala His Gln Phe Thr Gln Val Gln Arg Asp Met Phe Thr

130 135 140

Leu Glu Asp Thr Leu Leu Gly Tyr Leu Ala Asp Asp Leu Thr Trp Cys

145 150 155 160

Gly Glu Phe Asn Thr Ser Lys Ile Asn Tyr Gln Ser Cys Pro Asp Trp

165 170 175

Arg Lys Asp Cys Ser Asn Asn Pro Val Ser Val Phe Trp Lys Thr Val

180 185 190

Ser Arg Arg Phe Ala Glu Ala Ala Cys Asp Val Val His Val Met Leu

195 200 205

Asn Gly Ser Arg Ser Lys Ile Phe Asp Lys Asn Ser Thr Phe Gly Ser

210 215 220

Val Glu Val His Asn Leu Gln Pro Glu Lys Val Gln Thr Leu Glu Ala

225 230 235 240

Trp Val Ile His Gly Gly Arg Glu Asp Ser Arg Asp Leu Cys Gln Asp

245 250 255

Pro Thr Ile Lys Glu Leu Glu Ser Ile Ile Ser Lys Arg Asn Ile Gln

260 265 270

Phe Ser Cys Lys Asn Ile Tyr Arg Pro Asp Lys Phe Leu Gln Cys Val

275 280 285

Lys Asn Pro Glu Asp Ser Ser Cys Thr Ser Glu Ile

290 295 300

<210> 461

<211> 258

<212> PRT

<213> 人工序列

<220>

<223> CD38 (Extracellular domain only)

<400> 461

Val Pro Arg Trp Arg Gln Gln Trp Ser Gly Pro Gly Thr Thr Lys Arg

1 5 10 15

Phe Pro Glu Thr Val Leu Ala Arg Cys Val Lys Tyr Thr Glu Ile His

20 25 30

Pro Glu Met Arg His Val Asp Cys Gln Ser Val Trp Asp Ala Phe Lys

35 40 45

Gly Ala Phe Ile Ser Lys His Pro Cys Asn Ile Thr Glu Glu Asp Tyr

50 55 60

Gln Pro Leu Met Lys Leu Gly Thr Gln Thr Val Pro Cys Asn Lys Ile

65 70 75 80

Leu Leu Trp Ser Arg Ile Lys Asp Leu Ala His Gln Phe Thr Gln Val

85 90 95

Gln Arg Asp Met Phe Thr Leu Glu Asp Thr Leu Leu Gly Tyr Leu Ala

100 105 110

Asp Asp Leu Thr Trp Cys Gly Glu Phe Asn Thr Ser Lys Ile Asn Tyr

115 120 125

Gln Ser Cys Pro Asp Trp Arg Lys Asp Cys Ser Asn Asn Pro Val Ser

130 135 140

Val Phe Trp Lys Thr Val Ser Arg Arg Phe Ala Glu Ala Ala Cys Asp

145 150 155 160

Val Val His Val Met Leu Asn Gly Ser Arg Ser Lys Ile Phe Asp Lys

165 170 175

Asn Ser Thr Phe Gly Ser Val Glu Val His Asn Leu Gln Pro Glu Lys

180 185 190

Val Gln Thr Leu Glu Ala Trp Val Ile His Gly Gly Arg Glu Asp Ser

195 200 205

Arg Asp Leu Cys Gln Asp Pro Thr Ile Lys Glu Leu Glu Ser Ile Ile

210 215 220

Ser Lys Arg Asn Ile Gln Phe Ser Cys Lys Asn Ile Tyr Arg Pro Asp

225 230 235 240

Lys Phe Leu Gln Cys Val Lys Asn Pro Glu Asp Ser Ser Cys Thr Ser

245 250 255

Glu Ile

<210> 462

<211> 207

<212> PRT

<213> 人工序列

<220>

<223> HUMAN T-cell surface glycoprotein CD3 epsilon chain

<400> 462

Met Gln Ser Gly Thr His Trp Arg Val Leu Gly Leu Cys Leu Leu Ser

1 5 10 15

Val Gly Val Trp Gly Gln Asp Gly Asn Glu Glu Met Gly Gly Ile Thr

20 25 30

Gln Thr Pro Tyr Lys Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr

35 40 45

Cys Pro Gln Tyr Pro Gly Ser Glu Ile Leu Trp Gln His Asn Asp Lys

50 55 60

Asn Ile Gly Gly Asp Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp

65 70 75 80

His Leu Ser Leu Lys Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr

85 90 95

Val Cys Tyr Pro Arg Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu

100 105 110

Tyr Leu Arg Ala Arg Val Cys Glu Asn Cys Met Glu Met Asp Val Met

115 120 125

Ser Val Ala Thr Ile Val Ile Val Asp Ile Cys Ile Thr Gly Gly Leu

130 135 140

Leu Leu Leu Val Tyr Tyr Trp Ser Lys Asn Arg Lys Ala Lys Ala Lys

145 150 155 160

Pro Val Thr Arg Gly Ala Gly Ala Gly Gly Arg Gln Arg Gly Gln Asn

165 170 175

Lys Glu Arg Pro Pro Pro Val Pro Asn Pro Asp Tyr Glu Pro Ile Arg

180 185 190

Lys Gly Gln Arg Asp Leu Tyr Ser Gly Leu Asn Gln Arg Arg Ile

195 200 205

<210> 463

<211> 116

<212> PRT

<213> 人工序列

<220>

<223> OKT10 VH

<400> 463

Glu Val Lys Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Thr Thr Ser Leu

50 55 60

Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Thr Lys Val Arg Ser Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ala

115

<210> 464

<211> 107

<212> PRT

<213> 人工序列

<220>

<223> OKT10 VL

<400> 464

Asp Ile Val Met Thr Gln Ser Pro Lys Ile Met Pro Thr Ser Val Gly

1 5 10 15

Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn Val Asp Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr Asn Val Gln Ser

65 70 75 80

Glu Asp Leu Ala Glu Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Ala Gly Thr Lys Leu Asp Leu Lys

100 105

<210> 465

<211> 446

<212> PRT

<213> 人工序列

<220>

<223> XENP11855 Heavy chain

<400> 465

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 466

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> XENP11855 Light chain

<400> 466

Asp Ile Val 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 Asn Val Asp Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 467

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 467

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 468

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 468

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 469

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1)

<400> 469

Asp Ile Val 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 Asn Val Asp Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 470

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 470

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 471

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 471

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 472

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1)

<400> 472

Asp Ile Val 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 Asn Val Asp Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 473

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 473

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 474

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 474

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 475

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.24)

<400> 475

Asp Ile Val 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 Asn Val Asp Thr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 476

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 476

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 477

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 477

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 478

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 478

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 479

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 479

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 480

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 480

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 481

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 481

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 482

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 482

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 483

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 483

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 484

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.97)

<400> 484

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 485

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.72)

<400> 485

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 Asp Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 486

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 486

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 487

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.97)

<400> 487

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 488

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.71)

<400> 488

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 Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 489

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 489

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 490

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 490

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 491

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 491

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 492

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.30 L1.47)

<400> 492

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 493

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.24)

<400> 493

Asp Ile Val 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 Asn Val Asp Thr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 494

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 494

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 495

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 495

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 496

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.24)

<400> 496

Asp Ile Val 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 Asn Val Asp Thr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 497

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 497

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 498

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 498

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 499

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.24)

<400> 499

Asp Ile Val 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 Asn Val Asp Thr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 500

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1)

<400> 500

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 501

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 501

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 502

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 502

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 503

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 503

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 504

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 504

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 505

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 505

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 506

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.77)

<400> 506

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 507

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 507

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 508

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.97)

<400> 508

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 509

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.72)

<400> 509

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 Asp Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 510

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 510

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 511

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.97)

<400> 511

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 512

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> 重链1 (抗-CD38 H1.71)

<400> 512

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 Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 513

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> 重链2 (抗-CD3 H1.79 L1.48)

<400> 513

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 514

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> 轻链(抗-CD38 L1.96)

<400> 514

Asp Ile Val 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 Asn Val Asp Tyr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ala Ala Ser Trp Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Val Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 515

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> XENP13243 HC-Fab

<400> 515

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 Asp Phe Ser Arg Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 516

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> XENP13243 HC-scFv

<400> 516

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 517

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> XENP13243 LC

<400> 517

Asp Ile Val 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 Asn Val Asp Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 518

<211> 254

<212> PRT

<213> 人工序列

<220>

<223> XENP13242的scFv包括带电的连接子

<400> 518

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250

<210> 519

<211> 445

<212> PRT

<213> 人工序列

<220>

<223> XENP13551 HC-Fab

<400> 519

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 Phe Ser Tyr Ser

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210> 520

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> XENP13551 HC-scFv

<400> 520

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250 255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265 270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280 285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295 300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315 320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345 350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360 365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375 380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395 400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410 415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425 430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440 445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485

<210> 521

<211> 214

<212> PRT

<213> 人工序列

<220>

<223> XENP13551 LC

<400> 521

Asp Ile Val 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 Asn Val Asp Thr Trp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 522

<211> 254

<212> PRT

<213> 人工序列

<220>

<223> XENP13551的scFv包括带电的连接子

<400> 522

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250

<210> 523

<211> 1338

<212> DNA

<213> 人工序列

<220>

<223> XENP13243 HC-Fab (XenD08502)

<400> 523

gaagtccagc tcgtggagtc gggtggcggc ctcgtccagc ccggcggctc gctccggctg 60

tcatgcgccg cgagcgggtt cgatttcagt cgttcgtgga tgaactgggt acgccaggcc 120

ccgggcaagg gcctcgaatg ggtctccgag atcaacccgg acagcagcac gatcaactac 180

gccacctcgg tgaagggccg gttcacgatc agccgcgaca actccaagaa caccctctac 240

ctgcagatga actccctgcg cgccgaggac acggccgtct actactgcgc gcgctacgga 300

aactggttcc cgtactgggg ccagggcaca ctggtcactg tctccagcgc gtccacgaag 360

ggcccgtcgg tcttccccct ggcgccaagc tcgaaaagta cgtccggcgg gaccgcagcg 420

ctgggctgcc tggtcaagga ctacttcccc gagcccgtga ccgtgagctg gaactcgggc 480

gcgctgacct ccggcgtcca caccttcccg gcagtcctcc agtcgtcggg cctgtactcg 540

ctgtccagcg tcgtcacggt gccgtcgtcc tccctgggca cgcagacgta catctgcaac 600

gtgaaccaca agccgagcga caccaaggtc gacaagaagg tcgagcccaa gtcgtgcgac 660

aagacccaca cgtgcccgcc gtgcccggcc ccccctgtcg ccggccccag tgtcttcctc 720

ttcccgccga agccgaagga caccctcatg atctcgcgca cccccgaggt cacctgcgtg 780

gtcgtggacg tgaagcacga ggaccctgag gttaagttca actggtatgt cgacggggtg 840

gaggtccaca acgcgaagac caagccgcgc gaggaggagt acaacagtac gtaccgcgtg 900

gtctcggtgc tcaccgtcct ccaccaggac tggctgaacg gcaaggaata caagtgtaag 960

gtcagcaaca aggccttgcc cgcccccatc gagaagacca taagcaaggc caagggtcag 1020

ccaagggaac cgcaggtgta caccctcccg ccctcccgcg aggagatgac caagaaccag 1080

gtatcactga cctgcgacgt gtccgggttc tacccgtccg acatcgcggt ggagtgggag 1140

tccgacggcc agccggagaa caactacaag accacccccc cggtactcga ctccgacggt 1200

tcgttcttcc tctactccaa gctgacggtg gacaagtccc ggtgggagca aggcgacgtg 1260

ttcagctgtt ccgtcatgca cgaggccctg cacaaccact acacccagaa gagtctgtcc 1320

ctctcccctg gcaaatga 1338

<210> 524

<211> 1458

<212> DNA

<213> 人工序列

<220>

<223> XENP13243 HC-scFv (XenD08438)

<400> 524

gaagtccagc tcgtggagtc gggcggcggc ctcgtgcaac cgggtggctc gctgcggctc 60

tcctgcgccg cgtccggctt cacgttctcc acctacgcca tgaactgggt ccgccaggcg 120

ccgggcaagg ggctcgagtg ggtggggcgt atccgctcca agtacaacaa ctacgcgacg 180

tactacgccg atagcgtaaa gggacgcttc acaatctcgc gggacgacag caagaacacc 240

ctttacctcc agatgaacag cctgcgcgcc gaagacaccg ccgtgtacta ctgtgtccgg 300

cacgggaact tcggcgactc ctacgtctcg tggttcgcct actggggcca gggcaccctc 360

gtcaccgtgt cctcgggaaa gccggggagc ggaaagccgg gttcgggcaa gccaggctcc 420

ggtaagccgg gctcgcaggc ggtggtgacc caggagccat ccctgaccgt gtccccgggg 480

ggcaccgtca cgctgacttg cggctcctcg accggtgccg tcaccacctc caactacgcc 540

aactgggtgc agcagaagcc cggcaagagc ccccgcggcc tgatcggcgg cacgaacaag 600

cgcgcgcccg gcgtcccggc ccgcttctcc ggctccctgc tgggcgggaa ggccgcgctc 660

accatcagcg gcgcgcagcc cgaggacgag gccgactact actgcgcgct ctggtactcg 720

aaccactggg tcttcggcgg cgggaccaag ctcaccgtgc tcgagccgaa gtcctcggac 780

aagacccaca catgcccccc ctgcccggcc ccccccgtgg cgggcccctc tgtcttcctg 840

tttcccccga agccgaagga caccctgatg atctcgcgca cgccggaagt gacctgcgtc 900

gtcgtcgacg tgaagcacga ggacccagag gtcaagttca actggtacgt cgacggcgtc 960

gaggtgcaca acgcgaagac gaagccccgt gaggagcagt acaactccac ctaccgggtg 1020

gtgtcggtgc tgacggtgct ccaccaggac tggctgaacg gcaaggagta caagtgtaag 1080

gtctccaaca aggccctccc ggcccccatc gagaagacca tctcgaaggc caagggccag 1140

ccgcgcgagc cgcaggtgta cacgctcccg ccctcgcggg agcagatgac caagaaccag 1200

gtgaagctga cctgcctcgt gaagggcttc tacccgagcg acatcgcggt ggagtgggag 1260

tccaacggcc aaccggagaa caactacaag accactccgc cggtgctgga ctcggatggg 1320

tcgttcttcc tctactcgaa gctcacggta gacaagtccc gctggcagca gggcaacgtc 1380

ttctcctgct ccgtcatgca cgaggccctc cacaaccact atacccagaa gtcgctctcg 1440

ctctccccgg gaaagtga 1458

<210> 525

<211> 645

<212> DNA

<213> 人工序列

<220>

<223> XENP13243 LC (XenD07263)

<400> 525

gacatcgtca tgacgcagtc gccgagcagc ctctccgcat cggtgggtga ccgcgtcacc 60

atcacctgcc gggcgagcca gaacgtcgac accaacgtgg cctggtatca gcagaagccg 120

ggccagagtc cgaaggccct gatctacagc gcctcgtacc gctactcggg cgtgcccgac 180

cggttcacgg gcagcggctc ggggacggac ttcacgctga ccatctcctc gctgcagccg 240

gaggacttcg ccacctactt ctgccagcag tacgactcct atcccctgac gttcggggga 300

gggaccaagc tcgagatcaa gcgcaccgtc gccgccccct ccgtgttcat cttcccgccg 360

agcgacgagc agctgaagag cgggaccgcc agcgtggtgt gcctcctcaa caacttctac 420

ccgcgcgagg ccaaggtgca gtggaaggtg gacaacgcgc tgcagagcgg caactcccaa 480

gagtccgtga ccgagcagga cagcaaggat tccacctatt cgctgtcctc caccctgacc 540

ctctcgaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtcac gcaccagggt 600

ctcagcagcc ccgtcaccaa gtccttcaat cggggcgagt gctga 645

<210> 526

<211> 1338

<212> DNA

<213> 人工序列

<220>

<223> XENP13551 HC-Fab (XenD08503)

<400> 526

gaagtccagc tcgtggagtc gggtggcggc ctcgtccagc ccggcggctc gctccggctg 60

tcatgcgccg cgagcgggtt cactttcagt tactcgtgga tgaactgggt acgccaggcc 120

ccgggcaagg gcctcgaatg ggtctccgag atcaacccgc agagcagcac gatcaactac 180

gccacctcgg tgaagggccg gttcacgatc agccgcgaca actccaagaa caccctctac 240

ctgcagatga actccctgcg cgccgaggac acggccgtct actactgcgc gcgctacgga 300

aactggttcc cgtactgggg ccagggcaca ctggtcactg tctccagcgc gtccacgaag 360

ggcccgtcgg tcttccccct ggcgccaagc tcgaaaagta cgtccggcgg gaccgcagcg 420

ctgggctgcc tggtcaagga ctacttcccc gagcccgtga ccgtgagctg gaactcgggc 480

gcgctgacct ccggcgtcca caccttcccg gcagtcctcc agtcgtcggg cctgtactcg 540

ctgtccagcg tcgtcacggt gccgtcgtcc tccctgggca cgcagacgta catctgcaac 600

gtgaaccaca agccgagcga caccaaggtc gacaagaagg tcgagcccaa gtcgtgcgac 660

aagacccaca cgtgcccgcc gtgcccggcc ccccctgtcg ccggccccag tgtcttcctc 720

ttcccgccga agccgaagga caccctcatg atctcgcgca cccccgaggt cacctgcgtg 780

gtcgtggacg tgaagcacga ggaccctgag gttaagttca actggtatgt cgacggggtg 840

gaggtccaca acgcgaagac caagccgcgc gaggaggagt acaacagtac gtaccgcgtg 900

gtctcggtgc tcaccgtcct ccaccaggac tggctgaacg gcaaggaata caagtgtaag 960

gtcagcaaca aggccttgcc cgcccccatc gagaagacca taagcaaggc caagggtcag 1020

ccaagggaac cgcaggtgta caccctcccg ccctcccgcg aggagatgac caagaaccag 1080

gtatcactga cctgcgacgt gtccgggttc tacccgtccg acatcgcggt ggagtgggag 1140

tccgacggcc agccggagaa caactacaag accacccccc cggtactcga ctccgacggt 1200

tcgttcttcc tctactccaa gctgacggtg gacaagtccc ggtgggagca aggcgacgtg 1260

ttcagctgtt ccgtcatgca cgaggccctg cacaaccact acacccagaa gagtctgtcc 1320

ctctcccctg gcaaatga 1338

<210> 527

<211> 1458

<212> DNA

<213> 人工序列

<220>

<223> XENP13551 HC-scFv (XenD08438)

<400> 527

gaagtccagc tcgtggagtc gggcggcggc ctcgtgcaac cgggtggctc gctgcggctc 60

tcctgcgccg cgtccggctt cacgttctcc acctacgcca tgaactgggt ccgccaggcg 120

ccgggcaagg ggctcgagtg ggtggggcgt atccgctcca agtacaacaa ctacgcgacg 180

tactacgccg atagcgtaaa gggacgcttc acaatctcgc gggacgacag caagaacacc 240

ctttacctcc agatgaacag cctgcgcgcc gaagacaccg ccgtgtacta ctgtgtccgg 300

cacgggaact tcggcgactc ctacgtctcg tggttcgcct actggggcca gggcaccctc 360

gtcaccgtgt cctcgggaaa gccggggagc ggaaagccgg gttcgggcaa gccaggctcc 420

ggtaagccgg gctcgcaggc ggtggtgacc caggagccat ccctgaccgt gtccccgggg 480

ggcaccgtca cgctgacttg cggctcctcg accggtgccg tcaccacctc caactacgcc 540

aactgggtgc agcagaagcc cggcaagagc ccccgcggcc tgatcggcgg cacgaacaag 600

cgcgcgcccg gcgtcccggc ccgcttctcc ggctccctgc tgggcgggaa ggccgcgctc 660

accatcagcg gcgcgcagcc cgaggacgag gccgactact actgcgcgct ctggtactcg 720

aaccactggg tcttcggcgg cgggaccaag ctcaccgtgc tcgagccgaa gtcctcggac 780

aagacccaca catgcccccc ctgcccggcc ccccccgtgg cgggcccctc tgtcttcctg 840

tttcccccga agccgaagga caccctgatg atctcgcgca cgccggaagt gacctgcgtc 900

gtcgtcgacg tgaagcacga ggacccagag gtcaagttca actggtacgt cgacggcgtc 960

gaggtgcaca acgcgaagac gaagccccgt gaggagcagt acaactccac ctaccgggtg 1020

gtgtcggtgc tgacggtgct ccaccaggac tggctgaacg gcaaggagta caagtgtaag 1080

gtctccaaca aggccctccc ggcccccatc gagaagacca tctcgaaggc caagggccag 1140

ccgcgcgagc cgcaggtgta cacgctcccg ccctcgcggg agcagatgac caagaaccag 1200

gtgaagctga cctgcctcgt gaagggcttc tacccgagcg acatcgcggt ggagtgggag 1260

tccaacggcc aaccggagaa caactacaag accactccgc cggtgctgga ctcggatggg 1320

tcgttcttcc tctactcgaa gctcacggta gacaagtccc gctggcagca gggcaacgtc 1380

ttctcctgct ccgtcatgca cgaggccctc cacaaccact atacccagaa gtcgctctcg 1440

ctctccccgg gaaagtga 1458

<210> 528

<211> 645

<212> PRT

<213> 人工序列

<220>

<223> XENP13551 LC (XenD07821)

<400> 528

Gly Ala Cys Ala Thr Cys Gly Thr Cys Ala Thr Gly Ala Cys Gly Cys

1 5 10 15

Ala Gly Thr Cys Gly Cys Cys Gly Ala Gly Cys Ala Gly Cys Cys Thr

20 25 30

Cys Thr Cys Cys Gly Cys Ala Thr Cys Gly Gly Thr Gly Gly Gly Thr

35 40 45

Gly Ala Cys Cys Gly Cys Gly Thr Cys Ala Cys Cys Ala Thr Cys Ala

50 55 60

Cys Cys Thr Gly Cys Cys Gly Gly Gly Cys Gly Ala Gly Cys Cys Ala

65 70 75 80

Gly Ala Ala Cys Gly Thr Cys Gly Ala Cys Ala Cys Cys Thr Gly Gly

85 90 95

Gly Thr Gly Gly Cys Cys Thr Gly Gly Thr Ala Thr Cys Ala Gly Cys

100 105 110

Ala Gly Ala Ala Gly Cys Cys Gly Gly Gly Cys Cys Ala Gly Ala Gly

115 120 125

Thr Cys Cys Gly Ala Ala Gly Gly Cys Cys Cys Thr Gly Ala Thr Cys

130 135 140

Thr Ala Cys Ala Gly Cys Gly Cys Cys Thr Cys Gly Thr Ala Cys Cys

145 150 155 160

Gly Cys Thr Ala Cys Thr Cys Gly Gly Gly Cys Gly Thr Gly Cys Cys

165 170 175

Cys Gly Ala Cys Cys Gly Gly Thr Thr Cys Ala Cys Gly Gly Gly Cys

180 185 190

Ala Gly Cys Gly Gly Cys Thr Cys Gly Gly Gly Gly Ala Cys Gly Gly

195 200 205

Ala Cys Thr Thr Cys Ala Cys Gly Cys Thr Gly Ala Cys Cys Ala Thr

210 215 220

Cys Thr Cys Cys Thr Cys Gly Cys Thr Gly Cys Ala Gly Cys Cys Gly

225 230 235 240

Gly Ala Gly Gly Ala Cys Thr Thr Cys Gly Cys Cys Ala Cys Cys Thr

245 250 255

Ala Cys Thr Thr Cys Thr Gly Cys Cys Ala Gly Cys Ala Gly Thr Ala

260 265 270

Cys Gly Ala Cys Thr Cys Cys Thr Ala Thr Cys Cys Cys Cys Thr Gly

275 280 285

Ala Cys Gly Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly Gly Gly Ala

290 295 300

Cys Cys Ala Ala Gly Cys Thr Cys Gly Ala Gly Ala Thr Cys Ala Ala

305 310 315 320

Gly Cys Gly Cys Ala Cys Cys Gly Thr Cys Gly Cys Cys Gly Cys Cys

325 330 335

Cys Cys Cys Thr Cys Cys Gly Thr Gly Thr Thr Cys Ala Thr Cys Thr

340 345 350

Thr Cys Cys Cys Gly Cys Cys Gly Ala Gly Cys Gly Ala Cys Gly Ala

355 360 365

Gly Cys Ala Gly Cys Thr Gly Ala Ala Gly Ala Gly Cys Gly Gly Gly

370 375 380

Ala Cys Cys Gly Cys Cys Ala Gly Cys Gly Thr Gly Gly Thr Gly Thr

385 390 395 400

Gly Cys Cys Thr Cys Cys Thr Cys Ala Ala Cys Ala Ala Cys Thr Thr

405 410 415

Cys Thr Ala Cys Cys Cys Gly Cys Gly Cys Gly Ala Gly Gly Cys Cys

420 425 430

Ala Ala Gly Gly Thr Gly Cys Ala Gly Thr Gly Gly Ala Ala Gly Gly

435 440 445

Thr Gly Gly Ala Cys Ala Ala Cys Gly Cys Gly Cys Thr Gly Cys Ala

450 455 460

Gly Ala Gly Cys Gly Gly Cys Ala Ala Cys Thr Cys Cys Cys Ala Ala

465 470 475 480

Gly Ala Gly Thr Cys Cys Gly Thr Gly Ala Cys Cys Gly Ala Gly Cys

485 490 495

Ala Gly Gly Ala Cys Ala Gly Cys Ala Ala Gly Gly Ala Thr Thr Cys

500 505 510

Cys Ala Cys Cys Thr Ala Thr Thr Cys Gly Cys Thr Gly Thr Cys Cys

515 520 525

Thr Cys Cys Ala Cys Cys Cys Thr Gly Ala Cys Cys Cys Thr Cys Thr

530 535 540

Cys Gly Ala Ala Gly Gly Cys Cys Gly Ala Cys Thr Ala Cys Gly Ala

545 550 555 560

Gly Ala Ala Gly Cys Ala Cys Ala Ala Gly Gly Thr Gly Thr Ala Cys

565 570 575

Gly Cys Cys Thr Gly Cys Gly Ala Gly Gly Thr Cys Ala Cys Gly Cys

580 585 590

Ala Cys Cys Ala Gly Gly Gly Thr Cys Thr Cys Ala Gly Cys Ala Gly

595 600 605

Cys Cys Cys Cys Gly Thr Cys Ala Cys Cys Ala Ala Gly Thr Cys Cys

610 615 620

Thr Thr Cys Ala Ala Thr Cys Gly Gly Gly Gly Cys Gly Ala Gly Thr

625 630 635 640

Gly Cys Thr Gly Ala

645

<210> 529

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.31_L1.47 VH

<400> 529

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 Phe Ser Thr Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 530

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.31_L1.47 VL

<400> 530

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 531

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.32_L1.47 VH

<400> 531

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 532

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.32_L1.47 VL

<400> 532

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 533

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.33_L1.47 VH

<400> 533

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 534

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.33_L1.47 VL

<400> 534

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 535

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.89_L1.47 VH

<400> 535

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 536

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.89_L1.47 VL

<400> 536

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 537

<211> 125

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.90_L1.47 VH

<400> 537

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 Phe Ser Thr Tyr

20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 538

<211> 109

<212> PRT

<213> 人工序列

<220>

<223> alpha CD3_H1.90_L1.47 VL

<400> 538

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

1 5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

20 25 30

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

35 40 45

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

50 55 60

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

65 70 75 80

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 539

<211> 5

<212> PRT

<213> 人工序列

<220>

<223> 有用的连接子

<400> 539

Gly Ser Gly Gly Ser

1 5

<210> 540

<211> 4

<212> PRT

<213> 人工序列

<220>

<223> 有用的连接子

<400> 540

Gly Gly Gly Ser

1

Claims (10)

1.一种结合至CD38的抗原结合结构域，其包含第一可变轻链结构域和第一可变重链结构域；其中所述第一可变重链结构域和所述第一可变轻链结构域包含CDR序列，其选自：

(a)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域；

(b)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTNVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域；

(c)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(d)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(e)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、SASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(f)包含RSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；以及

(g)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域。

2.根据权利要求1的抗原结合结构域，其中所述第一可变重链结构域包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列，以及所述第一可变轻链结构域包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列。

3.一种结合至CD38的抗体，其包含含有第一可变轻链结构域和第一可变重链结构域的抗原结合结构域；其中所述第一可变重链结构域和所述第一可变轻链结构域包含CDR序列，其选自：

(a)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域；

(b)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTNVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域；

(c)包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(d)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(e)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、SASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；

(f)包含RSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDYWVA的CDR1序列、AASWRYS的CDR2序列和QQYDVYPLT的CDR3序列的第一可变轻链结构域；以及

(g)包含YSWMN的CDR1序列、EINPQSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列的第一可变重链结构域以及包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列的第一可变轻链结构域。

4.根据权利要求3的抗体，其中所述第一可变重链结构域包含RSWMN的CDR1序列、EINPDSSTINYATSVKG的CDR2序列和YGNWFPY的CDR3序列，以及所述第一可变轻链结构域包含RASQNVDTWVA的CDR1序列、SASYRYS的CDR2序列和QQYDSYPLT的CDR3序列。

5.一种药物组合物，其包含权利要求1或2的抗原结合结构域。

6.一种药物组合物，其包含权利要求3或4的抗体。

7.权利要求1或2的抗原结合结构域在制备用于治疗表达CD38的造血系统恶性肿瘤的药物中的用途。

8.权利要求3或4的抗体在制备用于治疗表达CD38的造血系统恶性肿瘤的药物中的用途。

9.根据权利要求7或8所述的用途，其中所述造血系统恶性肿瘤选自非霍奇金氏淋巴瘤、伯基特氏淋巴瘤、多发性骨髓瘤、B慢性淋巴细胞白血病、B和T急性淋巴细胞白血病、T细胞淋巴瘤、急性骨髓性白血病、毛细胞白血病、霍奇金氏淋巴瘤及慢性骨髓性白血病。

10.一种核酸组合物，其包含编码权利要求1或2的第一可变轻链结构域的第一核酸和编码权利要求1或2的第一可变重链结构域的第二核酸。