CN1826356B

CN1826356B - 针对sars冠状病毒的结合分子及其应用

Info

Publication number: CN1826356B
Application number: CN2004800211505A
Authority: CN
Inventors: 扬·亨里克·特尔莫伊伦; 科内利斯·阿德里安·德克吕夫; 爱德华·诺贝特·范登布林克; 亚普·古德斯米特
Original assignee: Crucell Holand BV
Current assignee: Janssen Vaccines and Prevention BV
Priority date: 2003-07-22
Filing date: 2004-07-21
Publication date: 2012-05-09
Anticipated expiration: 2024-07-21
Also published as: CN1826356A

Abstract

本发明提供了特异结合至SARS冠状病毒的结合分子、编码所述结合分子的核酸分子、包含所述结合分子的组合物、以及鉴别或产生所述结合分子的方法。所述结合分子能够特异结合到SARS冠状病毒并可被用于SARS冠状病毒导致的疾病的诊断、预防和/或治疗。

Description

针对SARS冠状病毒的结合分子及其应用

技术领域

本发明涉及药物，特别涉及能够特异结合至SARS冠状病毒(SARS-CoV)的结合分子。所述结合分子可用于诊断SARS-CoV以及SARS-CoV导致的疾病的预防和/或治疗。

背景技术

近来在人群中观察到了一种新的、在一些情况下甚至是致命的临床综合征，现已被命名为重症急性呼吸道综合征(severe acuterespiratory syndrome，SARS)(Holmes，2003)。此综合征是由一种被称为SARS-CoV的新的冠状病毒导致的(Ksiazek等，2003)。SARS-CoV的基因组序列已经被测定(Rota等，2003；Marra等，2003)。然而，关于这种病毒的许多知识还有待研究，同时对这种病毒和综合征的诊断、预防和/或治疗的手段和方法也是急需的。本发明提供了用于诊断、预防和/或治疗SARS-CoV的手段和方法。

附图简述

图1示出了ELISA的结果，其中测定了称为SC03-001、SC03-002、SC03-003、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的单链噬菌体抗体与固定的SARS-CoV制备物(左侧条柱)或固定的FBS(右侧条柱)的结合。同时还示出了称为SC03-006的对照单链噬菌体抗体的结合。y轴示出了在492nm处的吸收(OD)。

图2示出了ELISA的结果，其中测定了称为SC03-016、SC03-017和SC03-018的单链噬菌体抗体与固定的SARS-CoV制备物(左侧条柱)或固定的FBS(右侧条柱)的结合。同时还示出了对照单链噬菌体抗体SC02-300的结合。y轴示出了在492nm处的吸收(OD)。

图3示出了二价scFv表达载体pPICZbiFVH的构建。图3A示出了载体pPICZαB，图3B示出了二价scFv表达载体pPICZbiFVH。图3C示出了scFv进入pPICZbiFVH的克隆策略。

图4示出了称为SC03-001、SC03-002、SC03-003、SC03-004、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014、SC03-015、SC03-016、SC03-017和SC03-018的SARS-CoV特异性单链噬菌体抗体与称为03-001、03-002、03-009、03-013、03-014和03-018(对于每一个单链抗体从左至右排列)的人单克隆抗-SARS-CoV抗体的竞争性ELISA(competitionELISA)。称为02-361的抗体是对照抗体(从右数第二条柱)。X轴列出了被测试的单链噬菌体抗体，y轴示出了在存在人单克隆抗-SARS-CoV抗体存在的情况下单链噬菌体抗体与SARS-CoV制备物的残余结合(以％表示)。在不存在人单克隆抗-SARS-CoV抗体的情况下的结合值被设为100％。此数值列于每一种单链噬菌体抗体的右侧(无IgG)。

图5示出了称为03-001、03-002、03-009、03-013、03-014和03-018的人单克隆抗-SARS-CoV抗体和称为02-027的对照抗体(人单克隆抗-EPCAM抗体)与UV或γ射线照射过的SARS-CoV制备物的结合。对于每一种抗体取1和5μg/ml测试。抗体和492nm处的吸收(OD)分别示于x轴和y轴。对于每一种抗-SARS-CoV抗体，从左至右分别为5μg/ml该抗体与γ射线照射过的制备物的结合、5μg/ml该抗体与UV照射过的制备物的结合、1μg/ml该抗体与γ射线照射过的制备物的结合、以及1μg/ml该抗体与UV照射过的制备物的结合。仅在5μg/ml的浓度测试了对照抗体与UV和γ射线照射过的SARS-CoV制备物的结合。

图6A-D示出了称为03-001、03-002、03-009、03-013、03-014和03-018的固定化重组人单克隆抗-SARS-CoV抗体和对照抗体02-300(抗CD46抗体)与SARS-CoV制备物、变性SARS-CoV制备物和BSA(从左至右)的夹心ELISA(sandwich ELISA)。y轴示出了在492nm处的吸收(OD)。图6A中的测试用识别完整SARS-CoV的兔多克隆抗血清进行。图6B中的测试用识别SARS-CoV的刺突蛋白(spikeprotein)的兔多克隆抗血清(IMG-542)进行。图6C中的测试用识别SARS-CoV的核壳(N)蛋白(nucleocapsid protein)的兔多克隆抗血清(IMG-543)进行。图6D中的测试用识别SARS-CoV的刺突蛋白的另一种兔多克隆抗血清(IMG-557)进行。

图7示出了载体pDV-C05。

图8示出了SC03-009、SC03-014和对照SC02-006与SARS-CoV制备物、S565片段(SARS-CoV的S蛋白的氨基酸1-565)、SARS-CoV的核壳蛋白和对照蛋白结合的ELISA。y轴示出了在492nm处的吸收(OD)。

图9示出了抗体03-001、03-002、03-006、03-009、03-013、03-014、03-015、03-018和对照抗体02-027(抗-EPCAM)与SARS-CoV的核壳蛋白和对照蛋白结合的ELISA。y轴示出了在492nm处的吸收(OD)。

图10示出了抗体03-009、03-018和对照抗体02-027的稀释物与SARS-CoV的核壳蛋白结合的ELISA。y轴示出了在492nm处的吸收(OD)，x轴示出了抗体的量，单位为M。

图11示出了生物素化的抗体03-009在不存在竞争抗体或存在浓度为25或50μg/ml的竞争抗体03-009或03-018时与SARS-CoV的核壳蛋白的结合的竞争性ELISA。y轴示出了最大结合的百分比，x轴示出了竞争抗体的量，单位为μg/ml。

图12示出了抗体03-001、03-002、03-006、03-009、03-013、03-014、03-015、03-018和对照抗体02-027(抗-EPCAM)与HEK293T细胞上表达的全长S蛋白结合的FACS(左侧条柱)、这些抗体与S565片段结合的ELISA(SARS-CoV的S蛋白的氨基酸1-565；中间条柱)和这些抗体与S318-510片段结合的ELISA(SARS-CoV的S蛋白的氨基酸318-510；右侧条柱)。右侧y轴示出了在492nm处的吸收(OD)，左侧y轴示出了平均荧光强度。

图13示出了稀释的抗体03-006、03-013、03-014和对照抗体02-027与SARS-CoV的S蛋白的S565片段结合的ELISA。y轴示出了在492nm处的吸收(OD)，x轴示出了抗体的量，单位为M。

图14示出了生物素化的抗体03-014在不存在竞争抗体或存在浓度为25或50μg/ml的竞争抗体03-006或03-014时与SARS-CoV的S蛋白的S565片段结合的竞争性ELISA。y轴示出了最大结合的百分比，x轴示出了竞争抗体的量，单位为μg/ml。

图15示出了在存在或不存在抗体03-014的情况下SARS-CoV的S蛋白的S565片段与非洲绿猴肾细胞(Vero cell)结合的流式细胞术分析。点线表示与myc标记的对照蛋白(即二价scFv 02-006)一起温育的Vero细胞。实线和粗实线分别表示在抗体03-014不存在或存在的情况下与myc标记的S565片段一起温育的Vero细胞。

图16示出了在存在或不存在抗体03-018的情况下SARS-CoV的S蛋白的S565片段与Vero细胞结合的流式细胞术分析。点线表示与myc标记的对照蛋白(即二价scFv 02-006)一起温育的Vero细胞。实线和粗实线分别表示在抗体03-018不存在或存在的情况下与myc标记的S565片段一起温育的Vero细胞。

图17示出了在存在或不存在对照抗EPCAM抗体02-027的情况下SARS-CoV的S蛋白的S565片段与Vero细胞结合的流式细胞术分析。点线表示与myc标记的对照蛋白(即二价scFv 02-006)一起温育的Vero细胞。实线和粗实线分别表示在抗体02-027不存在或存在的情况下与myc标记的S565片段一起温育的Vero细胞。

图18示出了在接种了病毒-对照抗体混和物或病毒-03-014抗体混和物的雪貂中SARS-CoV在第2、4、7天的分泌。

图19示出了在接种了病毒-对照抗体混和物或病毒-03-014抗体混和物的雪貂中SARS-CoV在第4、7天的肺部滴度。虚线表示本测试的检测极限。

图20示出了在接种了病毒-对照抗体混和物或病毒-03-014抗体混和物的雪貂中在第4、7天的肺部病理学指数(lung pathology score)。

图21示出了攻击(challenge)后4天时肺组织匀浆(lunghomogenate)中的SARS-CoV滴定。示出了在施用了对照抗体(命名为对照)或03-014抗体(命名为CR3014)的雪貂中SARS-CoV的肺部滴度。

图22示出了通过RT/PCR在第2天和第4天的鼻咽部拭子中检测出的SARS-CoV分泌物，表示为SARS-CoV基因组当量(equivalent)。在03-014处理的组(命名为CR3014)中三只动物没有SARS-CoV分泌并且结果是重叠的。

图23示出了与单克隆抗SARS-CoV 03-014IgG1抗体(a组)或人单克隆对照IgG1抗体(b组)温育的SARS-CoV的电子显微镜照片。比例尺条为100nm。

图24示出了SARS-CoV感染的Vero细胞的超薄切片的电子显微镜照片。图24A：未染色的(对照)切片；图24B：用人单克隆对照IgG1抗体02-027(抗Epcam抗体)染色的切片；图24C：用单克隆抗SARS-CoV IgG1抗体03-009染色的切片；图24D：用单克隆抗SARS-CoV IgG1抗体03-018染色的切片。

图25示出了单克隆抗SARS-CoV IgG1抗体03-014和对照单克隆抗His6抗体与SARS-CoV病毒株Frankfurt 1的S蛋白的氨基酸区域318-510(称为WT S318-510)和各种变体S318-510片段(变体A，突变K344R；变体B，突变S353F；变体C，突变R426G和N437D；变体D，突变Y436H；变体E，突变Y442S；变体F，突变N479S；变体G，突变K344R、F360S、L472P、D480G和T487S；变体H，突变K344R、F501Y)的结合。对照是无关的myc-His标记的蛋白。Y轴示出的结合以相对于与WT 318-510的结合的百分比表示，对于两种抗体，与WT 318-510的结合均被设定为100％。

发明描述

下面是本发明中用到的术语的定义。

定义

氨基酸序列

如本文所用，术语“氨基酸序列”是指天然发生的或合成的分子，并且是指肽、寡肽、多肽或蛋白质序列。

结合分子

如本文所用，术语“结合分子”是指完整的(intact)免疫球蛋白，包括单克隆抗体如嵌合的、人源化的或人的单克隆抗体，或是指免疫球蛋白的抗原结合片段或免疫球蛋白的包含可变结构域的片段，所述片段与所述完整的免疫球蛋白竞争与所述免疫球蛋白的结合配体(例如SARS-CoV)的特异结合。不考虑结构，所述抗原结合片段与能被所述完整的免疫球蛋白识别的同一种抗原结合。一个抗原结合片段可包含一个肽或多肽，所述肽或多肽包含所述结合分子的氨基酸序列的至少2个相邻的氨基酸残基、至少5个相邻的氨基酸残基、至少10个相邻的氨基酸残基、至少15个相邻的氨基酸残基、至少20个相邻的氨基酸残基、至少25个相邻的氨基酸残基、至少30个相邻的氨基酸残基、至少35个相邻的氨基酸残基、至少40个相邻的氨基酸残基、至少50个相邻的氨基酸残基、至少60个相邻的氨基酸残基、至少70个相邻的氨基酸残基、至少80个相邻的氨基酸残基、至少90个相邻的氨基酸残基、至少100个相邻的氨基酸残基、至少125个相邻的氨基酸残基、至少150个相邻的氨基酸残基、至少175个相邻的氨基酸残基、至少200个相邻的氨基酸残基、或至少250个相邻的氨基酸残基的氨基酸序列。

如本文所用，术语“结合分子”包括所有本领域已知的免疫球蛋白种类和亚类。基于其重链的恒定区(constant domain)的氨基酸序列，结合分子可被分为五类主要的完整抗体：IgA、IgD、IgE、IgG和IgM，它们中的一些又可以进一步分为亚类(同种型)，例如IgAl，IgA2，IgGl，IgG2，IgG3和IgG4。

抗原结合片段特别包括Fab、F(ab′)、F(ab′)₂、Fv、dAb、Fd、互补决定区(complementarity determining region，CDR)片段、单链抗体(scFv)、二价单链抗体、单链噬菌体抗体、二聚抗体(diabodies)、三聚抗体(triabodies)、四聚抗体(tetrabodies)、包含免疫球蛋白的至少一个片段的(多)肽(所述片段足以使所述(多)肽进行特异性抗原结合)等等。上述片段可通过合成产生或通过对完整的免疫球蛋白进行酶学或化学切割产生，或者可以通过重组DNA技术而进行的遗传工程产生。这些产生方法是本领域所熟知的，并且被描述于例如Antibodies：ALaboratory Manual，Edited by：E.Harlow and D，Lane(1988)，ColdSpring Harbor Laboratory，Cold Spring Harbor，New York，其被引入本文作参考。一个结合分子或其抗原结合片段可具有一个或多个结合位点。如果具有多于一个的结合位点，这些结合位点可以是彼此相同的或彼此不同的。

所述结合分子可以是裸露的或未缀合的结合分子，但也可以是免疫缀合物的一部分。裸露的或未缀合的结合分子是指如下的一种结合分子，其未与一种效应物成分或标记物特别例如毒性物质、放射性物质、脂质体、酶缀合，其没有可操纵地与一种效应物成分或标记物特别例如毒性物质、放射性物质、脂质体、酶连接，或者其未与一种效应成分或标记特别例如毒性物质、放射性物质、脂质体、酶呈物理性或功能性相关。应理解裸露的或未缀合的结合分子不排除已经被稳定化的、多聚化的、人源化的或通过除了附着一种效应物成分或标记以外的其他任何方式操作的结合分子。根据本发明，所有进行了翻译后修饰的裸露的和未缀合的结合分子均包括在本发明中，这些翻译后修饰包括在产生天然结合分子的细胞环境中进行的、通过产生重组结合分子的细胞进行的、和在最初的结合分子制备后通过人工引入进行的修饰。当然，术语裸露的或未缀合的结合分子不排除在对机体给药后所述结合分子与效应细胞和/或分子形成功能性关联的能力，因为这些相互作用对于发挥生物学效应是必需的。因此“缺乏相关的效应基团或标记物”是被用来定义体外而不是体内的所述裸露的或未缀合的结合分子。

生物学样品

如本文所用，术语“生物学样品”涵盖各种样品类型，包括血液和生物学来源的其他液体样品、固体组织样品如活体解剖样品或组织培养物或由其衍生的细胞及其后代。该术语还包括在获得后又通过任何方式被操作的样品，如通过用试剂进行处理、溶解、或对某些成分如蛋白质或多核苷酸进行富集。该术语还包含各种得自任何物种的临床样品，还包括培养物中的细胞、细胞上清和细胞裂解物。

互补决定区(CDR)

如本文所用，术语“互补决定区(CDR)”是指处于结合分子如免疫球蛋白的可变区内部的序列，所述序列通常很大程度上促进与抗原上被识别的表位在形状和电荷分布方面互补的抗原结合位点的形成。CDR区可以特异于蛋白质或蛋白质片段的线性表位、非连续表位、或构象表位，所述表位可以以其天然构象位于蛋白质表面或在一些情况下以其例如通过溶于SDS而得到的变性构象位于蛋白质表面。表位还可以包括蛋白质的翻译后修饰。

缺失

如本文所用，术语“缺失”是指在氨基酸或核苷酸序列中的改变，所述改变分别是相对于原始(parent)分子(通常情况下是天然发生的分子)一个或多个氨基酸或核苷酸残基不存在。

表达调控核酸序列

如本文所用，术语“表达调控核酸序列”是指对于一个在特定宿主生物体中的被可操纵地连接的编码序列是必需的和/或影响所述编码序列表达的多核苷酸序列。所述表达调控核酸序列特别例如适当的转录起始、终止、启动子、增强子序列；阻抑子(repressor)或激活子(activator)序列；高效RNA加工信号如剪接和聚腺苷酸化信号；稳定细胞质中mRNA的序列；增强翻译效率的信号(例如核糖体结合位点)；增强蛋白质稳定性的信号；以及如果需要，增强蛋白质分泌的信号可以是任何在所选择的宿主生物体中表现活性的核酸序列，并且可以衍生自编码蛋白质的基因，所述基因是所述宿主生物体的同源或异源的。表达调控核酸序列的鉴别和应用对于本领域技术人员是常规技术。

功能性变体

如本文所用，术语“功能性变体”是指相对于原始结合分子的核苷酸和/或氨基酸序列包括具有一个或多个核苷酸和/或氨基酸改变的核苷酸和/或氨基酸序列的结合分子，所述核苷酸和/或氨基酸序列仍具有针对结合所述结合配体(例如SARS-CoV)与原始结合分子竞争的能力。也就是说，原始结合分子的氨基酸和/或核苷酸序列的修饰不会显著影响或改变由所述核苷酸序列编码的或包含所述氨基酸序列的结合分子的结合特性，即所述结合分子仍能够识别并结合其目标。所述功能性变体可以含有保守序列修饰，包括核苷酸和氨基酸取代、添加和缺失。这些修饰可以通过本领域已知的标准技术如定点诱变和随机PCR介导的诱变引入，并且可以包含天然的或非天然的核苷酸和氨基酸。

保守氨基酸取代包括氨基酸残基被具有相似结构性质或化学性质的氨基酸残基取代。本领域已经清楚地定义具有相似侧链的氨基酸残基家族。这些家族包括具有碱性侧链的氨基酸(例如赖氨酸、精氨酸、组氨酸)、具有酸性侧链的氨基酸(例如天冬氨酸、谷氨酸)、具有不带电荷的极性侧链的氨基酸(例如甘氨酸、天冬酰氨、谷氨酰氨、丝氨酸、苏氨酸、酪氨酸、胱氨酸、色氨酸)、具有非极性侧链的氨基酸(例如丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸)、具有β-分枝侧链的氨基酸(例如苏氨酸、缬氨酸、异亮氨酸)和具有芳香族侧链的氨基酸(例如苏氨酸、缬氨酸、异亮氨酸)。本领域技术人员清楚地知道上述分类方法之外的其他氨基酸残基家族分类也是可用的。另外，变体可以具有非保守的氨基酸取代，例如氨基酸残基被具有不同结构性质或化学性质的氨基酸残基取代。相似的微小改变还可以包括氨基酸缺失或插入，或同时具有缺失和插入。关于确定哪些氨基酸残基可以被取代、插入、或缺失而不消除其免疫活性的指导可以用本领域熟知的计算机程序获得。

核苷酸序列中的突变可以是在一个基因座上引入的单一改变(点突变)如碱基转换(transition)或碱基颠换(transversion)突变，或者可以在一个单一基因座上插入、缺失或改变多个核苷酸。另外，在一个核苷酸序列内部的任何数量的基因座上可以引入一个或多个改变。所述突变可以用本领域已知的任何合适的方法引入。

宿主

如本文所用，术语“宿主”是指被引入了一个载体如克隆载体或表达载体的生物体或细胞。所述生物体或细胞可以是原核或真核的。应理解此术语不仅是指特定的对象生物体或细胞，还指这样一个生物体或细胞的后代。由于在后代中可能发生某些由于突变或环境影响而导致的修饰，所述后代事实上可能不会与亲代生物体或细胞完全相同，但是仍旧包含在如本文所用的术语“宿主”的范围中

人的

当用于如本文所定义的结合分子时，术语“人的(human)”是指直接衍生自人的分子或基于人的序列的分子。当一个结合分子衍生自人的序列或基于人的序列并且被接下来后续修饰过时，如在通篇说明书中所用，其仍旧被视为人的。也就是说，当应用于结合分子时，术语“人的”包括具有衍生自人生殖系免疫球蛋白序列的可变区和恒定区的结合分子，或基于人或人淋巴细胞中发生或不发生的变化区或恒定区或其被修饰的形式的结合分子。因此，所述人的结合分子可以包括不被人生殖系免疫球蛋白序列编码的氨基酸残基，包括取代和/或缺失(例如通过例如体外随机或定点诱变或通过体内体细胞突变引入的突变)。如本文所用，“基于”是指核酸序列可以精确地复制自一个模板或具有微小突变的情况，如通过易错PCR(error-prone PCR)方法进行的复制，或者通过与模板精确相配或具有微小修饰而合成的情况。基于人的序列而半合成的分子同样如在本文所用被认为是人的。

插入

术语“插入”，也称为“添加”，是指在氨基酸或核苷酸序列中的改变，所述改变导致与原始分子(通常是天然发生的分子)相比分别添加了一个或多个氨基酸或核苷酸残基。

分离的

当应用于如本文所定义的结合分子时，术语“分离的”是指基本不含其他蛋白质或多肽的结合分子，尤其不含其他具有不同抗原特异性的结合分子，同时基本不含其他细胞物质和/或化学品。例如当所述结合分子是重组产生的时，它们优选地基本不含有培养基；当所述结合分子是通过化学合成产生的时，它们优选地基本不含有化学前体或其他化学品，即它们是从参与合成所述蛋白质的过程的化学前体或其他化学品中分离出来的。

当应用于如本文所定义的编码结合分子的核酸分子时，术语“分离的”是指这样一种核酸分子，所述核酸分子中编码所述结合分子的核苷酸序列不含其他核苷酸序列，尤其不含编码结合SARS-CoV之外的结合配体的结合分子的核苷酸序列。另外，术语“分离的”还指从其他在其天然宿主中与一种天然核酸分子天然共存的细胞成分中充分分离的核酸分子，所述细胞成分例如核糖体、聚合酶、或与所述核酸分子天然关联的基因组序列。而且，当通过重组技术产生时，“分离的”核酸分子如cDNA分子可以基本上不含其他细胞物质或培养基，或者当被化学合成时，可以基本上不含化学前体或其他化学品。

单克隆抗体

如本文所用，术语“单克隆抗体”是指单一分子组成的抗体分子的制备物。单克隆抗体表现出对于特定表位的单一结合特异性和亲和性。根据本发明，术语“人单克隆抗体”是指表现出单一结合特异性的抗体分子，所述抗体分子具有衍生自或基于人生殖系免疫球蛋白序列的可变区和恒定区或完全得自合成的序列的可变区和恒定区。制备所述单克隆抗体的方法是无关的。

天然发生的

如本文所用的应用于一个对象时，术语“天然发生的”是指所述对象能够在自然界中找到的情况。例如，存在于一个可分离自自然界来源的生物体中的、并且没有被人类在实验室中有意修饰的多肽或多核苷酸序列是天然发生的。

核酸分子

如本发明中所用，术语“核酸分子”是指核苷酸的多聚化形式，并且包括RNA、cDNA、基因组DNA、以及上述的合成形式和混和的多聚体的有义和反义链。核苷酸是指核糖核苷酸、脱氧核苷酸或任一种核苷酸的经过修饰的形式。该术语还包括DNA的单链和双链形式。另外，多核苷酸还可以包括通过天然发生的和/或非天然发生的核苷酸键合(linkage)连接起来的天然发生的和经过修饰的核苷酸的任一种或全部两种。所述核酸分子可以被化学方法或生物化学方法修饰或可以包含非天然的或衍生化的核苷酸碱基，如本领域技术人员所容易理解的。这些修饰包括例如标记、甲基化、用类似物取代一个或多个天然发生的核苷酸、核苷酸间修饰如不带电的键合(例如磷酸甲酯、磷酸三酯、氨基磷酸酯、氨基甲酸酯等)、带电键合(例如硫代磷酸酯、二硫代磷酸酯等)、未定成分(例如多肽)、嵌入剂(例如吖啶、补骨脂素等)、螯合剂、烷基化剂和修饰过的键合(例如α异头核酸等)。上述术语还包括任何拓扑构象，包括单链构象、双链构象、部分双链体构象、三链体构象、发夹构象、环状构象和挂锁(padlocked)构象。具有模拟多核苷酸的通过氢键和其他化学相互作用与一个设计的序列结合的能力的合成分子也包括在该术语中。一些分子是本领域已知的，包括例如在所述分子的骨架中肽键取代了磷酸键。除非另外说明，提到核酸序列时也涵盖了其互补序列。因此，当提到一个具有特定序列的核酸分子时应当理解也同时涵盖了所述核酸分子的具有其互补序列的互补链。所述互补链还可用于例如反义疗法、杂交探针和PCR引物。

可操纵地连接的

术语“可操纵地连接的”是指两个或更多的通常物理性地连接的并且互相功能性相关的核酸序列元件。例如，如果一个启动子能够起始或调控一个编码序列的转录或表达，那么所述启动子与所述编码序列是可操纵地连接的，在此情况下，所述编码序列应该被理解为“处于所述启动子的控制之下”。

药物学可接受的赋形剂

“药物学可接受的赋形剂”是指任何与活性分子如药物、药剂、或结合分子组合以制备适宜的或方便的剂型的惰性物质。所述“药物学可接受的赋形剂”是对于在所应用的剂量和浓度下对接受者无毒性、并且与包含所述药物、药剂、或结合分子的配制品的其他成分相容的赋形剂。

特异结合

如本文所用，术语“特异结合”在指结合分子例如抗体和其结合配体例如抗原的相互作用时，是指所述相互作用依赖于所述结合配体上一种独特结构例如抗原决定簇或表位的存在。也就是说，所述抗体优先结合或识别所述结合配体，即使所述结合配体存在于与其他分子或生物体组成的混和物中。所述结合可以通过共价或非共价相互作用或两者的组合来介导。另一种说法，术语“特异结合”是指免疫特异性地结合一种抗原或其片段同时不会免疫特异性地结合其他抗原。免疫特异性地结合一种抗原的结合分子可以以较低亲和性结合其他肽或多肽，如通过例如放射免疫测定(radioimmunoassay，RIA)、酶联免疫吸附测定(enzyme-linked immunosorbent assays，ELISA)、BIACORE或本领域已知的其他测定所确定的。免疫特异性地结合一种抗原的结合分子或其片段可以与相关抗原发生交叉反应。优选地，免疫特异性地结合一种抗原的结合分子或其片段不与其他抗原发生交叉反应。

取代

如本文所用，术语“取代”是指分别用不同的氨基酸或核苷酸置换一个或多个氨基酸或核苷酸。

治疗有效量

术语“治疗有效量”是指如本文所定义的结合分子对于预防、改善和/或治疗一种由于SARS-CoV感染而导致的疾病的有效量。

治疗

术语“治疗”是指治愈或停止或至少延缓疾病进程的治疗学上的处理和预防性的措施。需要治疗的对象包括已经患有由于SARS-CoV感染而导致的疾病的人以及需要预防SARS-CoV感染的人。部分地或彻底地从SARS-CoV感染中恢复的对象也可能同样需要治疗。预防涵盖了抑制或减轻SARS-CoV的蔓延或抑制或减轻一或多种与SARS-CoV感染相关的症状的发作、发展或进程。

载体

术语“载体”是指为了引入到宿主中，内部可以插入另一个核酸分子的核酸分子，所述核酸分子在宿主中复制并且在一些情况下表达。也就是说，载体能够将核酸分子运输到其已经相关的地方。如本文所用，术语“载体”包括克隆和表达载体。载体包括但不限于质粒、粘粒(cosmid)、细菌人工染色体(BAC)和酵母人工染色体(YAC)以及衍生自细菌噬菌体或植物病毒或动物(包括人)病毒的载体。载体包含所假设的宿主识别的复制起点和在表达载体的情况下所述宿主可识别的启动子和其他调节区。含有第二条核酸分子的载体通过转化、转染或应用病毒进入机制被引入到细胞中。某些载体能够在所被引入的宿主中自发复制(例如具有细菌复制起点的载体在细菌中可以复制)。其他载体可以在被引入宿主中后整合进宿主的基因组，从而与宿主基因组一起复制。

发明概述

本发明提供了能够特异结合至SARS-CoV的结合分子。在一个优选的实施方案中，所述结合分子是人的结合分子。另外，本发明涉及编码至少所述结合分子的结合区域的核酸分子。本发明进一步提供了本发明的结合分子在预防和/或治疗患有由SARS-CoV导致的疾病或至少具有患病危险的对象中的应用。另外，本发明涉及本发明的结合分子在诊断/检测SARS-CoV中的应用。

发明详述

本发明的第一个方面涵盖了能够特异结合至SARS-CoV的结合分子。所述结合分子可以具有以有活性的或失活的/减毒的(attenuated)形式特异结合至SARS-CoV的能力。本领域熟知用于使病毒失活/减毒的方法，所述方法包括但不限于热失活、通过UV照射失活、通过γ射线照射失活。所述结合分子还可以具有特异结合至SARS-CoV的一个或多个片段的能力，所述片段特别例如衍生自SARS-CoV的一种或多种蛋白质和/或(多肽)的制备物。对于SARS的治疗和/或预防方法，所述结合分子优选的能够特异结合至表面可接触蛋白质(surface accessible protein)，所述蛋白质包括但不限于内膜和外膜蛋白、粘附于细胞壁的蛋白质、以及潜在的分泌蛋白。SARS-CoV的表面可接触蛋白质包括但不限于刺突蛋白、膜(基质)蛋白、(小)包膜蛋白、Orf3、Orf4、Orf7、Orf8、Orf9、Orf10及Orf14。用于诊断目的时，所述结合分子还可以能够特异结合至不存在于SARS-CoV表面的蛋白质。因此，可以应用包括但不限于核壳(N)蛋白、Orf11及Orf13。在EMBL数据库和/或其他数据库中可以找到各种已知的SARS-CoV病毒株的蛋白质及潜在蛋白质的氨基酸序列。例如在EMBL数据库中可以找到登记号(accession number)为AY278741的SARS冠状病毒Urbani的完整基因组、登记号为AY323977的SARS冠状病毒HSR 1的完整基因组、登记号为AY291315的SARS冠状病毒Frankfurt 1的完整基因组、以及登记号为AY274119的SARS冠状病毒TOR2的完整基因组。优选地，所述片段至少包含能够被本发明的结合分子识别的抗原决定簇。如本文所用，“抗原决定簇”是一种成分，例如SARS-CoV(多)肽、蛋白质、糖蛋白、类似物或其片段，所述成分能够以足够高的亲和性结合至本发明的结合分子以形成一种可检测的抗原一结合分子复合物。

本发明的结合分子优选的是人的结合分子，优选的是人的单克隆抗体。它们可以是完整的免疫球蛋白分子如多克隆或单克隆抗体，尤其是人的单克隆抗体，或者所述结合分子可以是抗原结合片段包括但不限于Fab、F(ab’)、F(ab’)₂、Fv、dAb、Fd、互补决定区(CDR)片段、单链抗体(scFv)、二价单链抗体、单链噬菌体抗体、二聚抗体、三聚抗体、四聚抗体、以及包含免疫球蛋白的至少一个片段的(多)肽(所述片段足以使所述(多)肽进行特异性抗原结合)。本发明的结合分子可以以非分离的或分离的形式应用。另外，本发明的分子可以以单独的形式或以包含至少一个结合分子(或其变体或片段)的混和物的形式应用。也就是说，所述结合分子可以组合应用，例如作为包含两个或更多的结合分子、其变体或片段的药物组合物应用。例如具有不同但是互补活性的结合分子可以在单一治疗中组合应用以达到所希望的预防、治疗或诊断效果，但是可替换的，具有相同活性的结合分子也可以在单一治疗中组合应用以达到所希望的预防、治疗或诊断效果。所述混和物可以进一步包含至少一种其他的治疗剂。优选地，所述治疗剂可用于预防和/或治疗SARS-CoV导致的疾病。

典型地，本发明的结合分子可以以低于0.2×10^-4M、1.0×10^-5M、1.0×10^-6M、1.0×10^-7M、优选地低于1.0×10^-8M、更优选地低于1.0×10^-9M、更优选地低于1.0×10^-10M、更优选地低于1.0×10^-11M、尤其是低于1.0×10^-12M的亲和常数(affinity constant，K_d值)结合至它们的结合配体即SARS-CoV或其片段。所述亲和常数可以依据抗体同种型而变化。例如，对于IgM同种型的亲和结合(affinity binding)是至少大约1.0×10^-7M的结合亲和性。亲和常数可以用例如表面等离子共振技术(surface plasmon resonance)测量，即一种使得可以在一种生物感应器基质中(例如使用BIACORE系统(Pharmacia Biosensor AB，Uppsala，Sweden))通过检测蛋白质浓度的改变而分析实时生物特异性相互作用的光学现象。

本发明的结合分子可以以可溶形式结合至SARS-CoV，例如在样品中，或者可以结合至结合于或附着于一种载体或基材(例如微量滴定板(microtiter plate)、膜或珠等)的SARS-CoV。载体或基材可以由玻璃、塑料(例如聚苯乙烯)、多糖、尼龙、硝化纤维素、或特富龙(teflon)等制造。这些支持物的表面可以是固体或多孔的并且可以是任何方便的形状。另外，所述结合分子可以以纯化的/分离的或非纯化的/非分离的形式结合至SARS-CoV。

在本发明的一个优选的实施方案中，本发明的结合分子中和SARS-CoV感染性。这可以通过阻止SARS-CoV附着于宿主细胞上的可能的受体或抑制RNA释放进细胞的细胞质或阻止RNA转录或翻译来实现。在一个特定的实施方案中，相对于本发明的结合分子不存在时宿主细胞被SARS-CoV感染的情况，所述结合分子至少99％、至少95％、至少90％、至少85％、至少80％、至少75％、至少70％、至少60％、至少50％、至少45％、至少40％、至少45％、至少35％、至少30％、至少25％、至少20％、或至少10％阻止SARS-CoV感染细胞。可以如例如本文所描述的测量中和。

本发明的结合分子不阻止SARS-CoV结合其宿主细胞受体，但是抑制或减量调节(downregulate)SARS-CoV的复制，所述结合分子还可以施用于哺乳动物以治疗、预防或改善与SARS-CoV相关的一种或多种症状。结合分子抑制或减量调节SARS-CoV复制的能力可以通过本领域已知的技术确定，例如SARS-CoV复制的抑制或减量调节可以通过在哺乳动物(优选地是人)的生物学样品中检测SARS-CoV的滴度确定。相对于本发明的结合分子不存在时SARS-CoV的复制，所述结合分子至少99％、至少95％、至少90％、至少85％、至少80％、至少75％、至少70％、至少60％、至少50％、至少45％、至少40％、至少45％、至少35％、至少30％、至少25％、至少20％、或至少10％抑制或减量调节SARS-CoV的复制。另外，本发明的结合分子可以是能够在裂解具有包膜的SARS-CoV时具有协助作用的补体结合分子(complement fixing binding molecule)。本发明的结合分子还可以表现调理素的作用并通过促进SARS-CoV通过Fc或C3b受体摄入或通过聚集SARS-CoV以使其更易于被吞噬来增强SARS-CoV的吞噬作用。

在一个优选的实施方案中，本发明的结合分子包括至少一个CDR3区，优选一个重链CDR3区，所述CDR3区包括选自由如下序列组成的一组的氨基酸序列：SEQ ID NO：1、SEQ ID NO：2、SEQ IDNO：3、SEQ ID NO：4、SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：7、SEQ ID NO：8、SEQ ID NO：9、SEQ ID NO：10、SEQID NO：11、SEQ IDNO：12、SEQ ID NO：13、SEQ ID NO：75、SEQ ID NO：76、SEQ IDNO：77、SEQ ID NO：78、SEQ ID NO：291、SEQ ID NO：292、SEQ IDNO：293、SEQ ID NO：294、SEQ ID NO：295、SEQ ID NO：296、SEQ IDNO：297、SEQ ID NO：298、SEQ ID NO：299、SEQ ID NO：300和SEQ IDNO：301。

在另一个实施方案中，本发明的结合分子包括一条可变重链，所述可变重链包括选自由如下序列组成的一组的氨基酸序列：SEQ IDNO：15、SEQ ID NO：17、SEQ ID NO：19、SEQ ID NO：21、SEQ IDNO：23、SEQ ID NO：25、SEQ ID NO：27、SEQ ID NO：29、SEQ IDNO：31、SEQ ID NO：33、SEQ ID NO：35、SEQ ID NO：37、SEQ IDNO：39、SEQ ID NO：80、SEQ ID NO：82、SEQ ID NO：84、SEQ IDNO：86、SEQ ID NO：303、SEQ ID NO：307、SEQ ID NO：311、SEQ IDNO：315、SEQ ID NO：319、SEQ ID NO：323、SEQ ID NO：327、SEQ IDNO：331、SEQ ID NO：335、SEQ ID NO：339、SEQ ID NO：343、SEQ IDNO：347、SEQ ID NO：351、SEQ ID NO：355、SEQ ID NO：359、SEQ IDNO：363、SEQ ID NO：367、SEQ ID NO：371、SEQ ID NO：375、SEQ IDNO：379、SEQ ID NO：383、SEQ ID NO：387、SEQ ID NO：391、SEQ IDNO：395、SEQ ID NO：399、SEQ ID NO：403、SEQ ID NO：407、SEQ IDNO：411、SEQ ID NO：415、SEQ ID NO：419、SEQ ID NO：423、SEQ IDNO：427、SEQ ID NO：431、SEQ ID NO：435、SEQ ID NO：439、SEQ IDNO：443、SEQ ID NO：447、SEQ ID NO：451、SEQ ID NO：455和SEQ IDNO：459。

在一个另一实施方案中，本发明的结合分子包含：一个包含SEQID NO：15的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：19的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：21的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：23的氨基酸序列的可变重链和一个包含SEQ ID NO：43的氨基酸序列的可变轻链、一个包含SEQ ID NO：25的氨基酸序列的可变重链和一个包含SEQ IDNO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：27的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：29的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：31的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：33的氨基酸序列的可变重链和一个包含SEQ ID NO：45的氨基酸序列的可变轻链、一个包含SEQ IDNO：35的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：37的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQID NO：39的氨基酸序列的可变重链和一个包含SEQ ID NO：45的氨基酸序列的可变轻链、一个包含SEQ ID NO：80的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：82的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：84的氨基酸序列的可变重链和一个包含SEQ ID NO：88的氨基酸序列的可变轻链、一个包含SEQ ID NO：86的氨基酸序列的可变重链和一个包含SEQ IDNO：41的氨基酸序列的可变轻链、一个包含SEQ ID NO：303的氨基酸序列的可变重链和一个包含SEQ ID NO：305的氨基酸序列的可变轻链、一个包含SEQ ID NO：307的氨基酸序列的可变重链和一个包含SEQ ID NO：309的氨基酸序列的可变轻链、一个包含SEQ ID NO：311的氨基酸序列的可变重链和一个包含SEQ ID NO：313的氨基酸序列的可变轻链、一个包含SEQ ID NO：315的氨基酸序列的可变重链和一个包含SEQ ID NO：317的氨基酸序列的可变轻链、一个包含SEQID NO：319的氨基酸序列的可变重链和一个包含SEQ ID NO：321的氨基酸序列的可变轻链、一个包含SEQ ID NO：323的氨基酸序列的可变重链和一个包含SEQ ID NO：325的氨基酸序列的可变轻链、一个包含SEQ ID NO：327的氨基酸序列的可变重链和一个包含SEQ IDNO：329的氨基酸序列的可变轻链、一个包含SEQ ID NO：331的氨基酸序列的可变重链和一个包含SEQ ID NO：333的氨基酸序列的可变轻链、一个包含SEQ ID NO：335的氨基酸序列的可变重链和一个包含SEQ ID NO：337的氨基酸序列的可变轻链、一个包含SEQ IDNO：339的氨基酸序列的可变重链和一个包含SEQ ID NO：341的氨基酸序列的可变轻链、一个包含SEQ ID NO：343的氨基酸序列的可变重链和一个包含SEQ ID NO：345的氨基酸序列的可变轻链、一个包含SEQ ID NO：347的氨基酸序列的可变重链和一个包含SEQ IDNO：349的氨基酸序列的可变轻链、一个包含SEQ ID NO：351的氨基酸序列的可变重链和一个包含SEQ ID NO：353的氨基酸序列的可变轻链、一个包含SEQ ID NO：355的氨基酸序列的可变重链和一个包含SEQ ID NO：357的氨基酸序列的可变轻链、一个包含SEQ IDNO：359的氨基酸序列的可变重链和一个包含SEQ ID NO：361的氨基酸序列的可变轻链、一个包含SEQ ID NO：363的氨基酸序列的可变重链和一个包含SEQ ID NO：365的氨基酸序列的可变轻链、一个包含SEQ ID NO：367的氨基酸序列的可变重链和一个包含SEQ IDNO：369的氨基酸序列的可变轻链、一个包含SEQ ID NO：371的氨基酸序列的可变重链和一个包含SEQ ID NO：373的氨基酸序列的可变轻链、一个包含SEQ ID NO：375的氨基酸序列的可变重链和一个包含SEQ ID NO：377的氨基酸序列的可变轻链、一个包含SEQ IDNO：379的氨基酸序列的可变重链和一个包含SEQ ID NO：381的氨基酸序列的可变轻链、一个包含SEQ ID NO：383的氨基酸序列的可变重链和一个包含SEQ ID NO：385的氨基酸序列的可变轻链、一个包含SEQ ID NO：387的氨基酸序列的可变重链和一个包含SEQ IDNO：389的氨基酸序列的可变轻链、一个包含SEQ ID NO：391的氨基酸序列的可变重链和一个包含SEQ ID NO：393的氨基酸序列的可变轻链、一个包含SEQ ID NO：395的氨基酸序列的可变重链和一个包含SEQ ID NO：397的氨基酸序列的可变轻链、一个包含SEQ IDNO：399的氨基酸序列的可变重链和一个包含SEQ ID NO：401的氨基酸序列的可变轻链、一个包含SEQ ID NO：403的氨基酸序列的可变重链和一个包含SEQ ID NO：405的氨基酸序列的可变轻链、一个包含SEQ ID NO：407的氨基酸序列的可变重链和一个包含SEQ IDNO：409的氨基酸序列的可变轻链、一个包含SEQ ID NO：411的氨基酸序列的可变重链和一个包含SEQ ID NO：413的氨基酸序列的可变轻链、一个包含SEQ ID NO：415的氨基酸序列的可变重链和一个包含SEQ ID NO：417的氨基酸序列的可变轻链、一个包含SEQ IDNO：419的氨基酸序列的可变重链和一个包含SEQ ID NO：421的氨基酸序列的可变轻链、一个包含SEQ ID NO：423的氨基酸序列的可变重链和一个包含SEQ ID NO：425的氨基酸序列的可变轻链、一个包含SEQ ID NO：427的氨基酸序列的可变重链和一个包含SEQ IDNO：429的氨基酸序列的可变轻链、一个包含SEQ ID NO：431的氨基酸序列的可变重链和一个包含SEQ ID NO：433的氨基酸序列的可变轻链、一个包含SEQ ID NO：435的氨基酸序列的可变重链和一个包含SEQ ID NO：437的氨基酸序列的可变轻链、一个包含SEQ IDNO：439的氨基酸序列的可变重链和一个包含SEQ ID NO：441的氨基酸序列的可变轻链、一个包含SEQ ID NO：443的氨基酸序列的可变重链和一个包含SEQ ID NO：445的氨基酸序列的可变轻链、一个包含SEQ ID NO：447的氨基酸序列的可变重链和一个包含SEQ IDNO：449的氨基酸序列的可变轻链、一个包含SEQ ID NO：451的氨基酸序列的可变重链和一个包含SEQ ID NO：453的氨基酸序列的可变轻链、一个包含SEQ ID NO：455的氨基酸序列的可变重链和一个包含SEQ ID NO：457的氨基酸序列的可变轻链、或一个包含SEQ IDNO：459的氨基酸序列的可变重链和一个包含SEQ ID NO：461的氨基酸序列的可变轻链。

在本发明的一个实施方案中，具有SARS-CoV中和活性的所述结合分子是至少包含一个CDR3区，优选一个重链CDR3区的结合分子，所述CDR3区包含选自由SEQ ID NO：11和SEQ ID NO：12组成的一组的氨基酸序列。在一个另一实施方案中，具有SARS-CoV中和活性的所述结合分子是包含一个包含选自由SEQ ID NO：35和SEQID NO：37组成的一组的氨基酸序列的可变重链的结合分子。在另一个另一实施方案中，具有SARS-CoV中和活性的所述结合分子是包含一个包含SEQ ID NO：35的氨基酸序列的可变重链和一个包含SEQID NO：41的氨基酸序列的可变轻链的结合分子或一个包含SEQ IDNO：37的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链的结合分子。在一个优选的实施方案中，具有SARS-CoV中和活性的所述本发明的结合分子以IgG1或IgA(例如用于粘膜给药)的形式被给予。

本发明的另一方面包括如本文所定义的结合分子的功能性变体。如果一种分子能够与本发明的结合分子对特异结合至SARS-CoV或其片段进行竞争，那么所述分子被认为是本发明的亲代结合分子的功能性变体。也就是说，所述功能性变体依旧能够与SARS-CoV或其片段结合。功能性变体包括但不限于亲代结合分子的衍生物，所述衍生物在初级结构序列上基本相似，但是包含在亲代结合分子中没有的例如体外或体内的修饰、化学物质或生物化学物质。这些修饰特别包括乙酰化、酰化、ADP-核糖化、酰胺化、黄素的共价附着、血红素成分的共价附着、核苷酸或核苷酸衍生物的共价附着、脂类或脂类衍生物的共价附着、磷脂酰肌醇的共价附着、交联、环化、二硫键形成、脱甲基化、共价交联形成、胱氨酸形成、焦谷氨酸形成、甲酰化、γ-羧化、糖基化、GPI-锚定(GPI-anchor)形成、羟化、碘化、甲基化、豆蔻酰化、氧化、聚乙二醇化(pegylation)、蛋白质酶解加工、磷酸化、异戊二烯化、消旋化、硒化(selenoylation)、硫酸盐化(sulfation)、转移RNA介导的氨基酸加入到蛋白质上如精氨酰化、泛素化等等。

或者，功能性变体可以是如本发明所描述的结合分子，对比于亲代结合分子的氨基酸序列，所述结合分子包含含有一个或多个氨基酸的取代、插入、缺失或其组合的氨基酸序列。另外，功能性变体可以在氨基末端或羧基末端中的任一个或在两端同时包含氨基酸序列的截短(truncation)。对比于亲代结合分子，本发明的功能性变体可以具有相同的或不同的结合亲和性，所述不同可以是更高或更低，但还是能够与SARS-CoV或其片段结合。例如，对比于亲代结合分子，本发明的功能性变体可以具有对SARS-CoV或其片段升高的或降低的结合亲和性。优选地，可变区的氨基酸序列(包括但不限于构架区(framework region)、高变区、尤其是CDR3区)是被修饰的。一般地，轻链和重链可变区包括三个高变区和更保守的区域(即所谓的构架区(FR))，所述高变区包括三个CDR。所述高变区包括来自CDR的氨基酸残基和来自高变环的氨基酸残基。本发明包括的功能性变体具有与本文所描述的亲代结合分子具有至少大约50％至大约99％、优选地至少大约60％至大约99％、更优选地至少大约70％至大约99％、更优选地至少大约80％至大约99％、最优选地至少大约90％至大约99％、尤其至少大约95％至大约99％、尤其至少大约95％至大约99％的氨基酸序列同源性。可以应用本领域技术人员所知的计算机算法特别例如Gap或Bestfit来最优地排列对比氨基酸序列以对比及确定相似或相同的氨基酸残基。功能性变体可以通过由本领域所知的普通分子生物学方法改变亲代结合分子或其部分获得，所述方法包括但不限于易错PCR、寡核苷酸指导的诱变及定点诱变。优选地，本发明的功能性变体具有SARS-CoV中和活性。这种中和活性可以高于或低于亲代结合分子。另外，所述功能性变体可以抑制或减量调节SARS-CoV复制、可以是能够在具有包膜的SARS-CoV的裂解中发挥协助作用的补体结合分子、和/或可以表现调理素的作用并通过促进SARS-CoV通过Fc或C3b受体摄入或通过聚集SARS-CoV以使其更易于被吞噬。

在另一方面，本发明包括免疫缀合物，即包括至少一个本文所描述的结合分子或其功能性变体，并且进一步包括至少一个标记物的分子，所述标记物特别例如可被检测到的成分/物质。本发明还包括本发明的免疫缀合物的混和物或至少一种本发明的免疫缀合物和另一种分子(例如一种治疗剂或另一种结合分子或免疫缀合物)的混和物。在另一实施方案中，本发明的免疫缀合物可以包括多于一个的标记物。这些标记物可以是彼此相同的或不同的，并且可被非共价地结合/缀合至所述结合分子。所述标记物还可以通过共价键合被直接结合/缀合至所述结合分子，所述共价键合包括但不限于二硫键键合、氢键键合、静电键合、重组融合及构象键合。或者，所述标记物可以通过一个或多个连接化合物的方法结合/缀合至所述结合分子，本领域技术人员熟知用于将标记物缀合至结合分子的技术。

本发明的免疫缀合物的标记物可以是治疗剂，但是优选地它们是可检测到的成分/物质。包含可检测到的物质的免疫缀合物可以应用于诊断以例如评估一个对象是否已经被SARS-CoV感染，或监测SARS-CoV感染的发展或进程以作为用于例如确定一种特定的治疗方案效果的临床检测步骤的一部分。然而，它们还可用于其他检测和/或分析和/或诊断目的。可检测到的成分/物质包括但不限于酶、辅基、荧光物质、发光物质、生物发光物质、放射性物质、正电子发射金属、以及非放射性顺磁金属离子。

所述用于标记用于检测和/或分析和/或诊断目的的结合分子的标记物根据所用的特定检测/分析/诊断技术和/或方法确定，所述技术和/或方法特别例如(组织)样品的免疫组化染色、流式细胞检测、扫描激光细胞检测、荧光免疫测定、酶联免疫吸附测定(ELISA)、放射免疫测定(RIA)、生物测定(例如中和测定)、Western印迹应用等等。对于组织样品的免疫组化染色，优选的标记是催化可检测到的产物的产生和局部聚集的酶。本领域熟知典型地缀合至结合分子以使得其被免疫组化显色的酶，所述酶包括但不限于乙酰胆碱酯酶、碱性磷酸酶、β-半乳糖苷酶、葡萄糖氧化酶、辣根过氧化物酶、以及脲酶。用于产生和聚集可被显色检测到的产物的典型底物包括但不限于邻硝基苯基-β-D-半乳糖苷(ONPG)、盐酸邻苯二胺(OPD)、磷酸对硝基苯(PNPP)、对硝基苯基-β-D-半乳糖苷(PNPG)、3′，3′二氨基联苯胺(DAB)、3-氨基-9-乙基咔唑(AEC)、4-氯-1-萘酚(CN)、5-溴-4-氯-3-吲哚基磷酸钠盐(BCIP)、ABTS、BluoGal、碘硝基四唑(INT)、氯化氮蓝四唑(NBT)、吩嗪硫酸甲脂(PMS)、单磷酸酚酞(PMP)、四甲基联苯胺(TMB)、四硝基四氮唑蓝(TNBT)、X-Gal、X-Gluc、以及X-葡萄糖苷。其他可用于产生用于局部聚集的产物的底物是发光底物。例如在过氧化氢存在的情况下，辣根过氧化物酶可催化环二酰基肼类如鲁米诺的氧化。另外，本发明的免疫缀合物的结合分子还可以用胶体金标记，或者其可以用放射性同位素标记，例如³³P、³²P、³⁵S、³H和¹²⁵I。本发明的结合分子可以用本领域已知的方法通过螯合剂直接或间接附着至放射性核素。

当本发明的结合分子用于流式细胞检测、扫描激光细胞检测、或荧光免疫测定时，用荧光团标记它们是有用的。可用于荧光标记本发明的结合分子的各种荧光团包括但不限于Alexa Fluor和AlexaFluor&commat染料、BODIPY染料、Cascade Blue、Cascade Yellow、丹磺酰、丽丝胺罗丹明B(lissamine rhodamine B)、Marina Blue、OregonGreen 488、Oregon Green 514、Pacific Blue、罗丹明6G，、罗丹明绿、罗丹明红、四甲基罗丹明、Cy2、Cy3、Cy3.5、Cy5、Cy5.5、Cy7、异硫氰酸萤光素(FITC)、别藻蓝蛋白(APC)、R-藻红蛋白(PE)、叶丝素蛋白(peridinin chlorophyll protein，PerCP)、德克萨斯红、荧光共振能量串连荧光团(flrorescence resonance energy tandem fluorophore)如PerCP-Cy5.5、PE-Cy5、PE-Cy5.5、PE-Cy7、PE-德克萨斯红、以及APC-Cy7。当本发明的结合分子用于使用标记的亲和素、链亲和素、captavidin、和中性链亲和素(neutravidin)的次级检测时，所述结合分子可用生物素标记以形成适当的辅基复合物。

当本发明的免疫缀合物用于体内诊断时，所述结合分子还可以通过缀合至例如磁共振成像(MRI)造影剂(contrast agents)例如二乙烯三胺五乙酸钆、缀合至超声造影剂或缀合至X射线造影剂或通过放射性同位素标记而可被检测。

适当的发光物质包括但不限于鲁米诺，适当的生物发光物质包括但不限于萤光素酶、萤光素、和水母蛋白。

另外，本发明的结合分子、功能性变体或免疫缀合物还可以附着于固体支持物，这特别用于体外免疫测定或SARS-CoV或其片段的纯化。这种固体支持物可以是多孔的或非多孔的、平坦的或非平坦的，并且包括但不限于玻璃、纤维素、聚丙稀酰胺、尼龙、聚苯乙烯、聚氯乙烯、或聚丙烯支持物。所述结合分子还可以例如有用地被缀合至过滤介质，例如用于免疫亲和层析的NHS活化的琼脂糖凝胶(Sepharose)或CNBr-活化的琼脂糖凝胶。它们还可以例如典型地通过生物素-链霉亲和素相互作用而被有用地附着至顺磁性微球体。所述微球体可以用于从含有SARS-CoV或其片段的样品中分离SARS-CoV或其片段。另一个实例是本发明的结合分子可以被有用地附着至微量滴定板的表面用于ELISA。

本发明的结合分子或其功能性变体可以融合至标记序列(markersequence)例如肽以促进纯化。实例包括但不限于6-组氨酸标记、血凝素(HA)标记、myc标记或flag标记。

另外地，一种抗体可以被缀合至另一种抗体以形成一种抗体异源缀合物。在另一方面，本发明的结合分子可以被缀合/附着至一种或多种抗原。优选地，这些抗原是能够被对象的免疫系统识别的抗原，所述对象是给予所述结合分子-抗原缀合物的对象。所述抗原可以是相同的但是也可以是互相不同的。用于附着所述抗原和结合分子的缀合方法是本领域已知的，所述方法包括但不限于应用交联剂。所述结合分子会结合至SARS-CoV并且附着于所述结合分子的抗原会引起对所述缀合物有力的T细胞攻击并最终导致SARS-CoV的破坏。

除了由化学方法通过由例如接头(linker)的直接或间接的缀合来产生免疫缀合物外，所述免疫缀合物可以作为包括本发明的结合分子和适当标记物的融合蛋白产生。融合蛋白可以通过本领域已知的方法产生，例如通过构建包含符合读框地编码所述结合分子的核酸序列和编码所述适当的标记物的核酸序列的核酸分子并接下来表达所述核酸分子产生。

本发明的另一个方面提供了编码至少一种本发明的结合分子或其功能性片段的核酸分子。所述核酸分子可用作用于克隆目的的中间物，例如用于在前面所描述的亲和成熟的过程中。在一个优选的实施方案中，所述核酸分子是被分离的或被纯化的。

本领域技术人员应理解这些核酸分子的功能性变体也是本发明的一部分。功能性变体是可以通过标准遗传密码被直接翻译以提供与从亲代核酸分子翻译的氨基酸序列相同的氨基酸序列的核酸序列。

优选地，所述核酸序列编码包括一个CDR3区，优选重链CDR3区的结合分子，所述CDR3区包括选自由下列序列组成的一组的氨基酸序列：SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：5、SEQ ID NO：6、SEQ ID NO：7、SEQ ID NO：8、SEQ IDNO：9、SEQ ID NO：10、SEQ ID NO：11、SEQ ID NO：12、SEQ ID NO：13、SEQ ID NO：75、SEQ ID NO：76、SEQ ID NO：77、SEQ ID NO：78、SEQID NO：291、SEQ ID NO：292、SEQ ID NO：293、SEQ ID NO：294、SEQID NO：295、SEQ ID NO：296、SEQ ID NO：297、SEQ ID NO：298、SEQID NO：299、SEQ ID NO：300和SEQ ID NO：301。

更加优选地，所述核酸分子编码包括可变重链的结合分子，所述可变重链包括选自由下列序列组成的一组的氨基酸序列：SEQ IDNO：15、SEQ ID NO：17、SEQ ID NO：19、SEQ ID NO：21、SEQ IDNO：23、SEQ ID NO：25、SEQ ID NO：27、SEQ ID NO：29、SEQ IDNO：31、SEQ ID NO：33、SEQ ID NO：35、SEQ ID NO：37、SEQ IDNO：39、SEQ ID NO：80、SEQ ID NO：82、SEQ ID NO：84、SEQ IDNO：86、SEQ ID NO：303、SEQ ID NO：307、SEQ ID NO：311、SEQ IDNO：315、SEQ ID NO：319、SEQ ID NO：323、SEQ ID NO：327、SEQ IDNO：331、SEQ ID NO：335、SEQ ID NO：339、SEQ ID NO：343、SEQ IDNO：347、SEQ ID NO：351、SEQ ID NO：355、SEQ ID NO：359、SEQ IDNO：363、SEQ ID NO：367、SEQ ID NO：371、SEQ ID NO：375、SEQ IDNO：379、SEQ ID NO：383、SEQ ID NO：387、SEQ ID NO：391、SEQ IDNO：395、SEQ ID NO：399、SEQ ID NO：403、SEQ ID NO：407、SEQ IDNO：411、SEQ ID NO：415、SEQ ID NO：419、SEQ ID NO：423、SEQ IDNO：427、SEQ ID NO：431、SEQ ID NO：435、SEQ ID NO：439、SEQ IDNO：443、SEQ ID NO：447、SEQ ID NO：451、SEQ ID NO：455和SEQ IDNO：459。

在另一个实施方案中，所述核酸分子编码包含一个包含SEQ IDNO：15的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链的结合分子，或者它们编码一个包含SEQ ID NO：17的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：19的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：21的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQID NO：23的氨基酸序列的可变重链和一个包含SEQ ID NO：43的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：25的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：27的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：29的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：31的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：33的氨基酸序列的可变重链和一个包含SEQ ID NO：45的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：35的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：37的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：39的氨基酸序列的可变重链和一个包含SEQ ID NO：45的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：80的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：82的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：84的氨基酸序列的可变重链和一个包含SEQ ID NO：88的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：86的氨基酸序列的可变重链和一个包含SEQ ID NO：41的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：303的氨基酸序列的可变重链和一个包含SEQ ID NO：305的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：307的氨基酸序列的可变重链和一个包含SEQ ID NO：309的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：311的氨基酸序列的可变重链和一个包含SEQ ID NO：313的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：315的氨基酸序列的可变重链和一个包含SEQID NO：317的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：319的氨基酸序列的可变重链和一个包含SEQ ID NO：321的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：323的氨基酸序列的可变重链和一个包含SEQ ID NO：325的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：327的氨基酸序列的可变重链和一个包含SEQ ID NO：329的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：331的氨基酸序列的可变重链和一个包含SEQ ID NO：333的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：335的氨基酸序列的可变重链和一个包含SEQ IDNO：337的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：339的氨基酸序列的可变重链和一个包含SEQ ID NO：341的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：343的氨基酸序列的可变重链和一个包含SEQ ID NO：345的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：347的氨基酸序列的可变重链和一个包含SEQID NO：349的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：351的氨基酸序列的可变重链和一个包含SEQ ID NO：353的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：355的氨基酸序列的可变重链和一个包含SEQ IDNO：357的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：359的氨基酸序列的可变重链和一个包含SEQ ID NO：361的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：363的氨基酸序列的可变重链和一个包含SEQ ID NO：365的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：367的氨基酸序列的可变重链和一个包含SEQ ID NO：369的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：371的氨基酸序列的可变重链和一个包含SEQ ID NO：373的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：375的氨基酸序列的可变重链和一个包含SEQ IDNO：377的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：379的氨基酸序列的可变重链和一个包含SEQ ID NO：381的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：383的氨基酸序列的可变重链和一个包含SEQ ID NO：385的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：387的氨基酸序列的可变重链和一个包含SEQ ID NO：389的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：391的氨基酸序列的可变重链和一个包含SEQ ID NO：393的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：395的氨基酸序列的可变重链和一个包含SEQ IDNO：397的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：399的氨基酸序列的可变重链和一个包含SEQ ID NO：401的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：403的氨基酸序列的可变重链和一个包含SEQ ID NO：405的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：407的氨基酸序列的可变重链和一个包含SEQ ID NO：409的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：411的氨基酸序列的可变重链和一个包含SEQ ID NO：413的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：415的氨基酸序列的可变重链和一个包含SEQ IDNO：417的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：419的氨基酸序列的可变重链和一个包含SEQ ID NO：421的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：423的氨基酸序列的可变重链和一个包含SEQ ID NO：425的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：427的氨基酸序列的可变重链和一个包含SEQ ID NO：429的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：431的氨基酸序列的可变重链和一个包含SEQ ID NO：433的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：435的氨基酸序列的可变重链和一个包含SEQ IDNO：437的氨基酸序列的可变轻链，或者它们编码一个包含SEQ IDNO：439的氨基酸序列的可变重链和一个包含SEQ ID NO：441的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：443的氨基酸序列的可变重链和一个包含SEQ ID NO：445的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：447的氨基酸序列的可变重链和一个包含SEQ ID NO：449的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：451的氨基酸序列的可变重链和一个包含SEQ ID NO：453的氨基酸序列的可变轻链，或者它们编码一个包含SEQ ID NO：455的氨基酸序列的可变重链和一个包含SEQ IDNO：457的氨基酸序列的可变轻链，或者它们编码或一个包含SEQ IDNO：459的氨基酸序列的可变重链和一个包含SEQ ID NO：461的氨基酸序列的可变轻链。

在本发明的一个特别的实施方案中，所述编码本发明的结合分子的可变重链的核酸分子包括选自如下一组的的核苷酸序列：SEQ IDNO：14、SEQ ID NO：16、SEQ ID NO：18、SEQ ID NO：20、SEQ IDNO：22、SEQ ID NO：24、SEQ ID NO：26、SEQ ID NO：28、SEQ IDNO：30、SEQ ID NO：32、SEQ ID NO：34、SEQ ID NO：36、SEQ IDNO：38、SEQ ID NO：79、SEQ ID NO：81、SEQ ID NO：83、SEQ IDNO：85、SEQ ID NO：302、SEQ ID.NO：306、SEQ ID NO：310、SEQ IDNO：314、SEQ ID NO：318、SEQ ID NO：322、SEQ ID NO：326、SEQ IDNO：330、SEQ ID NO：334、SEQ ID NO：338、SEQ ID NO：342、SEQ IDNO：346、SEQ ID NO：350、SEQ ID NO：354、SEQ ID NO：358、SEQ IDNO：362、SEQ ID NO：366、SEQ ID NO：370、SEQ ID NO：374、SEQ IDNO：378、SEQ ID NO：382、SEQ ID NO：386、SEQ ID NO：390、SEQ IDNO：394、SEQ ID NO：398、SEQ ID NO：402、SEQ ID NO：406、SEQ IDNO：410、SEQ ID NO：414、SEQ ID NO：418、SEQ ID NO：422、SEQ IDNO：426、SEQ ID NO：430、SEQ ID NO：434、SEQ ID NO：438、SEQ IDNO：442、SEQ ID NO：446、SEQ ID NO：450、SEQ ID NO：454和SEQ IDNO：458。

在本发明的另一个特别的实施方案中，所述编码本发明的结合分子的可变轻链的核酸分子包括选自如下一组的的核苷酸序列：SEQID NO：40、SEQ ID NO：42、SEQ ID NO：44、SEQ ID NO：87、SEQ IDNO：304、SEQ ID.NO：308、SEQ ID NO：312、SEQ ID NO：316、SEQ IDNO：320、SEQ ID NO：324、SEQ ID NO：328、SEQ ID NO：332、SEQ IDNO：336、SEQ ID NO：340、SEQ ID NO：344、SEQ ID NO：348、SEQ IDNO：352、SEQ ID NO：356、SEQ ID NO：360、SEQ ID NO：364、SEQ IDNO：368、SEQ ID NO：372、SEQ ID NO：376、SEQ ID NO：380、SEQ IDNO：384、SEQ ID NO：388、SEQ ID NO：392、SEQ ID NO：396、SEQ IDNO：400、SEQ ID NO：404、SEQ ID NO：408、SEQ ID NO：412、SEQ IDNO：416、SEQ ID NO：420、SEQ ID NO：424、SEQ ID NO：428、SEQ IDNO：432、SEQ ID NO：436、SEQ ID NO：440、SEQ ID NO：444、SEQ IDNO：448、SEQ ID NO：452、SEQ ID NO：456和SEQ ID NO：460。

本发明的另一方面提供了包括一个或多个本发明的核酸分子的载体，即核酸构建体。载体可以衍生自质粒特别例如F、R1、RP1、Co1、pBR322、TOL、Ti等；粘粒(cosmid)；噬菌体例如λ、人字形噬菌体(lambdoid)、M13、Mu、P1、P22、Q_μ、T偶数、T奇数、T2、T4、T7等等；植物病毒特别例如苜蓿花叶病毒(alfalfa mosaic virus)、雀麦草花叶病毒属(bromovirus)、发状病毒属(capillovirus)、香石竹潜隐病毒属(carlavirus)、香石竹斑驳病毒属(carmovirus)、caulivirus、长线形病毒属(clostervirus)、豇豆花叶病毒属(comovirus)、潜隐病毒属(cryptovirus)、南瓜花叶病毒属(cucumovirus)、香石竹病毒属(dianthovirus)、蚕豆病毒属(fabavirus)、斐济病毒属(fijivirus)、真菌传杆状病毒属(furovirus)、双生病毒(geminivirus)、大麦病毒属(hordeivirus)、等轴不稳定环斑病毒属(ilarvirus)、黄症病毒属(luteovirus)、machlovirus、玉米雷亚朵非纳病毒属(marafivirus)、坏死病毒属(necrovirus)、线虫传多面体病毒属(nepovirus)、phytorepvirus、植物弹状病毒(plant rhabdovirus)、马铃薯X病毒属(potexvirus)、马铃薯Y病毒属(potyvirus)、南方菜豆花叶病毒属(sobemovirus)、纤细病毒属(tenuivirus)、烟草花叶病毒属(tobamovirus)、烟草脆裂病毒属(tobravirus)、番茄斑萎病毒(tomato spotted wilt virus)、番茄丛矮病毒属(tombusvirus)、芜菁黄花叶病毒属(tymovirus)等等；或动物病毒特别例如腺病毒(adenovirus)、沙粒状病毒科(arenaviridae)、杆状病毒科(baculoviridae)、双RNA病毒科(birnaviridae)、布尼亚病毒科(bunyaviridae)、杯状病毒科(calciviridae)、心病毒(cardioviruses)、冠状病毒科(coronaviridae)、覆盖噬菌体科(corticoviridae)、囊噬菌体科(cystoviridae)、EB病毒(Epstein-Barr virus)、肠病毒(enteroviruses)、丝状病毒科(filoviridae)、黄病毒科(flaviviridae)、口蹄疫病毒(Foot-and-Mouth disease virus)、嗜肝DNA病毒科(hepadnaviridae)、肝炎病毒(hepatitis viruses)、疱疹病毒科(herpesviridae)、免疫缺陷病毒(immunodeficiency viruses)、流行性感冒病毒(influenza virus)、丝杆噬菌体科(inoviridae)、虹彩病毒科(iridoviridae)、正粘病毒科(orthomyxoviridae)、乳多空病毒(papovaviruses)、副粘液病毒科(paramyxoviridae)、细小病毒科(parvoviridae)、微小核糖核酸病毒科(picornaviridae)、脊髓灰质炎病毒(poliovirus)、多DNA病毒科(polydnaviridae)、痘病毒科(poxviridae)、呼肠孤病毒科(reoviridae)、逆转录病毒(retroviruses)、弹状病毒科(rhabdoviridae)、鼻病毒(rhinoviruses)、西门里克森林病毒(Semliki Forest virus)、四病毒科(tetraviridae)、披膜病毒科(togaviridae)、环状病毒科(toroviridae)、牛痘病毒(vaccinia virus)、水泡性口炎病毒(vescular stomatitis virus)等等。载体可用于克隆和/或用于表达本发明的结合分子以及甚至可以用于基因治疗目的。包括一个或多个与一个或多个表达调节核酸分子可操纵地连接的本发明的核酸分子的载体同样包括在本发明中。载体的选择依赖于后续的重组程序和所用的宿主。将载体导入宿主细胞可能被包括磷酸钙转染、病毒感染、DEAE-葡聚糖介导的转染、脂转染胺试剂转染或电穿孔影响。载体可以自发复制或与它们整合进的染色体一起复制。优选地，所述载体包含一个或多个选择标记。所述标记的选择可依赖于所选择的宿主，尽管这对于本发明并不是关键的，因为其对于本领域技术人员是熟知的。所述标记包括但不限于卡那霉素、新霉素、嘌呤霉素、潮霉素、zeocin、来自单纯疱疹病毒的胸腺嘧啶激酶基因(HSV-TK)、来自小鼠的二氢叶酸还原酶基因(dhfr)。包括一个或多个与一个或多个编码能够用于分离所述结合分子的核酸分子可操纵地连接的如上所述的编码所述结合分子的核酸分子的载体同样包括在本发明中。这些蛋白质和肽包括但不限于谷胱甘肽-S-转移酶、麦芽糖结合蛋白、金属结合多聚组氨酸、绿色荧光蛋白、萤光素酶和β-半乳糖苷酶。

包含上述载体的一个或多个拷贝的宿主是本发明的另一个对象。优选地，所述宿主是宿主细胞。宿主细胞包括但不限于源自哺乳动物、植物、昆虫、真菌或细菌的细胞。细菌细胞包括但不限于源自革兰氏阳性细菌如芽孢杆菌属、链霉菌属和葡萄球菌属的一些种的细胞或源自革兰氏阴性细菌如埃希氏菌属(例如大肠埃希氏菌(E.coli))和假单胞菌属的一些种的细胞。在真菌细胞中，优选地使用酵母细胞。在酵母细胞中的表达可通过使用酵母菌株特别例如甲醇酵母、酿酒酵母和多形汉逊酵母得到。另外，昆虫细胞例如来源于果蝇的细胞和Sf9细胞可用作宿主细胞。除了这些，宿主细胞可以是植物细胞特别例如来自农作物如林间作物的细胞、或来自提供食物及原料的植物如谷物植物或药用植物的细胞、或来自观赏植物的细胞、或来自花卉种球作物(flower bulb crop)的细胞。转化的(转基因的)植物或植物细胞通过已知方法生产，所述方法例如农杆菌介导的基因传递、叶盘转化、通过聚乙二醇诱导的DNA传递的原生质体转化、电穿孔、超声波处理、显微注射或基因枪基因传递。另外地，合适的表达系统可以是杆状病毒系统。本发明优选使用哺乳动物细胞的表达系统，例如中国仓鼠卵巢(CHO)细胞、COS细胞、BHK细胞或Bowes黑色素瘤细胞。哺乳动物细胞提供具有翻译后修饰表达的的蛋白质，所述蛋白质与哺乳动物来源的天然蛋白质最为相似。由于本发明涉及可能必须给予人的分子，所以完整的人表达系统是特别优选的。因此，甚至更优选地，所述宿主细胞是人的细胞。人的细胞的实例特别例如HeLa、911、AT1080、A549、293和HEK293T细胞。优选的哺乳动物细胞是人视网膜细胞如911细胞或在1996年2月29日保藏于欧洲动物细胞保藏中心(European Collection of Cell Cultures(ECACC)，CAMR，Salisbury，Wiltshire SP4 OJG，Great Britain)保藏号为96022940并且以PER.C6

为商标销售的细胞系(PER.C6是CrucellHolland B.V.的注册商标)。对于此应用，“PER.C6”是指以保藏号96022940保藏的细胞或祖代细胞、上游或下游传代细胞、以及保藏的细胞的祖代细胞的传代细胞、以及任何上述细胞的衍生物。

在优选的实施方案中，所述人生产细胞(producer cell)至少包括编码处于可表达形式的腺病毒E1区域的核酸序列的一个功能性部分。在更优选的实施方案中，所述宿主细胞衍生自人视网膜并且被包括腺病毒E1序列的核酸永生化，例如在1996年2月29日保藏于欧洲动物细胞保藏中心(European Collection of Cell Cultures(ECACC)，CAMR，Salisbury，Wiltshire SP4 OJG，Great Britain)保藏号为96022940并且以PER.C6^TM为商标销售的细胞系及其衍生物。在宿主细胞中生产重组蛋白质可以根据本领域已知的方法进行。国际公开WO00/63403已经描述了使用以PER.C6^TM为商标销售的细胞作为用于感兴趣的蛋白质的生产平台，所述公开以其全文并入本文作为参考。

生产本发明的结合分子或功能性变体的方法也是本发明的一个另外部分。所述方法包括步骤：a)在有助于表达所述结合分子或功能性变体的条件下培养本发明的宿主；和b)任选地，回收所述表达的结合分子或功能性变体。所述表达的结合分子或其功能性变体可以从无细胞的提取物中回收，但是优选地它们从培养基中回收。从无细胞提取物或从培养基中回收蛋白质如结合分子的方法是本领域技术人员所熟知的。可通过上述方法获得的结合分子或其功能性变体也是本发明的一部分。

或者，除了在宿主如宿主细胞中表达之外，本发明的结合分子或其功能性变体还可以由常规肽合成仪或在无细胞翻译系统中应用衍生自本发明的DNA分子的RNA核酸通过合成产生。可通过上述合成生产方法或无细胞翻译系统获得的结合分子或其功能性变体也是本发明的一部分。

在另一个实施方案中，本发明的人的结合分子还可以在转基因的非人的哺乳动物特别例如兔、山羊或母牛中产生并被分泌进例如其乳汁中。

在另一个实施方案中，本发明的结合分子，优选特异地与SARS-CoV或其片段结合的人结合分子，可以通过转基因的非人的哺乳动物例如转基因小鼠或兔产生，所述哺乳动物表达人免疫球蛋白基因。优选地，所述转基因的非人的哺乳动物具有包括编码全部或一部分如上所述的人结合分子的人重链转基因和人轻链转基因的基因组。所述转基因的非人的哺乳动物可用纯化的或富集的SARS-CoV或其片段的制备物免疫。本领域已经熟知用于免疫非人的哺乳动物的方案。参见Using Antibodies：A Laboratory Manual，Edited by：E.Harlow，D.Lane(1998)，Cold Spring Harbor Laboratory，Cold Spring Harbor；New York and Current Protocols in Immunology，Edited by：J.E.Coligan，A.M.Kruisbeek，D.H.Margulies，E.M.Shevach，W.Strober(2001)，John Wiley&Sons Inc.，New York；这些文献以其全文并入本文作参考。免疫方案经常包括多次免疫，可以同时使用或不使用佐剂如弗氏完全佐剂和弗氏不完全佐剂，但是也可以包括裸DNA免疫。在另一个实施方案中，所述人结合分子通过衍生自所述转基因动物的B细胞或浆细胞产生。在另一个实施方案中，所述人结合分子通过由将得自上述转基因的非人的哺乳动物的B细胞和永生化的细胞融合产生的杂交瘤产生。可通过上述转基因的非人的哺乳动物获得的B细胞、浆细胞和杂交瘤以及可通过上述转基因的非人的哺乳动物、B细胞、浆细胞和杂交瘤获得的人结合分子也是本发明的一部分。

本发明的另一方面提供了用于鉴别本发明的结合分子，优选人结合分子例如人单克隆抗体或其片段的方法，或鉴别本发明的核酸分子的方法，并且包括下述步骤：a)使SARS-CoV或其片段接触结合分子，优选人结合分子的噬菌体文库，b)至少选择一次结合至所述SARS-CoV或其片段的噬菌体，和c)分离并回收所述结合至SARS-CoV或其片段的噬菌体。本发明的选择步骤优选地在存在失活的SARS-CoV的情况下进行。所述SARS-CoV可以是分离的或未分离的，例如存在于被感染个体的血清中和/或血液中。或者，所述选择步骤可以在存在SARS-CoV的片段的情况下进行，所述片段例如SARS-CoV的一个细胞外部分、衍生自SARS-CoV的一个或多个蛋白质或(多)肽、包括这些蛋白质或(多)肽的融合蛋白等等。用于鉴别和获得结合分子(例如抗体)的噬菌体展示方法现在已经是本领域技术人员所熟知的常规方法。这些方法被描述于例如美国专利5,696,108；Burton and Barbas，1994；de Kruif et al.，1995b；以及Phage Display：ALaboratory Manual.Edited by：CF Barbas，DR Burton，JK Scott and GJSilverman(2001)，Cold Spring Harbor Laboratory Press，Cold SpringHarbor，New York。所有这些文献以其全文并入本文作参考。对于构建噬菌体展示文库，收集的人单克隆抗体重链和轻链可变区基因在噬菌体颗粒，优选丝状噬菌体颗粒的表面上以例如单链Fv(scFv)或以Fab形式表达(参见de Kruif et al.，1995b)。抗体片段表达噬菌体的大文库典型地含有多于1.0×10⁹抗体特异性并且可以由得自在被免疫的或未被免疫的个体的B淋巴细胞中表达的免疫球蛋白V区组装。在本发明的特殊的实施方案中，所述结合分子的噬菌体文库，优选scFv噬菌体文库，制备自RNA，所述RNA分离自得自己经接种疫苗或已经接触SARS-CoV的对象的细胞。RNA可以分离自特别例如骨髓或外周血液，优选外周血液淋巴细胞。所述对象可以是已接种疫苗的或已接触SARS-CoV的动物，但是优选已经接种疫苗或已经接触SARS-CoV的人。优选地所述人已经由SARS-CoV痊愈。

或者，噬菌体展示文库可以构建自免疫球蛋白可变区，所述免疫球蛋白可变区已经在体外部分组装以在所述文库中导入另外的抗体多样性(半合成文库)。例如，在那些对于抗体特异性重要的所述分子的区域(例如CDR区域)中，体外组装的可变区包含合成产生的、随机化的或部分随机化的DNA的连续片段。SARS-CoV特异的噬菌体抗体可以通过在一固相上固定靶抗原(例如来自SARS-CoV的抗原)，然后将所述靶抗原接触噬菌体文库以使得表达特异于结合在所述固相上的抗原的抗体片段的噬菌体结合而从所述文库选择出。未结合的噬菌体通过漂洗而清除，结合的噬菌体从所述固相上洗脱以用于感染大肠杆菌(E.coli)并接下来繁殖。通常需要几轮选择和繁殖以充分富集特异结合于靶抗原的噬菌体。如果需要，在将所述噬菌体文库接触靶抗原之前，所述噬菌体文库可以首先通过将所述噬菌体文库接触结合在一种固相上的非靶抗原而预选择。还可以选择结合至复合物抗原例如SARS-CoV蛋白或(多)肽、表达SARS-CoV的一种或多种蛋白或(多)肽的宿主细胞、或SARS-CoV自身的混和物的噬菌体。抗原特异的噬菌体抗体可以通过将在其上结合了失活的SARS-CoV的制备物的固相和所述噬菌体抗体文库一起温育以使得例如所述噬菌体的scFv或Fab部分与所述SARS-CoV制备物的蛋白质/(多)肽结合而选择自所述文库。在温育和几次漂洗以清除未结合的和松散附着的噬菌体之后，已经通过其scFv或Fab部分与所述制备物结合的噬菌体被洗脱并用于感染大肠杆菌以使得所述新的特异性得以扩增。一般地，需要进行一轮或多轮选择以从远远过量的未结合的噬菌体中分离感兴趣的噬菌体。或者，SARS-CoV的已知的蛋白质或(多)肽可以在宿主细胞中表达，这些细胞可用于选择特异于所述蛋白质或(多)肽的噬菌体抗体。应用这些宿主细胞的噬菌体展示方法可以扩展并且通过由加入过量的不包含靶分子或包含与靶分子相似但不相同的非靶分子的宿主细胞而在筛选过程中清除无关的结合物而改进，从而显著地提高发现相关结合分子的机会(本方法也称Mabstract^TM方法。Mabstract^TM是Crucell Holland B.V.正在申请的商标，同时参见美国专利6,265,150，其并入本文作为参考)。

本发明的另一方面提供了获得本发明的结合分子，优选人结合分子或核酸分子的方法，其中所述方法包括以下步骤：a)进行上述鉴别本发明的结合分子，优选人结合分子例如人单克隆抗体或其片段的方法，或鉴别本发明的核酸分子的方法，以及b)从所述回收的噬菌体中分离所述人结合分子和/或编码所述人结合分子的核酸。一旦使用上述鉴别结合分子或编码所述结合分子的核酸的方法鉴定或鉴别出一种新的单克隆噬菌体抗体，编码所述scFv或Fab的DNA可以从所述细菌或噬菌体中分离出来，并且结合标准分子生物学技术构建编码二价scFv或具有所希望的特异性的完整的人免疫球蛋白(例如IgG，、IgA或IgM)的构建体。这些构建体可以转染进合适的细胞系，然后可以产生完整的人单克隆抗体(参见Huls et al.，1999；Boel et al.，2000)。

本发明的另一方面涉及结合分子的噬菌体文库，优选scFv噬菌体展示文库，所述文库由分离自从已经接种疫苗或已经接触SARS-CoV的对象的细胞获得的RNA制备。RNA可以分离自特别例如骨髓或外周血液，优选外周血液淋巴细胞。所述对象可以是被接种疫苗的或接触SARS-CoV的动物，但是优选已经接种疫苗或已经接触SARS-CoV的人。优选地所述人已经由SARS-CoV痊愈。

本发明的另一方面提供了包含至少一种本发明的结合分子、至少一种本发明的功能性变体或其片段、至少一种本发明的免疫缀合物、或其组合的组合物。另外，所述组合物可特别包括稳定分子(stabilizingmolecule)，例如血清白蛋白或聚乙二醇或盐。优选地，所用的盐是保留所述结合分子的所希望的生物活性的盐，并且不引入任何不希望的毒物学作用。此类盐的实例包括但不限于酸加成盐和碱加成盐。酸加成盐包括但不限于衍生自无毒的无机酸类的物质，所述无机酸如盐酸、硝酸、磷酸、硫酸、氢溴酸、氢碘酸、亚磷酸等等，同时还包括但不限于衍生自无毒的有机酸类的物质，所述有机酸如脂肪族一元羧酸和二元羧酸、苯基取代的烷酸、羟基烷酸、芳香酸、脂肪族和芳香族磺酸等等。碱加成盐包括但不限于衍生自碱土金属的物质，所述碱土金属如钠、钾、镁、钙等等，同时还包括但不限于衍生自无毒的有机胺类的物质，所述有机胺类如N，N′-双苄基乙撑二胺、N-葡甲胺、氯普鲁卡因、胆碱、二乙醇胺、乙亚胺、普鲁卡因等等。如果需要，本发明的结合分子可以覆盖在一种物质之上或之内以使所述结合分子不受可能使其失活的酸或其他自然的或非自然的条件的作用影响。

本发明的另一方面提供了包含至少一种本发明所描述的核酸分子的组合物。所述组合物可包括水溶液如包含盐(例如NaCl或前面所描述的盐)、去污剂(例如SDS)和/或其他适当成分的水溶液。

另外，本发明涉及包含至少一种本发明的结合分子、至少一种本发明的功能性变体或其片段、至少一种本发明的免疫缀合物、至少一种本发明的组合物、或其组合的药物组合物。本发明的药物组合物进一步包括至少一种药物学可接受的赋形剂。

本发明的药物组合物可以另外包括至少一种其他治疗剂、预防剂和/或诊断剂。优选地，所述药物组合物包括至少一种其他预防剂和/或治疗剂。优选地，所述另外的治疗剂和/或预防剂是能够预防和/或治疗SARS-CoV导致的感染和/或疾病的物质。治疗剂和/或预防剂包括但不限于抗病毒剂。这类物质可以是结合分子、小分子、有机或无机化合物、酶、多核苷酸序列等等。

抗病毒剂的实例包括但不限于阿巴卡韦(abacavir)、阿昔洛韦(acyclovir)、阿德福韦(adefovir)、阿福韦生(afovirsen)、金刚烷胺(amantadine)、安普那韦(amprenavir)、AZT、喜树碱(camptothecins)、栗树精胺(castanospermine)、西多服韦(cidofovir)、D4T、ddC、ddI、d4T、地拉韦啶(delavirdine)、地丹诺辛(didanosine)、艾发韦安(efavirenz)、泛昔洛韦(famciclovir)、非阿尿苷(fialuridine)、膦甲酸(foscarnet)、FTC、更昔洛韦(ganciclovir)、GG167、碘苷(idoxuridine)、印地那韦(indinavir)、α-干扰素、拉米夫定(lamivudine)、洛布卡韦(lobucavir)、罗韦拉得(loviride)、奈非那韦(nelfinavir)、奈韦拉平(nevirapine)、奥斯他韦(oseltamivir)、喷昔洛韦(penciclovir)、吡罗达韦(pirodavir)、利巴韦林(ribavirin)、金刚乙胺(rimantadine)、利托那韦(ritonavir)、沙奎那韦(saquinavir)、sICAM-1、索利洛韦(sorivudine)、司他夫定(stavudine)、三氟胸苷(trifluridine)、3TC、伐昔洛韦(valacyclovir)、阿糖腺苷(vidarabine)、扎西他滨(zalcitabine)、扎那米韦(zanamivir)、齐多夫定(zidovudine)、以及药物学可接受的盐、酸或上述任何一种的衍生物。目前应用于治疗感染SARS-CoV的患者的其他物质是α-干扰素、类固醇和潜在的复制酶抑制剂。另外，感染SARS-CoV的患者目前通过输入得自正在康复/已康复的SARS患者捐献的血液的血清治疗，所述SARS患者在接触SARS-CoV后已经产生了抗体。在实验阶段的能够预防和/或治疗SARS-CoV感染和/或SARS-CoV导致的疾病的物质也可用作其他在本发明中有用的治疗剂和/或预防剂。

本发明的结合分子或本发明的药物组合物可以在应用于人体之前在合适的动物模型系统中测试。这类动物模型系统包括但不限于小鼠、大鼠、鸡、牛、猴、猪、狗、兔等。任何本领域熟知的动物系统都可以应用。

典型地，药物组合物必须是无菌的，并且在生产和保存条件下稳定。本发明的结合分子、变体或其片段、免疫缀合物、核酸分子或组合物可以是粉末形式以用于在给药之前或之中在适当的药物学可接受的赋形剂中重构。在用于制备无菌注射液的无菌散剂的情况下，优选的制备方法是真空干燥和冷冻干燥(lyophilization)，所述干燥可以得到活性成分加上任何附加的所希望的成分的散剂，所述散剂得自其经过无菌过滤的溶液。

或者，本发明的结合分子、变体或其片段、免疫缀合物、核酸分子或组合物可以在溶液中并且所述适当的药物学可接受的赋形剂可以在给药之前或之中加入和/或混和以提供可注射形式的单元剂量。优选地，本发明使用的药物学可接受的赋形剂适于高药物浓度、可以维持适当的流动性、并且如果需要的话可以延迟吸收。

所述药物组合物的最佳给药途径的选择受几种因素影响，包括所述组合物中的活性分子的物理化学性质、临床状况的紧急程度以及所述活性分子的血浆浓度和所希望的治疗效果之间的关系。例如，如果需要的话，本发明的结合分子可以与保护其不至于被迅速释放的载体一起制备，例如制备成控释配制品包括植入物、透皮贴片、以及微囊给药系统。还可以特别应用生物可降解的、生物相容的聚合物例如乙烯-醋酸乙烯共聚物、聚酐、聚乙二醇酸、胶原、聚正酯、以及聚乙醇酸。另外，可能还需要用防止所述结合分子失活的材料或化合物包被所述结合分子或与所述结合分子共同给药。例如，所述结合分子可以在适当的载体中给药，所述载体例如脂质体或稀释剂。

给药途径可以分为两个主要的类别：口服给药和非胃肠道给药。这两个类别包括但不限于推注(bolus)给药、口腔给药、表皮给药、硬脑膜外给药、吸入给药、腹腔内给药、动脉内给药、关节内给药、支气管内给药、胶囊内给药、心内给药、软骨内给药、腔内给药、intracelial给药、小脑内(intracelebellar)给药、侧脑室内(intracerebronventricular)给药、结肠内给药、宫颈内给药、皮内给药、胃内给药、肝内给药、髓内给药、肌内给药、心肌内给药、鼻内给药、眼内给药、眼眶内给药、骨内给药、骨盆内给药、心包内给药、腹膜内给药、色斑给药、胸膜内给药、前列腺内给药、肺内给药、直肠内给药、肾内给药、视网膜内给药、脊髓内给药、胸骨内给药、滑膜内给药、鞘内给药、胸内给药、肿瘤内给药、子宫内药、静脉内给药、心室内给药、膀胱内给药、直肠给药、脊柱给药、蛛网膜下给药、囊下给药、皮下给药、表皮下给药、舌下给药、局部给药、透皮给药、透粘膜给药、经气管给药、以及阴道给药。优选的给药途径是静脉内给药，尤其优选肌内给药。

口服剂型可以配制成特别如片剂、锭剂(troche)、糖锭(lozenge)、水质或油质混悬剂、可分散的散剂或粒剂、乳剂、硬胶囊剂、软凝胶胶囊剂、糖浆或酏剂、丸剂(pill)、糖衣丸剂、液体、凝胶、或浆状。这些配制品可以含有药物赋形剂包括但不限于惰性稀释剂例如碳酸钙、碳酸钠、乳糖、磷酸钙或磷酸钠；粒化剂和分裂剂例如谷物淀粉或褐藻酸；结合剂例如淀粉、明胶或阿拉伯树胶；润滑剂例如硬脂酸钙、山嵛酸丙三酯、氢化植物油、硬脂酸镁、矿物油、聚乙二醇、硬脂醇钠、延胡索酸、硬脂酸、滑石、硬脂酸锌；防腐剂例如对羟苯甲酸正丙酯；着色剂、调味剂或甜味剂例如蔗糖、糖精、甘油、丙二醇或山梨醇；植物油例如花生油、橄榄油、芝麻油或椰子油；矿物油例如液体石蜡；乳化剂如苯扎氯铵、多库脂钠、卵磷脂、泊洛沙姆(poloxamer)、十二烷基硫酸钠、脱水山梨醇酯；以及增稠剂例如琼脂、褐藻酸、蜂蜡、羧甲纤维素钙、卡拉胶(carageenan)、糊精或明胶。

本发明的药物组合物还可以配制成非胃肠道给药的物质。用于非胃肠道给药的物质可以特别如水质的或非水质的生理无菌无毒注射溶液或输入溶液或混悬液的形式。优选的非胃肠道给药途径包括静脉内、腹膜内、硬脑膜内、肌内和肿瘤内注射或输入。所述溶液或混悬液可以包含在所用剂量和浓度对接受者无毒的物质，例如1，3-丁二醇、林格氏液(Ringer′s solution)、Hank′s液、生理食盐水、脂类例如合成的单-或二-甘油酯或脂肪酸例如油酸、局部麻醉剂、防腐剂、缓冲液、增粘剂或增溶剂、水溶性抗氧化剂例如抗坏血酸、半胱氨酸盐、硫酸氢钠、焦亚硫酸钠、亚硫酸钠等等、脂溶性抗氧化剂例如维生素C棕榈酸酯、丁羟甲醚(BHA)、丁羟甲苯(BHT)、卵磷脂、没食子酸丙酯、α-维生素E等等、以及金属螯和剂例如柠檬酸、乙二胺四乙酸(EDTA)、山梨醇、酒石酸、磷酸等等。

在一个另一方面，本发明的结合分子、功能性变体、免疫缀合物、组合物、或药物组合物可以用作药物。因此，应用本发明的结合分子、功能性变体、免疫缀合物、组合物、或药物组合物的治疗和/或预防SARS-CoV感染的方法是本发明的另一部分。上述分子可以特别被应用于SARS-CoV导致的一种或多种疾病的诊断、预防、治疗、或其组合。它们适于治疗尚未得到治疗的患有SARS-CoV导致的疾病的患者以及已经得到治疗或正在接受治疗的患有SARS-CoV导致的疾病的患者。它们防止进一步的SARS-CoV感染和/或可以延迟SARS相关症状的发作或发展。它们甚至还可以在例如接触SARS-CoV的人群中用于预防SARS，所述人群例如照顾SARS疑似患者的医护人员。

上述分子或组合物可以与其他用于诊断、预防和/或治疗的分子共同应用。它们可以体外、回体或体内应用。例如，本发明的结合分子、功能性变体、免疫缀合物或药物组合物可以与针对SARS-CoV的疫苗共同给药。或者，所述疫苗还可以在给予本发明的分子之前或之后给予。与疫苗一起给予本发明的分子可适于接触后预防并且可以降低活减毒疫苗在免疫缺陷的接受者中可能的副作用。

所述分子典型地以治疗或诊断有效量配制在本发明的组合物及药物组合物中。可以调整给药方案以提供需要的最佳应答(例如治疗性应答)。合适的剂量范围可以是例如0.1-100mg/kg体重，优选0.5-15mg/kg体重。另外，例如可以给予单一大药丸、可以将一个剂量分几次给予、或者所述剂量可以根据治疗状况的急迫性按比例减少或增加。本发明的分子和组合物优选是无菌的。本领域熟知使这些分子和组合物无菌的方法。其他可用于诊断、预防和/或治疗的分子可以以相似于设定的用于本发明的结合分子的给药方案给予。如果分开给予其他分子，它们可以在给予一种或多种本发明的结合分子或药物组合物之前(例如2分钟、5分钟、10分钟、15分钟、30分钟、45分钟、60分钟、2小时、4小时、6小时、8小时、10小时、12小时、14小时、16小时、18小时、20小时、22小时、24小时、2天、3天、4天、5天、7天、2周、4周或6周之前)或同时或之后(例如2分钟、5分钟、10分钟、15分钟、30分钟、45分钟、60分钟，6小时、8小时、10小时、12小时、14小时、16小时、18小时、20小时、22小时、24小时、2天、3天、4天、5天、7天、2周、4周或6周之后)给予患者。对于人患者，确切的给药方案通常在临床测试中确定。

当作为体内治疗剂被给予人时，人结合分子和包含人结合分子的药物组合物是尤其有用的，并且通常是优选的，因为接受者对于所给予的抗体的免疫应答通常显著地低于给予单克隆鼠类结合分子、嵌合结合分子或人源化的结合分子所引起的免疫应答。

本发明的另一方面涉及在制备用于SARS-CoV导致的疾病的诊断、预防、治疗、或其组合中本发明的结合分子(优选人结合分子)、其功能性变体、本发明的免疫缀合物、本发明的核酸分子、本发明的组合物或药物组合物的应用。

另外，包括至少一种本发明的结合分子(优选人结合分子)、至少一种其功能性变体、至少一种本发明的免疫缀合物、至少一种本发明的核酸分子、至少一种本发明的组合物、至少一种本发明的药物组合物、至少一种本发明的载体、至少一种本发明的宿主或其组合的试剂盒也是本发明的一部分。任选地，以上描述的本发明的试剂盒的成分被包装于适当的容器中并且标记为用于所述疾病的诊断、预防和/或治疗。上述成分可以作为水(优选无菌)溶液或用于重构的冷冻干燥的(优选无菌)配制品保存于单位容器或多次剂量容器中，所述容器例如密封安瓿、小药水瓶，瓶子，注射器以及试管。所述容器可以由各种材料制造，例如玻璃或塑料，并且所述容器可以具有无菌的接口(access port)(例如所述容器可以是静脉输入溶液袋或具有可被皮下注射针头刺穿的塞子(stopper)的小药水瓶)。所述试剂盒可以进一步包括更多的容器，所述容器包括药物学可接受的缓冲液例如磷酸盐缓冲液、林格氏液或葡萄糖溶液。它可以进一步包括其他从商业视角及使用者视角看所希望的材料，包括其他用于一种或多种合适的宿主的缓冲液、稀释剂、滤器、针头、注射器、培养基。相关的说明书可以包括在治疗、预防或诊断产品的试剂盒中，所述说明书可以包含关于涉及此类治疗、预防或诊断产品的例如适应症、用法、剂量、生产、给药、禁忌症和/或注意事项的信息。

本发明进一步涉及在样品中检测SARS-CoV的方法，其中所述方法包括下述步骤：a)用一种诊断有效量的本发明的结合分子、功能性变体或免疫组合物接触所述样品，和b)确定是否所述结合分子、功能性变体或免疫组合物特异性地结合至所述样品的分子。所述样品可以是来自(潜在的)感染对象的生物学样品包括但不限于血液、血清、尿液、组织或其他生物学物质，或者是非生物学样品例如水、饮料等等。所述(潜在的)感染对象可以是人，但是也可以用本发明的结合分子、其功能性变体或本发明的免疫缀合物在被怀疑为SARS-CoV携带者的动物中检测SARS-CoV的存在。所述样品可以首先被处理以使其更适于检测方法。处理特别是指处理所述被怀疑含有和/或含有SARS-CoV的样品以使得所述SARS-CoV分解为抗原性成分如蛋白质、(多)肽或其他抗原性片段。优选地，本发明的结合分子、功能性变体、本发明的免疫缀合物与所述样品在使得在所述结合分子和可能存在于样品中的SARS-CoV或其抗原性成分之间形成免疫复合物的条件下接触。如果形成提示在样品中存在SARS-CoV的所述免疫复合物，那么通过适当的方法检测并测量所述免疫复合物。这些方法特别包括同源或异源结合免疫测定，例如放射免疫测定(RIA)、ELISA、免疫荧光、免疫组化、FACS、BIOCORE和Western印迹分析。

优选的测定技术，尤其是用于大量患者血清、血液和血液衍生物的临床筛选的测定技术是ELISA和Western印迹技术。ELISA测试是特别优选的。为了在这些测定中用作试剂，本发明的结合分子、功能性变体或免疫缀合物被方便地键合至微量滴定孔的内表面。本发明的结合分子、功能性变体或免疫缀合物可以被直接结合至所述微量滴定孔。然而，本发明的结合分子、功能性变体或免疫缀合物的最大结合可通过在加入本发明的结合分子、功能性变体或免疫缀合物之前用多聚赖氨酸预处理所述孔而得到。另外，本发明的结合分子、功能性变体或免疫缀合物可通过已知手段共价附着至所述孔。一般地，本发明的结合分子、功能性变体或免疫缀合物以0.01至100μg/ml的浓度应用于包被，尽管也可以应用更高或更低的浓度。然后将样品加入到被本发明的结合分子、功能性变体或免疫缀合物包被的孔中。

另外，本发明的结合分子或功能性变体可用于鉴别SARS-CoV的表位。所述表位可以是线性表位，但也可以是结构表位和/或构象表位。在一个实施方案中，本发明的结合分子或功能性变体与得自SARS-CoV的蛋白质的一系列有重叠的肽(例如15肽)的结合可以通过PEPSCAN分析的手段分析(特别参见WO84/03564、WO93/09872、Slootstra et al.1996)。结合分子与每一个肽的结合可以在基于PEPSCAN的酶联免疫测定(ELISA)中测定。在另一个实施方案中，包含得自SARS-CoV的肽的随机肽文库可用于筛选能够与本发明的结合分子或功能性变体结合的肽。在上述测定中，应用中和结合分子可鉴别一个或多个中和表位。所发现的肽/表位可用作疫苗并且用于诊断SARS。在一个另一实施方案中，可以分析本发明的结合分子与SARS-CoV的表面蛋白(例如刺突糖蛋白)的结构域的结合(中和)。或者，本发明的结合分子可以鉴别SARS-CoV的另一个蛋白的一个或多个表位，所述蛋白包括但不限于膜蛋白(M蛋白)、小包膜蛋白(E蛋白)和核壳蛋白(N蛋白)。在一个优选的实施方案中，结合分子018识别了N蛋白上的表位。这些表位可用于治疗和检测SARS-CoV。

本发明的另一方面提供了一种用于筛选特异结合至SARS-CoV的与本发明的结合分子或功能性变体结合的表位相同的表位的结合分子或结合分子的功能性变体的方法，其中所述方法包括下述步骤：a)使待筛选的结合分子或功能性变体、本发明的结合分子或功能性变体与SARS-CoV或其片段接触，b)测量待筛选的结合分子或功能性变体是否能够与本发明的结合分子或功能性变体竞争与SARS-CoV的特异结合。在另一步骤中，可以确定是否所述能够竞争与所述SARS-CoV或其片段的特异结合的被筛选的结合分子具有中和活性。能够与本发明的结合分子或功能性变体竞争与SARS-CoV或其片段的特异结合的结合分子或功能性变体是本发明的另一部分。在上述筛选方法中，“特异结合至与...相同的表位”还包括充分地或基本上特异结合至所述相同的表位，如同所述表位被本发明的结合分子结合。阻止本发明的结合分子与SARS-CoV的结合或与本发明的结合分子竞争与SARS-CoV的结合的能力典型地提示待筛选的结合分子与SARS-CoV表面的一个表位或结合位点结合，所述表位或结合位点与被本发明的结合分子免疫特异性地识别的SARS-CoV表面的结合位点结构性地重叠。或者，这可以提示待筛选的结合分子与充分接近于被本发明的结合分子免疫特异性地识别的结合位点的表位或结合位点结合，从而通过空间位阻或其他方式抑制本发明的结合分子于SARS-CoV的结合。

一般说来，竞争性抑制通过一种测定手段测量，其中一种抗原组合物(即一种包含SARS-CoV或其片段的组合物)与参考结合分子(即本发明的结合分子)及待筛选的结合分子混和。通常，待筛选的结合分子过量存在。基于ELISA和Western印迹的方案适用于这种简单竞争研究中。在特定的实施方案中，人们可以在施加所述抗原组合物之前预先将所述参考结合分子和各种量的待筛选的结合分子(例如1∶10、1∶20、1∶30、1∶40、1∶50、1∶60、1∶70、1∶80、1∶90或1∶100)混和一段时间。在另外的实施方案中，所述参考结合分子和各种量的待筛选的结合分子可以简单地在接触所述抗原组合物时混和。在任何情况下，通过应用同种(species)二级抗体或同种型二级抗体，人们可以仅检测到结合的参考结合分子，其结合将由于存在充分识别相同表位的待筛选的结合分子而减少。在进行参考结合分子和任何待筛选的结合分子(不考虑同种或同种型)之间的结合分子竞争研究时，人们可以首先用一种可被检测到的标记来标记所述参考结合分子以进行后续鉴别，所述标记例如生物素标记、酶标记、放射性标记或其他标记。在这些情况中，人们应将所述标记的参考结合分子和待筛选的结合分子以各种比例(例如1∶10、1∶20、1∶30、1∶40、1∶50、1∶60、1∶70、1∶80、1∶90或1∶100)预先混和或温育，然后(任选地经过一段合适的时间)测定所述标记的参考结合分子的反应性并将其与对照值比较，在所述对照值中在温育中没有潜在的竞争性结合分子。所述测定可以是许多基于抗体杂交的免疫学测定中的任何一种，所述参考结合分子可以通过检测它们的标记的手段检测到，例如在生物素化的参考结合分子的情况下使用链霉亲和素，或者通过一起使用生色底物和酶标记(例如3，3’5，5’-四甲基联苯胺(TMB)底物与过氧化物酶)检测，或者通过简单地检测放射性标记检测。与所述参考结合分子结合于同样表位的待筛选的结合分子将能有效地竞争结合，从而显著地降低参考结合分子结合，可由减少的结合标记证明。在不存在完全无关的结合分子时，(标记的)参考结合分子的反应性将作为对照上限值。对照下限值可通过在竞争会发生并且降低所述标记的参考结合分子的结合时，将标记的参考结合分子与未标记的完全相同类型的参考结合分子一起温育获得。在测定中，在存在待筛选的结合分子的情况下，显著降低的标记的参考结合分子的反应性提示存在一种识别相同表位的结合分子，即与所述标记的参考结合分子“交叉反应(cross-react)”的结合分子。

通过这些竞争测定鉴别的分子(“竞争性结合分子”或“交叉反应性结合分子”)包括但不限于可与与所述参考结合分子(即本发明的结合分子)结合的表位或结合位点结合的抗体、抗体片段和其他结合剂，还包括可与充分接近于与所述参考结合分子结合的表位的表位或结合位点结合以使在所述待筛选的结合分子和所述参考结合分子之间可以发生竞争性结合的抗体、抗体片段和其他结合剂。优选地，本发明的竞争性结合分子当过量存在时将抑制参考结合分子与选择出的靶种类之间的特异结合，所述抑制至少为抑制10％、优选地至少抑制25％、更优选地至少抑制50％、最优选地至少抑制75％-90％或甚至更高。鉴别一种或多种结合至与本发明的结合分子结合的大约、充分地、基本上或完全相同的表位的竞争性结合分子是一种直截了当的技术。鉴于竞争性结合分子的鉴别与参考结合分子(即本发明的结合分子)对比而确定，应理解实际上在任何方面都不需要确定与所述参考结合分子和所述竞争性结合分子结合的表位以鉴别与所述参考结合分子所结合的相同或充分相同的表位结合的竞争性结合分子。

本发明的另一方面涉及一种用于鉴别结合分子，优选人结合分子的方法，所述结合分子潜在地具有针对SARS-CoV的中和活性，其中所述方法包括下述步骤：a)使收集到的位于可复制的遗传包装(genetic package)表面的结合分子与SARS-CoV在可使得结合发生的条件下接触，b)从不结合的结合分子中分离并回收结合至SARS-CoV的结合分子，c)分离至少一种回收的结合分子，d)确认是否所述分离的结合分子具有针对SARS-CoV的中和活性，所述步骤的特征是步骤a)中的SARS-CoV是失活的。所述失活的SARS-CoV可以在被灭活之前纯化。纯化可以通过任何已知的适于病毒的纯化方法进行，例如通过甘油衬垫(glycerol cushion)的离心。步骤a)中的失活的SARS-CoV可以在使用前固定至适当的材料。

本文所用的可复制的遗传包装(genetic package)可以是原核或真核的，包括细胞、孢子、细菌、病毒、噬菌体和多核糖体(polysome)。优选的可复制的遗传包装是噬菌体。所述结合分子例如单链Fv被展示在所述可复制的遗传包装上，即它们附着于位于所述可复制的遗传包装外表面的基团或分子上。所述可复制的遗传包装是一种与编码待筛选的结合分子的核酸分子相连接的包含待筛选的结合分子的可筛选的单位。所述核酸分子应在体内或体外是可复制的，例如在体内作为载体，在体外通过PCR、转录及翻译复制。体内复制可以是自主的(例如对于细胞来说)、宿主因子协助的(例如对于病毒来说)或宿主和辅助病毒(helper virus)都要协助的(例如对于噬菌粒(phagemid)来说)。展示收集的结合分子的可复制的遗传包装通过引入编码外源结合分子的核酸分子而形成，所述外源结合分子要在所述可复制的遗传包装的基因组中以与正常表达于所述可复制的遗传包装的外表面的内源蛋白形成融合蛋白。所述融合分子的表达、转运至外表面和组装导致外源结合分子展示在所述可复制的遗传包装的外表面。

SARS-CoV的灭活可以通过本领域技术人员熟知的病毒灭活方法进行，所述方法特别例如巴氏灭菌法(湿热)，即在仍处于水溶液中时在60℃进行10小时热处理；干热处理，即在冻干阶段进行热处理，80℃72小时；蒸汽热处理，60℃10小时后80℃1小时；低pH处理，即pH4处理6小时至21天；有机溶剂/去污剂处理，例如向病毒加入有机溶剂和去污剂(Triton X-100或Tween-80)；低温乙醇蛋白分离法(cold ethanol fractionation)处理；柱层析；纳米过滤；UV/可见光照射；γ射线照射；以及加入碘。优选地，所述灭活通过γ射线或UV照射进行。测试病毒是否仍旧具有感染能力或已经部分地或完全地失活的方法是本领域技术人员所熟知的。

本发明的另一方面涉及具有针对SARS-CoV的中和活性并且通过以上描述的鉴别方法获得的结合分子。包含所述结合分子的药物组合物、另外包含至少一种药物学可接受的赋形剂的所述药物组合物也是本发明的一个方面。药物学可接受的赋形剂在前面已经描述。本发明的药物组合物可以另外包括至少一种其他的治疗剂。适当的物质在前面已经描述。

本发明另外涉及本发明的结合分子或药物组合物用作药品。它们可以在SARS-CoV导致的疾病的诊断、预防、治疗、和/或其组合中应用。

实施例

提供了下面的实施例以说明本发明。在任何方面这些实施例都不是为了限制本发明的范围。

实施例1

选择携带特异识别SARS-CoV的单链Fv片段的噬菌体

使用抗体噬菌体展示文库和技术选择抗体片段，基本上如美国专利6,265,150和WO 98/15833中所描述的，此两篇文献以其全文并入本文作参考。所有步骤均在室温进行，除非另外说明。一种失活的SARS-CoV制备物(Frankfurt 1病毒株)如下述所制备。当观察到细胞病变效应(cytopathic effect，CPE)时立刻收集来自用SARS-CoV病毒株Frankfurt 1感染的Vero细胞的培养基。细胞碎片通过将所收集的培养基在3000rpm进行15分钟离心而清除。收集所得到的上清，再次在3000rpm进行15分钟离心并转移至干净试管。接下来，将10ml含有25％甘油的无菌PBS装入超速离心管，将20ml清澈上清慢慢加到所述甘油衬垫上并将所述试管在4℃以20,000rpm离心2小时。弃去上清，将病毒沉淀重悬于1ml TNE缓冲液(10mMTris-HC1 pH7.4，1mM EDTA，200mM NaCl)中并保存在-80℃。接下来，所述重悬的病毒沉淀在干冰上以45kGy进行γ射线照射。然后在细胞培养物中测试它们是否已丧失感染性。如果确定已丧失感染性，那么所获得的失活的SARS-CoV制备物可用于选择特异结合于SARS-CoV的单链噬菌体抗体。

所述失活的病毒制备物和热失活的胎牛血清(FBS)在4℃过夜包被至分离的Maxisorp^TM塑料试管(Nunc)表面上。所述试管在含有2％FBS和2％脱脂奶粉(2％PBS-FM)的3ml PBS中封闭2小时。2小时后，清空所述FBS包被的试管并用PBS洗3次，然后向这个试管中加入500μl(大约10¹³cfu)表达单链Fv片段(scFv)的噬菌体展示文库(基本上如De Kruif et al.(1995a)和其引用的参考文献(全文并入本文)中的描述所制备的)、500μl 4％PBS-FM和2ml 2％PBS-FM。密封所述试管并在室温缓慢旋转2小时。接下来，将所得到的被封闭的噬菌体文库(3ml)转移至已用PBS清洗3次的SARS-CoV制备物包被的试管。加入Tween-20至终浓度为0.05％，在室温或37℃的缓慢旋转轮上使结合进行2小时。清空所述试管并用含有0.05％Tween-20的PBS洗10次，再用PBS洗10次。加入1ml甘氨酸-HCL(0.05M，pH 2.2)以洗脱结合的噬菌体，再将所述试管缓慢旋转10分钟。对于中和目的，将被洗脱的噬菌体加入到500μl 1M Tris-HC1pH 7.4中。再向此混和物中加入5ml指数生长的XL-1蓝色细菌培养物。所得到的培养物再在37℃进行30分钟温育，不要摇动。接下来，将所述细菌铺板至含有氨苄青霉素、四环素和葡萄糖的TYE琼脂平板。经过在37℃过夜温育所述平板，从平板上刮下菌落并用于制备富集的噬菌体文库，基本上如De Kruif et al.(1995a)和WO 02/103012所描述的(两篇文献均并入本文作参考)。简短而言，刮下的细菌被用于接种至含有氨苄青霉素、四环素和葡萄糖的2TY培养基并在37℃生长至OD600nm为大约0.3。加入CT或VCSM13辅助噬菌体并使它们感染细菌，之后将培养基更换为含有氨苄青霉素、四环素和卡那霉素的2TY培养基。继续进行温育，30℃过夜。第二天，通过离心将细菌从2TY培养基移除，然后用聚乙二醇6000/NaCl沉淀上清中的噬菌体。最后，所述噬菌体溶于少量含有1％BSA的PBS、过滤消毒并用于下一轮的选择。所述选择/再感染过程进行2至3次。在每一轮选择后，单个E.coli菌落被用于制备单克隆噬菌体抗体。必要地，单个菌落生长至对数期并用VCSM13辅助噬菌体感染，之后可以过夜进行噬菌体抗体生产。用ELISA测试含有噬菌体抗体的上清与包被于96孔板的SARS-CoV制备物的结合活性。在上述选择中，获得了称为SC03-001、SC03-002、SC03-003、SC03-004、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的噬菌体抗体。

为了避免选择以前已经鉴别的噬菌体抗体，如下所述在相应于以前已经鉴别的噬菌体抗体的scFv存在的情况下进行另一种选择。如之前在De Kruif et al.(1995b)中所描述的生产噬菌体抗体SC03-001、SC03-002、SC03-003、SC03-004、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的ScFv，调节所述ScFv的缓冲液至1×PBS。然后将所述scFv与500μl(大约10¹³ cfu)基本上如DeKruif et al.(1995a)和其引用的参考文献(全文并入本文)中的描述所制备的表达单链Fv片段的噬菌体展示文库混和。接下来在FBS包被的试管中如上面所描述的封闭所获得的混和物，接下来用基本上如上面所描述的所获得的封闭的混和物对封闭的噬菌体文库进行选择。在这种另外的选择中，获得了称为SC03-016、SC03-017和SC03-018的噬菌体抗体。

实施例2

确认SARS-CoV特异的单链噬菌体抗体

在前面描述的筛选过程中获得的选择出的单链噬菌体抗体用ELISA确认其特异性，即与如前面所描述的制备的SARS-CoV制备物的结合。另外，还测试了所述单链噬菌体抗体与10％FBS的结合。用于此目的，所述SARS-CoV制备物或10％FBS制备物被包被于Maxisorp^TM ELISA平板。在包被之后，所述平板在2％PBS-FM中封闭。所选择的单链噬菌体抗体在等体积4％PBS-FM中温育以获得封闭的噬菌体抗体。所述平板被清空、用PBS洗3次，之后加入所述封闭的噬菌体抗体。进行1小时温育，所述平板在含有0.05％Tween-20的PBS中漂洗，结合的噬菌体抗体用与过氧化物酶缀合的抗-M13抗体检测(使用OD492nm测定)。作为对照，不使用单链噬菌体抗体或使用针对甲状腺球蛋白的对照单链噬菌体抗体(SC02-006)(参见De Kruif et al.1995a和1995b)或针对CD46的对照单链噬菌体抗体(SC02-300)的步骤同时进行。两种对照都作为负对照。如表1和图1所示，称为SC03-001、SC03-002、SC03-003、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的所选择的噬菌体抗体表现出与固定的SARS-CoV制备物显著的结合，然而未观察到与FBS的结合。

如表2和图2所示，称为SC03-018的所选择的噬菌体抗体表现出与固定的SARS-CoV制备物显著的结合，然而未观察到与FBS的结合。相比于与FBS的结合，称为SC03-016和SC03-017的所选择的噬菌体抗体表现出与固定的SARS-CoV制备物的结合，尽管比SC03-018的量要少一些。

实施例3

特异于SARS-CoV的scFv的特性鉴定

从选择出的特异单链噬菌体抗体(scFv)克隆中获得了质粒DNA，并且根据标准技术确定了核苷酸序列。称为SC03-001、SC03-002、SC03-003、SC03-004、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的scFv的核苷酸序列(包括用于克隆的限制性位点)分别示于SEQ IDNO：46、SEQ ID NO：48、SEQ ID NO：50、SEQ ID NO：89、SEQ IDNO：52、SEQ ID NO：54、SEQ ID NO：56、SEQ ID NO：58、SEQ IDNO：60、SEQ ID NO：62、SEQ ID NO：64、SEQ ID NO：66、SEQ ID NO：68和SEQ ID NO：70。称为SC03-001、SC03-002、SC03-003、SC03-004、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的scFv的氨基酸序列分别示于SEQ ID NO：47、SEQ ID NO：49、SEQID NO：51、SEQ IDNO：90、SEQ ID NO：53、SEQ ID NO：55、SEQ ID NO：57、SEQ IDNO：59、SEQ ID NO：61、SEQ ID NO：63、SEQ ID NO：65、SEQ IDNO：67、SEQ ID NO：69和SEQ ID NO：71。另外，称为SC03-016、SC03-017和SC03-018的scFv的核苷酸序列(包括用于克隆的限制位点)分别示于SEQ ID NO：91、SEQ ID NO：93和SEQ ID NO：95。称为SC03-016、SC03-017和SC03-018的scFv的氨基酸序列分别示于SEQID NO：92、SEQ ID NO：94和SEQ ID NO：96。

特异结合所述SARS-CoV制备物的scFv的V_H和V_L基因特征(gene identity)(参见Tomlinson IM，Williams SC，Ignatovitch O，CorbettSJ，Winter G.V-BASE Sequence Directory.Cambridge United Kingdom：MRC Centre for Protein Engineering(1997))和重链CDR3组成列于表3。

实施例4

在甲醇酵母(Pichia Pastoris)中生产人SARS-CoV特异的二价scFv

在甲醇酵母(Pichia Pastoris)系统中克隆和表达二价scFv片段的方法基于提供者(Invitrogen)在″A Manual of Methods for Expression ofRecombinant Proteins Using pPICZ and pPICZa in Pichia pastoris(Version F)″中所提供的方案。二价scFv表达载体pPicZbiFVH(见图3B)由载体pPICZμB(见图3A)(Invitrogen)通过本领域技术人员所知的标准分子生物学技术构建。在pPICZμB中引入了3个修饰(见图3C)：

1.通过PCR产生的点突变在信号肽KEK2切割位点后面引入一个限制位点(NcoI)以协助克隆进载体，

2.通过PCR产生的点突变清除在sh ble基因编码区内部的另一个NcoI限制位点，

3.一个包含鼠IgG3的铰合区和一个接头片段的合成片段被引入NotI和XbaI的限制位点之间。

所有修饰都通过测序确定。scFv通过使用限制位点NcoI和NotI的定向克隆从噬菌体展示表达载体克隆进pPicZbiFVH。通过根据生产商的方案的电穿孔技术(见上)用5-10μg线性化的构建体cDNA转化甲醇酵母菌株SMD1168kek1；suc1(ATCC#204414)。转化的细胞铺板于含有250μg/ml Zeocin的YPDS琼脂并在30℃温育3-4天。高产克隆通过菌落转移免疫印迹筛选(colony lift immunoblot screening)选择，如下所述。将预先湿润的硝酸纤维素膜有层次地置于转化平板上，并且每个克隆的一部分都转移至膜上。接下来将所述膜以有菌落面向上置于含有0.5％甲醇的YPD琼脂上在30℃温育过夜。然后用含有0.5％Tween-20的Tris缓冲液(TBST)反复漂洗以除去菌落。然后用TBST和4％脱脂奶粉封闭30分钟。然后将所述膜置于含有4％脱脂奶粉和辣根过氧化物酶缀合的抗-c-myc抗体(Roche)的TBST中1小时。最后，在TBST中充分漂洗所述膜，接下来用PBS漂洗并使分泌scFv的菌落通过化学荧光检测系统(Apbiochem)被看到。选择出的高产者通过在YPD平板上画线分离而纯化，并且接下来用于表达二价scFv。可在摇动培养瓶中进行小量表达培养，基本上如生产商的方案(见上)所描述的。BMGY培养基用于细胞扩展阶段，BMMY培养基用于二价scFv表达阶段。在诱导48小时后，通过反复离心使上清澄清。处理所述上清以纯化，所述处理包括加入1M Na₂HPO₄pH8至浓度为20mM、加入0.5M咪唑至浓度为10mM、加入5M NaCl至浓度为500mM。此后，所述样品通过在AKTAprime FPLC-系统(Pharmacia)上的固定金属亲和层析和之后的阴离子交换层析纯化。5ml HiTrap螯和柱(Pharmacia)填充了NiSO₄并根据生产商指导进行平衡。直接将处理过的上清上样至所述柱并用平衡缓冲液(20mM Na₂PO₄pH8、10mM咪唑)充分洗涤。二价scFv在存在250mM咪唑(pH8.5)的情况下被直接从柱上洗脱至1ml琼脂糖凝胶Q HP柱(Pharmacia)。所述柱接下来用20mM Tris-HC1 pH 8洗涤，然后用20mM Na₂PO₄pH 7.3短暂洗涤，接着二价scFv被从柱上洗脱至7个柱床体积的0-0.5M NaCl梯度中。然后测定各个级分的蛋白质含量并分析各个级分的活性和纯度。所述称为SC03-001、SC03-002、SC03-003、SC03-005、SC03-006、SC03-007、SC03-008、SC03-009、SC03-0010、SC03-012、SC03-013、SC03-014和SC03-015的选择出的scFv的二价scFv分别称为pyBi03-001C02、pyBi03-002C02、pyBi03-003C02、pyBi03-005C02、pyBi03-006C02、pyBi03-007C02、pyBi03-008C02、pyBi03-009C02、pyBi03-010C02、pyBi03-012C02、pyBi03-013C02、pyBi03-014C02、pyBi03-015C02。

实施例5

由所选择的抗-SARS-CoV单链Fv构建完整人免疫球蛋白(人单克隆抗-SARS-CoV抗体)

称为SC03-001、SC03-002、SC03-009、SC03-013、SC03-014和SC03-018的scFv的重链和轻链可变区通过使用寡核苷酸进行PCR扩增以添加分别用于在IgG表达载体pSyn-C03-HCμ1(参见SEQ IDNo：110)和pSyn-C05-Cμ(参见SEQ ID No：111)中表达的限制位点和/或序列。scFv共有的V_L基因用寡核苷酸5K-I(SEQ ID NO：112)和sy3K-C(SEQ ID NO：113)(见下)扩增，并且PCR产物克隆进载体pSyn-C05-Cμ。用于全部构建体的核苷酸序列根据本领域技术人员熟知的标准技术确认。V_H基因用下述寡核苷酸组扩增：5H-B(SEQ IDNO：114)和sy3H-A(SEQ ID NO：115)。之后，PCR产物被克隆进载体pSyn-C03-HCμl并且核苷酸序列根据本领域技术人员熟知的标准技术确认。

5H-B

acctgtcttgaattctccatggccgaggtgcagctggtggagtctg

sy3H-A

gcccttggtgctagcgctggagacggtcaccagggtgccctggcccc

5K-I

acctgtctcgagttttccatggctgacatccagatgacccagtctccatcctcc

sy3K-C

gggaccaaggtggagatcaaacggaccgtggccgcccccagc

得到的编码抗-SARS-CoV人IgG1重链的表达构建体pgG103-OO1C03、pgG103-002C03、pgG103-009C03、pgG103-013C03、pgG103-014C03和pgG103-018C03与293T细胞中编码常规轻链的pSyn-C05-VkI构建体短暂地一同表达，并且得到了含有IgG1抗体的上清。称为03-001、03-002、03-009、03-013、03-014和03-018的抗体的重链的核苷酸序列分别示于SEQ ID NO 116、118、120、122、124和126。称为03-001、03-002、03-009、03-013、03-014和03-018的抗体的重链的氨基酸序列分别示于SEQ ID NO 117、119、121、123、125和127。

抗体03-001、03-002、03-009、03-013、03-014和03-018的轻链的核苷酸序列示于SEQ ID NO 128。抗体03-001、03-002、03-009、03-013、03-014和03-018的轻链的氨基酸序列示于SEQ ID NO 129。基本上如上面所描述的产生了称为03-006和03-015的抗体。称为03-006和03-015的抗体的重链的核苷酸序列分别示于SEQ IDNO：471和SEQ ID NO：473。称为03-006和03-015的抗体的重链的氨基酸序列分别示于SEQ ID NO：472和SEQ ID NO：474。称为03-006和03-015的抗体的轻链的核苷酸序列分别示于SEQ ID NO：475和SEQ ID NO：477。称为03-006和03-015的抗体的轻链的氨基酸序列分别示于SEQ ID NO：476和SEQ ID NO：478。接下来，重组人单克隆抗体通过A蛋白柱和大小排阻层析柱使用一般用于免疫球蛋白的标准纯化方法纯化(参见例如WO00/63403，其并入本文作参考)

实施例6

人单克隆抗-SARS-CoV抗体和特异于SARS-CoV的单链噬菌体抗体的竞争性ELISA

为了确定是否上述选择的单链噬菌体抗体与相似的或重叠的表位结合，进行竞争ELISA，所述表位被本发明的重组人单克隆抗-SARS-CoV抗体识别。简短而言，γ射线照射过的SARS-CoV制备物被如前述方法固定。所述固定的SARS-CoV制备物和所选择的单链噬菌体抗体在等体积的含有4％ELK的PBS封闭。然后被封闭的固定的SARS-CoV制备物与封闭的单链噬菌体抗体在存在或不存在1μg/ml的抗-SARS-CoV IgG的情况下在室温温育1小时。如前面所描述的监测所述单链噬菌体抗体的结合。与单链噬菌体抗体独自结合相比，在存在抗-SARS-CoV IgG的情况下所述单链噬菌体抗体与SARS-CoV制备物的降低的结合提示相似的或重叠的表位被所述单链噬菌体抗体和所述抗-SARS-CoV IgG识别。如图4所示，称为03-001的所述抗-SARS-CoV IgG能够显著降低单链噬菌体抗体SC03-001、SC03-005和SC03-0010的结合。称为03-002的抗-SARS-CoV IgG降低SC03-002和SC03-012的结合，然而称为03-009和03-018的抗-SARS-CoV IgG分别降低称为SC03-009和SC03-018的单链噬菌体抗体的结合。称为03-013和03-014的抗-SARS-CoV IgG降低SC03-013、SC03-014和SC03-006的结合。另外，IgG pGg03-013轻微降低SC03-015的结合。

实施例7

用于重组人抗-SARS-CoV二价scFv和重组人抗-SARS-CoV抗体的SARS-CoV中和活性的筛选测定

SARS-CoV中和测定在Vero细胞(ATCC CCL 81)上进行。在所述中和测定中使用的SARS-CoV病毒株是Frankfurt 1病毒株(此病毒株的完整基因组参见EMBL-数据库，登记号AY291315)和Frankfurt 2病毒株，所述病毒株衍生自被Frankfurt 1病毒株感染的首例患者(index case)(Rickerts et al.2003)。后一种SARS分离株尚未测序。所述病毒株的病毒储存物以4×10³TCID₅₀/ml(每ml的半数组织感染剂量)的滴度应用，所述滴度根据众所周知的Spearman and Kaerber方法计算。如前面所描述的产生的重组人抗-SARS-CoV二价scFv和重组人抗-SARS-CoV抗体通过在PBS中的未稀释原液的系列2倍稀释预筛选，所述稀释始自1∶10(稀释范围1∶10-1∶320)。中和滴度≥1∶10被认为在所述预筛选测定中特异性地证明了所述二价scFv或所述抗体针对SARS-CoV的反应性。为了确定抗体浓度依赖性中和活性，针对SARS-CoV的所述二价scFv或所述抗体接下来被调节至10μg/ml蛋白浓度并在PBS中进行系列2倍稀释(稀释范围1∶2-1∶512)。一般说来，所述中和测定如下进行。25μl所研究的scFv或抗体稀释物与25μl病毒悬浮液(大约是100TCID₅₀/25μl)混和并在37℃温育1小时。然后将所述悬浮液吸出2次以在96孔板中分成3份。然后加入50μl刚刚用胰蛋白酶消化并被匀浆的Vero细胞悬浮液(T75培养瓶中铺满的单细胞层的1/3)，所述细胞重悬在含有10％w/v胎牛血清和抗生素的DMEM中。所接种的细胞在37℃培养3-4天，并每天观察细胞病变效应(cytopathic effect，CPE)的发展。CPE与正对照(接种了病毒的细胞)和负对照(模拟接种的细胞或仅与二价scFv或抗体温育的细胞)对比。将在单独的细胞培养物中完全不存在CPE的情况定义为保护(＝100％滴度降低(titer reduction))。在66％的孔中显示保护的血清稀释物定义为中和抗体滴度。得自两名确定为SARS患者之一的血清在所述中和测定中被用作正对照；这两名患者的临床记录已经公开(见Rickerts et al.2003)。

如表4所示，检测被称为pyBi03-OO1C02、pyBi03-002C02、pyBi03-003C02、pyBi03-005C02、pyBi03-006C02、pyBi03-007C02、pyBi03-008C02、pyBi03-009C02、pyBi03-010C02、pyBi03-012C02、pyBi03-013C02、pyBi03-014C02、pyBi03-015C02的二价scFv的SARS-CoV中和活性。另外，测试两个负对照，即pyBi02-148C02(与抗原L6结合的二价scFv)和pyBi02-006C02(与甲状腺球蛋白结合的二价scFv)，和一个正对照(即得自SARS患者的血清)的中和活性。表4清楚地显示二价scFv pyBi03-013C02和pyBi03-014C02显示显著的中和活性。所述二价物在上述预筛选测定中在稀释因子为80或160时中和Frankfurt 1或Frankfurt 2病毒株。根据OD值和中和滴度，所述中和抗体可用于预防和/或治疗SARS感染导致的疾病。由人单克隆抗-SARS-CoV抗体获得的中和数据提示称为03-013和03-014的抗体显示中和活性(数据未列出)。这确认了上述关于二价单链Fv的结果。

在另一个实施方案中，所述SARS-CoV中和测定在Vero细胞(ATCC CCL 81)上进行。用于此测定中的SARS-CoV病毒株是Frankfurt 1病毒株(此病毒株的完整基因组参见EMBL-数据库，登记号AY291315)。所述病毒株以1.6×10⁶TCID₅₀/ml(每ml的半数组织感染剂量)的滴度应用。重组抗体(噬菌体抗体、scFv、二价或IgG1形式)被调节至10μg/ml浓度然后在PBS中系列10倍或2倍稀释以确定最佳抑制浓度。25μl所述重组抗体与25μl病毒悬浮液(＝150TCID₅₀/5μl)混和并在37℃温育1小时。然后将所述悬浮液分成3份接种至生长在96孔细胞培养板中的亚铺满Vero细胞(大约80％密度)上。所接种的细胞在37℃培养3-4天，并每天观察细胞病变效应(CPE)的发展。CPE与正对照(接种了病毒的细胞)和负对照(模拟接种的细胞或仅与重组抗体温育的细胞)对比。

在另一个实施方案中，所述SARS-CoV中和测定在Vero细胞(ATCC CCL 81)上如下进行。此次测定中所用的SARS-CoV病毒株SCV-P4(5688)得自患者5688(死于SARS)，然后在Vero细胞上传代4次(参见Fouchier et al.(2003)，Kuiken et al.(2003)；病毒株也称为HK-39849(GenBank登记号AY278491))。所述病毒株以2×10³TCID₅₀/ml(每ml的半数组织感染剂量)的滴度应用，所述滴度根据本领域技术人员熟知的Spearman and Kaerber方法计算。重组表达的人抗-SARS-CoV抗体通过在PBS中的系列2倍稀释筛选，所述稀释始自50μg/ml的浓度(稀释范围50-0.025μg/ml)。50μl病毒悬浮液(10、30或100TCID₅₀/50μl)与50μl所研究的重组人抗-SARS-CoV抗体稀释物混和并在37℃温育1小时。然后将所述悬浮液吸出2次以在含有80％铺满的Vero细胞单细胞层(在16-20小时之前以每孔1×10⁴细胞的密度接种于含有5％FBS的DMEM中)的96孔板中分成3份。所述Vero细胞在37℃培养4天，并每天观察细胞病变效应(CPE)的发展。CPE与正对照(接种了病毒的细胞)和负对照(模拟接种的细胞或仅与重组抗体温育的细胞)对比。将在单独的细胞培养物中完全不存在CPE的情况定义为保护(＝100％滴度降低(titer reduction))。在66％的孔中显示保护的稀释物定义为中和抗体滴度。结果示于表7。顶端的一行以μg/ml显示了抗体浓度。在表7的左栏显示了抗体的TCID₅₀和名称。从表7可以很清楚地得出称为03-013和03-014的人抗-SARS-CoV抗体含有SARS-CoV中和活性。03-013在170nM达到对100TCID₅₀的感染性的完全保护，03-014在42nM达到。作为对比，对照抗体02-027(一种人单克隆抗EpCAM抗体)不含有任何中和活性。称为03-006的抗体在普通IgG稀释范围不显示中和能力，但是后续中和测定显示03-006能够中和SARS-CoV，但是仅仅在μM浓度范围(数据未列出)。

实施例8

用间接免疫荧光染色测定(IIF)进行重组人抗-SARS-CoV抗体和SARS感染的细胞的结合的筛选测定

生长至亚铺满状态的Vero细胞(ATCCCCL 81)被接种感染复数(multiplicity of infection，moi)为0.1的SARS-CoV的Franfurt-1病毒株。每天观察所述细胞的细胞病变效应(CPE)，通常在第二天初步可见。在CPE出现后，马上用细胞刮刀(cell scraper)轻轻收集所述细胞，在PBS中漂洗一次，并以一薄层铺展于覆盖了特富龙(Teflon)载网的显微镜载片上。使所述细胞悬液干燥30分钟，然后在冰冷的丙酮中固定15分钟并保存于-80℃直至进一步的使用。针对SARS-CoV的重组人抗体配制成浓度为10μg/ml并进一步在PBS中稀释2倍。将所述显微载片放置于室温并在每个视野(field)中滴入20μl重组抗体悬液(所述载片包含10-12个视野)。得自已经感染了SARS-CoV的患者的血清被用作正对照，得自未感染SARS-CoV的对象的血清被用作负对照(参见Rickerts et al.2003)。载片在37℃的潮湿温箱中温育1小时，在室温用PBS漂洗2次。用本领域已知的方法制备荧光素-异硫氰酸盐标记的二级抗体(即抗-huIgG-FITC)的工作溶液。向所述载片的每一个视野加入20μl所述二级抗体。在37℃进一步温育30分钟后，载片再次漂洗2次并加上盖片。用荧光显微镜观察载片，将与所述重组抗体接触的载片的特异荧光(荧光细胞的数量及形态)与与正对照或负对照接触的载片相比较。表5显示了IIF测定的数据。称为03-014和03-018的重组人单克隆抗-SARS-CoV抗体显示被SARS-CoV感染的细胞的清楚的细胞质染色。称为03-009的重组人单克隆抗-SARS-CoV抗体也显示了清楚的染色(数据未列出)。

实施例9

被γ射线或UV照射而失活的SARS-CoV制备物的特性鉴定

除非另外说明，全部步骤都在室温进行。失活的SARS-CoV制备物(Frankfurt 1病毒株)如下述制备。当观察到细胞病变效应(CPE)后立即收集被O.I.moi SARS-CoV病毒株Frankfurt 1感染的Vero细胞的培养基。细胞在-20℃冷冻后融化。细胞碎片通过将收集的培养基在3000rpm离心15分钟清除。收集所获得的上清，再次在3000rpm离心15分钟并转移至干净试管。接下来，将10ml含有25％(v/v)甘油的无菌PBS装入超速离心管，将20ml清澈上清慢慢加到所述甘油衬垫上并将所述试管用Beckman SW28转头在4℃以20,000rpm离心2小时。弃去上清，将病毒沉淀重悬于1ml TNE缓冲液(10mM Tris-HClpH 7.4，1mM EDTA，200mM NaCl)中并保存在-80℃。接下来，所述重悬的病毒沉淀在干冰上以45kGy进行γ射线照射，或在4℃进行15分钟UV照射(UV-B射线280-350nm；μmax 306nm)。然后在细胞培养物中测试它们是否已丧失感染性。如果确定已丧失感染性，那么所获得的失活的SARS-CoV制备物可用于进一步的实验。为了确定所述分离的抗-SARS-CoV人IgG抗体能够结合上述失活的SARS-CoV制备物，进行ELISA实验。所述SARS-CoV制备物在包被缓冲液(50mM碳酸盐缓冲液，pH 9.6)中以1∶250稀释并在4℃过夜固定于Maxisorp^TMELISA平板。用PBS漂洗所述ELISA平板3次并与含有1％BSA的PBS中的1和5μg/ml的人抗-SARS-CoV IgG和对照IgG(称为02-027)一起在室温温育1小时。然后，用含有0.05％Tween-20的PBS漂洗2次所述平板，结合的IgG用抗-人-IgG-HRP-缀合物(Pharmingen)在492nm检测。

如图5所示，称为03-001和03-002的抗-SARS-CoV抗体能够以相似程度结合UV-和γ-射线照射过的SARS-CoV制备物。相反，称为03-009和03-018的抗体优选地结合至γ-射线照射过的SARS-CoV制备物，而称为03-013和03-014的抗体优选地结合至UV照射过的SARS-CoV制备物。上述结果提示称为03-009和03-018的抗体与经过强γ-射线照射病毒后更加暴露的病毒抗原结合。上述结果还提示γ-射线可能破坏被抗体03-013和03-014识别的抗原。

实施例10

夹心ELISA(sandwich ELISA)中抗-SARS-CoVIgG抗体的特性鉴定

为了确定是否当SARS-CoV制备物变性后更多的抗原变得可被分离的重组人单克隆抗-SARS-CoV抗体接触，以及确定哪些抗原被人单克隆抗-SARS-CoV抗体检测到，进行下述夹心ELISA。为了检测结合的抗原，应用了不同的抗-SARS-CoV兔抗血清。所述夹心ELISA按照如下所述进行。人抗-SARS-CoV抗体或称为02-300的对照抗体(针对CD46的抗体)在包被缓冲液(50mM碳酸盐缓冲液，pH9.6)中以5μg/ml的浓度被固定于Maxisorp^TM ELISA平板，所述固定在4℃过夜进行。所述平板用PBS洗3次并且用含有1％BSA的PBS封闭。然后，如本文所描述的制备的γ射线照射过的SARS-CoV制备物通过在RIPA缓冲液(150mM NaCl、1％Nonidet P-40、0.5％脱氧胆酸、0.1％十二烷基硫酸钠、50mM Tris、pH 8.0)中稀释1∶10变性，然后在室温温育1小时。接下来，变性的病毒制备物在含有1％BSA的PBS中稀释1∶10，然后固定的人IgG与所述变性的病毒制备物在室温温育1小时。为了识别哪些SARS-CoV的蛋白被固定的重组人单克隆抗-SARS-CoV抗体检测到，加入识别完整SARS-CoV、SARS-CoV的刺突蛋白(Imgenex IMG-542or IMG-557)或SARS-CoV的核壳蛋白(Imgenex IMG-543)的多克隆兔抗体。最后，用结合的抗-兔-IgG-HRP-缀合物(Dako)检测到了结合的兔IgG(使用OD 492nm测量)。

如图6A所示(通过针对完整SARS-CoV的多克隆血清检测)，称为03-009、03-013、03-014和03-018的重组人单克隆抗-SARS-CoV抗体都能够结合天然的及变性的SARS-CoV制备物。变性后增加的信号可能是由于变性使更多的抗原位点暴露而导致的。当检测通过两种针对SARS-CoV刺突蛋白的多克隆兔抗体进行时(图6B及6D分别对于称为IMG-542和IMG-557的抗体)，称为03-013和03-014的抗体的值相对于03-009和03-018的值要高一些，这提示称为03-013和03-014的抗体是针对SARS-CoV刺突蛋白的。当检测通过使用针对SARS-CoV核壳蛋白的多克隆抗体进行时(图6C对于称为IMG-543的抗体)，称为03-009和03-018的抗体的值相对于称为03-013和03-014的抗体的值要高一些，特别是当所述病毒是变性的时，这提示03-009和03-018是针对SARS-CoV核壳(N)蛋白的。基于上述结果，得到下述结论：称为03-009和03-018的重组人单克隆抗-SARS-CoV抗体是针对SARS-CoV核壳蛋白的，称为03-013和03-014的重组人单克隆抗-SARS-CoV抗体是针对SARS-CoV刺突蛋白的。

实施例11

通过PEPSCAN-ELISA鉴别重组人抗-SARS-Co V抗体识别的表位

由SARS-CoV的蛋白合成线性的和环形的15肽并用信用卡形式的微PEPSCAN卡(credit-card format mini-PEPSCAN card)(455个肽形式/卡)筛选，如以前所描述的(特别参见WO 84/03564、WO 93/09872，Slootstra et al.1996)。所有肽都在氨基末端被乙酰化。简单说来，所有SARS-CoV Urbani的(潜在的)蛋白的系列重叠肽，无论是线性的或是环形的，都被产生出来并通过PEPSCAN分析的手段检测其与本发明的重组人抗-SARS-CoV抗体的结合，所述蛋白被称为刺突蛋白(EMBL-数据库中的表面刺突糖蛋白的蛋白质编号(protein-id)是AAP13441)、蛋白质X1(蛋白质X1的蛋白质编号是AAP13446)、蛋白质X2(蛋白质X2的蛋白质编号是AAP13447)、E蛋白(小包膜蛋白(E蛋白)的蛋白质编号是AAP13443)、M蛋白(膜蛋白(M蛋白)的蛋白质编号是AAP13444)、蛋白质X3(蛋白质X3的蛋白质编号是AAP13448)、蛋白质X4(蛋白质X4的蛋白质编号是AAP13449)、蛋白质X5(蛋白质X5的蛋白质编号是AAP13450)、以及N蛋白(核壳蛋白(N蛋白)的蛋白质编号是AAP13445)。

因为上述Urbani蛋白质也在其他SARS-CoV病毒株中发现，并且具有相同的或高度同源的形式，所以在所述分析方法中发现的抗原肽可以不仅仅用于检测SARS-CoV病毒株Urbani以及预防和/或治疗SARS-CoV病毒株Urbani导致的疾病，还可以用于普遍检测SARS-CoV以及普遍预防和/或治疗SARS-CoV导致的疾病。例如SARS-CoV病毒株TOR2、Frankfurt 1和HSR1的表面刺突糖蛋白在EMBL-数据库中的蛋白质编号是AAP41037、AAP33697和AAP72986。病毒株TOR2、Frankfurt 1和HSR1的完整基因组在EMBL-数据库中的登记号分别是AY274119、AY291315和AY323977。在这些登记号下可以找到这些病毒株的其他(潜在的)蛋白质的氨基酸序列。

如上所述，SARS-CoV的一些蛋白质，特别例如刺突蛋白和N蛋白，是所有SARS-CoV共有的。然而，病毒株TOR2、Frankfurt 1和HSR 1含有编码SARS-CoV病毒株Urbani中不存在的(潜在的)蛋白质的开放阅读框(open reading frame)。在SARS-CoV病毒株TOR2中，这些(潜在的)蛋白质称为Orf9、Orf10，Orf13和Orf14。这些(潜在的)蛋白质的前3种在SARS-CoV病毒株Frankfurt 1和HSR 1也有发现。在这些病毒株中所述(潜在的)蛋白质分别称为Orf7b、Orf8a和Orf9b。SARS-CoV TOR2的(潜在的)蛋白质的编码序列(CDS)显示于EMBL-数据库，登记号AY274119；SARS-CoV HSR1的(潜在的)蛋白质的编码序列(CDS)显示于EMBL-数据库，登记号AY323977；SARS-CoVFrankfurt 1的(潜在的)蛋白质的编码序列(CDS)显示于EMBL-数据库，登记号AY291315。所有SARS-CoV TOR2的(潜在的)蛋白的系列重叠肽，无论是线性的或是环形的，也都被产生出来并通过PEPSCAN分析的手段检测其与本发明的重组人抗-SARS-CoV抗体的结合。因为上述TOR2蛋白质也在其他一些SARS-CoV病毒株(例如在病毒株Frankfurt 1和HSR1)中发现，并且具有相同的或高度同源的形式，所以在所述分析方法中发现的肽可以不仅仅用于检测SARS-CoV病毒株TOR2以及预防和/或治疗SARS-CoV病毒株TOR2导致的疾病，还可以用于检测表达这些(潜在的)蛋白质的SARS-CoV病毒株以及预防和/或治疗表达这些(潜在的)蛋白质的SARS-CoV导致的疾病。

在所有环形的肽中，第2位和第14位被半胱氨酸取代(乙酰-XCXXXXXXXXXXXCX-微卡片)。如果在所制备的肽中还存在除了所述在第2位和第14位的半胱氨酸之外的半胱氨酸，其他的半胱氨酸被丙氨酸取代。所述环形肽用标准Fmoc-chemistry法合成，并且用三氟乙酸和清除剂去保护(deprotect)。接下来，被去保护的肽在卡片上与碳酸铵(20mM，pH7.9/乙腈(1∶1(v/v))中的0.5mM 1，3-双(溴甲基)苯溶液反应。将所述卡片在所述溶液中轻轻摇动30-60分钟，同时要完全浸入所述溶液中。最后，用过量水充分清洗所述卡片，并在含有含有1％SDS/0.1％β-巯基乙醇的PBS(pH 7.2)的裂解缓冲液中在70℃用超声波裂解30分钟，然后在水中再用超声波裂解45分钟。

用基于PEPSCAN的酶联免疫测定(ELISA)检测重组人抗-SARS-CoV抗体与每一种线性的或环形的肽的结合。所述含有共价连接的肽的455孔信用卡形式的聚丙烯卡片与所述抗体(1μg/ml；在含有5％马血清(v/v)和5％卵清蛋白(w/v)的封闭溶液中稀释)温育(4℃，过夜)。在漂洗后，所述肽与抗-人抗体过氧化物酶(稀释物1/1000)温育(1小时，25℃)，并且接下来在漂洗之后加入过氧化物酶底物2，2′-连氮-双-3-乙基苯并噻唑啉磺酸(ABTS)和2μl/ml 3％H₂O₂。对照(用于线性和环状的)仅与抗-人抗体过氧化物酶温育。1小时之后测量颜色形成。ELISA的颜色形成用CCD-照相机(CCD Camera)和成像加工系统(image processing system)定量。所述装置包括一个CCD-照相机和一个55mm镜头(Sony CCD Video Camera XC-77RR，Nikonmicro-nikkor 55mmf/2.8镜头)、一个照相机转换器(adaptor)(SonyCamera adaptor DC-77RR)和Image Processing Software packageOptimas，version 6.5(Media Cybernetics，Silver Spring，MD 20910，U.S.A.)。Optimas在奔腾II(pentium II)计算机系统上运行。所述重组人抗-SARS-CoV抗体被测试与所述由前所述的方法合成的线性和环形15肽的结合。肽和重组人抗-SARS-CoV抗体的相关结合如下所述计算。每个抗体的平均OD值针对各自蛋白质而计算(全部肽的OD值的总和/肽的总数)。下一步计算此平均值的标准偏差。所述标准偏差乘以2，所得值再加至所述平均值以得到校正因子。接下来用此校正因子去除每一个肽的OD值。如果得到0.9或更大的数，那么认为在所述特异性的肽和所研究的抗体之间存在相关结合。尤其感兴趣的是包括几个相关肽的结构域。这些结构域示于表6(灰色)。称为03-018的重组人抗-SARS-CoV抗体与核壳(N)蛋白的肽反应。被识别的肽包括NGPQSNQRSAPRITF(SEQ ID NO：97)、GPQSNQRSAPRITFG(SEQID NO：98)、PQSNQRSAPRITFGG(SEQ ID NO：99)、QSNQRSAPRITFGGP(SEQ ID NO：100)、SNQRSAPRIRITFGGPT(SEQID NO：101)、NQRSAPRITFGGPTD(SEQ ID NO：102)、QRSAPRITFGGPTDS(SEQ ID NO：103)、RSAPRITFGGPTDST(SEQID NO：104)、SAPRITFGGPTDSTD(SEQ ID NO：105)、APRITFGGPTDSTDN(SEQ ID NO：106)、PRITFGGPTDSTDNN(SEQID NO：107)、RITFGGPTDSTDNNQ(SEQ ID NO：108)和ITFGGPTDSTDNNQN(SEQ ID NO：109)。称为03-018的重组人抗-SARS-CoV抗体的最大结合是与连续的系列线性或环形的肽的结合，所述肽始自序列GPQSNQRSAPRITFG(SEQ ID NO：98)，结束于序列RSAPRITFGGPTDST(SEQ ID NO：104)，从而可以将03-018的最小结合位点定位于序列RSAPRITFG(SEQ ID NO：468)，对应于N蛋白的残基11-19。惊人的是，此线性表位在所有已公开的人SARS-CoV和动物SARS-CoV类似分离株的N蛋白序列中是保守的，但是在冠状病毒科家族(Coronaviridae)的其他成员中是缺乏的。PEPSCAN分析进一步显示称为03-009的重组人N蛋白特异性抗-SARS-CoV抗体不能识别N蛋白上的一段线性或环形氨基酸，提示此抗体识别N蛋白的非线性/构象表位。全部上述肽或其部分可用于普遍检测SARS-CoV。

实施例12

利用转染的HEK293T细胞选择特异识别衍生自SARS-CoV的蛋白质的单链噬菌体抗体

在另一种测定中，分析所述单链噬菌体抗体与重组表达SARS-CoV的蛋白的HEK293T细胞结合的能力。为此目的，用携带编码来自SARS-CoV病毒株Frankfurt 1的包膜(E)蛋白、膜(M)蛋白或刺突(S)蛋白的cDNA序列的质粒或空载体转染HEK293T细胞。用本领域技术人员熟知的标准技术(参见Coligan JE，Dunn BM，Ploegh HL，Speicher DW和Wingfield PT(eds.)(2001)Current protocols in proteinscience，volume I.John Wiley&Sons，Inc.，New York)选择稳定的转染子。对于流式细胞术分析，单链噬菌体抗体首先在等体积4％PBS-M中于4℃封闭15分钟，然后对转染的HEK293T细胞进行染色。向作为对照的转染的HEK293T细胞和用前面描述过的SARS-CoV的蛋白质转染的HEK293T细胞中加入所述封闭的噬菌体抗体。使用生物素标记的抗-M13抗体(Santa Cruz Biotechnology)和后续加入的链霉亲和素-藻红蛋白(Caltag)观测所述单链噬菌体抗体与所述细胞的结合。

在另一测定中，分析scFv抗体与SARS-CoV的刺突(S)蛋白的一些部分和完整核壳(N)蛋白结合的能力。编码SARS-CoV病毒株Frankfurt 1的S蛋白的cDNA被调整为适合于人类基因的密码子偏好，并且基因被最优化以通过Geneart(Regensburg，Germany)最优地表达。所述S蛋白的密码子优化的核苷酸序列显示于SEQ ID NO：462。此密码子优化的核苷酸序列编码的氨基酸序列显示于SEQ IDNO：463。

编码N-末端565个氨基酸(称为S565的部分)的DNA作为KpnI-BamHI片段被克隆进pAdapt(Havenga et al.，2001)中，所述pAdapt通过插入称为pcDNA3.1/myc-His C(Invitrogen)的载体的多接头(polylinker)而修饰，所述被修饰的pAdapt载体称为pAdapt/myc-HisC。

编码N-末端826个氨基酸(称为S826的部分)的DNA作为KpnI-EcoRV片段被克隆进pAdapt中，所述pAdapt通过插入称为pcDNA3.1/myc-His B(Invitrogen)的载体的多接头(polylinker)而修饰，所述被修饰的pAdapt载体称为pAdapt/myc-His B。

编码N-末端1195个氨基酸(称为S1195的部分)的DNA被如下构建。DNA片段通过使用寡核苷酸引物XhoISpikeRevCOG5′-gttcctcgaggggccacttgatgtactgc-3′(SEQ ID NO：464)和SpikeCOG seq 15′-ccaggtgaagcagatgta-3′(SEQ ID NO：465)而从密码子优化的S蛋白cDNA中扩增出来。得到的片段作为BstEII-XhoI片段与衍生自密码子优化的S蛋白cDNA的KpnI-BstEII片段(或者可以应用BstEII之外的，在所扩增的片段中独特的限制位点)一起被克隆进pAdapt中，所述pAdapt通过插入称为pcDNA3.1/myc-His A(Invitrogen)的载体的多接头(polylinker)而修饰，所述被修饰的pAdapt载体称为pAdapt/myc-His A。

相应于S蛋白氨基酸残基318-510的片段(称为S318-510部分)通过使用寡核苷酸引物EcoRIspikeFor3185′-cctggaattctccatggccaacatcaccaacc-3′(SEQ ID NO：469)和XbaIspikeRev5105′-gaagggccctctagacacggtggcagg-3′(SEQ ID NO：470)而从S基因cDNA中扩增出来。得到的片段用EcoRI-Xbal消化并被克隆进pHAVT20/myc His A以得到pHAVT20/myc-His A S318-510。在此载体中，与HAVT20前导序列融合的片段S318-510的表达由人全长立即早期(immediate-early)CMV启动子控制。

编码核壳蛋白的DNA通过使用寡核苷酸引物KpnINCFor5′-cttggtaccgccaccatgtctgataatggacc-3′(SEQ ID NO：466)和XbaINCRev5′-gttctctagatgcctgagttgaatcagc-3′(SEQ ID NO：467)从得自SARS-CoV病毒株Frankfurt 1的全部随机六邻体(hexamer)cDNA中扩增出来并作为KpnI-XbaI片段克隆进pAdapt/myc-His A。使用标准技术进行在HEK293T细胞中的DNA转染以进行短暂表达。直接从培养物上清或细菌裂解物应用衍生自S蛋白的片段和核壳(N)蛋白。或者使用Ni-NTA(Qiagen)从培养物上清中纯化所述片段和核壳(N)蛋白。

如下述进行对针对衍生自S蛋白的片段或核壳(N)蛋白的scFv抗体的ELISA检测。ELISA平板的孔用5μg/ml的50mM碳酸氢盐缓冲液pH 9.6中的抗-myc抗体包被过夜。在用UV灭活的SARS-CoV制备物的情况下，所述孔用上述制备物包被过夜，如前面所述的方法。用含有0.05％Tween的PBS对所述平板上的孔洗涤3次，然后用含有1％BSA的PBS在37℃封闭2小时。包被了抗-myc抗体的孔与含有在含有1％BSA的PBS中稀释的myc-标记的片段S565或核壳蛋白的培养物上清或细胞裂解物一起在室温温育1小时。用含有0.05％Tween的PBS对所述孔洗涤3次。然后scFv SC03-014和SC03-009在含有0.05％Tween的PBS中稀释并在室温温育1小时。用含有0.05％Tween的PBS对所述孔洗涤3次并用抗-VSV-HRP缀合物(对于scFv)在室温温育1小时。如图8所示，在ELISA中SC03-009和SC03-014都能够结合失活的SARS-CoV制备物，而对照scFvSC02-006(抗-甲状腺球蛋白scFv)则相反。测试scFv与衍生自SARS-CoV的，通过其myc标记而被捕获的蛋白质或部分的反应性显示SC03-009能够与核壳(N)蛋白结合，但是不与刺突蛋白片段S565和无关对照myc标记的蛋白质(称为02-300的二价scFv)结合。相反，SC03-014仅与S565片段反应，但是不与核壳(N)蛋白和对照蛋白质02-300反应。对于用IgG的ELISA实验(见下)，使用了鼠抗-Hu-IgGHRP缀合物而不是抗-VSV-HRP缀合物。使用邻苯二胺底物显色，反应通过加入1M H₂SO₄终止，在492nM测定吸收。当包被了抗-myc抗体的孔与myc标记的，首先用Ni-NTA纯化自培养物上清或细胞裂解物的片段S蛋白或核壳(N)蛋白温育时，在ELISA实验中得到了相似的结果(数据未列出)。

为了进一步研究与SARS冠状病毒片段和蛋白的结合，用单克隆抗体03-001、03-002、03-006、03-009、03-013、03-014、03-015和03-018进行下述实验。得自转化的HEK293T细胞裂解物的全长N蛋白通过如前面所述的抗myc抗体被捕获于ELISA平板上并与上述IgG分子温育。图9显示了单克隆抗体03-009和03-018特异地结合所述N蛋白，但是不结合对照蛋白，即二价scFv 02-300。

为了对与所述N蛋白结合的单克隆抗体的亲和性进行排序，进行了IgG浓度滴定(通过在含有1％ELK的PBS中对所述抗体进行稀释)和接下来的如前面所描述的ELISA。所述单克隆抗体的滴定显示03-009与所述N蛋白的结合好于03-018(见图10)。这可能反映了亲和性方面的差异。

为了进一步研究在N蛋白中的抗体结合位点，在固定的N蛋白上进行了竞争ELISA。被捕获的N蛋白与1μg/ml(未饱和)生物素化的抗体03-009在不存在竞争抗体或存在25倍或50倍过量的竞争抗体(抗体03-009或03-018)的情况下温育。结合的生物素化的抗体03-009通过链霉亲和素缀合的HRP(BD Pharmingen)检测并显色，如上面所描述的方法。结果(见图11)显示单克隆抗体03-009的结合不受存在的25倍或50倍过量的未标记的单克隆抗体03-018影响。这证明了所述抗体03-009和03-018对于与所述N蛋白的结合不互相竞争，它们识别不同的表位。

接下来评估上述抗体与S蛋白的相互作用。所述抗体与表达在HEK293T细胞上的全长S蛋白的结合首先通过流式细胞术分析研究。转染的细胞与浓度为10μg/ml的人IgG在冰上温育1小时。将细胞洗涤3次，与生物素化的山羊抗人IgG温育45分钟，然后与链霉亲和素缀合的甲状腺球蛋白温育10分钟。分析显示单克隆抗体03-006、03-013、03-014和03-015特异地结合S蛋白转染的HEK293T细胞(见图12)。

为了进一步定位在所述S蛋白中这些抗体的结合位点，用如上面所描述的ELISA方法测试了与包含S蛋白残基1-565(S565)的重组可溶性片段的结合。在所述结合HEK293T细胞上的全长S蛋白的抗体组中，除了03-015外，所有抗体都结合片段S565(见图12)。

为了进一步精确定位所述抗体的结合位点，评估了与包含S蛋白残基318-510(S318-510)的重组片段的结合。图12显示只有03-006、03-013和03-014能够结合所述S318-510片段。

如通过类似于前面所述的滴定实验进行的滴定实验所显示的，抗体03-014显示以比抗体03-006和03-013更高的亲和性与S565结合(见图13)。

使用与如前面所描述的相似的装置进行竞争ELISA。被捕获的S565与1μg/ml(未饱和)生物素化的抗体03-014在不存在竞争抗体或存在25倍或50倍过量的竞争IgG(抗体03-006或03-014)的情况下温育。结合的生物素化的抗体03-014通过链霉亲和素缀合的HRP(BDPharmingen)检测并显色，如上面所描述的方法。所述竞争ELISA显示抗体03-014的结合不受存在的25倍或50倍过量的未标记的抗体03-006影响。并且推断它们的结合位点不相互重叠(见图14)。

使用流式细胞术分析测定所述S蛋白的片段与血管紧张素转换酶2(ACE2)的结合，所述ACE2是SARS-CoV感染性的天然受体(Li etal.，2003)。表达ACE2的Vero细胞(通过多克隆抗-ACE2抗体(R&Dsystems)的方法测定)与饱和浓度的所述myc标记的S565片段在4℃温育1小时。作为对照，所述Vero细胞与myc标记的二价scFv 02-006温育。或者，在与所述Vero细胞温育前，所述S565片段与IgG抗体03-014(抗-SARS-CoV S蛋白抗体)、03-018(抗-SARS-CoVN蛋白抗体)或02-027(抗EPCAM对照抗体)温育。洗涤3次后，结合的片段和对照蛋白质通过生物素化的抗myc抗体(Santa Cruz Biotechnology Inc.)和链霉亲和素缀合的藻红蛋白(Caltag)用流式细胞术分析检测。全部温育和洗涤在4℃补充了0.5％牛血清白蛋白(BSA)的PBS中进行。如图15所示，在存在0.5μM抗体03-014的情况下对片段S565进行预温育导致S565与Vero细胞的结合的完全丧失，但是在存在0.5μM抗体03-018(见图16)或0.5μM抗体02-027(见图17)的情况下S565与Vero细胞的结合不受影响。总之，单克隆抗体03-014阻断S565结合至Vero细胞，但是抗体03-018和02-027不阻断。在同样的实验中，显示抗体03-006能够部分地阻断S565结合至Vero细胞(数据未列出)。总之，这些数据提示抗体03-014通过阻止S蛋白与细胞受体如ACE2的相互作用而中和SARS-CoV。

实施例13

用已经接触了SARS-CoV的患者的外周血液淋巴细胞构建scFv噬菌体展示文库

从痊愈自SARS-CoV的患者获得淋巴细胞(参见Rickerts et al.2003)并冷冻在液氮中。在37℃水浴中迅速融化所述淋巴细胞并转移至冰上。在50ml试管中用冷的DMEM培养基将所述淋巴细胞稀释至终体积50ml并在350xg离心5分钟。所得到的细胞沉淀在5mlDMEM中重悬，用台盼蓝染色排除法(trypan-blue exclusion)使死细胞显色以用显微镜确定细胞密度。将全部细胞(～5×10⁶)在350xg再次离心5分钟，移出细胞并重悬于很少量液体(DMEM)中。用有机相分离(organic phase separation)(TRIZOL^TM)和后续乙醇沉淀从这些细胞中制备总RNA。将所得到的RNA溶于DEPC处理的超纯水并通过OD260nm测定确定其浓度。之后，将所述RNA稀释至100ng/μl浓度。然后将1μg RNA如下所述转化为cDNA：对于10μl总RNA，加入13μl DEPC处理的超纯水和1μl随机六邻体(500ng/μl)，将所得到的混和物在65℃加热5分钟并在冰上迅速冷却。然后向所述混和物中加入8μl 5X第一链反应液(First-Strand buffer)、2μl dNTP(每种10mM)、2μl DTT(0.1M)、2μl RNase-抑制剂(40U/μl)和2μl Superscript^TMIIIMMLV逆转录酶(200U/μl)，室温温育5分钟后在50℃温育1小时。

通过热失活，即在75℃将所述混和物温育15分钟，而终止所述反应。

所获得的cDNA产物用DEPC处理的超纯水稀释至200μl终体积。所获得的cDNA产物的所述稀释物的50倍稀释的溶液(处于10mM Tris缓冲液中)的OD260nm值为0.1。

用5至10μl所稀释的cDNA产物作为模板用于免疫球蛋白γ重链家族和κ或λ轻链序列的PCR扩增，所述PCR扩增使用特异寡核苷酸引物(见表8-15)。除了稀释的cDNA产物之外，PCR反应混和物还包括终体积为50μl的20mM Tris-HCl(pH 8.4)中25pmol有义引物和25pmol反义引物、50mM KCl、2.5mM MgCl₂、250μM dNTP和1.25单位的Taq聚合酶。在温度为96℃的热盖热循环仪(heated-lidthermal cycler)中所获得的混和物被迅速融化2分钟，然后进行30个扩增循环：96℃30秒；60℃30秒和72℃60秒。在第一轮扩增中，9个正向引物中的每一个(见表8；包括了重链可变区的全部家族)都与IgG特异恒定区反义引物HuCIgG 5′-GTC CAC CTT GGT GTTGCT GGG CTT-3′(SEQ ID NO：131)组合以产生9种大约650碱基对的产物。这些产物在2％琼脂糖凝胶上纯化并用Qiagen凝胶提取柱(gel-extraction column)分离。每一种分离产物的1/10用于与上面描述的相同的PCR反应，所述PCR反应使用同样的9种有义引物(包括了重链可变区的全部家族)，其中每一种有义引物与四种J-区特异的反义引物之一组合(见表9)。这产生36种大约350碱基对的产物。所获得的产物在2％琼脂糖凝胶上纯化并用Qiagen凝胶提取柱(gel-extraction column)分离。在第3轮，每一种分离产物的1/10用于用与第2轮相同的引物组合进行的再扩增，其中所用的引物被引入多个限制位点而延伸(见表10)，以允许在噬菌体展示载体pDV-C05(见图7及SEQ ID NO：130)中定向克隆。这又一次产生了36种产物。这些产物依据每一种使用的(VH)有义引物而被收集并分为9组。在下一步中，用NcoI和XhoI消化2.5μg所收集的组和100μgpDV-C05载体并通过凝胶纯化。之后如下述在16℃过夜进行连接。对于每500ngpDV-C05载体加入70ng收集的组至含有50mM Tris-HCl(pH 7.5)、10mM MgCl₂、10mMDTT、1mM ATP、25μg/ml BSA和2.5μl T4DNA连接酶(400u/μl)的总体积为50μl的连接混和物中。对每一个收集的组进行此步骤。所述连接混和物用酚/氯仿纯化。之后用氯仿抽提并用乙醇沉淀，本领域技术人员熟知这些方法。将所得到的DNA溶解于50μl超纯水，然后根据生产商(Stratagene)手册将每个连接混和物的2份2.5μl等分试样经电穿孔导入40μl TG1感受态E.coli细菌中。转化子在37℃过夜生长于总数为27个的含有补充了50μg/ml氨苄青霉素和4.5％葡萄糖的2TY琼脂的平皿中(每个收集的组使用3个平皿；平皿尺寸：240mm ×240mm)。通过将所述转化子从所述琼脂平板上刮下而得到可变重链区域的(亚)文库。此(亚)文库直接用于使用Qiagen^TM试剂盒的质粒DNA制备。

得自同样cDNA制备物的轻链免疫球蛋白序列用与上面描述的用于重链区域的方法相似的3轮PCR步骤和相同的反应参数扩增，只是使用了表11-15中所列出的引物。第一轮扩增用一套17个轻链可变区有义引物进行(其中11个用于λ轻链(见表11)，6个用于κ轻链(见表12))，每一个引物与一个识别C-κ的反义引物HuCk5′-ACACTCTCCCCTGTTGAAGCTCTT-3′(见SEQ ID NO：158)或识别C-λ恒定区的反义引物HuCμ25′-TGAACATTCTGTAGGGGCCACTG-3′(见SEQ ID NO：159)或HuCμ75′-AGAGCATTCTGCAGGGGCCACTG-3′(见SEQ ID NO：160)组合(HuCμ2和HuCμ7反义引物在使用前等摩尔混和)，产生17种大约600碱基对的产物。这些产物在2％琼脂糖凝胶上纯化并用Qiagen凝胶提取柱(gel-extraction column)从所述凝胶分离。每一种分离产物的1/10用于与上面描述的相同的PCR反应，所述PCR反应使用同样的17种有义引物，其中每一种λ轻链有义引物与三种Jλ-区特异的反义引物之一组合(见表13)，每一种κ轻链有义引物与五种Jκ-区特异的反义引物之一组合(见表14)。这产生63种大约350碱基对的产物。所获得的产物在2％琼脂糖凝胶上纯化并用Qiagen凝胶提取柱(gel-extraction column)从所述凝胶分离。在第3轮，每一种分离产物的1/10用于用与第2轮相同的引物组合进行的再扩增，其中所用的引物被引入多个限制位点而延伸(见表15)，以允许在重链(亚)文库载体中定向克隆。这又一次产生了63种产物。这些产物被收集并分为10组。选用这个数目是为了维持不同轻链家族在所述文库中的天然分布并过量或不足量地存在特定家族。一个家族中的等位基因数目用来确定在一个文库中存在的百分比(见表16)。在下一步中，用SalI和NotI消化所述组并在重链(亚)文库载体中连接，所述重链(亚)文库载体用同样的限制酶切割，所述连接使用与上面所描述的用于重链(亚)文库的连接步骤和体积相同的连接步骤和体积。所得到的确定的文库的连接、纯化和接下来的转化同样如与上面所描述的用于重链(亚)文库的方法一样进行。转化子生长于总数为30个的含有补充了50μg/ml氨苄青霉素和4.5％葡萄糖的2TY琼脂的平皿中(每个收集的组使用3个平皿；平皿尺寸：240mm×240mm)。在含有50μg/ml氨苄青霉素和4.5％葡萄糖的2TY培养基中收集全部细菌，与甘油混和至15％(v/v)并在-80℃冰冻于1.5ml等分试样中。对于所述文库的恢复(rescue)和选择如前面所描述的用于非免疫文库的方法进行。

另外，制备scFv的原始噬菌体展示文库。对于此目的，使用健康供体的外周血液淋巴细胞作为免疫球蛋白转录物的来源。使用上面描述的方案，免疫球蛋白γVH区被扩增并克隆进已经含有VκIII轻链片段的PDV-C05载体。这产生了一个未免疫的表达具有已定型的VκIII轻链可变区的原始文库，大小为大约10×10⁶。

实施例14

从原始和免疫噬菌体展示文库中选择携带特异识别SARS-CoV的单链Fv片段的噬菌体

基本上如前面所述选择抗体片断(见实施例1)。对于下面描述的选择，使用了UV灭活的SARS-CoV制备物(对于其制备物参见实施例9)。不同于实施例1中所描述的选择，没有进行使用热灭活的胎牛血清包被的Maxisorp^TM试管(Nunc)的预去除(pre-subtraction)。对于SARS-CoV包被的试管，加入500μl(大约10¹³cfu)表达单链Fv片段(scFv)的原始或免疫噬菌体展示文库(这些文库的构建参见实施例13)、1体积的4％PBS-FM和至终浓度为0.05％的Tween-20。

对于原始噬菌体展示文库的选择，使结合在37℃的缓慢旋转轮上进行1小时，然后不加刺激进行30分钟温育。清空所述试管并如下述洗涤：第一轮，用含有0.05％Tween-20的PBS(PBST)洗涤10次后用PBS洗涤10次；第二轮，用PBST洗涤15次后用PBS洗涤15次；第三轮，用PBST洗涤15次后用PBS洗涤15次。

对于免疫噬菌体展示文库的选择只包括单一的一轮，使上面所描述的结合在37℃或室温进行。进行如下所述的选择和洗涤：在37℃温育，用PBST洗涤5次后用PBS洗涤5次；在37℃温育，用PBST洗10次后用PBS洗涤10次；在室温温育，用PBST洗涤10次后用PBS洗涤10次。洗脱结合的噬菌体并如实施例1中所描述的进行加工。用ELISA测试衍生自单个菌落的噬菌体与包被至96孔板上的SARS-CoV的结合活性。

在原始噬菌体展示文库的选择中获得了称为SC03-019和SC03-059的噬菌体抗体。在免疫噬菌体展示文库的选择中获得了称为SC03-020、SC03-021、SC03-022、SC03-023、SC03-024、SC03-025、SC03-026、SC03-027、SC03-029、SC03-030，SC03-031、SC03-032、SC03-033、SC03-034、SC03-035、SC03-036、SC03-037、SC03-038、SC03-039、SC03-040、SC03-041、SC03-042、SC03-043、SC03-044、SC03-045、SC03-046、SC03-047、SC03-048、SC03-049、SC03-050、SC03-051、SC03-052、SC03-053、SC03-054、SC03-055、SC03-056、SC03-057和SC03-058的噬菌体抗体。

实施例15

确认衍生自原始和免疫噬菌体展示文库的SARS-CoV特异的单链噬菌体抗体

获得自实施例14所描述的筛选的，被选择出的单链噬菌体抗体由ELISA确认其特异性，即与实施例14所述的SARS-CoV制备物的结合，实验基本上如实施例2中所描述的进行。不同于实施例2，所述单链噬菌体抗体没有被测试与10％FBS的结合。

如表17所显示，称为SC03-019、SC03-020，SC03-021、SC03-022、SC03-023、SC03-024、SC03-025，SC03-026、SC03-027、SC03-029、SC03-030、SC03-031、SC03-032、SC03-033、SC03-034、SC03-035、SC03-036、SC03-037、SC03-038、SC03-039、SC03-040、SC03-041、SC03-042、SC03-043、SC03-044、SC03-045、SC03-046、SC03-047、SC03-048、SC03-049、SC03-050、SC03-051、SC03-052、SC03-053、SC03-054、SC03-055、SC03-056、SC03-057、SC03-058和SC03-059的被选择出的噬菌体抗体显示与固定的SARS-CoV制备物的显著结合。作为对照，同时进行不使用单链噬菌体抗体的所述步骤。

实施例16

衍生自原始和免疫噬菌体展示文库特异于SARS-CoV的scFv的特性鉴定

从选择出的特异单链噬菌体抗体(scFv)克隆(见实施例14)得到质粒DNA并根据标准技术确定核苷酸序列。称为SC03-019、SC03-020、SC03-021、SC03-022、SC03-023、SC03-024、SC03-025、SC03-026、SC03-027、SC03-029、SC03-030、SC03-031、SC03-032、SC03-033、SC03-034、SC03-035、SC03-036、SC03-037、SC03-038、SC03-039、SC03-040、SC03-041、SC03-042、SC03-043、SC03-044、SC03-045、SC03-046、SC03-047、SC03-048、SC03-049、SC03-050、SC03-051、SC03-052、SC03-053、SC03-054、SC03-055、SC03-056、SC03-057、SC03-058和SC03-059的scFv的核苷酸序列分别显示于SEQ IDNO：211、SEQ ID NO：213、SEQ ID NO：215、SEQ ID NO：217、SEQ IDNO：219、SEQ ID NO：221、SEQ ID NO：223、SEQ ID NO：225、SEQ IDNO：227、SEQ ID NO：229、SEQ ID NO：231、SEQ ID NO：233、SEQ IDNO：235、SEQ ID NO：237、SEQ ID NO：239、SEQ ID NO：241、SEQ IDNO：243、SEQ ID NO：245、SEQ ID NO：247、SEQ ID NO：249、SEQ IDNO：251、SEQ ID NO：253、SEQ ID NO：255、SEQ ID NO：257、SEQ IDNO：259、SEQ ID NO：261、SEQ ID NO：263、SEQ ID NO：265、SEQ IDNO：267、SEQ ID NO：269、SEQ ID NO：271、SEQ ID NO：273、SEQ IDNO：275、SEQ ID NO：277、SEQ ID NO：279、SEQ ID NO：281、SEQ IDNO：283、SEQ ID NO：285、SEQ ID NO：287和SEQ ID NO：289。

称为SC03-019、SC03-020、SC03-021、SC03-022、SC03-023、SC03-024、SC03-025、SC03-026、SC03-027、SC03-029、SC03-030、SC03-031、SC03-032、SC03-033、SC03-034、SC03-035、SC03-036、SC03-037、SC03-038、SC03-039、SC03-040、SC03-041、SC03-042、SC03-043、SC03-044、SC03-045、SC03-046、SC03-047、SC03-048、SC03-049、SC03-050、SC03-051、SC03-052、SC03-053、SC03-054、SC03-055、SC03-056、SC03-057、SC03-058和SC03-059的scFv的氨基酸序列分别显示于SEQ ID NO：212、SEQ ID NO：214、SEQ IDNO：216、SEQ ID NO：218、SEQ ID NO：220、SEQ ID NO：222、SEQ IDNO：224、SEQ ID NO：226、SEQ ID NO：228、SEQ ID NO：230、SEQ IDNO：232、SEQ ID NO：234、SEQ ID NO：236、SEQ ID NO：238、SEQ IDNO：240、SEQ ID NO：242、SEQ ID NO：244、SEQ ID NO：246、SEQ IDNO：248、SEQ ID NO：250、SEQ ID NO：252、SEQ ID NO：254、SEQ IDNO：256、SEQ ID NO：258、SEQ ID NO：260、SEQ ID NO：262、SEQ IDNO：264、SEQ ID NO：266、SEQ ID NO：268、SEQ ID NO：270、SEQ IDNO：272、SEQ ID NO：274、SEQ ID NO：276、SEQ ID NO：278、SEQ IDNO：280、SEQ ID NO：282、SEQ ID NO：284、SEQ ID NO：286、SEQ IDNO：288和SEQ ID NO：290。

VH和VL基因同一性(identity)(参见Tomlinson IM，Williams SC，Ignatovitch O，Corbett SJ，Winter G.V-BASE Sequence Directory.Cambridge United Kingdom：MRC Center for Protein Engineering(1997))和与SARS-CoV制备物特异结合的scFv重链CDR3组成示于表18。

实施例17

在雪貂中使用具有中和活性的重组人抗-SARS-CoV抗体的体内实验

进行此实验以研究本发明的抗-SARS-CoV单克隆抗体在体内的中和能力，基本上如Emini et al.(1990)所描述的方法。简短而言，人单克隆抗-SARS-CoV抗体03-014和对照抗-Epcam抗体02-027在体外与SARS-CoV病毒株SCV-P4(5688)(得自患者5688，见上)的两个不同滴度(10³和10⁴TCID₅₀)预温育。所用的抗体浓度从在100μl体积中中和病毒所需抗体的浓度(即6.25μg/ml；参见实施例7中的体外中和数据)外推得到，并乘以20(即对于1000TCID₅₀是0.13mg/ml，对于10000TCID₅₀是1.3mg/ml)。所得到的病毒/抗体混和物被用于通过气管内途径感染雪貂(Fouchier et al.2003)。同时平行接种Vero 118细胞的细胞培养物以验证所述单克隆抗体03-014的体外中和活性和与对照抗体预温育时所述病毒的所期望的感染性。监控雪貂生病的信号和病毒的排出(RT-PCR)，并最终处死雪貂并进行组织病理学检测。

如下述制备所述单克隆抗体03-014和对照抗体的高剂量和低剂量溶液。所述单克隆抗体03-014的工作溶液的浓度是1.44mg/ml。将4.87ml所述工作溶液移入15ml试管(高剂量溶液，1.44mg/ml终浓度)。为了获得低剂量溶液，将541μl所述工作溶液加入到2.46mlPBS中(低剂量溶液，0.26mg/ml终浓度)并充分混匀。将2.7ml所述低剂量溶液移入15ml试管。

对照抗体的起始溶液浓度是3.90mg/ml。将2.10ml此起始溶液加入到3.58ml PBS以得到终浓度为1.44mg/ml的工作溶液。将4.87ml此工作溶液移入15ml试管(高剂量溶液，1.44mg/ml终浓度)。为了获得低剂量溶液，将541μl所述工作溶液加入到2.46ml PBS中(低剂量溶液，0.26mg/ml终浓度)并充分混匀。将2.7ml所述低剂量溶液移入15ml试管。

在制备所述单克隆抗体的高剂量和低剂量溶液后，制备SARS-CoV的高剂量和低剂量溶液。SARS-CoV的起始溶液浓度是10⁷TCID₅₀/ml。所述起始溶液在37℃融化，将100μl所述溶液加入到900μl PBS中并充分混匀。由此得到的工作溶液浓度为10⁶TCID₅₀/ml。

为了得到高剂量SARS-CoV溶液，将200μl工作溶液加入到1.8mlPBS中并充分混匀(高剂量SARS-CoV溶液，100,000TCID₅₀/ml)。为了得到低剂量SARS-CoV溶液，将200μl高剂量溶液加入到1.8ml PBS中并充分混匀。之后将所得到的稀释的高剂量溶液进一步稀释，即将1.2ml此稀释的高剂量溶液加入到4.8ml PBS中并混和(低剂量SARS-CoV溶液，2,000TCID₅₀/ml)。

接下来将所述单克隆抗体的高剂量和低剂量溶液与SARS-CoV的高剂量和低剂量溶液在37℃混和1小时，制备下述组。

第1组：将2.7ml低剂量SARS-CoV溶液加入到2.7ml单克隆抗体03-014的低剂量溶液中并混匀(SARS-CoV的终浓度是1,000TCID₅₀/ml；单克隆抗体03-014的终浓度是0.13mg/ml；总体积5.4ml)。

第2组：将0.54ml高剂量SARS-CoV溶液加入到4.87ml单克隆抗体03-014的高剂量溶液中并混匀(SARS-CoV的终浓度是10,000TCID₅₀/ml；单克隆抗体03-014的终浓度是1.3mg/ml；总体积5.4ml)。

第3组：将2.7ml低剂量SARS-CoV溶液加入到2.7ml单克隆对照抗体的低剂量溶液中并混匀(SARS-CoV的终浓度是1,000TCID₅₀/ml；单克隆对照抗体的终浓度是0.13mg/ml；总体积5.4ml)。

第4组：将0.54ml高剂量SARS-CoV溶液加入到4.87ml单克隆对照抗体的高剂量溶液中并混匀(SARS-CoV的终浓度是10,000TCID₅₀/ml；单克隆对照抗体的终浓度是1.3mg/ml；总体积5.4ml)。

从4组中的每一组移出1.1ml溶液用于接种Vero 118细胞培养物。从4组中的每一组移出1.0ml溶液加入到底物平板的一个分开的孔中(每个平板包含6个孔)。每个孔含有Vero 118细胞的80％单细胞层。所述单细胞层通过用胰蛋白酶消化Vero 118细胞制备，将其在含有5％FBS的DMEM中稀释，每个分离的孔接种2*10⁶Vero 118细胞并在37℃将所述细胞与2ml含有0.75％碳酸氢钠、2mM L-谷氨酰胺和青霉素/链霉素(10U/ml)的DMEM一起温育16-20小时。将具有上述溶液的平板在37℃温育过夜。将培养基用新鲜培养基替换，将所述平板在37℃进一步温育3-5天并检测CPE。

向4组中的每一组剩下的量(4.3ml)中加入8.6ml PBS。在进行任何操作或取样之前，将动物通过小剂量ketamine(2.5mg/kg)和domitor(0.1ml/kg)麻醉，之后施用antisedan(0.05ml/kg)。在接种前，对于每一只雪貂取一支鼻咽拭子(第0天)。每一只雪貂通过气管内接种3ml分别要研究的溶液，如表19所显示的图解所阐明的。从每一只雪貂采集单独的鼻咽拭子，如表19所显示的图解所阐明的(第2天)。每天检查动物的临床症状例如呼吸问题、红斑或嗜睡。每天对动物进行称重。从每一只雪貂采集鼻咽拭子，如表19所显示的图解所阐明的(第4或7天)。在标准病毒运输培养基中保存拭子并保存在-80℃。在通过ketamine(5mg/kg)和domitor(0.1ml/kg)完全麻醉的情况下通过完全放血对雪貂施行安乐死，如表19所显示的图解所阐明的(第4或7天)。接下来样品通过使用引物和特异于SARS-CoV核蛋白(NP)基因的探针的RT-PCR分析以在肺组织中对SARS-CoV进行量化，如Kuiken et al.2003所描述的。

如图18所示，在接种给予后第2、4和7天，接种了病毒-对照抗体混和物的雪貂显示剂量依赖性SARS-CoV分泌。相反，在任何时间，接种了病毒-03-014抗体混和物的雪貂中检测不到SARS-CoV，提示没有病毒从接种位置散布开。

在肺中的SARS-CoV滴度使用体外病毒滴定测定获得。收集肺样品并称重，然后转移至含有1ml RPMI1640培养基的5ml试管。样品转移至冰上，被匀浆并且通过离心沉淀出细胞碎片。从上清中制备10倍系列稀释，起始稀释为1∶10。将100μl匀浆稀释物加入到96孔板上的Vero 118细胞的80％铺满的单细胞层。将细胞温育5天并记录细胞病变效应(CPE)。SARS-CoV肺滴度表示为TCID₅₀/ml并根据Reed and Muench方法计算。

如图19所示，在第4天，接种了病毒-对照抗体混和物的雪貂显示同样高的SARS-CoV滴度(10E6.5/ml肺部匀浆)，与病毒激发剂量无关。在第7天，两个对照组的肺部的病毒显著降低(10E4/ml肺部匀浆)，提示所述动物能够清除所述病毒。令人吃惊地，在接种了病毒-03-014抗体混和物(10E1.5/ml肺部匀浆是所用测定的检测极限)的高剂量和低剂量的两个组中都检测到了非常低的SARS-CoV的量。

在雪貂肺部的病理学的分析根据下述步骤进行。根据标准方案进行尸检；每一只雪貂的一个肺通过支气管内插管注入10％中性缓冲福尔马林，并悬于10％中性缓冲福尔马林过夜。以标准操作收集样品(一个取自肺的前部，一个取自中部，两个取自后部)，包埋在石蜡中，以5μm切割并用苏木精及曙红(HE)染色。对于肺部的SARS-CoV感染相关性炎症的半定量评估，通过光显微镜使用2.5x物镜观察每一个HE染色切片检查发炎点。如果看到任何可疑的病变，在高倍镜下检查以确定是否具有典型特征(肺泡内水肿、肺泡腔内存在嗜中性白细胞和巨噬细胞、2型肺细胞细胞增生)。肺部切片如下述打分：-，无SARS病变；+，轻微SARS病变；++，中等SARS病变；+++，显著SARS病变。每一只动物的最终打分是两个肺部切片的累积打分。以不知情的方式观察切片。

如图20所示，在第4天，接种了病毒-对照抗体混和物的雪貂显示显著的肺部病状，与病毒激发剂量无关。在第7天，低剂量对照组的肺部的病理学症状消失，表面这些动物能够从所述疾病中痊愈。在接种了病毒-03-014抗体混和物的高剂量和低剂量的两个组中，在处理后4天和7天都没有发现症状，提示肺部存在的很少量的病毒不诱导组织损伤。

实施例18

雪貂中被动转移和SARS-CoV激发后人抗-SARS-CoV抗体的效力

为了研究是否人抗-SARS-CoV抗体在用于预防时是有效的，在雪貂中进行SARS-CoV激发(challenge)实验。在SARS-CoV激发前一天，雪貂被通过腹膜内(i.p.)施用10mg/kg单克隆03-014IgG1抗体。在全部实验步骤之前，动物被如以上描述的麻醉。两组4只动物用人单克隆对照IgG1抗体(02-027，抗-Epcam抗体)或单克隆抗-SARS-CoV 03-014IgG1抗体处理。抗-SARS-CoV 03-014IgG1抗体(浓度1.23mg/ml)不稀释用于i.p.给药。所述02-027对照IgG1抗体(浓度3.9mg/ml)在PBS中1∶2稀释以获得终浓度1.3mg/ml。10mg/kg剂量的注射所需的体积基于个体雪貂的体重可以在6.5和8ml之间变化。所述抗体在环境温度注射。在抗体转移之前和SARS-CoV激发之前，从每一只动物中获得血清样品以评估SARS-CoV中和滴度，用如前所述的方法。全部动物用10⁴TCID₅₀的SARS-CoV病毒株SCV-P4(5688)激发。为此目的，所述5866SARS-CoV病毒储液(浓度：10⁷TCID₅₀/ml)被融化并取100μl所述病毒储液加入到900μl PBS(室温)中以获得10⁶TCID₅₀/ml的工作病毒储液。为获得含有10⁴TCID₅₀/3ml激发剂的激发剂量的终溶液，取100μl病毒工作储液加入到30mlPBS(室温)中。如上所述在每一只雪貂中经气管内接种3ml病毒混和物。血清、咽部拭子和组织样品根据表20获得。咽部拭子中的SARS-CoV分泌、肺部组织中的SARS-CoV滴度和肺部病理学如上所述进行分析。

图21显示所有对照动物具有高肺部SCV滴度，在肺匀浆物中的平均TCID₅₀是6.0logs(SD 0.3)，相比之下03-014组中只有2.7logs(SD 0.5)，即TCID₅₀相差3.3logs(95％CI：2.5-4.1logs；p＜＝0.001)。数据用斯氏T检验(Students′s T-test)进行对比，当p值小于0.05时认为差异是显著的。

在对照组中，在激发后第2天和第4天在喉部明显出现SARS-CoV的排出。相反，在三只03-014处理的动物中完全消除了咽部排出(见图22)。然而，在一只动物中，SARS-CoV的分泌与在对照组中观察到的相当。对这只雪貂在激发前的人IgG1血清水平进行确定，显示这只动物只具有低于5μg/ml的03-014血清浓度，但是在其他三只动物中血清IgG1水平处于65-84μg/ml范围，这提示了不适当的抗体给予。此发现被认为是腹膜内抗体施用程序的人为后果。与此观点一致，相对于未表现咽部SARS-CoV排出的三只动物，此动物表现降低的血清中和滴度。在第0天，此动物中的中和血清滴度少于其他动物的一半(针对100TCID₅₀，滴度为5)，并且在注射后第2天即已检测不到，相比之下，其他动物在第2天针对100TCID₅₀，滴度为5-10。

重要的是，对照组和03-014组在咽部和肺部病毒滴度的差异都伴随着03-014处理的组对宏观肺部病理的完全保护，相比之下对照组显示多发病变(multifocal lesion)(p＝0.029)。在显微镜分析中，这些病变显示肺泡的改变，类似于弥漫性肺泡损伤和外周支气管、外周细支气管、和外周血管淋巴细胞袖口征(cuffing)。

总而言之，这些结果表明03-014抗-SARS-CoV的被动转移能够消除SARS-CoV诱导的肺部病变以及在已经获得充足的03-014IgG血清滴度的动物中消除SARS-CoV排出(参见Ter Meulen et al.2004)。

实施例19

通过电子显微镜进行抗-SARS-CoV IgG抗体的特性鉴定

在24小时p.i.收获产生SARS-CoV的Vero细胞的上清，并直接用于间接两步免疫金标记。将SARS-CoV吸附至碳和聚乙烯醇缩醛(Pioloform)覆盖的铜载网。用封闭缓冲液(含有0.1％牛血清白蛋白的PBS)洗涤两次后，所述载网与人单克隆对照IgG1抗体(02-027，抗-Epcam抗体)或与单克隆抗-SARS-CoV 03-014IgG1抗体一起通过漂浮在各自的小液滴上在室温温育30分钟。接下来用一条滤纸清除多余的抗体并用封闭缓冲液进行两次洗涤步骤。通过在抗-hu-IgG-金-5nm缀合物(British Biocell Corp)小液滴上的温育检测结合的单克隆抗体。所述载网用1％乙酸双氧铀负显影并在ZEISS EM 10A透射电子显微镜(transmission electron microscope)上评估。与单克隆抗-SARS-CoV 03-014IgG1抗体的温育引起SARS-CoV外包膜突起区的密金标记(见图23a)，而与人单克隆对照IgG1抗体的温育不引起任何标记(见图23b)。

以同样的方式，感染了SARS-CoV的Vero细胞的超薄切片通过电子显微镜分析。图24A显示了未染色的感染了SARS-CoV的Vero细胞的超薄切片。图24B显示了用人单克隆对照IgG1抗体(02-027，抗-Epcam抗体)染色的切片，在图24C和24D中切片分别用单克隆抗-SARS-CoV 03-014IgG1抗体03-009和03-018染色。金标记的定位清楚地提示核壳蛋白滞留于病毒体中。

实施例20

构建并廉评估所述单克隆抗-SARS-CoV抗体与变体S318-510片段的结合

如下确定S蛋白的318-510区域内的多样性。汇集了一个包括多于146个基因组或编码完整人SARS-CoV或其片段的基因的列表。在114个实例中，鉴别了一个编码全长刺突(S)蛋白的开放阅读框。所述刺突蛋白的氨基酸残基318-510的序列对比显示了30个刺突蛋白，其中所述318-510区域与本文所用的病毒株Frankfurt 1(见Genbank登记号AY291315)的刺突蛋白的318-510区域不同。突变、病毒株和Genbank登记号显示于表21。为了研究是否03-014结合所有目前已知人SARS-CoV分离株的S蛋白，产生8个包含如表21所示的不同氨基酸取代的重组刺突片段。为此，根据生产商的指导，使用Stratagene的QuikChange II定点诱变试剂盒将上述取代引入pHAVT20/myc-His AS318-510载体。如果一个序列包含多个氨基酸取代，则针对每一个单独的取代重复诱变、序列分析和确认的过程。为了排除在感兴趣的基因之外将另外的突变引入质粒，将突变的(592bpEcoRI-XbaI)片段重克隆在EcoRI-XbaI切割的pHAVT20/myc-His A中。将所得到的质粒转染进293T细胞，并通过如实施例12中所描述的ELISA方法评估03-014的结合。另外，基本上如前面所描述的评估HRP缀合的单克隆抗His6抗体(Roche)和每一个突变体的结合。抗His6和03-014与得自Frankfurt 1病毒株的野生型S318-510片段的结合被设定为100％。单克隆抗His6抗体和03-014与突变的S318-510片段的结合被表示为与野生型S318-510片段相比的结合的百分比。

如图25所示，单克隆抗His6抗体和03-014能够以与野生型(未突变的)S318-510片段相似的程度结合所有变体S318-510片段，其中例外的是单克隆抗体03-014与变体F(N479S取代)的结合是与其他变体片段以及野生型S318-510片段的结合的大约50％。这提示残基N479参与了03-014的结合，或者通过作为03-014的结合位点的一部分直接参与，或者对于刺突蛋白中的03-014的结合位点的正确构象重要而间接参与。总之，03-014能够结合Frankfurt 1病毒株的S318-510区域，还可以结合包含突变的重组S318-510片段的S318-510区域，其中所述突变在表21中描述的人SARS-CoV分离株的S318-510区域中可以发现。这提示03-014可用于中和所有目前已知人SARS-CoV分离株。

实施例21

单克隆抗-SARS-CoV抗体保护范围的筛选测定

使用不同的SARS-CoV病毒株评估抗-SARS-CoV抗体的保护潜能和范围。测试前SARS-CoV病毒株HKU-36、HKU-39849、HKU-66和HKU-61567在FRhK-4细胞上传代2或3次(见表22)。病毒株HKU-61644在Vero细胞上传代并在传代1次和15次后测试。在FRhK-4细胞上如下进行SARS-CoV中和测定。在维持培养基(补充了1％胎牛血清的MM、MEM)中制备500μl 100μg/ml的抗体储液。由此储液制备2倍系列稀释液。在96孔板中加入220μl 100μg/ml的储液(双份(in duplo))并在9个后续孔的每一个中取出110μl在下一个孔中与110μl MM混和。弃去第10个孔中的110μl，得到含有110μl0.2-100μg/ml抗体的10个孔。110μl所述抗体稀释物与110μl浓度为2000TCID₅₀/ml的不同的SARS-CoV分离株混和，所述滴度根据Reedand Muench方法获得。在此阶段，在220μl体积中，在1000TCID₅₀/mlSARS-CoV存在的情况下，抗体浓度在0.1至50μg/ml范围内变化。含有所述抗体病毒混和物的96孔板在37℃预温育1-2小时。向第二块组织培养平板的孔中加入100μl的所述病毒-抗体混和物(一式四份)并在37℃温育，所述孔中含有在100μl MM中铺满的FRhK-4细胞。在此最终温育步骤中，在存在浓度在0.05至25μg/ml范围内变化的抗体的情况下，存在1000TCID₅₀的SARS-CoV。细胞在37℃培养并在72和96小时观察CPE的发展。CPE与正对照(接种了SARS-CoV的细胞)和负对照(仅接种了MM的细胞)进行对比。抗体中和滴度被确定，表示为100％保护所述四份细胞培养物的抗体浓度。单克隆抗-SARS-CoV抗体03-014在12.5μg/ml的浓度完全中和100TCID₅₀的所有被测SARS-CoV分离株(见表22)。这提示抗体03-014能够中和各种SARS-CoV分离株。

表1：单链(scFv)噬菌体抗体-与SARS-CoV制备物(Frankfurt 1病毒株)和与FBS的结合，通过ELISA测量

噬菌体抗体命名	SARS-Cov制备物(OD492nm)	FBS(OD492nm)
			SC03-001	0.979	0.142
SC03-002	0.841	0.091
			SC03-003	0.192	0.092
SC03-005	0.869	0.098
			SC03-006	1.056	0.086
SC03-007	0.876	0.096
			SC03-008	0.358	0.114
SC03-009	0.760	0.087
			SC03-010	0.327	0.082
SC03-012	0.495	0.100
			SC03-013	0.979	0.101
SC03-014	0.917	0.089
			SC03-015	0.796	0.077
抗甲状腺球蛋白(SC02-006)	0.108	0.090
			无噬菌体抗体	0.072	0.083

表2：另外被选择的单链(scFv)噬菌体抗体与SARS-CoV制备物(Frankfurt 1病毒株)和与FBS的结合，通过ELISA测量

噬菌体抗体命名	SARs-CoV制备物(OD492nm)	FBS(OD492nm)
			SC03-016	0.313	0.205
SC03-017	0.106	0.059
			SC03-018	1.523	0.072
抗-CD46(sc02-300)	0.171	0.070
			无噬菌体抗体	0.081	0.045

表3：能够结合SARS-CoV的单链(scFv)的数据

scFv命名	核苷酸序列SEQ ID NO	氨基酸序列SEQ ID NO	HCDR3	V_H-生殖系	V_L-生殖系
						SC03-001	46	47	HRFRHVFDY	V_H3 V_H3-38	V_kI DFK9(02/012)
SC03-002	48	49	YYSRSLKAFDY	V_H3 DP29(V_H3-72)	V_kI DPK9(02/012)
						SC03-003	50	51	RSYFRRFDY	V_H3 DP47(V_H3-23)	V_kI DPK9(02/012)
SC03-004	89	90	DGSRFPARFDY	V_H3 (V_H3-73)	V_kI DPK9(02/012)
						SC03-005	52	53	GGGRPYNPFDY	V_H3 V_H3-38	V_kI DPK9(02/012)
SC03-006	54	55	DGSPRTPSFDY	V_H3 DP49(V_H3-30)	V_kI DPK4(A20)
						SC03-007	56	57	GYWTSLTGFDY	V_H3 DP49(V_H3-30)	V_kI DPK9(02/012)
SC03-008	58	59	RVRPRRFDY	V_H3 DP47(V_H3-23)	V_kI DPK9(02/012)
						SC03-009	60	61	GLFMVTTYAFDY	V_H3 DP47(V_H3-23)	V_kI DPK9(02/012)
SC03-010	62	63	GGGLPYLSFDY	V_H3 V_H3-38	V_kI DPK9(02/012)
						SC03-012	64	65	MFRKSSFDS	V_H1 DP14(V_H1-18)	V_LIIIDPL16(2-13，31)
SC03-013	66	67	GLTPLYFDY	V_H3 DP29(V_H3-72)	V_kI DPK9(02/012)
						SC03-014	68	69	GISPFYFDY	V_H3 DP29(V_H3-72)	V_kI DPK9(02/012)
SC03-015	70	71	GLSLRP	V_H3 DP32(V_H3-20)	V_LIIIDPL16(2-13，31)
						SC03-016	91	92	YGSAYRPPFDY	V_H3 (V_H3-49)	V_kI DPK9(02/012)
SC03-017	93	94	3RSAGFFDY	V_H4 DP66(V_H4-61)	V_kIII(L6)
						SC03-018	95	96	FNPFTSFDY	V_H3 DP47(V_H3-23)	V_kI DPK9(02/012)

表4：二价scFv的SARS-CoV(病毒株Frankfurt 1和Frankfurt 2)中和活性测定的数据

二价scFv命名	OD 280(mg/ml)	针对Frankfurt 1病毒株的中和滴度	针对Frankfurt 2病毒株的中和滴度
				pyBi03-001C02	0.0238	＜20	＜20
pyBi03-002C02	0.0518	＜20	＜20
				pyBi03-003C02	0.0406	＜20	＜20
pyBi03-005C02	0.0658	＜20	＜20
				pyBi03-006C02	0.0343	＜20	＜20
pyBi03-007C02	0.0280	＜20	＜20
				pyBi03-008C02	0.0210	＜20	＜20
pyBi03-009C02	0.0434	＜20	＜20
				pyBi03-010C02	0.0567	＜20	＜20
pyBi03-012C02	0.0168	＜20	＜20
				pyBi03-013C02	0.1743	160	80
pyBi03-014C02	0.1561	80	80
				pyBi03-015C02	0.4816	＜20	＜20
pyBi02-148C02	0.0763	＜20	＜20
				pyBi02-006C02	0.0791	＜20	＜20
SARS患者的血清		320	160

表5：重组人抗SARS抗体与SARS感染的细胞的结合，通过间接免疫荧光染色测量

抗体	染色
		负对照	-
正对照	+
		03-014	+
03-018	+

-表示无SARS感染的细胞的染色

+表示有SARS感染的细胞的染色

表6：抗体03-018与SARS-CoV Urbani的N蛋白的线性和环形肽的结合

表7：人单克隆抗SARS-CoV抗体的SARS-CoV(得自患者5688的香港病毒株)中和活性测定的数据

-：No CPE

+：CPE≤50％

2+：CPE 50-90％

3+：CPE 100％

表8：人IgG重链可变区引物(有义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuVH1B/7A	5′-CAGRTGCAGCTGGTGCARTCTGG-3′	SEQ ID NO：132
HuVH1C	5′-SAGGTCCAGCTGGTRCAGTCTGG-3′	SEQ ID NO：133
			HuVH2B	5′-SAGGTGCAGCTGGTGGAGTCTGG-3′	SEQ ID NO：134
HuVH3B	5′-SAGGTGCAGCTGGTGGAGTCTGG-3′	SEQ ID NO：135
			HuVH3C	5′-GAGGTGCAGCTGGTGGAGWCYGG-3′	SEQ ID NO：136
HuVH4B	5′-CAGGTGCAGCTACAGCAGTGGGG-3′	SEQ ID NO：137
			HuVH4C	5′-CAGSTGCAGCTGCAGGAGTCSGG-3′	SEQ ID NO：138
HuVH5B	5′-GARGTGCAGCTGGTGCAGTCTGG-3′	SEQ ID NO：139
			HuVH6A	5′-CAGGTACAGCTGCAGCAGTCAGG-3′	SEQ ID NO：140

表9：人IgG重链J-区引物(反义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuJH1/2	5′-TGAGGAGACGGTGACCAGGGTGCC-3′	SEQ ID NO：141
HuJH3	5′-TGAAGAGACGGTGACCATTGTCCC-3′	SEQ ID NO：142
			HuJH4/5	5′-TGAGGAGACGGTGACCAGGGTTCC-3′	SEQ ID NO：143
HuJH6	5′-TGAGGAGACGGTGACCGTGGTCCC-3′	SEQ ID NO：144

表10：引入SfiI/NcoI限制位点而延伸的人IgG重链可变区引物(有义)和引入XhoI/BstEII限制位点而延伸的人IgG重链J-区引物(反义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuVH1B/7A-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCCAGRTGCAGCTGGTGCARTCTGG-3′	SEQ ID NO：145
HuVH1C-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCSAGGTCCAGCTGGTRCAGTCTGG-3′	SEQ ID NO：146
			HuVH2B-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCCAGRTCACCTTGAAGGAGTCTGG-3′	SEQ ID NO：147
HuVH3B-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCSAGGTGCAGCTGGTGGAGTCTGG-3′	SEQ ID NO：148
			HuVH3C-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCGAGGTGCAGCTGGTGGAGWCYGG-3′	SEQ ID NO：149
HuVH4B-NcoI	5′-GTCCTCGCAACTGCGGCC CAGCCGGCCATGGCCCAGGTGCAGCTACAGCAGTGGGG-3′	SEQ ID NO：150
			HuVH4C-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCCAGSTGCAGCTGCAGGAGTCSGG-3′	SEQ ID NO：151

HuVH5B-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCGARGTGCAGCTGGTGCAGTCTGG-3′	SEQ ID NO：152
			HuVH6A-NcoI	5′-GTCCTCGCAACTGCGGCCCAGCCGGCCATGGCCCAGGTACAGCTGCAGCAGTCAGG-3′	SEQ ID NO：153
HuJH1/2-XhoI	5′-GAGTCATTCTCGACTCGAGACGGTGACCAGGGTGCC-3′	SEQ ID NO：154
			HuJH3-XhoI	5′-GAGTCATTCTCGACTCGAGACGGTGACCATTGTCCC-3′	SEQ ID NO：155
HuJH4/5-XhoI	5′-GAGTCATTCTCGACTCGAGACGGTGACCAGGGTTCC-3′	SEQ ID NO：156
			HuJH6-XhoI	5′-GAGTCATTCTCGACTCGAGACGGTGACCGTGGTCCC-3′	SEQ ID NO：157

表11：人λ链可变区引物(有义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuVμ1A	5′-CAGTCTGTGCTGACTCAGCCACC-3′	SEQ ID NO：161
HuVμ1B	5′-CAGTCTGTGYTGACGCAGCCGCC-3′	SEQ ID NO：162
			HuVμ1C	5′-CAGTCTGTCGTGACGCAGCCGCC-3′	SEQ ID NO：163
HuVμ2	5′-CARTCTGCCCTGACTCAGCCT-3′	SEQ ID NO：164
			HuVμ3A	5′-TCCTATGWGCTGACTCAGCCACC-3′	SEQ ID NO：165
HuVμ3B	5′-TCTTCTGAGCTGACTCAGGACCC-3′	SEQ ID NO：166
			HuVμ4	5′-CACGTTATACTGACTCAACCGCC-3′	SEQ ID NO：167
HuVμ5	5′-CAGGCTGTGCTGACTCAGCCGTC-3′	SEQ ID NO：168
			HuVμ6	5′-AATTTTATGCTGACTCAGCCCCA-3′	SEQ ID NO：169
HuVμ7/8	5′-CAGRCTGTGGTGACYCAGGAGCC-3′	SEQ ID NO：170
			HuVμ9	5′-CWGCCTGTGCTGACTCAGCCMCC-3′	SEQ ID NO：171

表12：人κ链可变区引物(有义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuVμ1B	5′-GACATCCAGWTGACCCAGTCTCC-3′	SEQ ID NO：172
HuVμ2	5′-GATGTTGTGATGACTCAGTCTCC-3′	SEQ ID NO：173
			HuVμ3	5′-GAAATTG TGWTGACRCAGTCTCC-3′	SEQ ID NO：174
HuVμ4	5′-GATATTGTGATGACCCACACTCC-3′	SEQ ID NO：175
			HuVμ5	5′-GAAACGACACTCACGCAGTCTCC-3′	SEQ ID NO：176
HuVμ6	5′-GAAATTGTGCTGACTCAGTCTCC-3′	SEQ ID NO：l77

表13：人λ链J-区引物(反义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuJμ1	5′-ACCTAGGACGGTGACCTTGGTCCC-3′	SEQ ID NO：178
HuJμ2/3	5′-ACCTAGGACGGTCAGCTTGGTCCC-3′	SEQ ID NO：179
			HuJμ4/5	5′-ACYTAAAACGGTGAGCTGGGTCCC-3′	SEQ ID NO：180

表14：人λ链J-区引物(反义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuJμ1	5′-ACGTTTGATTTCCACCTTGGTCCC-3′	SEQ ID NO：181
HuJμ2	5′-ACGTTTGATCTCCAGCTTGGTCCC-3′	SEQ ID NO：182
			HuJμ3	5′-ACGTTTGATATCCACTTTGGTCCC-3′	SEQ ID NO：183
HuJμ4	5′-ACGTTTGATCTCCACCTTGGTCCC-3′	SEQ ID NO：184
			HuJμ5	5′-ACGTTTAATCTCCAGTCGTGTCCC-3′	SEQ ID NO：185

表15：引入SalI限制位点而延伸的人κ链可变区引物(有义)、引入NotI限制位点而延伸的人κ链J-区引物(反义)、引入SalI限制位点而延伸的人λ链可变区引物(有义)和引入NotI限制位点而延伸的人λ链J-区引物(反义)、引入NotI限制位点而延伸的IgG重链J-区引物(反义)

引物命名	引物核苷酸序列	SEQ ID NO
			HuVμ1B-SalI	5′-TGAGCACACAGGTCGACGGACATCCAGWTGACCCAGTCTCC-3′	SEQ ID NO：186
HuVμ2-SalI	5′-TGAGCACACAGGTCGACGGATGTTGTGATGACTCAGTCTCC-3′	SEQ ID NO：187
			HuVμ3B-SalI	5′-TGAGCACACAGGTCGACGGAAATTGTGWTGACRCAGTCTCC-3′	SEQ ID NO：188

HuVμ4B-SalI	5′-TGAGCACACAGGTCGACGGATATTGTGATGACCCACACTCC-3′	SEQ ID NO：189
			HuVμ5-SalI	5′-TGAGCACACAGGTCGACGGAAACGACACTCACGCAGTCTCC-3′	SEQ ID NO：190
HuVμ6-SalT	5′-TGAGCACACAGGTCGACGGAAATTGTGCTGACTCAGTCTCC-3′	SEQ ID NO：191
			HuJμ1-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACGTTTGATTTCCACCTTGGTCCC-3′	SEQ ID NO：192
HuJμ2-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACGTTTGATCTCCAGCTTGGTCCC-3′	SEQ ID NO：193
			HuJμ3-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACGTTTGATATCCACTTTGGTCCC-3′	SEQ ID NO：194
HuJμ4-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACGTTTGATCTCCACCTTGGTCCC-3′	SEQ ID NO：195
			HuJμ5-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACGTTTAATCTCCAGTCGTGTCCC-3′	SEQ ID NO：196
HuVμ1A-SalI	5′-TGAGCACACAGGTCGACGCAGTCTGTGCTGACTCAGCCACC-3′	SEQ ID NO：197
			HuVμ1B-SalI	5′-TGAGCACACAGGTCGACGCAGTCTGTGYTGACGCAGCCGCC-3′	SEQ ID NO：198
HuVμ1C-SalI	5′-TGAGCACACAGGTCGACG	SEQ ID NO：199

	CAGTCTGTCGTGACGCAGCCGCC-3′
			HuVμ2-SalI	5′-TGAGCACACAGGTCGACGCARTCTGCCCTGACTCAGCCT-3′	SEQ ID NO：200
HuVμ3A-SalI	5′-TGAGCACACAGGTCGACGTCCTATGWGCTGACTCAGCCACC-3′	SEQ ID NO：201
			HuVμ3B-SalI	5′-TGAGCACACAGGTCGACGTCTTCTGACCTGACTCAGGACCC-3′	SEQ ID NO：202
HuVμ4-SalI	5′-TGAGCACACAGGTCGACGCACGTTATACTGACTCAACCGCC-3′	SEQ ID NO：203
			HuVμ5-SalI	5′-TGAGCACACAGGTCGACGCAGGCTGTGCTGACTCAGCCGTC-3′	SEQ ID NO：204
HuVμ6-SalI	5′-TGAGCACACAGGTCGACGAATTTTATGCTGACTCAGCCCCA-3′	SEQ ID NO：205
			HuVμ7/8-SalI	5′-TGAGCACACAGGTCGACGCAGRCTGTGGTGACYCAGGAGCC-3′	SEQ ID NO：206
HuVμ9-SalI	5′-TGAGCACACAGGTCGACGCWGCCTGTGCTGACTCAGCCMCC-3′	SEQ ID NO：207
			HuJμ1-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACCTAGGACGGTGACCTTGGTCCC-3′	SEQ ID NO：208
HuJμ2/3-NotI	5′-GAGTCATTCTCGACTTGCGGCCG CACCTAGGACGGTCAG	SEQ ID NO：209

	CTTGGTCCC-3′
			HuJμ4/5-NotI	5′-GAGTCATTCTCGACTTGCGGCCGCACYTAAAACGGTGAGCTGGGTCCC-3′	SEQ ID NO：210

表16：不同轻链产物在10个组中的分布

表17：选择自原始或免疫噬菌体展示文库的单链(scFv)噬菌体抗体与SARS-CoV制备物(Frankfurt 1病毒株)的结合

噬菌体抗体命名	SARS-CoV制备物(OD492nm)	ELISA平板编号
			sc03-019	0.333	1
sc03-020	0.671	2
			sc03-021	0.215	2
sc03-022	1.18	2
			sc03-023	1.311	2
sc03-024	0.235	2
			sc03-025	1.636	2
sc03-026	1.071	2
			sc03-027	1.163	2
sc03-029	0.629	4
			sc03-030	1.15	3
sc03-031	0.635	4
			sc03-032	1.219	3
sc03-033	0.288	4
			sc03-034	0.802	3
sc03-035	0.596	3
			sc03-036	0.24	3
sc03-037	0.287	4
			sc03-038	0.314	4
sc03-039	0.851	3
			sc03-040	0.616	4
sc03-041	0.861	4
			sc03-042	0.645	4
sc03-043	1.271	3
			Sc03-044	0.518	4
sc03-045	0.577	4
			sc03-046	1.897	3
sc03-047	0.866	4
			sc03-048	0.397	3
sc03-049	1.006	3
			sc03-050	1.184	3
sc03-051	0.602	3
			sc03-052	0.355	4
sc03-053	0.218	3
			sc03-054	0.428	4
sc03-055	0.608	3
			sc03-056	0.924	3
sc03-057	1.19	3
			sc03-058	0.355	4
sc03-059	0.293	1

平板1：用于无单链噬菌体抗体的SARS-CoV制备物(OD492nm)是0.060。

平板1：用于无单链噬菌体抗体的SARS-CoV制备物(OD492nm)是0.211。

平板1：用于无单链噬菌体抗体的SARS-CoV制备物(OD492nm)是0.054。

平板1：用于无单链噬菌体抗体的SARS-CoV制备物(OD492nm)是0.051。

表18：能够结合SARS-CoV并且得自原始或免疫噬菌体展示文库的单链Fv的数据

scFv命名	核苷酸序列的SEQ ID NO	氨基酸序列的SEQ ID NO	HCDR3	V_H-生殖系	V_L-生殖系
						sc03-019	211	212	FPGGTRSRGYMDV(SEQ ID NO：291)	V_H3-30.3(DP-46)	V_KIII(L6)
sc03-020	213	214	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
						sc03-021	215	216	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3DPK24)
sc03-022	217	218	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
						sc03-023	219	220	RVEVVEYQLLRPRYKSWFDP(SEQ ID NO：293)	V_H4-34(DP-63)	V_LII (2a2-V1-04)
Sc03-024	221	222	KSAGSNAFDI(SEQ ID NO：294)	V_H7-04.1(DP-21)	V_L1(1b-V1-19)
						sc03-025	223	224	TTNRAFDI(SEQ ID NO：295)	V_H3-64	VKIV (B3-DPK24)
sc03-026	225	226	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-027	227	228	TTNRAFDI	V_H3-64	V_KIV(B3-

			(SEQ ID NO：295)		DPK24)
						sc03-029	229	230	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-030	231	232	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-031	233	234	ESGGGYDNEFDY(SEQ ID NO：296)	V_H1-69(DP-10)	V_L1(1c-V1-16)
sc03-032	235	236	DGWDLTGSFLGYGMDV(SEQ ID NO：297)	V_H1-c(DP-88)	V_L1(1c-V1-16)
						sc03-033	237	238	GSGISTPEDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
sc03-034	239	240	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
						sc03-035	241	242	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
sc03-036	243	244	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
						sc03-037	245	246	DAHRGFGMDV(SEQ ID NO：298)	V_H3-53(DP-42)	V_L3(31-V2-13)
sc03-038	247	248	DAHRGFGMDV(SEQ ID NO：298)	V_H3-53(DP-42)	V_L3(31-V2-13)
						sc03-039	249	250	GSKWNDVGGGDY(SEQ ID NO：299)	V_H3-23(DP-47)	V_L6(6A-V1-22)
sc03-040	251	252	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-041	253	254	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-042	255	256	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-043	257	258	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-044	259	260	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-045	261	262	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-046	263	264	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)

sc03-047	265	266	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-048	267	268	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-049	269	270	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
						sc03-050	271	272	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-051	273	274	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
						sc03-052	275	276	GSGTSTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
sc03-053	277	278	GTGYLRSYHGMDV(SEQ ID NO：300)	V_H1-03(DP-25)	V_KII(A19/A03-DPK15)
						sc03-054	279	280	TTNRAFDI(SEO ID NO：295)	V_H3-64	V_KIV(B3-DPK24)
sc03-055	281	282	RVEVVEYQLLRPRYKSWFDP(SEQ ID NO：293)	V_H4-34(DP-63)	V_L1(1b-V1-19)
						sc03-056	283	284	GSGISTPMDV(SEQ ID NO：292)	V_H5-51(DP-73)	V_KIV(B3-DPK24)
sc03-057	285	286	PDLVVAGESPPHYTMDV(SEQ ID NO：301)	V_H1-69(DP-10)	V_KIL11-DPK3
						sc03-058	287	288	TTNRAFDI(SEQ ID NO：295)	V_H3-64	V_KVIA14-DPK25
sc03-059	289	290	FPGGTRSRGYMDV(SEQ ID NO：291)	V_H1-46(DP-7)	V_KIII(L6)

表19：体内雪貂实验的图解

a：预混和激发剂和最适浓度的抗体

b：基于处死分开

c：S表示拭子；LT表示处死后的肺部组织

表20：组织和体液取样的图解

^*B，血液；S，咽部拭子；LT；用于病毒滴定和病理学的待处理肺部组织

表21：具有与SARS-CoV Frankfurt 1病毒株的S蛋白的318-510区域不同的S蛋白的318-510区域的SARS-CoV病毒株的列表

突变	病毒株	Genbank
			K344R	GZ02	AY390556
	GZ60	AY304491
				JMD	AY394988
	ZS-B	AY394996
				GZ43	AY304490
	HGZ8L1-A	AY394981
				ZS-A	AY394997
	ZS-C	AY395003
			K344RF501Y	GD01	AY278489
K344RF360SL472PD480GT487S	GD03T0013	AY525636
			S353F	Sin3408Sin3765VSin845Sin847Sin849Sin852Sin3725VSin842Sin846Sin848Sin850	AY559083AY559084AY559093AY559095AY559086AY559082AY559087AY559081AY559094AY559085AY559096
R426G	ShanghaiLY	AY322205S3

N437D
			Y436H	GZ-C	AY394979
Y442S	Sino1-11	AY485277
			N479S	BJ302cl.2BJ302cl.4BJ302cl.6BJ302cl.3BJ302cl.5BJ302cl.8	AY429073AY429075AY429077AY429074AY429076AY429079

与Frankfurt 1的S蛋白相对比的氨基酸取代示于左栏。病毒株和GenBank登记号示于第二栏和第三栏。

表22：针对100TCID₅₀的不同SARS-CoV分离株，显示完全保护的单克隆抗-SARS-CoV抗体03-014的浓度，示于体外中和测定中

SARS-CoV病毒株^＊	引起针对100TCID50的100％保护的03-014的浓度(μg/ml)
		36(3)	12.5
39849(3)	12.5
		66(2)	12.5
61567(2)	12.5
		61644(1)	12.5
61644(15)	12.5

^*括号中示出了所述各自病毒株的传代数目

参考文献

Boel E，Verlaan S，Poppelier MJ，Westerdaal NA，Van Strijp JA andLogtenberg T(2000)，Functional human monoclonal antibodies of allisotypes constructed from phage display library-derived single-chain Fvantibody fragments.J.Immunol.Methods 239：153-166.

Burton DR and Barbas CF(1994)，Human antibodies fromcombinatorial libraries.Adv.Immunol.57：191-280.

De KruifJ，Terstappen L，Boel E and Logtenberg T(1995a)，Rapidselection of cell subpopulation-specific human monoclonal antibodiesfrom a synthetic phage antibody library.Proc.Natl.Acad.Sci.USA 92：3938.

De Kruif J，Boel E and Logtenberg T(1995b)，Selection andapplication of human single-chain Fv antibody fragments from asemi-synthetic phage antibody display library with designed CDR3regions.J.Mol.Biol.248：97-105.

Emini EA，Nara PL，Schleif WA，Lewis JA，Davide JP，Lee DR，Kessler J，Conley S，MatSushita S，Putney SDJ，Gerety RJ and EichbergJW，Antibody-mediated in vitro neutralization of humanimmunodeficiency virus type 1 abolishes infectivity for chimpanzees.J.Virol.64：3674-3678.

Fouchier RA，Kuiken T，Schutten M，van Amerongen G，vanDoornum GJ，van den Hoogen BG，Peiris M，Lim W，Stohr K，OsterhausAD(2003)，Koch′s postulates fulfliled for SARS virus.Nature 243：240.

Havenga MJ，Lemckert AA，Grimbergen JM，Vogels R，HuismanLG，Valerio D，Bout A and Quax PH(2001)，Improved adenovirusvectors for infection of cardiovascular tissues.J.Virol.75：3335-3342.

Holmes KV.2003.SARS coronavirus：a new challenge forprevention and therapy.J.Clin.Invest.Ill，1605-1609.

Huls G，Heijnen IJ，Cuomo E，vander Linden J，Boel E，van deWinkel J and Logtenberg T(1999)，Antitumor immune effectormechanisms recruited by phage display-derived fully human IgG1 andIgA1 monoclonal antibodies.Cancer Res.59：5778-5784.

Ksiazek TG，Erdman D，Goldsmith CS，Zaki SR，Peret T，Emery S，Tong S，Urbani C，Comer JA，Lim W，Rollin PE，Dowell SF，Ling AE，Humphrey CD，Shieh WJ，Guarner J，Paddock CD，Rota P，Fields B，DeRisi J，Yang JY，Cox N，Hughes JM，LeDuc JW，Bellini WJ，AndersonLJ(2003)，A novel coronavirus associated with severe acute respiratorysyndrome.N.Eng.J.Med.348：1953-1966.

Kuiken T，Fouchier RA，Schutten M，Rimmelzwaan GF，vanAmerongen G，van Riel D，Laman JD，de Jong T，van Doornum G，LimW，Ling AE，Chan PK，Tam JS，Zambon MC，Gopal R，Drosten C，vander Werf S，Escriou N，Manuguerra JC，Stohr K，Peiris JS and OsterhausAD(2003)，Newly discovered coronavirus as the primary cause of severeacute respiratory syndrome.Lancet 362：263-270.

Li W，Moore MJ，Vasilieva N，Sui J，Wong SK，Berne MA，Somasundaran M，Sullivan JL，Luzuriaga K，Greenough TC，Choe H andFarzanM(2003)，Angiotensin-converting enzyme 2is a functionalreceptor for the SARS coronavirus.Nature 2003426：450-454.

Marra MA，Jones SJ，Astell CR，Holt RA，Brooks-Wilson A，Butterfield YS，Khattra J，Asano JK，Barber SA，Chan SY，Cloutier A，Coughlin SM，Freeman D，Girn N，Griffith OL，Leach SR，Mayo M，McDonald H，Montgomery SB，Pandoh PK，Petrescu AS，Robertson AG，Schein JE，Siddiqui A，Smailus DE，Stott JM，Yang GS，Plummer F，Andonov A，Artsob H，Bastien N，Bernard K，Booth TF，Bowness D，Czub M，Drebot M，Fernando L，Flick R，Garbutt M，Gray M，Grolla A，Jones S，Feldmann H，Meyers A，Kabani A，Li Y，Normand S，Stroher U，Tipples GA，Tyler S，Vogrig R，Ward D，Watson B，Brunham RC，Krajden M，Petric M，Skowronski DM，Upton C，Roper RL 2003.Thegenome sequence of the SARS-associated coronavirus.Science300，1399-1404.

Rickerts V，Wolf T，Rottmann C，Preiser W，Drosten C，Jakobi V，Leong HN，Brodt HR 2003.Klinik und Behandlung des schweren akutenrespiratorischen Syndroms.Dtsch.Med.Wochenschrift 128：1109-1114.

Rota PA，Oberste MS，Monroe SS，Nix WA，Campagnoli R，Icenogle JP，Penaranda S，Bankamp B，Maher K，Chen MH，Tong S，Tamin A，Lowe L，Frace M，DeRisi JL，Chen Q，Wang D，Erdman DD，Peret TC，Burns C，Ksiazek TG，Rollin PE，Sanchez A，Liffick S，Holloway B，Limor J，McCaustland K，Olsen-Rasmussen M，Fouchier R，Gunther S，Osterhaus AD，Drosten C，Pallansch MA，Anderson LJ，Bellini WJ.2003.Characterization of a novel coronavirus associated withsevere acute respiratory syndrome.Science 300，1394-1399.

Slootstra JW，Puijk WC，Ligtvoet GJ，Langeveld JP，Meloen RH1996.Structural aspects of antibody-antigen interaction revealed throughsmall random peptide libraries.Mol.Divers.1，87-96.

Ter Meulen J，Bakker ABH，van den Brink EN，Weverling GJ，Martina BEE，Haagmans BL，Kuiken T，de Kruif J，Preiser W，Spaan W，Gelderblom HR，Goudsmit J，Osterhaus ADME 2004.Humanmonoclonal antibody as prophylaxis for SARS coronavirus infection inferrets.The Lancet 363，2139-2141.

序列表

<110>克鲁塞尔荷兰公司

<120>针对SARS冠状病毒的结合分子及其应用

<160>478

<170>PatentIn version 3.1

<210>1

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-001

<400>1

His Arg Phe Arg His Val Phe Asp Tyr

1 5

<210>2

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-002

<400>2

Tyr Tyr Ser Arg Ser Leu Lys Ala Phe Asp Tyr

1 5 10

<210>3

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-003

<400>3

Arg Ser Tyr Phe Arg Arg Phe Asp Tyr

1 5

<210>4

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-005

<400>4

Gly Gly Gly Arg Pro Tyr Asn Pro Phe Asp Tyr

1 5 10

<210>5

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-006

<400>5

Asp Gly Ser Pro Arg Thr Pro Ser Phe Asp Tyr

1 5 10

<210>6

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-007

<400>6

Gly Tyr Trp Thr Ser Leu Thr Gly Phe Asp Tyr

1 5 10

<210>7

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-008

<400>7

Arg Val Arg Pro Arg Arg Phe Asp Tyr

1 5

<210>8

<211>12

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-009

<400>8

Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp Tyr

1 5 10

<210>9

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-010

<400>9

Gly Gly Gly Leu Pro Tyr Leu Ser Phe Asp Tyr

1 5 10

<210>10

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-012

<400>10

Met Phe Arg Lys Ser Ser Phe Asp Ser

1 5

<210>11

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-013

<400>11

Gly Leu Thr Pro Leu Tyr Phe Asp Tyr

1 5

<210>12

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-014

<400>12

Gly Ile Ser Pro Phe Tyr Phe Asp Tyr

1 5

<210>13

<211>6

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-015

<400>13

Gly Leu Ser Leu Arg Pro

1 5

<210>14

<211>354

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-001

<220>

<221>CDS

<222>(1)..(354)

<223>

<400>14

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta aag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

ggc tac tcg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc agg 192

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

50 55 60

aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

ctt cag atg aac aac ctg aga gct gag gac acg gct gtg tat tac tgt 288

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

85 90 95

gca aga cac cgg ttc cgg cac gtc ttc gat tac tgg ggc cag ggc acc 336

Ala Arg His Arg Phe Arg His Val Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

ctg gtg acc gtg ctc gag 354

Leu Val Thr Val Leu Glu

115

<210>15

<211>118

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-001

<400>15

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

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 Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg His Arg Phe Arg His Val Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Leu Glu

115

<210>16

<211>372

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-002

<220>

<221>CDS

<222>(1)..(372)

<223>

<400>16

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ctg gtc aag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

ggc tac agc atg agc tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac 192

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

50 55 60

gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag 240

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

65 70 75 80

aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc 288

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

gtg tat tac tgt gct aga tac tac tcc cgc tcc ctc aag gcc ttc gat 336

Val Tyr Tyr Cys Ala Arg Tyr Tyr Ser Arg Ser Leu Lys Ala Phe Asp

100 105 110

tac tgg ggc cag ggc acc ctg gtg acc gtg ctc gag 372

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>17

<211>124

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-002

<400>17

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

Val Tyr Tyr Cys Ala Arg Tyr Tyr Ser Arg Ser Leu Lys Ala Phe Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>18

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-003

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>18

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct 48

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

1 5 10 15

gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

agc tac ccg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca gac 192

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gcc aga cgc agc tac ttc cgc cgc ttc gat tac tgg ggc cag 336

Tyr Cys Ala Arg Arg Ser Tyr Phe Arg Arg Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtg ctc gag 360

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>19

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-003

<400>19

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser 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 Ala Arg Arg Ser Tyr Phe Arg Arg Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>20

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC93-005

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>20

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg atc cag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

ggc tac act atg agc tgg gtc cgc cag gcg ccc ggg cag ggg ctg gag 144

Gly Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc agg 192

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

50 55 60

aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Ash Thr Leu Tyr

65 70 75 80

ctt caa atg aac aac ctg aga gct gag gac acg gcc gtg tat tac tgt 288

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

85 90 95

gca aaa ggc ggc ggc cgc ccg tac aac ccc ttc gat tac tgg ggc cag 336

Ala Lys Gly Gly Gly Arg Pro Tyr Asn Pro Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtg ctc gag 360

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>21

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-005

<400>21

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

1 5 10 15

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

20 25 30

Gly Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

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 Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Gly Gly Gly Arg Pro Tyr Asn Pro Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>22

<211>366

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-006

<220>

<221>CDS

<222>(1)..(366)

<223>

<400>22

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

ggc tac cct atg cac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtg gca gtt ata tca tat gac gga agt aat aaa tac tat gca gac 192

Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gct gag gac aca gct gtg tat 288

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

85 90 95

tac tgt gct aaa gac ggc agc ccc cgc acc ccc agc ttc gat tac tgg 336

Tyr Cys Ala Lys Asp Gly Ser Pro Arg Thr Pro Ser Phe Asp Tyr Trp

100 105 110

ggc cag ggc acc ctg gtg acc gtg ctc gag 366

Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>23

<211>122

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-006

<400>23

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys 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 Ala Lys Asp Gly Ser Pro Arg Thr Pro Ser Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>24

<211>366

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heaVy chain of SC03-007

<220>

<221>CDS

<222>(1)..(366)

<223>

<400>24

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct 48

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

1 5 10 15

agg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

gac tac cgg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

agg gtg gca gtt ata tca tat gat gga agc aat aaa tac tac gca gac 192

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

50 55 60

tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gct gag gac aca gcc gtg tat 288

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

85 90 95

tac tgt gca aga ggc tac tgg acg tcg ctc acg ggc ttc gat tac tgg 336

Tyr Cys Ala Arg Gly Tyr Trp Thr Ser Leu Thr Gly Phe Asp Tyr Trp

100 105 110

ggc cag ggc acc ctg gtg acc gtg ctc gag 366

Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>25

<211>122

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-007

<400>25

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

1 5 10 15

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

20 25 30

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

35 40 45

Arg Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys 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 Ala Arg Gly Tyr Trp Thr Ser Leu Thr Gly Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>26

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-008

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>26

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag cct 48

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

1 5 10 15

ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc 96

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

20 25 30

agc tac ccg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca gac 192

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gcc gag gac aca gcc gtg tat 288

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

85 90 95

tac tgt gca aga cgc gtc cgc ccc cgc cgc ttc gat tat tgg ggc cag 336

Tyr Cys Ala Arg Arg Val Arg Pro Arg Arg Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtg ctc gag 360

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>27

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-008

<400>27

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser 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 Ala Arg Arg Val Arg Pro Arg Arg Phe Asp Tyr Trp Gly Gln

100 105 110

G1y Thr Leu Val Thr Val Leu Glu

115 120

<210>28

<211>369

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-009

<220>

<221>CDS

<222>(1)..(369)

<223>

<400>28

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag cct 48

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

1 5 10 15

ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc 96

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

20 25 30

gac tac ccc atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca tcc att agt ggt agt ggt ggt agc aca tac tac gca gac 192

Trp Val Ser Ser Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gcc gag gac aca gcc gtg tat 288

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

85 90 95

tac tgt gca aaa ggc ctc ttc atg gtc acc acg tac gcg ttc gat tac 336

Tyr Cys Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp Tyr

100 105 110

tgg ggc cag ggc acc ctg gtg acc gtg ctc gag 369

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>29

<211>123

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-009

<400>29

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ser Ile Ser Gly Ser Gly Gly Ser 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 Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>30

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-010

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>30

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag cct 48

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

1 5 10 15

ggg agg tcc ctg aga ctc tcc tgt gca acc tct gga ttc acc ttc agc 96

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

20 25 30

ggc tac acg atg cac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc agg 192

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

50 55 60

aag ggc aga ttc acc atc tcc aga gac aac tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

ctt caa atg aac aac ctg aga gct gag gac aca gct gtg tat tac tgt 288

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

85 90 95

gca aaa ggc ggc ggc ctc ccc tac ttg agc ttc gat tac tgg ggc cag 336

Ala Lys Gly Gly Gly Leu Pro Tyr Leu Ser Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtg ctc gag 360

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>31

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-010

<400>31

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Arg

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 Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Gly Gly Gly Leu Pro Tyr Leu Ser Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>32

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-012

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>32

atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag cct 48

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

1 5 10 15

ggg gcc tca gtg aag gtc tcc tgc aag gct tct ggt tac acc ttt acc 96

Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr

20 25 30

agc tat ggt atc agc tgg gtg cga cag gcc cct gga caa ggg ctt gag 144

Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg atg gga tgg atc agc gct tac aat ggt aac aca aac tat gca cag 192

Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln

50 55 60

aag ctc cag ggc aga gtc acc atg acc aca gac aca tcc acg agc aca 240

Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr

65 70 75 80

gcc tac atg gag ctg agc agc ctg aga tct gac gac acg gcc gtg tat 288

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

85 90 95

tac tgt gca agg atg ttt agg aag agt tcc ttt gac tcc tgg ggc caa 336

Tyr Cys Ala Arg Met Phe Arg Lys Ser Ser Phe Asp Ser Trp Gly Gln

100 105 110

ggt acc ctg gtc acc gtc tcg aga 360

Gly Thr Leu Val Thr Val Ser Arg

115 120

<210>33

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-012

<400>33

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

1 5 10 15

Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr

20 25 30

Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln

50 55 60

Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg Met Phe Arg Lys Ser Ser Phe Asp Ser Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Arg

115 120

<210>34

<211>366

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-013

<220>

<221>CDS

<222>(1)..(366)

<223>

<400>34

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct 48

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

1 5 10 15

gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

gac cac tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

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

35 40 45

tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac 192

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

50 55 60

gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag 240

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

65 70 75 80

aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc 288

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

gtg tat tac tgt gca aag ggg ttg act cct ttg tac ttt gac tac tgg 336

Val Tyr Tyr Cys Ala Lys Gly Leu Thr Pro Leu Tyr Phe Asp Tyr Trp

100 105 110

ggc caa ggt acc ctg gtc acc gtc tcg agt 366

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>35

<211>122

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-013

<400>35

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

Val Tyr Tyr Cys Ala Lys Gly Leu Thr Pro Leu Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>36

<211>366

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-014

<220>

<221>CDS

<222>(1)..(366)

<223>

<400>36

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct 48

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

1 5 10 15

gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

gac cac tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

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

35 40 45

tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac 192

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

50 55 60

gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag 240

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

65 70 75 80

aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc 288

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

gtg tat tac tgt gca agg ggg att tcg ccg ttt tac ttt gac tac tgg 336

Val Tyr Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp Tyr Trp

100 105 110

ggc caa ggt acc ctg gtc acc gtc tcg agt 366

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>37

<211>122

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-014

<400>37

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

Val Tyr Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>38

<211>351

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-015

<220>

<221>CDS

<222>(1)..(351)

<223>

<400>38

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggt gtg gta cgg cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt gat 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp

20 25 30

gat tat ggc atg agc tgg gtc cgc caa gct cca ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tct ggt att aat tgg aat ggt ggt agc aca ggt tat gca gac 192

Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala Asp

50 55 60

tct gtg aag ggc cga ttc acc atc tcc aga gac aac gcc aag aac tcc 240

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

65 70 75 80

ctg tat ctg caa atg aac agt ctg aga gcc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gca aga ggt ttg tct ctt cgt cct tgg ggc caa ggt acc ctg 336

Tyr Cys Ala Arg Gly Leu Ser Leu Arg Pro Trp Gly Gln Gly Thr Leu

100 105 110

gtc acc gtc tcg aga 351

Val Thr Val Ser Arg

115

<210>39

<211>117

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-015

<400>39

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

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp

20 25 30

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

35 40 45

Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala Asp

50 55 60

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

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

100 105 110

Val Thr Val Ser Arg

115

<210>40

<211>318

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-001，SC03-002，SC03-003，SC03-004，S

C03-005，SC03-007，SC03-008，SC03-009，SC03-010，SC03-013，SC03-0

14，SC03-016 and SC03-018

<220>

<221>CDS

<222>(1)..(318)

<223>

<400>40

gag ctc acc cag tct cca tcc tcc ctg tct gca tct gta gga gac aga 48

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

1 5 10 15

gtc acc atc act tgc cgg gca agt cag agc att agc agc tac tta aat 96

Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

20 25 30

tgg tat cag cag aaa cca ggg aaa gcc cct aag ctc ctg atc tat gct 144

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

35 40 45

gca tcc agt ttg caa agt ggg gtc cca tca agg ttc agt ggc agt gga 192

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

50 55 60

tct ggg aca gat ttc act ctc acc atc agc agt ctg caa cct gaa gat 240

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

65 70 75 80

ttt gca act tac tac tgt caa cag agt tac agt acc cct cca acg ttc 288

Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe

85 90 95

ggc caa ggg acc aag gtg gag atc aaa cgt 318

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg

100 105

<210>41

<211>106

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-001，SC03-002，SC03-003，SC03-004，S

C03-005，SC03-007，SC03-008，SC03-009，SC03-010，SC03-013，SC03-0

14，SC03-016and SC03-018

<400>41

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

1 5 10 15

Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

20 25 30

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

35 40 45

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

50 55 60

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

65 70 75 80

Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe

85 90 95

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg

100 105

<210>42

<211>324

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-006

<220>

<221>CDS

<222>(1)..(324)

<223>

<400>42

gac atc cag atg act cag tct cca cac tct ctg tct gca tct gta gga 48

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

1 5 10 15

gac aga gtc acc atc act tgc cgg gcg agt cag ggc att agc aat tat 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr

20 25 30

tta gcc tgg tat cag cag aaa cca ggg aaa gtt cct aag ctc ctg atc 144

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

35 40 45

tat gct gca tcc act ttg caa tca ggg gtc cca tct cgg ttc agt ggc 192

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

50 55 60

agt gga tct ggg aca gat ttc act ctc acc atc agc agc ctg cag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

gaa gat gtt ggg gtt tat tac tgc cag cag agg ttc cgc acg ccg gtc 288

Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val

85 90 95

acc ttc ggc cag ggc acc aaa ctg gaa atc aaa cgc 324

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg

100 105

<210>43

<211>108

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-006

<400>43

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr

20 25 30

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

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg

100 105

<210>44

<211>324

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-012 and SC03-015

<220>

<221>CDS

<222>(1)..(324)

<223>

<400>44

tct gag ctg act cag gac cct gct gtg tct gtg gcc ttg gga cag aca 48

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

1 5 10 15

gtc agg atc aca tgc caa gga gac agc ctc aga agc tat tat gca agc 96

Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

20 25 30

tgg tac cag cag aag cca gga cag gcc cct gta ctt gtc atc tat ggt 144

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

35 40 45

aaa aac aac cgg ccc tca ggg atc cca gac cga ttc tct ggc tcc agc 192

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

50 55 60

tca gga aac aca gct tcc ttg acc atc act ggg gct cag gcg gaa gat 240

Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp

65 70 75 80

gag gct gac tat tac tgt aac tcc cgg gac agc agt ggt aac cat gtg 288

Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His Val

85 90 95

gta ttc ggc gga ggg acc aag ctg acc gtc cta ggt 324

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

100 105

<210>45

<211>108

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-012 and SC03-015

<400>45

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

1 5 10 15

Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

20 25 30

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

35 40 45

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

50 55 60

Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp

65 70 75 80

Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His Val

85 90 95

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

100 105

<210>46

<211>729

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-001

<220>

<221>CDS

<222>(1)..(729)

<223>

<400>46

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta aag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc ggc tac tcg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Gly Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc 192

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

agg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg ctg 240

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

65 70 75 80

tat ctt cag atg aac aac ctg aga gct gag gac acg gct gtg tat tac 288

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

85 90 95

tgt gca aga cac cgg ttc cgg cac gtc ttc gat tac tgg ggc cag ggc 336

Cys Ala Arg His Arg Phe Arg His Val Phe Asp Tyr Trp Gly Gln Gly

100 105 110

acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc ggc gga acc ggg 384

Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser Gly Gly Thr Gly

115 120 125

tct ggg act ggt acg agc gag ctc acc cag tct cca tcc tcc ctg tct 432

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

130 135 140

gca tct gta gga gac aga gtc acc atc act tgc cgg gca agt cag agc 480

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

145 150 155 160

att agc agc tac tta aat tgg tat cag cag aaa cca ggg aaa gcc cct 528

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

165 170 175

aag ctc ctg atc tat gct gca tcc agt ttg caa agt ggg gtc cca tca 576

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

180 185 190

agg ttc agt ggc agt gga tct ggg aca gat ttc act ctc acc atc agc 624

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

195 200 205

agt ctg caa cct gaa gat ttt gca act tac tac tgt caa cag agt tac 672

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

210 215 220

agt acc cct cca acg ttc ggc caa ggg acc aag gtg gag atc aaa cgt 720

Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg

225 230 235 240

gcg gcc gca 729

Ala Ala Ala

<210>47

<211>243

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-001

<400>47

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Gly Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

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

65 70 75 80

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

85 90 95

Cys Ala Arg His Arg Phe Arg His Val Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser Gly Gly Thr Gly

115 120 125

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

130 135 140

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

145 150 155 160

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

165 170 175

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

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

210 215 220

Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg

225 230 235 240

Ala Ala Ala

<210>48

<211>747

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-002

<220>

<221>CDS

<222>(1)..(747)

<223>

<400>48

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ctg gtc aag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc ggc tac agc atg agc tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

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

35 40 45

gag tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa 192

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

50 55 60

tac gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca 240

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

aag aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg 288

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

gcc gtg tat tac tgt gct aga tac tac tcc cgc tcc ctc aag gcc ttc 336

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

100 105 110

gat tac tgg ggc cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga 384

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly

115 120 125

ggt tcc ggc gga acc ggg tct ggg act ggt acg agc gag ctc acc cag 432

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln

130 135 140

tct cca tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act 480

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

145 150 155 160

tgc cgg gca agt cag agc att agc agc tac tta aat tgg tat cag cag 528

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

aaa cca ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg 576

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

caa agt ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat 624

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

ttc act ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac 672

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

tac tgt caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc 720

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

aag gtg gag atc aaa cgt gcg gcc gca 747

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>49

<211>249

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-002

<400>49

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

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

35 40 45

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

50 55 60

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

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

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly

115 120 125

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln

130 135 140

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

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>50

<211>735

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-003

<220>

<221>CDS

<222>(1)..(735)

<223>

<400>50

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc agc tac ccg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Ser Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca 192

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gtg 288

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

85 90 95

tat tac tgt gcc aga cgc agc tac ttc cgc cgc ttc gat tac tgg ggc 336

Tyr Tyr Cys Ala Arg Arg Ser Tyr Phe Arg Arg Phe Asp Tyr Trp Gly

100 105 110

cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc ggc gga 384

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

115 120 125

acc ggg tct ggg act ggt acg agc gag ctc acc cag tct cca tcc tcc 432

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

130 135 140

ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg gca agt 480

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

cag agc att agc agc tac tta aat tgg tat cag cag aaa cca ggg aaa 528

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt ggg gtc 576

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

180 185 190

cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act ctc acc 624

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt caa cag 672

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg gag atc 720

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

aaa cgt gcg gcc gca 735

Lys Arg Ala Ala Ala

245

<210>51

<211>245

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-003

<400>51

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Arg Ser Tyr Phe Arg Arg Phe Asp Tyr Trp Gly

100 105 110

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

115 120 125

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

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

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

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys Arg Ala Ala Ala

245

<210>52

<211>735

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-005

<220>

<221>CDS

<222>(1)..(735)

<223>

<400>52

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg atc cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc ggc tac act atg agc tgg gtc cgc cag gcg ccc ggg cag ggg ctg 144

Ser Gly Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc 192

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

agg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg ctg 240

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

65 70 75 80

tat ctt caa atg aac aac ctg aga gct gag gac acg gcc gtg tat tac 288

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

85 90 95

tgt gca aaa ggc ggc ggc cgc ccg tac aac ccc ttc gat tac tgg ggc 336

Cys Ala Lys Gly Gly Gly Arg Pro Tyr Asn Pro Phe Asp Tyr Trp Gly

100 105 110

cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc ggc gga 384

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

115 120 125

acc ggg tct ggg act ggt acg agc gag ctc acc cag tct cca tcc tcc 432

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

130 135 140

ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg gca agt 480

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

cag agc att agc agc tac tta aat tgg tat cag cag aaa cca ggg aaa 528

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt ggg gtc 576

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

180 185 190

cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act ctc acc 624

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt caa cag 672

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg gag atc 720

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

aaa cgt gcg gcc gca 735

Lys Arg Ala Ala Ala

245

<210>53

<211>245

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-005

<400>53

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Gly Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

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

65 70 75 80

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

85 90 95

Cys Ala Lys Gly Gly Gly Arg Pro Tyr Asn Pro Phe Asp Tyr Trp Gly

100 105 110

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

115 120 125

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

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

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

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys Arg Ala Ala Ala

245

<210>54

<211>753

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-006

<220>

<221>CDS

<222>(1)..(753)

<223>

<400>54

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc ggc tac cct atg cac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Gly Tyr Pro Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtg gca gtt ata tca tat gac gga agt aat aaa tac tat gca 192

Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gct gag gac aca gct gtg 288

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

85 90 95

tat tac tgt gct aaa gac ggc agc ccc cgc acc ccc agc ttc gat tac 336

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

100 105 110

tgg ggc cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc 384

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser

115 120 125

ggc gga acc ggg tct ggg act ggt acg agc gag ctc gac atc cag atg 432

Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Asp Ile Gln Met

130 135 140

act cag tct cca cac tct ctg tct gca tct gta gga gac aga gtc acc 480

Thr Gln Ser Pro His Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

145 150 155 160

atc act tgc cgg gcg agt cag ggc att agc aat tat tta gcc tgg tat 528

Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr Leu Ala Trp Tyr

165 170 175

cag cag aaa cca ggg aaa gtt cct aag ctc ctg atc tat gct gca tcc 576

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

180 185 190

act ttg caa tca ggg gtc cca tct cgg ttc agt ggc agt gga tct ggg 624

Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

aca gat ttc act ctc acc atc agc agc ctg cag cct gaa gat gtt ggg 672

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Gly

210 215 220

gtt tat tac tgc cag cag agg ttc cgc acg ccg gtc acc ttc ggc cag 720

Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val Thr Phe Gly Gln

225 230 235 240

ggc acc aaa ctg gaa atc aaa cgc gcg gcc gca 753

Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala

245 250

<210>55

<211>251

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-006

<400>55

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Gly Tyr Pro Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser

115 120 125

Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Asp Ile Gln Met

130 135 140

Thr Gln Ser Pro His Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

145 150 155 160

Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr Leu Ala Trp Tyr

165 170 175

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

180 185 190

Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Gly

210 215 220

Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala

245 250

<210>56

<211>741

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-007

<220>

<221>CDS

<222>(1)..(741)

<223>

<400>56

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct agg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Arg Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc gac tac cgg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Asp Tyr Arg Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag agg gtg gca gtt ata tca tat gat gga agc aat aaa tac tac gca 192

Glu Arg Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gct gag gac aca gcc gtg 288

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

85 90 95

tat tac tgt gca aga ggc tac tgg acg tcg ctc acg ggc ttc gat tac 336

Tyr Tyr Cys Ala Arg Gly Tyr Trp Thr Ser Leu Thr Gly Phe Asp Tyr

100 105 110

tgg ggc cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc 384

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser

115 120 125

ggc gga acc ggg tct ggg act ggt acg agc gag ctc acc cag tct cca 432

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

130 135 140

tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg 480

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155 160

gca agt cag agc att agc agc tac tta aat tgg tat cag cag aaa cca 528

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

165 170 175

ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt 576

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

180 185 190

ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act 624

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt 672

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

210 215 220

caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg 720

Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

gag atc aaa cgt gcg gcc gca 741

Glu Ile Lys Arg Ala Ala Ala

245

<210>57

<211>247

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-007

<400>57

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Arg Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asp Tyr Arg Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Arg Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Gly Tyr Trp Thr Ser Leu Thr Gly Phe Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly Ser

115 120 125

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

130 135 140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155 160

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

180 185 190

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

210 215 220

Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

Glu Ile Lys Arg Ala Ala Ala

245

<210>58

<211>735

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-008

<220>

<221>CDS

<222>(1)..(735)

<223>

<400>58

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

cct ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc agc tac ccg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Ser Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca 192

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gcc gag gac aca gcc gtg 288

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

85 90 95

tat tac tgt gca aga cgc gtc cgc ccc cgc cgc ttc gat tat tgg ggc 336

Tyr Tyr Cys Ala Arg Arg Val Arg Pro Arg Arg Phe Asp Tyr Trp Gly

100 105 110

cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc ggc gga 384

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

115 120 125

acc ggg tct ggg act ggt acg agc gag ctc acc cag tct cca tcc tcc 432

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

130 135 140

ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg gca agt 480

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

cag agc att agc agc tac tta aat tgg tat cag cag aaa cca ggg aaa 528

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt ggg gtc 576

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

180 185 190

cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act ctc acc 624

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt caa cag 672

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg gag atc 720

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

aaa cgt gcg gcc gca 735

Lys Arg Ala Ala Ala

245

<210>59

<211>245

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-008

<400>59

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Arg Val Arg Pro Arg Arg Phe Asp Tyr Trp Gly

100 105 110

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

115 120 125

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

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

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

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys Arg Ala Ala Ala

245

<210>60

<211>744

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-009

<220>

<221>CDS

<222>(1)..(744)

<223>

<400>60

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

cct ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt 96

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc gac tac ccc atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Asp Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca tcc att agt ggt agt ggt ggt agc aca tac tac gca 192

Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gcc gag gac aca gcc gtg 288

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

85 90 95

tat tac tgt gca aaa ggc ctc ttc atg gtc acc acg tac gcg ttc gat 336

Tyr Tyr Cys Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp

100 105 110

tac tgg ggc cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt 384

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly

115 120 125

tcc ggc gga acc ggg tct ggg act ggt acg agc gag ctc acc cag tct 432

Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln Ser

130 135 140

cca tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act tgc 480

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

145 150 155 160

cgg gca agt cag agc att agc agc tac tta aat tgg tat cag cag aaa 528

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys

165 170 175

cca ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa 576

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln

180 185 190

agt ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc 624

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

act ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac tac 672

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr

210 215 220

tgt caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc aag 720

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

225 230 235 240

gtg gag atc aaa cgt gcg gcc gca 744

Val Glu Ile Lys Arg Ala Ala Ala

245

<210>61

<211>248

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-009

<400>61

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asp Tyr Pro Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly Gly

115 120 125

Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln Ser

130 135 140

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

145 150 155 160

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln

180 185 190

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr

210 215 220

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

225 230 235 240

Val Glu Ile Lys Arg Ala Ala Ala

245

<210>62

<211>735

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-010

<220>

<221>CDS

<222>(1)..(735)

<223>

<400>62

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

cct ggg agg tcc ctg aga ctc tcc tgt gca acc tct gga ttc acc ttc 96

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe

20 25 30

agc ggc tac acg atg cac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Gly Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca tcc att agt ggt ggt agc aca tac tac gca gac tcc 192

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

agg aag ggc aga ttc acc atc tcc aga gac aac tcc aag aac acg ctg 240

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

65 70 75 80

tat ctt caa atg aac aac ctg aga gct gag gac aca gct gtg tat tac 288

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

85 90 95

tgt gca aaa ggc ggc ggc ctc ccc tac ttg agc ttc gat tac tgg ggc 336

Cys Ala Lys Gly Gly Gly Leu Pro Tyr Leu Ser Phe Asp Tyr Trp Gly

100 105 110

cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga ggt tcc ggc gga 384

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

115 120 125

acc ggg tct ggg act ggt acg agc gag ctc acc cag tct cca tcc tcc 432

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

130 135 140

ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg gca agt 480

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

cag agc att agc agc tac tta aat tgg tat cag cag aaa cca ggg aaa 528

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt ggg gtc 576

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

180 185 190

cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act ctc acc 624

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt caa cag 672

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg gag atc 720

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

aaa cgt gcg gcc gca 735

Lys Arg Ala Ala Ala

245

<210>63

<211>245

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-010

<400>63

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

1 5 10 15

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe

20 25 30

Ser Gly Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ser Ile Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

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

65 70 75 80

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

85 90 95

Cys Ala Lys Gly Gly Gly Leu Pro Tyr Leu Ser Phe Asp Tyr Trp Gly

100 105 110

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

115 120 125

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

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

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

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys Arg Ala Ala Ala

245

<210>64

<211>741

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-012

<220>

<221>CDS

<222>(1)..(741)

<223>

<400>64

gcc atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

cct ggg gcc rca gtg aag gtc tcc tgc aag gct tct ggt tac acc ttt 96

Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe

20 25 30

acc agc tat ggt atc agc tgg gtg cga cag gcc cct gga caa ggg ctt 144

Thr Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg atg gga tgg atc agc gct tac aat ggt aac aca aac tat gca 192

Glu Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala

50 55 60

cag aag ctc cag ggc aga gtc acc atg acc aca gac aca tcc acg agc 240

Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser

65 70 75 80

aca gcc tac atg gag ctg agc agc ctg aga tct gac gac acg gcc gtg 288

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

85 90 95

tat tac tgt gca agg atg ttt agg aag agt tcc ttt gac tcc tgg ggc 336

Tyr Tyr Cys Ala Arg Met Phe Arg Lys Ser Ser Phe Asp Ser Trp Gly

100 105 110

caa ggt acc ctg gtc acc gtc tcg aga ggt gga ggc ggt tca ggc gga 384

Gln Gly Thr Leu Val Thr Val Ser Arg Gly Gly Gly Gly Ser Gly Gly

115 120 125

ggt ggc tct ggc ggt ggc gga tcg tct gag ctg act cag gac cct gct 432

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

130 135 140

gtg tct gtg gcc ttg gga cag aca gtc agg atc aca tgc caa gga gac 480

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

145 150 155 160

agc ctc aga agc tat tat gca agc tgg tac cag cag aag cca gga cag 528

Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln

165 170 175

gcc cct gta ctt gtc atc tat ggt aaa aac aac cgg ccc tca ggg atc 576

Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile

180 185 190

cca gac cga ttc tct ggc tcc agc tca gga aac aca gct tcc ttg acc 624

Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr

195 200 205

atc act ggg gct cag gcg gaa gat gag gct gac tat tac tgt aac tcc 672

Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser

210 215 220

cgg gac agc agt ggt aac cat gtg gta ttc ggc gga ggg acc aag ctg 720

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

225 230 235 240

acc gtc cta ggt gcg gcc gca 741

Thr Val Leu Gly Ala Ala Ala

245

<210>65

<211>247

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-012

<400>65

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe

20 25 30

Thr Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala

50 55 60

Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Met Phe Arg Lys Ser Ser Phe Asp Ser Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Arg Gly Gly Gly Gly Ser Gly Gly

115 120 125

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

130 135 140

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

145 150 155 160

Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln

165 170 175

Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile

180 185 190

Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr

195 200 205

Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser

210 215 220

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

225 230 235 240

Thr Val Leu Gly Ala Ala Ala

245

<210>66

<211>747

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-013

<220>

<221>CDS

<222>(1)..(747)

<223>

<400>66

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt gac cac tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg 144

Ser Asp His Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa 192

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

50 55 60

tac gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca 240

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

aag aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg 288

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

gcc gtg tat tac tgt gca aag ggg ttg act cct ttg tac ttt gac tac 336

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

100 105 110

tgg ggc caa ggt acc ctg gtc acc gtc tcg agt ggt gga ggc ggt tca 384

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

ggc gga ggt ggc tct ggc ggt ggc gga tcg gaa att gag ctc acc cag 432

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln

130 135 140

tct cca tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act 480

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

145 150 155 160

tgc cgg gca agt cag agc att agc agc tac tta aat tgg tat cag cag 528

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

aaa cca ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg 576

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

caa agt ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat 624

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

ttc act ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac 672

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

tac tgt caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc 720

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

aag gtg gag atc aaa cgt gcg gcc gca 747

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>67

<211>249

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-013

<400>67

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asp His Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

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

50 55 60

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

Ala Val Tyr Tyr Cys Ala Lys Gly Leu Thr Pro Leu Tyr Phe Asp 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 Glu Ile Glu Leu Thr Gln

130 135 140

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

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>68

<211>747

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-014

<220>

<221>CDS

<222>(1)..(747)

<223>

<400>68

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct gga ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt gac cac tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg 144

Ser Asp His Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtt ggc cgt act aga aac aaa gct aac agt tac acc aca gaa 192

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

50 55 60

tac gcc gcg tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca 240

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

aag aac tca ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg 288

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

gcc gtg tat tac tgt gca agg ggg att tcg ccg ttt tac ttt gac tac 336

Ala Val Tyr Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp Tyr

100 105 110

tgg ggc caa ggt acc ctg gtc acc gtc tcg agt ggt gga ggc ggt tca 384

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

ggc gga ggt ggc tct ggc ggt ggc gga tcg gaa att gag ctc acc cag 432

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln

130 135 140

tct cca tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act 480

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

145 150 155 160

tgc cgg gca agt cag agc att agc agc tac tta aat tgg tat cag cag 528

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

aaa cca ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg 576

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

caa agt ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat 624

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

ttc act ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac 672

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

tac tgt caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc 720

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

aag gtg gag atc aaa cgt gcg gcc gca 747

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>69

<211>249

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-014

<400>69

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asp His Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

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

50 55 60

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

Ala Val Tyr Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp 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 Glu Ile Glu Leu Thr Gln

130 135 140

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

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>70

<211>732

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-015

<220>

<221>CDS

<222>(1)..(732)

<223>

<400>70

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggt gtg gta cgg 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

gat gat tat ggc atg agc tgg gtc cgc caa gct cca ggg aag ggg ctg 144

Asp Asp Tyr Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tct ggt att aat tgg aat ggt ggt agc aca ggt tat gca 192

Glu Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala

50 55 60

gac tct gtg aag ggc cga ttc acc atc tcc aga gac aac gcc aag aac 240

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

65 70 75 80

tcc ctg tat ctg caa atg aac agt ctg aga gcc gag gac acg gcc gtg 288

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

85 90 95

tat tac tgt gca aga ggt ttg tct ctt cgt cct tgg ggc caa ggt acc 336

Tyr Tyr Cys Ala Arg Gly Leu Ser Leu Arg Pro Trp Gly Gln Gly Thr

100 105 110

ctg gtc acc gtc tcg aga ggt gga ggc ggt tca ggc gga ggt ggc tct 384

Leu Val Thr Val Ser Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

ggc ggt ggc gga tcg tct gag ctg act cag gac cct gct gtg tct gtg 432

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

130 135 140

gcc ttg gga cag aca gtc agg atc aca tgc caa gga gac agc ctc aga 480

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

145 150 155 160

agc tat tat gca agc tgg tac cag cag aag cca gga cag gcc cct gta 528

Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val

165 170 175

ctt gtc atc tat ggt aaa aac aac cgg ccc tca ggg atc cca gac cga 576

Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg

180 185 190

ttc tct ggc tcc agc tca gga aac aca gct tcc ttg acc atc act ggg 624

Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly

195 200 205

gct cag gcg gaa gat gag gct gac tat tac tgt aac tcc cgg gac agc 672

Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser

210 215 220

agt ggt aac cat gtg gta ttc ggc gga ggg acc aag ctg acc gtc cta 720

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

225 230 235 240

ggt gcg gcc gca 732

Gly Ala Ala Ala

<210>71

<211>244

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-015

<400>71

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Asp Asp Tyr Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Gly Leu Ser Leu Arg Pro Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

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

130 135 140

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

145 150 155 160

Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val

165 170 175

Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg

180 185 190

Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly

195 200 205

Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser

210 215 220

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

225 230 235 240

Gly Ala Ala Ala

<210>72

<211>55

<212>DNA

<213>Artificial sequence

<220>

<223>5′cloning site of pPicZalphaB

<400>72

tctctcgaga aaagagaggc tgaagctgca ggaattcacg tggcccagcc ggccg 55

<210>73

<211>55

<212>DNA

<213>Artificial sequence

<220>

<223>5′cloning site of pPicZFVH

<400>73

tctctcgaga aaagagccat ggaagctgca ggaattcacg tggcccagcc ggccg 55

<210>74

<211>92

<212>DNA

<213>Artificial sequence

<220>

<223>Synthetic hinge fragment

<400>74

gcggccgcgc caaagccaag taccccacca ggttcttcat gtccaccatg tccaggctct 60

ggcggtgcgc caatcgatag cggctttcta ga 92

<210>75

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-004

<400>75

Asp Gly Ser Arg Phe Pro Ala Arg Phe Asp Tyr

1 5 10

<210>76

<211>11

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-016

<400>76

Tyr Gly Ser Ala Tyr Arg Pro Pro Phe Asp Tyr

1 5 10

<210>77

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-017

<400>77

Ser Arg Ser Ala Gly Phe Phe Asp Tyr

1 5

<210>78

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-018

<400>78

Phe Asn Pro Phe Thr Ser Phe Asp Tyr

1 5

<210>79

<211>372

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-004

<220>

<221>CDS

<222>(1)..(372)

<223>

<400>79

atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc 96

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

20 25 30

gac tac ttg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag 144

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

35 40 45

tgg gtt ggc cgt att aga agc aaa gct aac agt tac gcg aca gca tat 192

Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Ala Tyr

50 55 60

gct gcg tcg gtg aaa ggc agg ttc acc atc tcc aga gat gat tca aag 240

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

65 70 75 80

aac acg gcg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc 288

Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

gtg tat tac tgt gct aaa gac ggc agc cgg ttc ccc gcc cgc ttc gat 336

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

100 105 110

tac tgg ggc cag ggc acc ctg gtg acc gtg ctc gag 372

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>80

<211>124

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-004

<400>80

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Ala Tyr

50 55 60

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

65 70 75 80

Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala

85 90 95

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

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120

<210>81

<211>372

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-016

<400>81

atggctgagg tgtagctggt ggagtctggg ggaggcttgg tccagcctgg agggtccctg 60

agactctccc gtgcagcctc tggattcacc tttagcaact accccatgcg ctgggtccgc 120

caggcgcccg ggaaggggct ggagtgggta ggtttcatta gaaacaaagc taatggtggg 180

acaacagaat agaccacgtc tgtgagaggc agattcacaa tctcaagaga tgattccaaa 240

agcatcacct atctgcaaat gaacagcctg agagccgagg acacagccgt gtattactgt 300

gctaaatacg gcagcgccta ccgcccgccc ttcgattact ggggccaggg caccctggtg 360

accgtgctcg ag 372

<210>82

<211>125

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-016

<400>82

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Arg Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asn Tyr Pro Met Arg Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Gly Phe Ile Arg Asn Lys Ala Asn Gly Gly Thr Thr Glu

50 55 60

Gln Thr Thr Ser Val Arg Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Ser Ile Thr Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

85 90 95

Ala Val Tyr Tyr Cys Ala Lys Tyr Gly Ser Ala Tyr Arg Pro Pro Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu

115 120 125

<210>83

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-017

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>83

atg gcc cag gtg cag ctg cag gag tcg ggc gca gga ctg ttg aag cct 48

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

1 5 10 15

tcg gag acc ctg tcc ctc acc tgc act gtc tct ggt ggc tcc gtc agc 96

Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser

20 25 30

agt ggt agt tac tac tgg agc tgg atc cgg cag ccc cca ggg aag gga 144

Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

35 40 45

ctg gag tgg att ggg tat atc tat tac agt ggg agc acc aac tac aac 192

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

50 55 60

ccc tcc ctc aag agt cga gtc acc ata tca gta gac acg tcc aag aac 240

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

65 70 75 80

cag ttc tcc ctg aag ctg agc tct gtg acc gct gcg gac acg gcc gtg 288

Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

85 90 95

tat tac tgt gca aag tct cgt tct gct ggt ttc ttt gac tac tgg ggc 336

Tyr Tyr Cys Ala Lys Ser Arg Ser Ala Gly Phe Phe Asp Tyr Trp Gly

100 105 110

caa ggt acc ctg gtc acc gtc tcg agt 363

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>84

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-017

<400>84

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

1 5 10 15

Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Set Gly Gly Ser Val Ser

20 25 30

Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

35 40 45

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

50 55 60

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

65 70 75 80

Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

85 90 95

Tyr Tyr Cys Ala Lys Ser Arg Ser Ala Gly Phe Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>85

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-018

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>85

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc 96

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

20 25 30

agc tat gcc atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

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

35 40 45

tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca gac 192

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gca aag ttt aat ccg ttt act tcc ttt gac tac tgg ggc caa 336

Tyr Cys Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly Gln

100 105 110

ggt acc ctg gtc acc gtc tcg agt 360

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>86

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-018

<400>86

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

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser 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 Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>87

<211>324

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-017

<220>

<221>CDS

<222>(1)..(324)

<223>

<400>87

gaa att gag ctc aca cag tct cca gcc acc ctg tct ttg tct cca ggg 48

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

1 5 10 15

gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt agc agc tac 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

tta gcc tgg tac caa cag aaa cct ggc cag gct ccc agg ctc ctc atc 144

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

35 40 45

tat gat gca tcc aac agg gcc act ggc atc cca gcc agg ttc agt ggc 192

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

agt ggg tct ggg aca gac ttc act ctc acc atc agc agc cta gag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

gaa gat ttt gca gtt tat tac tgt cag cag cgt agc aac tgg cct ccg 288

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

gct ttc ggc gga ggg acc aag gtg gag atc aaa cgt 324

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg

100 105

<210>88

<211>108

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-017

<400>88

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg

100 105

<210>89

<211>747

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-004

<220>

<221>CDS

<222>(1)..(747)

<223>

<400>89

tcc atg gct gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag 48

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc gac tac ttg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg 144

Ser Asp Tyr Leu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtt ggc cgt att aga agc aaa gct aac agt tac gcg aca gca 192

Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Ala

50 55 60

tat gct gcg tcg gtg aaa ggc agg ttc acc atc tcc aga gat gat tca 240

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

aag aac acg gcg tat ctg caa atg aac agc ctg aaa acc gag gac acg 288

Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

gcc gtg tat tac tgt gct aaa gac ggc agc cgg ttc ccc gcc cgc ttc 336

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

100 105 110

gat tac tgg ggc cag ggc acc ctg gtg acc gtg ctc gag ggt acc gga 384

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly

115 120 125

ggt tcc ggc gga acc ggg tct ggg act ggt acg agc gag ctc acc cag 432

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln

130 135 140

tct cca tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act 480

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

145 150 155 160

tgc cgg gca agt cag agc att agc agc tac tta aat tgg tat cag cag 528

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

aaa cca ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg 576

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

caa agt ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat 624

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

ttc act ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac 672

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

tac tgt caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc 720

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

aag gtg gag atc aaa cgt gcg gcc gca 747

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>90

<211>249

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-004

<400>90

Ser Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asp Tyr Leu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Gly Arg Ile Arg Ser Lys Ala Asn Ser Tyr Ala Thr Ala

50 55 60

Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr

85 90 95

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

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly

115 120 125

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln

130 135 140

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

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>91

<211>747

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-016

<400>91

gccatggctg aggtgtagct ggtggagtct gggggaggct tggtccagcc tggagggtcc 60

ctgagactct cccgtgcagc ctctggattc acctttagca actaccccat gcgctgggtc 120

cgccaggcgc ccgggaaggg gctggagtgg gtaggtttca ttagaaacaa agctaatggt 180

gggacaacag aatagaccac gtctgtgaga ggcagattca caatctcaag agatgattcc 240

aaaagcatca cctatctgca aatgaacagc ctgagagccg aggacacagc cgtgtattac 300

tgtgctaaat acggcagcgc ctaccgcccg cccttcgatt actggggcca gggcaccctg 360

gtgaccgtgc tcgagggtac cggaggttcc ggcggaaccg ggtctgggac tggtacgagc 420

gagctcaccc agtctccatc ctccctgtct gcatctgtag gagacagagt caccatcact 480

tgccgggcaa gtcagagcat tagcagctac ttaaattggt atcagcagaa accagggaaa 540

gcccctaagc tcctgatcta tgctgcatcc agtttgcaaa gtggggtccc atcaaggttc 600

agtggcagtg gatctgggac agatttcact ctcaccatca gcagtctgca acctgaagat 660

tttgcaactt actactgtca acagagttac agtacccctc caacgttcgg ccaagggacc 720

aaggtggaga tcaaacgtgc ggccgca 747

<210>92

<211>249

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-016

<400>92

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Arg Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Asn Tyr Pro Met Arg Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Gly Phe Ile Arg Asn Lys Ala Asn Gly Gly Thr Thr Glu

50 55 60

Gln Thr Thr Ser Val Arg Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser

65 70 75 80

Lys Ser Ile Thr Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

85 90 95

Ala Val Tyr Tyr Cys Ala Lys Tyr Gly Ser Ala Tyr Arg Pro Pro Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Leu Glu Gly Thr Gly

115 120 125

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Thr Ser Glu Leu Thr Gln

130 135 140

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

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr

225 230 235 240

Lys Val Glu Ile Lys Arg Ala Ala Ala

245

<210>93

<211>744

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-017

<220>

<221>CDS

<222>(1)..(744)

<223>

<400>93

gcc atg gcc cag gtg cag ctg cag gag tcg ggc gca gga ctg ttg aag 48

Ala Met Ala Gln Val Gln Leu Gln Glu Ser Gly Ala Gly Leu Leu Lys

5 10 15

cct tcg gag acc ctg tcc ctc acc tgc act gtc tct ggt ggc tcc gtc 96

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

20 25 30

agc agt ggt agt tac tac tgg agc tgg atc cgg cag ccc cca ggg aag 144

Ser Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys

35 40 45

gga ctg gag tgg att ggg tat atc tat tac agt ggg agc acc aac tac 192

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

50 55 60

aac ccc tcc ctc aag agt cga gtc acc ata tca gta gac acg tcc aag 240

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

65 70 75 80

aac cag ttc tcc ctg aag ctg agc tct gtg acc gct gcg gac acg gcc 288

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

85 90 95

gtg tat tac tgt gca aag tct cgt tct gct ggt ttc ttt gac tac tgg 336

Val Tyr Tyr Cys Ala Lys Ser Arg Ser Ala Gly Phe Phe Asp Tyr Trp

100 105 110

ggc caa ggt acc ctg gtc acc gtc tcg agt ggt gga ggc ggt tca ggc 384

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

gga ggt ggc tct ggc ggt ggc gga tcg gaa att gag ctc aca cag tct 432

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln Ser

130 135 140

cca gcc acc ctg tct ttg tct cca ggg gaa aga gcc acc ctc tcc tgc 480

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

145 150 155 160

agg gcc agt cag agt gtt agc agc tac tta gcc tgg tac caa cag aaa 528

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys

165 170 175

cct ggc cag gct ccc agg ctc ctc atc tat gat gca tcc aac agg gcc 576

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Asn Arg Ala

180 185 190

act ggc atc cca gcc agg ttc agt ggc agt ggg tct ggg aca gac ttc 624

Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

act ctc acc atc agc agc cta gag cct gaa gat ttt gca gtt tat tac 672

Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr

210 215 220

tgt cag cag cgt agc aac tgg cct ccg gct ttc ggc gga ggg acc aag 720

Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe Gly Gly Gly Thr Lys

225 230 235 240

gtg gag atc aaa cgt gcg gcc gca 744

Val Glu Ile Lys Arg Ala Ala Ala

245

<210>94

<211>248

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-017

<400>94

Ala Met Ala Gln Val Gln Leu Gln Glu Ser Gly Ala Gly Leu Leu Lys

1 5 10 15

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

20 25 30

Ser Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Val Tyr Tyr Cys Ala Lys Ser Arg Ser Ala Gly Phe Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln Ser

130 135 140

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

145 150 155 160

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Asn Arg Ala

180 185 190

Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr

210 215 220

Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe Gly Gly Gly Thr Lys

225 230 235 240

Val Glu Ile Lys Arg Ala Ala Ala

245

<210>95

<211>741

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-018

<220>

<221>CDS

<222>(1)..(741)

<223>

<400>95

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc agc tat gcc atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg 144

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

35 40 45

gag tgg gtc tca gct att agt ggt agt ggt ggt agc aca tac tac gca 192

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gtg 288

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

85 90 95

tat tac tgt gca aag ttt aat ccg ttt act tcc ttt gac tac tgg ggc 336

Tyr Tyr Cys Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly

100 105 110

caa ggt acc ctg gtc acc gtc tcg agt ggt gga ggc ggt tca ggc gga 384

Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

ggt ggc tct ggc ggt ggc gga tcg gaa att gag ctc acc cag tct cca 432

Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln Ser Pro

130 135 140

tcc tcc ctg tct gca tct gta gga gac aga gtc acc atc act tgc cgg 480

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155 160

gca agt cag agc att agc agc tac tta aat tgg tat cag cag aaa cca 528

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

165 170 175

ggg aaa gcc cct aag ctc ctg atc tat gct gca tcc agt ttg caa agt 576

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

180 185 190

ggg gtc cca tca agg ttc agt ggc agt gga tct ggg aca gat ttc act 624

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

ctc acc atc agc agt ctg caa cct gaa gat ttt gca act tac tac tgt 672

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

210 215 220

caa cag agt tac agt acc cct cca acg ttc ggc caa ggg acc aag gtg 720

Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

gag atc aaa cgt gcg gcc gca 741

Glu Ile Lys Arg Ala Ala Ala

245

<210>96

<211>247

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-018

<400>96

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

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

35 40 45

Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Glu Leu Thr Gln Ser Pro

130 135 140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155 160

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

180 185 190

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

210 215 220

Gln Gln Ser Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

Glu Ile Lys Arg Ala Ala Ala

245

<210>97

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>97

Asn Gly Pro Gln Ser Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe

1 5 10 15

<210>98

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>98

Gly Pro Gln Ser Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly

1 5 10 15

<210>99

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>99

Pro Gln Ser Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly

1 5 10 15

<210>100

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>100

Gln Ser Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro

1 5 10 15

<210>101

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>101

Ser Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr

1 5 10 15

<210>102

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>102

Asn Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp

1 5 10 15

<210>103

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>103

Gln Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser

1 5 10 15

<210>104

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>104

Arg Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr

1 5 10 15

<210>105

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>105

Ser Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp

1 5 10 15

<210>106

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>106

Ala Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp Asn

1 5 10 15

<210>107

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>107

Pro Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp Asn Asn

1 5 10 15

<210>108

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>108

Arg Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp Asn Asn Gln

1 5 10 15

<210>109

<211>15

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>109

Ile Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp Asn Asn Gln Asn

1 5 10 15

<210>110

<211>6778

<212>DNA

<213>Artificial sequence

<220>

<223>Vector pSyn-C03-HCgammal

<400>110

gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60

ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120

cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180

ttagggttag gcgttttgcg ctgcttcgct aggtggtcaa tattggccat tagccatatt 240

attcattggt tatatagcat aaatcaatat tggctattgg ccattgcata cgttgtatcc 300

atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat gttgacattg 360

attattgact agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat 420

ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc 480

ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca 540

ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta 600

tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 660

tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 720

cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 780

ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggcacca 840

aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 900

taggcgtgta cggtgggagg tctatataag cagagctcgt ttagtgaacc gtcagatcgc 960

ctggagacgc catccacgct gttttgacct ccatagaaga caccgggacc gatccagcct 1020

ccgcggccgg gaacggtgca ttggaagctg gcctggatgg cctgactctc ttaggtagcc 1080

ttgcagaagt tggtcgtgag gcactgggca ggtaagtatc aaggttacaa gacaggttta 1140

aggagatcaa tagaaactgg gcttgtcgag acagagaaga ctcttgcgtt tctgataggc 1200

acctattggt cttactgaca tccactttgc ctttctctcc acaggtgtcc actcccagtt 1260

caattacagc tcgccaccat ggcctgcccc ggcttcctgt gggccctggt gatcagcacc 1320

tgcctggaat tcagcatgag cagcgctagc accaagggcc ccagcgtgtt ccccctggcc 1380

cccagcagca agagcaccag cggcggcaca gccgccctgg gctgcctggt gaaggactac 1440

ttccccgagc ccgtgaccgt gagctggaac agcggcgcct tgaccagcgg cgtgcacacc 1500

ttccccgccg tgctgcagag cagcggcctg tacagcctga gcagcgtggt gaccgtgccc 1560

agcagcagcc tgggcaccca gacctacatc tgcaacgtga accacaagcc cagcaacacc 1620

aaggtggaca aacgcgtgga gcccaagagc tgcgacaaga cccacacctg ccccccctgc 1680

cctgcccccg agctgctggg cggaccctcc gtgttcctgt tcccccccaa gcccaaggac 1740

accctcatga tcagccggac ccccgaggtg acctgcgtgg tggtggacgt gagccacgag 1800

gaccccgagg tgaagttcaa ctggtacgtg gacggcgtgg aggtgcacaa cgccaagacc 1860

aagccccggg aggagcagta caacagcacc taccgggtgg tgagcgtgct caccgtgctg 1920

caccaggact ggctgaacgg caaggagtac aagtgcaagg tgagcaacaa ggccctgcct 1980

gcccccatcg agaagaccat cagcaaggcc aagggccagc cccgggagcc ccaggtgtac 2040

accctgcccc ccagccggga ggagatgacc aagaaccagg tgtccctcac ctgtctggtg 2100

aagggcttct accccagcga catcgccgtg gagtgggaga gcaacggcca gcccgagaac 2160

aactacaaga ccaccccccc tgtgctggac agcgacggca gcttcttcct gtacagcaag 2220

ctcaccgtgg acaagagccg gtggcagcag ggcaacgtgt tcagctgcag cgtgatgcac 2280

gaggccctgc acaaccacta cacccagaag agcctgagcc tgagccccgg caagtgataa 2340

tctagagggc ccgtttaaac ccgctgatca gcctcgactg tgccttctag ttgccagcca 2400

tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc 2460

ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg 2520

gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct 2580

ggggatgcgg tgggctctat ggcttctgag gcggaaagaa ccagctgggg ctctaggggg 2640

tatccccacg cgccctgtag cggcgcatta agcgcggcgg gtgtggtggt tacgcgcagc 2700

gtgaccgcta cacttgccag cgccctagcg cccgctcctt tcgctttctt cccttccttt 2760

ctcgccacgt tcgccggctt tccccgtcaa gctctaaatc gggggctccc tttagggttc 2820

cgatttagtg ctttacggca cctcgacccc aaaaaacttg attagggtga tggttcacgt 2880

agtgggccat cgccctgata gacggttttt cgccctttga cgttggagtc cacgttcttt 2940

aatagtggac tcttgttcca aactggaaca acactcaacc ctatctcggt ctattctttt 3000

gatttataag ggattttgcc gatttcggcc tattggttaa aaaatgagct gatttaacaa 3060

aaatttaacg cgaattaatt ctgtggaatg tgtgtcagtt agggtgtgga aagtccccag 3120

gctccccagc aggcagaagt atgcaaagca tgcatctcaa ttagtcagca accaggtgtg 3180

gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag catgcatctc aattagtcag 3240

caaccatagt cccgccccta actccgccca tcccgcccct aactccgccc agttccgccc 3300

attctccgcc ccatggctga ctaatttttt ttatttatgc agaggccgag gccgcctctg 3360

cctctgagct attccagaag tagtgaggag gcttttttgg aggcctaggc ttttgcaaaa 3420

agctcccggg agcttgtata tccattttcg gatctgatca agagacagga tgaggatcgt 3480

ttcgcatgat tgaacaagat ggattgcacg caggttctcc ggccgcttgg gtggagaggc 3540

tattcggcta tgactgggca caacagacaa tcggctgctc tgatgccgcc gtgttccggc 3600

tgtcagcgca ggggcgcccg gttctttttg tcaagaccga cctgtccggt gccctgaatg 3660

aactgcagga cgaggcagcg cggctatcgt ggctggccac gacgggcgtt ccttgcgcag 3720

ctgtgctcga cgttgtcact gaagcgggaa gggactggct gctattgggc gaagtgccgg 3780

ggcaggatct cctgtcatct caccttgctc ctgccgagaa agtatccatc atggctgatg 3840

caatgcggcg gctgcatacg cttgatccgg ctacctgccc attcgaccac caagcgaaac 3900

atcgcatcga gcgagcacgt actcggatgg aagccggtct tgtcgatcag gatgatctgg 3960

acgaagagca tcaggggctc gcgccagccg aactgttcgc caggctcaag gcgcgcatgc 4020

ccgacggcga ggatctcgtc gtgacccatg gcgatgcctg cttgccgaat atcatggtgg 4080

aaaatggccg cttttctgga ttcatcgact gtggccggct gggtgtggcg gatcgctatc 4140

aggacatagc gttggctacc cgtgatattg ctgaagagct tggcggcgaa tgggctgacc 4200

gcttcctcgt gctttacggt atcgccgctc ccgattcgca gcgcatcgcc ttctatcgcc 4260

ttcttgacga gttcttctga gcgggactct ggggttcgaa atgaccgacc aagcgacgcc 4320

caacctgcca tcacgagatt tcgattccac cgccgccttc tatgaaaggt tgggcttcgg 4380

aatcgttttc cgggacgccg gctggatgat cctccagcgc ggggatctca tgctggagtt 4440

cttcgcccac cccaacttgt ttattgcagc ttataatggt tacaaataaa gcaatagcat 4500

cacaaatttc acaaataaag catttttttc actgcattct agttgtggtt tgtccaaact 4560

catcaatgta tcttatcatg tctgtatacc gtcgacctct agctagagct tggcgtaatc 4620

atggtcatag ctgtttcctg tgtgaaattg ttatccgctc acaattccac acaacatacg 4680

agccggaagc ataaagtgta aagcctgggg tgcctaatga gtgagctaac tcacattaat 4740

tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg tcgtgccagc tgcattaatg 4800

aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttcctcgct 4860

cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc actcaaaggc 4920

ggtaatacgg ttatccacag aatcagggga taacgcagga aagaacatgt gagcaaaagg 4980

ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc ataggctccg 5040

cccccctgac gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa acccgacagg 5100

actataaaga taccaggcgt ttccccctgg aagctccctc gtgcgctctc ctgttccgac 5160

cctgccgctt accggatacc tgtccgcctt tctcccttcg ggaagcgtgg cgctttctca 5220

tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt cgctccaagc tgggctgtgt 5280

gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc 5340

caacccggta agacacgact tatcgccact ggcagcagcc actggtaaca ggattagcag 5400

agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg tggcctaact acggctacac 5460

tagaagaaca gtatttggta tctgcgctct gctgaagcca gttaccttcg gaaaaagagt 5520

tggtagctct tgatccggca aacaaaccac cgctggtagc ggtttttttg tttgcaagca 5580

gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 5640

tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 5700

gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 5760

tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat 5820

ctgtctattt cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg 5880

ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc 5940

tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc 6000

aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc 6060

gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc 6120

gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc 6180

ccccatgttg tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa 6240

gttggccgca gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat 6300

gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata 6360

gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca 6420

tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag 6480

gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc 6540

agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc 6600

aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata 6660

ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta 6720

gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtc 6778

<210>111

<211>6267

<212>DNA

<213>Artificial scquence

<220>

<223>Vector pSyn-C05-Ckappa

<400>111

gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60

ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120

cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgttaa ttaacatgaa 180

gaatctgctt agggttaggc gttttgcgct gcttcgctag gtggtcaata ttggccatta 240

gccatattat tcattggtta tatagcataa atcaatattg gctattggcc attgcatacg 300

ttgtatccat atcataatat gtacatttat attggctcat gtccaacatt accgccatgt 360

tgacattgat tattgactag ttattaatag taatcaatta cggggtcatt agttcatagc 420

ccatatatgg agttccgcgt tacataactt acggtaaatg gcccgcctgg ctgaccgccc 480

aacgaccccc gcccattgac gtcaataatg acgtatgttc ccatagtaac gccaataggg 540

actttccatt gacgtcaatg ggtggagtat ttacggtaaa ctgcccactt ggcagtacat 600

caagtgtatc atatgccaag tacgccccct attgacgtca atgacggtaa atggcccgcc 660

tggcattatg cccagtacat gaccttatgg gactttccta cttggcagta catctacgta 720

ttagtcatcg ctattaccat ggtgatgcgg ttttggcagt acatcaatgg gcgtggatag 780

cggtttgact cacggggatt tccaagtctc caccccattg acgtcaatgg gagtttgttt 840

tggcaccaaa atcaacggga ctttccaaaa tgtcgtaaca actccgcccc attgacgcaa 900

atgggcggta ggcgtgtacg gtgggaggtc tatataagca gagctcgttt agtgaaccgt 960

cagatcgcct ggagacgcca tccacgctgt tttgacctcc atagaagaca ccgggaccga 1020

tccagcctcc gcggccggga acggtgcatt ggaatcgatg actctcttag gtagccttgc 1080

agaagttggt cgtgaggcac tgggcaggta agtatcaagg ttacaagaca ggtttaagga 1140

gatcaataga aactgggctt gtcgagacag agaagactct tgcgtttctg ataggcacct 1200

attggtctta ctgacatcca ctttgccttt ctctccacag gtgtccactc ccagttcaat 1260

tacagctcgc caccatggcc tgccccggct tcctgtgggc cctggtgatc agcacctgcc 1320

tcgagttcag cggccctaag cggaccgtgg ccgctcccag cgtgttcatc ttccccccct 1380

ccgacgagca gctgaagagc ggcaccgcca gcgtggtgtg cctgctgaac aacttctacc 1440

cccgggaggc caaggtgcag tggaaggtgg acaacgccct gcagagcggc aacagccagg 1500

agagcgtgac cgagcaggac agcaaggact ccacctacag cctgagcagc accctcaccc 1560

tgagcaaggc cgactacgag aagcacaagg tgtacgcctg cgaggtgacc caccagggcc 1620

tgagcagccc cgtgaccaag agcttcaacc ggggcgagtg ttaatagact taagtttaaa 1680

ccgctgatca gcctcgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc 1740

cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga 1800

aattgcatcg cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga 1860

cagcaagggg gaggattggg aagacaatag caggcatgct ggggatgcgg tgggctctat 1920

ggcttctgag gcggaaagaa ccagctgggg ctctaggggg tatccccacg cgccctgtag 1980

cggcgcatta agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag 2040

cgccctagcg cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt 2100

tccccgtcaa gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca 2160

cctcgacccc aaaaaacttg attagggtga tggttcacgt agtgggccat cgccctgata 2220

gacggttttt cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca 2280

aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttggc 2340

catttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattaatt 2400

ctgtggaatg tgtgtcagtt agggtgtgga aagtccccag gctccccagc aggcagaagt 2460

atgcaaagca tgcatctcaa ttagtcagca accaggtgtg gaaagtcccc aggctcccca 2520

gcaggcagaa gtatgcaaag catgcatctc aattagtcag caaccatagt cccgccccta 2580

actccgccca tcccgcccct aactccgccc agttccgccc attctccgcc ccatggctga 2640

ctaatttttt ttatttatgc agaggccgag gccgcctctg cctctgagct attccagaag 2700

tagtgaggag gcttttttgg aggcctaggc ttttgcaaaa agctcccggg agcttgtata 2760

tccattttcg gatctgatca gcacgtgatg aaaaagcctg aactcaccgc gacgtctgtc 2820

gagaagtttc tgatcgaaaa gttcgacagc gtctccgacc tgatgcagct ctcggagggc 2880

gaagaatctc gtgctttcag cttcgatgta ggagggcgtg gatatgtcct gcgggtaaat 2940

agctgcgccg atggtttcta caaagatcgt tatgtttatc ggcactttgc atcggccgcg 3000

ctcccgattc cggaagtgct tgacattggg gaattcagcg agagcctgac ctattgcatc 3060

tcccgccgtg cacagggtgt cacgttgcaa gacctgcctg aaaccgaact gcccgctgtt 3120

ctgcagccgg tcgcggaggc catggatgcg atcgctgcgg ccgatcttag ccagacgagc 3180

gggttcggcc cattcggacc acaaggaatc ggtcaataca ctacatggcg tgatttcata 3240

tgcgcgattg ctgatcccca tgtgtatcac tggcaaactg tgatggacga caccgtcagt 3300

gcgtccgtcg cgcaggctct cgatgagctg atgctttggg ccgaggactg ccccgaagtc 3360

cggcacctcg tgcacgcgga tttcggctcc aacaatgtcc tgacggacaa tggccgcata 3420

acagcggtca ttgactggag cgaggcgatg ttcggggatt cccaatacga ggtcgccaac 3480

atcttcttct ggaggccgtg gttggcttgt atggagcagc agacgcgcta cttcgagcgg 3540

aggcatccgg agcttgcagg atcgccgcgg ctccgggcgt atatgctccg cattggtctt 3600

gaccaactct atcagagctt ggttgacggc aatttcgatg atgcagcttg ggcgcagggt 3660

cgatgcgacg caatcgtccg atccggagcc gggactgtcg ggcgtacaca aatcgcccgc 3720

agaagcgcgg ccgtctggac cgatggctgt gtagaagtac tcgccgatag tggaaaccga 3780

cgccccagca ctcgtccgag ggcaaaggaa tagcacgtgc tacgagattt cgattccacc 3840

gccgccttct atgaaaggtt gggcttcgga atcgttttcc gggacgccgg ctggatgatc 3900

ctccagcgcg gggatctcat gctggagttc ttcgcccacc ccaacttgtt tattgcagct 3960

tataatggtt acaaataaag caatagcatc acaaatttca caaataaagc atttttttca 4020

ctgcattcta gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg 4080

tcgacctcta gctagagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt 4140

tatccgctca caattccaca caacatacga gccggaagca taaagtgtaa agcctggggt 4200

gcctaatgag tgagctaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg 4260

ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg 4320

cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg 4380

cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga atcaggggat 4440

aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc 4500

gcgttgctgg cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc 4560

tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga 4620

agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt 4680

ctcccttcgg gaagcgtggc gctttctcat agctcacgct gtaggtatct cagttcggtg 4740

taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc 4800

gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg 4860

gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc 4920

ttgaagtggt ggcctaacta cggctacact agaagaacag tatttggtat ctgcgctctg 4980

ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc 5040

gctggtagcg gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa 5100

gaagatcctt tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa 5160

gggattttgg tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa 5220

tgaagtttta aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc 5280

ttaatcagtg aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga 5340

ctccccgtcg tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca 5400

atgataccgc gagacccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc 5460

ggaagggccg agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat 5520

tgttgccggg aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc 5580

attgctacag gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt 5640

tcccaacgat caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc 5700

ttcggtcctc cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg 5760

gcagcactgc ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt 5820

gagtactcaa ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg 5880

gcgtcaatac gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga 5940

aaacgttctt cggggcgaaa actctcaagg atcttaccgc tgttgagatc cagttcgatg 6000

taacccactc gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg 6060

tgagcaaaaa caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt 6120

tgaatactca tactcttcct ttttcaatat tattgaagca tttatcaggg ttattgtctc 6180

atgagcggat acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca 6240

tttccccgaa aagtgccacc tgacgtc 6267

<210>112

<211>54

<212>DNA

<213>Artificial sequence

<220>

<223>Oligonucleotide 5K-I

<400>112

acctgtctcg agttttccat ggctgacatc cagatgaccc agtctccatc ctcc 54

<210>113

<211>42

<212>DNA

<213>Artificial sequence

<220>

<223>Oligonucleotide sy3K-C

<400>113

gggaccaagg tggagatcaa acggaccgtg gccgccccca gc 42

<210>114

<211>46

<212>DNA

<213>Artificial sequence

<220>

<223>Oligonucleotide 5H-B

<400>114

acctgtcttg aattctccat ggccgaggtg cagctggtgg agtctg 46

<210>115

<211>47

<212>DNA

<213>Artificial sequence

<220>

<223>Oligonucleotide sy3H-A

<400>115

gcccttggtg ctagcgctgg agacggtcac cagggtgccc tggcccc 47

<210>116

<211>1338

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heaVy chain sequence 03-001

<220>

<221>CDS

<222>(1)..(1338)

<223>

<400>116

gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta aag cct ggg ggg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc ggc tac 96

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

20 25 30

tcg atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag tgg gtc 144

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

35 40 45

tca tcc att agt ggt ggt agc aca tac tac gca gac tcc agg aag ggc 192

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

50 55 60

aga ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat ctt cag 240

Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln

65 70 75 80

atg aac aac ctg aga gct gag gac acg gct gtg tat tac tgt gca aga 288

Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

cac cgg ttc cgg cac gtc ttc gat tac tgg ggc cag ggc acc ctg gtg 336

His Arg Phe Arg His Val Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

acc gtc tcc agc gct agc acc aag ggc ccc agc gtg ttc ccc ctg gcc 384

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

115 120 125

ccc agc agc aag agc acc agc ggc ggc aca gcc gcc ctg ggc tgc ctg 432

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

gtg aag gac tac ttc ccc gag ccc gtg acc gtg agc tgg aac agc ggc 480

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

145 150 155 160

gcc ttg acc agc ggc gtg cac acc ttc ccc gcc gtg ctg cag agc agc 528

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

ggc ctg tac agc ctg agc agc gtg gtg acc gtg ccc agc agc agc ctg 576

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

ggc acc cag acc tac atc tgc aac gtg aac cac aag ccc agc aac acc 624

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

aag gtg gac aaa cgc gtg gag ccc aag agc tgc gac aag acc cac acc 672

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

210 215 220

tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga ccc tcc gtg ttc 720

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

225 230 235 240

ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc agc cgg acc ccc 768

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

gag gtg acc tgc gtg gtg gtg gac gtg agc cac gag gac ccc gag gtg 816

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

260 265 270

aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac aac gcc aag acc 864

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

aag ccc cgg gag gag cag tac aac agc acc tac cgg gtg gtg agc gtg 912

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

290 295 300

ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag gag tac aag tgc 960

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

aag gtg agc aac aag gcc ctg cct gcc ccc atc gag aag acc atc agc 1008

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

325 330 335

aag gcc aag ggc cag ccc cgg gag ccc cag gtg tac acc ctg ccc ccc 1056

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

340 345 350

agc cgg gag gag atg acc aag aac cag gtg tcc ctc acc tgt ctg gtg 1104

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

aag ggc ttc tac ccc agc gac atc gcc gtg gag tgg gag agc aac ggc 1152

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

cag ccc gag aac aac tac aag acc acc ccc cct gtg ctg gac agc gac 1200

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

385 390 395 400

ggc agc ttc ttc ctg tac agc aag ctc acc gtg gac aag agc cgg tgg 1248

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

405 410 415

cag cag ggc aac gtg ttc agc tgc agc gtg atg cac gag gcc ctg cac 1296

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

aac cac tac acc cag aag agc ctg agc ctg agc ccc ggc aag 1338

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

435 440 445

<210>117

<211>446

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain sequence 03-001

<400>117

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln

65 70 75 80

Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

85 90 95

His Arg Phe Arg His Val Phe Asp 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 Arg 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>118

<211>1356

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain sequence of 03-002

<220>

<221>CDS

<222>(1)..(1356)

<223>

<400>118

gag gtg cag ctg gtg gag tct ggg gga ggc ctg gtc aag cct ggg ggg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc ggc tac 96

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

20 25 30

agc atg agc tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag tgg gtt 144

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

35 40 45

ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac gcc gcg 192

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag aac tca 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gct aga tac tac tcc cgc tcc ctc aag gcc ttc gat tac tgg 336

Tyr Cys Ala Arg Tyr Tyr Ser Arg Ser Leu Lys Ala Phe Asp Tyr Trp

100 105 110

ggc cag ggc acc ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc 384

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

115 120 125

agc gtg ttc ccc ctg gcc ccc agc agc aag agc acc agc ggc ggc aca 432

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

130 135 140

gcc gcc ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc 480

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

145 150 155 160

gtg agc tgg aac agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc 528

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

165 170 175

gcc gtg ctg cag agc agc ggc ctg tac agc ctg agc agc gtg gtg acc 576

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

180 185 190

gtg ccc agc agc agc ctg ggc acc cag acc tac atc tgc aac gtg aac 624

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

195 200 205

cac aag ccc agc aac acc aag gtg gac aaa cgc gtg gag ccc aag agc 672

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

210 215 220

tgc gac aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg 720

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

225 230 235 240

ggc gga ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc 768

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

245 250 255

atg atc agc cgg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc 816

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

260 265 270

cac gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag 864

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

275 280 285

gtg cac aac gcc aag acc aag ccc cgg gag gag cag tac aac agc acc 912

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

290 295 300

tac cgg gtg gtg agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac 960

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

305 310 315 320

ggc aag gag tac aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc 1008

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

325 330 335

atc gag aag acc atc agc aag gcc aag ggc cag ccc cgg gag ccc cag 1056

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

340 345 350

gtg tac acc ctg ccc ccc agc cgg gag gag atg acc aag aac cag gtg 1104

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

tcc ctc acc tgt ctg gtg aag ggc ttc tac ccc agc gac atc gcc gtg 1152

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

370 375 380

gag tgg gag agc aac ggc cag ccc gag aac aac tac aag acc acc ccc 1200

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

385 390 395 400

cct gtg ctg gac agc gac ggc agc ttc ttc ctg tac agc aag ctc acc 1248

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

405 410 415

gtg gac aag agc cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg 1296

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

420 425 430

atg cac gag gcc ctg cac aac cac tac acc cag aag agc ctg agc ctg 1344

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

435 440 445

agc ccc ggc aag 1356

Ser Pro Gly Lys

450

<210>119

<211>452

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain sequence of 03-002

<400>119

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg Tyr Tyr Ser Arg Ser Leu Lys Ala Phe Asp Tyr Trp

100 105 110

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

115 120 125

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

130 135 140

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

145 150 155 160

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

165 170 175

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

180 185 190

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

195 200 205

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

210 215 220

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

225 230 235 240

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

245 250 255

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

260 265 270

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

275 280 285

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

290 295 300

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

305 310 315 320

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

325 330 335

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

340 345 350

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

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

370 375 380

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

385 390 395 400

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

405 410 415

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

420 425 430

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

435 440 445

Ser Pro Gly Lys

450

<210>120

<211>1353

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain sequence 03-009

<220>

<221>CDS

<222>(1)..(1353)

<223>

<400>120

gag gtg cag ctg gtg gag tct ggg gga ggc gtg gtc cag cct ggg agg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc gac tac 96

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

20 25 30

ccc atg aac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag tgg gtc 144

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

35 40 45

tca tcc att agt ggt agt ggt ggt agc aca tac tac gca gac tcc gtg 192

Ser Ser Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

ctg caa atg aac agc ctg aga gcc gag gac aca gcc gtg tat tac tgt 288

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

85 90 95

gca aaa ggc ctc ttc atg gtc acc acg tac gcg ttc gat tac tgg ggc 336

Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp Tyr Trp Gly

100 105 110

cag ggc acc ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc agc 384

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

115 120 125

gtg ttc ccc ctg gcc ccc agc agc aag agc acc agc ggc ggc aca gcc 432

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

130 135 140

gcc ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

agc tgg aac agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc gcc 528

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

gtg ctg cag agc agc ggc ctg tac agc ctg agc agc gtg gtg acc gtg 576

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

ccc agc agc agc ctg ggc acc cag acc tac atc tgc aac gtg aac cac 624

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

aag ccc agc aac acc aag gtg gac aaa cgc gtg gag ccc aag agc tgc 672

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

210 215 220

gac aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc 720

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

gga ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg 768

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

atc agc cgg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc cac 816

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

260 265 270

gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg 864

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

cac aac gcc aag acc aag ccc cgg gag gag cag tac aac agc acc tac 912

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

290 295 300

cgg gtg gtg agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc 960

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

aag gag tac aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc atc 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

325 330 335

gag aag acc atc agc aag gcc aag ggc cag ccc cgg gag ccc cag gtg 1056

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

340 345 350

tac acc ctg ccc ccc agc cgg gag gag atg acc aag aac cag gtg tcc 1104

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser

355 360 365

ctc acc tgt ctg gtg aag ggcttc tac ccc agc gac atc gcc gtg gag 1152

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

370 375 380

tgg gag agc aac ggc cag ccc gag aac aac tac aag acc acc ccc cct 1200

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

385 390 395 400

gtg ctg gac agc gac ggc agc ttc ttc ctg tac agc aag ctc acc gtg 1248

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

405 410 415

gac aag agc cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg atg 1296

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

420 425 430

cac gag gcc ctg cac aac cac tac acc cag aag agc ctg agc ctg agc 1344

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435 440 445

ccc ggc aag 1353

Pro Gly Lys

450

<210>121

<211>451

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain sequence 03-009

<400>121

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Ser Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Lys Gly Leu Phe Met Val Thr Thr Tyr Ala Phe Asp Tyr Trp Gly

100 105 110

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

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

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

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

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

260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

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

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

325 330 335

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

340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser

355 360 365

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

370 375 380

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

385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

405 410 415

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435 440 445

Pro Gly Lys

450

<210>122

<211>1350

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-013

<220>

<221>CDS

<222>(1)..(1350)

<223>

<400>122

gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct gga ggg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt gac cac 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp His

20 25 30

tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg gag tgg gtt 144

Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac gcc gcg 192

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag aac tca 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gca aag ggg ttg act cct ttg tac ttt gac tac tgg ggc cag 336

Tyr Cys Ala Lys Gly Leu Thr Pro Leu Tyr Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc agc gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

ttc ccc ctg gcc ccc agc agc aag agc acc agc ggc ggc aca gcc gcc 432

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

130 135 140

ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg agc 480

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

145 150 155 160

tgg aac agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc gcc gtg 528

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

ctg cag agc agc ggc ctg tac agc ctg agc agc gtg gtg acc gtg ccc 576

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

agc agc agc ctg ggc acc cag acc tac atc tgc aac gtg aac cac aag 624

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

ccc agc aac acc aag gtg gac aaa cgc gtg gag ccc aag agc tgc gac 672

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

210 215 220

aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga 720

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

225 230 235 240

ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc 768

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

agc cgg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc cac gag 816

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

260 265 270

gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac 864

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

aac gcc aag acc aag ccc cgg gag gag cag tac aac agc acc tac cgg 912

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

290 295 300

gtg gtg agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag 960

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

gag tac aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc atc gag 1008

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

aag acc atc agc aag gcc aag ggc cag ccc cgg gag ccc cag gtg tac 1056

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

340 345 350

acc ctg ccc ccc agc cgg gag gag atg acc aag aac cag gtg tcc ctc 1104

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

acc tgt ctg gtg aag ggc ttc tac ccc agc gac atc gcc gtg gag tgg 1152

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

370 375 380

gag agc aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg 1200

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

ctg gac agc gac ggc agc ttc ttc ctg tac agc aag ctc acc gtg gac 1248

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

aag agc cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg atg cac 1296

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

gag gcc ctg cac aac cac tac acc cag aag agc ctg agc ctg agc ccc 1344

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

ggc aag 1350

Gly Lys

450

<210>123

<211>450

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-013

<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 Ser Asp His

20 25 30

Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Cys Ala Lys Gly Leu Thr Pro Leu Tyr Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

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

210 215 220

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

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

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

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210>124

<211>1350

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-014

<220>

<221>CDS

<222>(1)..(1350)

<223>

<400>124

gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct gga ggg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt gac cac 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp His

20 25 30

tac atg gac tgg gtc cgc cag gct cca ggg aag ggg ctg gag tgg gtt 144

Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

ggc cgt act aga aac aaa gct aac agt tac acc aca gaa tac gcc gcg 192

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

tct gtg aaa ggc aga ttc acc atc tca aga gat gat tca aag aac tca 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aaa acc gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gca agg ggg att tcg ccg ttt tac ttt gac tac tgg ggc cag 336

Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc agc gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

ttc ccc ctg gcc ccc agc agc aag agc acc agc ggc ggc aca gcc gcc 432

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

130 135 140

ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg agc 480

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

145 150 155 160

tgg aac agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc gcc gtg 528

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

ctg cag agc agc ggc ctg tac agc ctg agc agc gtg gtg acc gtg ccc 576

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

agc agc agc ctg ggc acc cag acc tac atc tgc aac gtg aac cac aag 624

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

ccc agc aac acc aag gtg gac aaa cgc gtg gag ccc aag agc tgc gac 672

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

210 215 220

aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga 720

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

225 230 235 240

ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc 768

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

agc cgg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc cac gag 816

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

260 265 270

gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac 864

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

aac gcc aag acc aag ccc cgg gag gag cag tac aac agc acc tac cgg 912

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

290 295 300

gtg gtg agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag 960

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

gag tac aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc atc gag 1008

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

aag acc atc agc aag gcc aag ggc cag ccc cgg gag ccc cag gtg tac 1056

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

340 345 350

acc ctg ccc ccc agc cgg gag gag atg acc aag aac cag gtg tcc ctc 1104

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

acc tgt ctg gtg aag ggc ttc tac ccc agc gac atc gcc gtg gag tgg 1152

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

370 375 380

gag agc aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg 1200

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

ctg gac agc gac ggc agc ttc ttc ctg tac agc aag ctc acc gtg gac 1248

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

aag agc cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg atg cac 1296

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

gag gcc ctg cac aac cac tac acc cag aag agc ctg agc ctg agc ccc 1344

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

ggc aag 1350

Gly Lys

450

<210>125

<211>450

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-014

<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 Ser Asp His

20 25 30

Tyr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Gly Arg Thr Arg Asn Lys Ala Asn Ser Tyr Thr Thr Glu Tyr Ala Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg Gly Ile Ser Pro Phe Tyr Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

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

210 215 220

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

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

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

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210>126

<211>1344

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-018

<220>

<221>CDS

<222>(1)..(1344)

<223>

<400>126

gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct ggg ggg 48

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

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc agc tat 96

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

20 25 30

gcc atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg gag tgg gtc 144

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

35 40 45

tca gct att agt ggt agt ggt ggt agc aca tac tac gca gac tcc gtg 192

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

aag ggc cgg ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

ctg caa atg aac agc ctg aga gcc gag gac acg gcc gtg tat tac tgt 288

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

85 90 95

gca aag ttt aat ccg ttt act tcc ttt gac tac tgg ggc cag ggc acc 336

Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc agc gtg ttc ccc 384

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

115 120 125

ctg gcc ccc agc agc aag agc acc agc ggc ggc aca gcc gcc ctg ggc 432

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

130 135 140

tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg agc tgg aac 480

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

145 150 155 160

agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc gcc gtg ctg cag 528

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

agc agc ggc ctg tac agc ctg agc agc gtg gtg acc gtg ccc agc agc 576

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

180 185 190

agc ctg ggc acc cag acc tac atc tgc aac gtg aac cac aag ccc agc 624

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

195 200 205

aac acc aag gtg gac aaa cgc gtg gag ccc aag agc tgc gac aag acc 672

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

210 215 220

cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga ccc tcc 720

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

225 230 235 240

gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc agc cgg 768

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc cac gag gac ccc 816

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

260 265 270

gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac aac gcc 864

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

aag acc aag ccc cgg gag gag cag tac aac agc acc tac cgg gtg gtg 912

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

290 295 300

agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag gag tac 960

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc atc gag aag acc 1008

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

325 330 335

atc agc aag gcc aag ggc cag ccc cgg gag ccc cag gtg tac acc ctg 1056

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

340 345 350

ccc ccc agc cgg gag gag atg acc aag aac cag gtg tcc ctc acc tgt 1104

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

ctg gtg aag ggc ttc tac ccc agc gac atc gcc gtg gag tgg gag agc 1152

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg ctg gac 1200

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

agc gac ggc agc ttc ttc ctg tac agc aag ctc acc gtg gac aag agc 1248

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

405 410 415

cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg atg cac gag gcc 1296

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

ctg cac aac cac tac acc cag aag agc ctg agc ctg agc ccc ggc aag 1344

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

435 440 445

<210>127

<211>448

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-018

<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 Ser Ser Tyr

20 25 30

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

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Lys Phe Asn Pro Phe Thr Ser Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

145 150 155 160

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

180 185 190

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

195 200 205

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

210 215 220

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

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

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

260 265 270

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

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

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

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

325 330 335

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

340 345 350

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

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

435 440 445

<210>128

<211>642

<212>DNA

<213>Artificial sequence

<220>

<223>IgG light chain of 03-001，03-002，03-009，03-013，03-014and 03-

018

<220>

<221>CDS

<222>(1)..(642)

<223>

<400>128

gac att cag atg acc cag tct cca tcc tcc ctg tct gca tct gta gga 48

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

1 5 10 15

gac aga gtc acc atc act tgc cgg gca agt cag agc att agc agc tac 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

tta aat tgg tat cag cag aaa cca ggg aaa gcc cct aag ctc ctg atc 144

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

tat gct gca tcc agt ttg caa agt ggg gtc cca tca agg ttc agt ggc 192

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

50 55 60

agt gga tct ggg aca gat ttc act ctc acc atc agc agt ctg caa cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

gaa gat ttt gca act tac tac tgt caa cag agt tac agt acc cct cca 288

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro

85 90 95

acg ttc ggc caa ggg acc aag gtg gag atc aaa cgg acc gtg gcc gct 336

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

ccc agc gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag agc ggc 384

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

115 120 125

acc gcc agc gtg gtg tgc ctg ctg aac aac ttc tac ccc cgg gag gcc 432

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

aag gtg cag tgg aag gtg gac aac gcc ctg cag agc ggc aac agc cag 480

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

145 150 155 160

gag agc gtg acc gag cag gac agc aag gac tcc acc tac agc ctg agc 528

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

165 170 175

agc acc ctc acc ctg agc aag gcc gac tac gag aag cac aag gtg tac 576

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

gcc tgc gag gtg acc cac cag ggc ctg agc agc ccc gtg acc aag agc 624

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

ttc aac cgg ggc gag tgt 642

Phe Asn Arg Gly Glu Cys

210

<210>129

<211>214

<212>PRT

<213>Artificial sequence

<220>

<223>IgG light chain of 03-001，03-002，03-009，03-013，03-014and 03-

018

<400>129

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val 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>130

<211>4914

<212>DNA

<213>Artificial sequence

<220>

<223>Vector pDV-C05

<400>130

aagcttgcat gcaaattcta tttcaaggag acagtcataa tgaaatacct attgcctacg 60

gcagccgctg gattgttatt actcgcggcc cagccggcca tggccgaggt gtttgactaa 120

tggggcgcgc ctcagggaac cctggtcacc gtctcgagcg gtacgggcgg ttcaggcgga 180

accggcagcg gcactggcgg gtcgacggaa attgtgctca cacagtctcc agccaccctg 240

tctttgtctc caggggaaag agccaccctc tcctgcaggg ccagtcagag tgttagcagc 300

tacttagcct ggtaccaaca gaaacctggc caggctccca ggctcctcat ctatgatgca 360

tccaacaggg ccactggcat cccagccagg ttcagtggca gtgggtctgg gacagacttc 420

actctcacca tcagcagcct agagcctgaa gattttgcag tttattactg tcagcagcgt 480

agcaactggc ctccggcttt cggcggaggg accaaggtgg agatcaaacg tgcggccgca 540

tataccgata ttgaaatgaa ccgcctgggc aaaggggccg catagactgt tgaaagttgt 600

ttagcaaaac ctcatacaga aaattcattt actaacgtct ggaaagacga caaaacttta 660

gatcgttacg ctaactatga gggctgtctg tggaatgcta caggcgttgt ggtttgtact 720

ggtgacgaaa ctcagtgtta cggtacatgg gttcctattg ggcttgctat ccctgaaaat 780

gagggtggtg gctctgaggg tggcggttct gagggtggcg gttctgaggg tggcggtact 840

aaacctcctg agtacggtga tacacctatt ccgggctata cttatatcaa ccctctcgac 900

ggcacttatc cgcctggtac tgagcaaaac cccgctaatc ctaatccttc tcttgaggag 960

tctcagcctc ttaatacttt catgtttcag aataataggt tccgaaatag gcagggtgca 1020

ttaactgttt atacgggcac tgttactcaa ggcactgacc ccgttaaaac ttattaccaq 1080

tacactcctg tatcatcaaa agccatgtat gacgcttact ggaacggtaa attcagagac 1140

tgcgctttcc attctggctt taatgaggat ccattcgttt gtgaatatca aggccaatcg 1200

tctgacctgc ctcaacctcc tgtcaatgct ggcggcggct ctggtggtgg ttctggtggc 1260

ggctctgagg gtggcggctc tgagggtggc ggttctgagg gtggcggctc tgagggtggc 1320

ggttccggtg gcggctccgg ttccggtgat tttgattatg aaaaaatggc aaacgctaat 1380

aagggggcta tgaccgaaaa tgccgatgaa aacgcgctac agtctgacgc taaaggcaaa 1440

cttgattctg tcgctactga ttacggtgct gctatcgatg gtttcattgg tgacgtttcc 1500

ggccttgcta atggtaatgg tgctactggt gattttgctg gctctaattc ccaaatggct 1560

caagtcggtg acggtgataa ttcaccttta atgaataatt tccgtcaata tttaccttct 1620

ttgcctcagt cggttgaatg tcgcccttat gtctttggcg ctggtaaacc atatgaattt 1680

tctattgatt gtgacaaaat aaacttattc cgtggtgtct ttgcgtttct tttatatgtt 1740

gccaccttta tgtatgtatt ttcgacgttt gctaacatac tgcgtaataa ggagtcttaa 1800

taagaattca ctggccgtcg ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca 1860

acttaatcgc cttgcagcac atcccccttt cgccagctgg cgtaatagcg aagaggcccg 1920

caccgatcgc ccttcccaac agttgcgcag cctgaatggc gaatggcgcc tgatgcggta 1980

ttttctcctt acgcatctgt gcggtatttc acaccgcata cgtcaaagca accatagtac 2040

gcgccctgta gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct 2100

acacttgcca gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg 2160

ttcgccggct ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt 2220

gctttacggc acctcgaccc caaaaaactt gatttgggtg atggttcacg tagtgggcca 2280

tcgccctgat agacggtttt tcgccctttg acgttggagt ccacgttctt taatagtgga 2340

ctcttgttcc aaactggaac aacactcaac cctatctcgg gctattcttt tgatttataa 2400

gggattttgc cgatttcggc ctattggtta aaaaatgagc tgatttaaca aaaatttaac 2460

gcgaatttta acaaaatatt aacgtttaca attttatggt gcactctcag tacaatctgc 2520

tctgatgccg catagttaag ccagccccga cacccgccaa cacccgctga cgcgccctga 2580

cgggcttgtc tgctcccggc atccgcttac agacaagctg tgaccgtctc cgggagctgc 2640

atgtgtcaga ggttttcacc gtcatcaccg aaacgcgcga gacgaaaggg cctcgtgata 2700

cgcctatttt tataggttaa tgtcatgata ataatggttt cttagacgtc aggtggcact 2760

tttcggggaa atgtgcgcgg aacccctatt tgtttatttt tctaaataca ttcaaatatg 2820

tatccgctca tgagacaata accctgataa atgcttcaat aatattgaaa aaggaagagt 2880

atgagtattc aacatttccg tgtcgccctt attccctttt ttgcggcatt ttgccttcct 2940

gtttttgctc acccagaaac gctggtgaaa gtaaaagatg ctgaagatca gttgggtgca 3000

cgagtgggtt acatcgaact ggatctcaac agcggtaaga tccttgagag ttttcgcccc 3060

gaagaacgtt ttccaatgat gagcactttt aaagttctgc tatgtggcgc ggtattatcc 3120

cgtattgacg ccgggcaaga gcaactcggt cgccgcatac actattctca gaatgacttg 3180

gttgagtact caccagtcac agaaaagcat cttacggatg gcatgacagt aagagaatta 3240

tgcagtgctg ccataaccat gagtgataac actgcggcca acttacttct gacaacgatc 3300

ggaggaccga aggagctaac cgcttttttg cacaacatgg gggatcatgt aactcgcctt 3360

gatcgttggg aaccggagct gaatgaagcc ataccaaacg acgagcgtga caccacgatg 3420

cctgtagcaa tggcaacaac gttgcgcaaa ctattaactg gcgaactact tactctagct 3480

tcccggcaac aattaataga ctggatggag gcggataaag ttgcaggacc acttctgcgc 3540

tcggcccttc cggctggctg gtttattgct gataaatctg gagccggtga gcgtgggtct 3600

cgcggtatca ttgcagcact ggggccagat ggtaagccct cccgtatcgt agttatctac 3660

acgacgggga gtcaggcaac tatggatgaa cgaaatagac agatcgctga gataggtgcc 3720

tcactgatta agcattggta actgtcagac caagtttact catatatact ttagattgat 3780

ttaaaacttc atttttaatt taaaaggatc taggtgaaga tcctttttga taatctcatg 3840

accaaaatcc cttaacgtga gttttcgttc cactgagcgt cagaccccgt agaaaagatc 3900

aaaggatctt cttgagatcc tttttttctg cgcgtaatct gctgcttgca aacaaaaaaa 3960

ccaccgctac cagcggtggt ttgtttgccg gatcaagagc taccaactct ttttccgaag 4020

gtaactggct tcagcagagc gcagatacca aatactgtcc ttctagtgta gccgtagtta 4080

ggccaccact tcaagaactc tgtagcaccg cctacatacc tcgctctgct aatcctgtta 4140

ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg ggttggactc aagacgatag 4200

ttaccggata aggcgcagcg gtcgggctga acggggggtt cgtgcacaca gcccagcttg 4260

gagcgaacga cctacaccga actgagatac ctacagcgtg agctatgaga aagcgccacg 4320

cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg gcagggtcgg aacaggagag 4380

cgcacgaggg agcttccagg gggaaacgcc tggtatcttt atagtcctgt cgggtttcgc 4440

cacctctgac ttgagcgtcg atttttgtga tgctcgtcag gggggcggag cctatggaaa 4500

aacgccagca acgcggcctt tttacggttc ctggcctttt gctggccttt tgctcacatg 4560

ttctttcctg cgttatcccc tgattctgtg gataaccgta ttaccgcctt tgagtgagct 4620

gataccgctc gccgcagccg aacgaccgag cgcagcgagt cagtgagcga ggaagcggaa 4680

gagcgcccaa tacgcaaacc gcctctcccc gcgcgttggc cgattcatta atgcagctgg 4740

cacgacaggt ttcccgactg gaaagcgggc agtgagcgca acgcaattaa tgtgagttag 4800

ctcactcatt aggcacccca ggctttacac tttatgcttc cggctcgtat gttgtgtgga 4860

attgtgagcg gataacaatt tcacacagga aacagctatg accatgatta cgcc 4914

<210>131

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuCIgG

<400>131

gtccaccttg gtgttgctgg gctt 24

<210>132

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH1B/7A

<400>132

cagrtgcagc tggtgcartc tgg 23

<210>133

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH1C

<400>133

saggtccagc tggtrcagtc tgg 23

<210>134

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH2B

<400>134

saggtgcagc tggtggagtc tgg 23

<210>135

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH3B

<400>135

saggtgcagc tggtggagtc tgg 23

<210>136

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH3C

<400>136

gaggtgcagc tggtggagwc ygg 23

<210>137

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH4B

<400>137

caggtgcagc tacagcagtg ggg 23

<210>138

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH4C

<400>138

cagstgcagc tgcaggagtc sgg 23

<210>139

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH5B

<400>139

gargtgcagc tggtgcagtc tgg 23

<210>140

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH6A

<400>140

caggtacagc tgcagcagtc agg 23

<210>141

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH1/2

<400>141

tgaggagacg gtgaccaggg tgcc 24

<210>142

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH3

<400>142

tgaagagacg gtgaccattg tccc 24

<210>143

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH4/5

<400>143

tgaggagacg gtgaccaggg ttcc 24

<210>144

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH6

<400>144

tgaggagacg gtgaccgtgg tccc 24

<210>145

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH1B/7A-NcoI

<400>145

gtcctcgcaa ctgcggccca gccggccatg gcccagrtgc agctggtgca rtctgg 56

<210>146

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH1C-NcoI

<400>146

gtcctcgcaa ctgcggccca gccggccatg gccsaggtcc agctggtrca gtctgg 56

<210>147

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH2B-NcoI

<400>147

gtcctcgcaa ctgcggccca gccggccatg gcccagrtca ccttgaagga gtctgg 56

<210>148

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH3B-NcoI

<400>148

gtcctcgcaa ctgcggccca gccggccatg gccsaggtgc agctggtgga gtctgg 56

<210>149

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH3C-NcoI

<400>149

gtcctcgcaa ctgcggccca gccggccatg gccgaggtgc agctggtgga gwcygg 56

<210>150

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH4B-NcoI

<400>150

gtcctcgcaa ctgcggccca gccggccatg gcccaggtgc agctacagca gtgggg 56

<210>151

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH4C-NcoI

<400>151

gtcctcgcaa ctgcggccca gccggccatg gcccagstgc agctgcagga gtcsgg 56

<210>152

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH5B-NcoI

<400>152

gtcctcgcaa ctgcggccca gccggccatg gccgargtgc agctggtgca gtctgg 56

<210>153

<211>56

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVH6A-NcoI

<400>153

gtcctcgcaa ctgcggccca gccggccatg gcccaggtac agctgcagca gtcagg 56

<210>154

<211>36

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH1/2-XhoI

<400>154

gagtcattct cgactcgaga cggtgaccag ggtgcc 36

<210>155

<211>36

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH3-XhoI

<400>155

gagtcattct cgactcgaga cggtgaccat tgtccc 36

<210>156

<211>36

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH4/5-XhoI

<400>156

gagtcattct cgactcgaga cggtgaccag ggttcc 36

<210>157

<211>36

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJH6-XhoI

<400>157

gagtcattct cgactcgaga cggtgaccgt ggtccc 36

<210>158

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuCk

<400>158

acactctccc ctgttgaagc tctt 24

<210>159

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuClambda2

<400>159

tgaacattct gtaggggcca ctg 23

<210>160

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuClambda7

<400>160

agagcattct gcaggggcca ctg 23

<210>161

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1A

<400>161

cagtctgtgc tgactcagcc acc 23

<210>162

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1B

<400>162

cagtctgtgy tgacgcagcc gcc 23

<210>163

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1C

<400>163

cagtctgtcg tgacgcagcc gcc 23

<210>164

<211>21

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda2

<400>164

cartctgccc tgactcagcc t 21

<210>165

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda3A

<400>165

tcctatgwgc tgactcagcc acc 23

<210>166

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda3B

<400>166

tcttctgagc tgactcagga ccc 23

<210>167

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda4

<400>167

cacgttatac tgactcaacc gcc 23

<210>168

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda5

<400>168

caggctgtgc tgactcagcc gtc 23

<210>169

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda6

<400>169

aattttatgc tgactcagcc cca 23

<210>170

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda7/8

<400>170

cagrctgtgg tgacycagga gcc 23

<210>171

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda9

<400>171

cwgcctgtgc tgactcagcc mcc 23

<210>172

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa1B

<400>172

gacatccagw tgacccagtc tcc 23

<210>173

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa2

<400>173

gatgttgtga tgactcagtc tcc 23

<210>174

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa3

<400>174

gaaattgtgw tgacrcagtc tcc 23

<210>175

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa4

<400>175

gatattgtga tgacccacac tcc 23

<210>176

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa5

<400>176

gaaacgacac tcacgcagtc tcc 23

<210>177

<211>23

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa6

<400>177

gaaattgtgc tgactcagtc tcc 23

<210>178

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda1

<400>178

acctaggacg gtgaccttgg tccc 24

<210>179

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda2/3

<400>179

acctaggacg gtcagcttgg tccc 24

<210>180

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda4/5

<400>180

acytaaaacg gtgagctggg tccc 24

<210>181

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa1

<400>181

acgtttgatt tccaccttgg tccc 24

<210>182

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa2

<400>182

acgtttgatc tccagcttgg tccc 24

<210>183

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa3

<400>183

acgtttgata tccactttgg tccc 24

<210>184

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa4

<400>184

acgtttgatc tccaccttgg tccc 24

<210>185

<211>24

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa5

<400>185

acgtttaatc tccagtcgtg tccc 24

<210>186

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa1B-SalI

<400>186

tgagcacaca ggtcgacgga catccagwtg acccagtctc c 41

<210>187

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa2-SalI

<400>187

tgagcacaca ggtcgacgga tgttgtgatg actcagtctc c 41

<210>188

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa3B-SalI

<400>188

tgagcacaca ggtcgacgga aattgtgwtg acrcagtctc c 41

<210>189

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa4B-SalI

<400>189

tgagcacaca ggtcgacgga tattgtgatg acccacactc c 41

<210>190

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa5-SalI

<400>190

tgagcacaca ggtcgacgga aacgacactc acgcagtctc c 41

<210>191

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVkappa6-SalI

<400>191

tgagcacaca ggtcgacgga aattgtgctg actcagtctc c 41

<210>192

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa1-NotI

<400>192

gagtcattct cgacttgcgg ccgcacgttt gatttccacc ttggtccc 48

<210>193

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa2-NotI

<400>193

gagtcattct cgacttgcgg ccgcacgttt gatctccagc ttggtccc 48

<210>194

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa3-NotI

<400>194

gagtcattct cgacttgcgg ccgcacgttt gatatccact ttggtccc 48

<210>195

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa4-NotI

<400>195

gagtcattct cgacttgcgg ccgcacgttt gatctccacc ttggtccc 48

<210>196

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJkappa5-NotI

<400>196

gagtcattct cgacttgcgg ccgcacgttt aatctccagt cgtgtccc 48

<210>197

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1A-SalI

<400>197

tgagcacaca ggtcgacgca gtctgtgctg actcagccac c 41

<210>198

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1B-SalI

<400>198

tgagcacaca ggtcgacgca gtctgtgytg acgcagccgc c 41

<210>199

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda1C-SalI

<400>199

tgagcacaca ggtcgacgca gtctgtcgtg acgcagccgc c 41

<210>200

<211>39

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda2-SalI

<400>200

tgagcacaca ggtcgacgca rtctgccctg actcagcct 39

<210>201

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda3A-SalI

<400>201

tgagcacaca ggtcgacgtc ctatgwgctg actcagccac c 41

<210>202

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda3B-SalI

<400>202

tgagcacaca ggtcgacgtc ttctgagctg actcaggacc c 41

<210>203

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda4-SalI

<400>203

tgagcacaca ggtcgacgca cgttatactg actcaaccgc c 41

<210>204

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda5-SalI

<400>204

tgagcacaca ggtcgacgca ggctgtgctg actcagccgt c 41

<210>205

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda6-SalI

<400>205

tgagcacaca ggtcgacgaa ttttatgctg actcagcccc a 41

<210>206

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda7/8-SalI

<400>206

tgagcacaca ggtcgacgca grctgtggtg acycaggagc c 41

<210>207

<211>41

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuVlambda9-SalI

<400>207

tgagcacaca ggtcgacgcw gcctgtgctg actcagccmc c 41

<210>208

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda1-NotI

<400>208

gagtcattct cgacttgcgg ccgcacctag gacggtgacc ttggtccc 48

<210>209

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda2/3-NotI

<400>209

gagtcattct cgacttgcgg ccgcacctag gacggtcagc ttggtccc 48

<210>210

<211>48

<212>DNA

<213>Artificial sequence

<220>

<223>primer HuJlambda4/5-NotI

<400>210

gagtcattct cgacttgcgg ccgcacytaa aacggtgagc tgggtccc 48

<210>211

<211>753

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-019

<220>

<221>CDS

<222>(1)..(753)

<223>

<400>211

gcc atg gcc cag atg cag ctg gtg cag tct ggg gga ggc gtg gtc cag 48

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln

1 5 10 15

cct ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt ggc tat gct atg cac tgg gtc cgc cag gct cca ggc aag ggg ctg 144

Ser Gly Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtg gca gtt ata tca tat gat gga agc aat aaa tac tac gca 192

Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cga ttc gcc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctg caa atg aac agc ctg aga gct gag gac acg gct gtg 288

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

85 90 95

tat tac tgt gcg aga ttc cct ggt ggt acc aga agc cgc ggc tac atg 336

Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met

100 105 110

gac gtc tgg ggc aaa ggg acc acg gtc acc gtc tcg agc ggt acg ggc 384

Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly

115 120 125

ggt tca ggc gga acc ggc agc ggc act ggc ggg tcg acg gaa att gtg 432

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile Val

130 135 140

ctc aca cag tct cca gcc acc ctg tct ttg tct cca ggg gaa aga gcc 480

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

145 150 155 160

acc ctc tcc tgc agg gcc agt cag agt gtt agc agc tac tta gcc tgg 528

Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala Trp

165 170 175

tac caa cag aaa cct ggc cag gct ccc agg ctc ctc atc tat gat gca 576

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala

180 185 190

tcc aac agg gcc act ggc atc cca gcc agg ttc agt ggc agt ggg tct 624

Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

195 200 205

ggg aca gac ttc act ctc acc atc agc agc cta gag cct gaa gat ttt 672

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe

210 215 220

gca gtt tat tac tgt cag cag cgt agc aac tgg cct ccg gct ttc ggc 720

Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe Gly

225 230 235 240

gga ggg acc aag gtg gag atc aaa cgt gcg gcc 753

Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>212

<211>251

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-019

<400>212

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln

1 5 10 15

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Gly Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met

100 105 110

Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly

115 120 125

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile Val

130 135 140

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

145 150 155 160

Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala Trp

165 170 175

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala

180 185 190

Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

195 200 205

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe

210 215 220

Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe Gly

225 230 235 240

Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>213

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-020

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>213

gcc atg gcc gaa gtg cag ctg gtg cag tct ggg tca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ser Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tct tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag aaa att tta cac agc tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Lys Ile Leu His Ser Ser Asn Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act cct ccg 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Pro

225 230 235 240

gtt ttc ggc gga ggg acc aag gtg gaa atc aaa cgt gcg gcc 762

Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>214

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-020

<400>214

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ser Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Lys Ile Leu His Ser Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Pro

225 230 235 240

Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>215

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-021

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>215

gcc atg gcc cag gtc cag ctg gta cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt gtt tta cac agc tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu His Ser Ser Asn Asn Lys Asn Tyr

165 170 175

cta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg caa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act cct ccg 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Pro

225 230 235 240

acg ttc ggc caa ggg acc aag gtg gaa atc aaa cgt gcg gcc 762

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>216

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-021

<400>216

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

15 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu His Ser Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Pro

225 230 235 240

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>217

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-022

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>217

gcc atg gcc cag atg cag ctg gtg caa tct gga aca gag gtg aaa aag 48

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt gtt tta tac agc tcc atc aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

act ttt ggc cag ggg acc aag gtg gaa atc aaa cgt gcg gcc 762

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>218

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-022

<400>218

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>219

<211>780

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-023

<220>

<221>CDS

<222>(1)..(780)

<223>

<400>219

gcc atg gcc cag gtg cag cta cag cag tgg ggc gca gga ctg ttg aag 48

Ala Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys

1 5 10 15

cct tcg gag acc ctg tcc ctc acc tgc gct gtc tat ggt ggg tct ttc 96

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

20 25 30

agt ggt ttc tac tgg agc tgg atc cgc cag ccc cca ggg aag ggg ctg 144

Ser Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

35 40 45

gag tgg att ggg gaa atc aat cat agt gga agc acc aac tac aac ccg 192

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

50 55 60

tcc ctc aag agt cga gtc acc ata tca gta gac acg tcc aag aac cag 240

Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln

65 70 75 80

ttc tcc ctg aag ctg agc tct gtg acc gcc gcg gac acg gct gtg tat 288

Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

85 90 95

tac tgt gcg aga agg gtg gag gta gta gag tac cag ctg ctc cgt ccc 336

Tyr Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro

100 105 110

cga tat aaa agt tgg ttc gac ccc tgg ggc cag ggc acc ctg gtc acc 384

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

115 120 125

gtc tcg agc ggt acg ggc ggt tca ggc gga acc ggc agc ggc act ggc 432

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly

130 135 140

ggg tcg acg cag tct gcc ctg act cag cct cgc tca gtg tcc ggg tct 480

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

145 150 155 160

cct gga cag tca gtc acc atc tcc tgc act gga tcc agc agt act gtt 528

Pro Gly Gln Ser Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Thr Val

165 170 175

ggt ggt tat aac tat gtc tcc tgg tac caa cag cac cca ggc aaa gcc 576

Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala

180 185 190

ccc aaa ctc atg att tat gat gtc agt aag cgg ccc tca ggg gtt tct 624

Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser

195 200 205

aat cgc ttc tct ggc tcc aag tct ggc aac acg gcc tcc ctg acc atc 672

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

210 215 220

tct ggg ctc cag gct gag gac gag gct gat tat tac tgc agc tca tat 720

Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr

225 230 235 240

aca agc agc agc act tat gtc ttc gga act ggg acc aag gtc acc gtc 768

Thr Ser Ser Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val

245 250 255

cta ggt gcg gcc 780

Leu Gly Ala Ala

260

<210>220

<211>260

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-023

<400>220

Ala Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys

1 5 10 15

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

20 25 30

Ser Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

35 40 45

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

50 55 60

Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln

65 70 75 80

Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro

100 105 110

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

115 120 125

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly

130 135 140

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

145 150 155 160

Pro Gly Gln Ser Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Thr Val

165 170 175

Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala

180 185 190

Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser

195 200 205

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

210 215 220

Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr

225 230 235 240

Thr Ser Ser Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val

245 250 255

Leu Gly Ala Ala

260

<210>221

<211>753

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-024

<220>

<221>CDS

<222>(1)..(753)

<223>

<400>221

gcc atg gcc cag gtg cag ctg gtg gag tct ggg tct gag ttg aag atc 48

Ala Met Ala Gln Val Gln Leu Val Glu Ser Gly Ser Glu Leu Lys Ile

1 5 10 15

cct ggg gcc tca gtg aag gtt tcc tgc aag gct act gga tac acc ttc 96

Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Thr Gly Tyr Thr Phe

20 25 30

act cgt tat tct ctg aat tgg gtg cgg cag gcc cct gga caa ggg ctt 144

Thr Arg Tyr Ser Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg gtg ggg tgg att aac acc cag act gga aac tca aac tat ggc 192

Glu Trp Val Gly Trp Ile Asn Thr Gln Thr Gly Asn Ser Asn Tyr Gly

50 55 60

cag gcc ttc tca gga cgg ttt gtc ttc tcc ttg gac acc tca gtc agc 240

Gln Ala Phe Ser Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser

65 70 75 80

acg gca tat ttg caa atc agc agc cta cag gcc gag gac act gcc aca 288

Thr Ala Tyr Leu Gln Ile Ser Ser Leu Gln Ala Glu Asp Thr Ala Thr

85 90 95

tac tac tgt gcg agg aag agt gcg ggt tcg aat gct ttc gac att tgg 336

Tyr Tyr Cys Ala Arg Lys Ser Ala Gly Ser Asn Ala Phe Asp Ile Trp

100 105 110

ggc caa ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg cag tct gtc gtg acg cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Gln Ser Val Val Thr Gln

130 135 140

ccg ccc tca gtg tct gcg gcc cca gga cag aag gcc acc atc tcc tgc 480

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

145 150 155 160

tct gga agc agc tcc aac att ggg aat aat tat gta tcc tgg tac cag 528

Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn Tyr Val Ser Trp Tyr Gln

165 170 175

cag ctc cca gga aca gcc ccc aaa ctc ctc att tat gac aat aat aag 576

Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Asp Asn Asn Lys

180 185 190

cga ccc tca ggg att cct aac cga ttc tct ggc tcc aag tct ggc acg 624

Arg Pro Ser Gly Ile Pro Asn Arg Phe Ser Gly Ser Lys Ser Gly Thr

195 200 205

tca gcc acc ctg ggc atc acc gga ctc cag act ggg gac gag gcc gat 672

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

210 215 220

tat tac tgc gga aca tgg gat agc agc ctg agt gct tat gtc ttc gga 720

Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu Ser Ala Tyr Val Phe Gly

225 230 235 240

act ggg acc aag gtc acc gtc cta ggt gcg gcc 753

Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala

245 250

<210>222

<211>251

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-024

<400>222

Ala Met Ala Gln Val Gln Leu Val Glu Ser Gly Ser Glu Leu Lys Ile

1 5 10 15

Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Thr Gly Tyr Thr Phe

20 25 30

Thr Arg Tyr Ser Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Val Gly Trp Ile Asn Thr Gln Thr Gly Asn Ser Asn Tyr Gly

50 55 60

Gln Ala Phe Ser Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser

65 70 75 80

Thr Ala Tyr Leu Gln Ile Ser Ser Leu Gln Ala Glu Asp Thr Ala Thr

85 90 95

Tyr Tyr Cys Ala Arg Lys Ser Ala Gly Ser Asn Ala Phe Asp Ile Trp

100 105 110

Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Gln Ser Val Val Thr Gln

130 135 140

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

145 150 155 160

Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn Tyr Val Ser Trp Tyr Gln

165 170 175

Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Asp Asn Asn Lys

180 185 190

Arg Pro Ser Gly Ile Pro Asn Arg Phe Ser Gly Ser Lys Ser Gly Thr

195 200 205

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

210 215 220

Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu Ser Ala Tyr Val Phe Gly

225 230 235 240

Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala

245 250

<210>223

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-025

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>223

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct atc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Ile Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat aat att ccg tat gct ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Asn Ile Pro Tyr Ala Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>224

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-025

<400>224

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Ile Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Asn Ile Pro Tyr Ala Phe

225 230 235 240

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

245 250

<210>225

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-026

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>225

gcc atg gcc cag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gcc atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt att tta tac agc tcc aac agt aag aac tac tta ggt 528

Ser Ser Gln Ser Ile Leu Tyr Ser Ser Asn Ser Lys Asn Tyr Leu Gly

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag gtg gag atc aaa cgt gcg gcc 756

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>226

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-026

<400>226

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Ile Leu Tyr Ser Ser Asn Ser Lys Asn Tyr Leu Gly

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>227

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-027

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>227

gcc atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aaa gtg gat atc aaa cgt gcg gcc 756

Gly Gln Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>228

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-027

<400>228

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>229

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-029

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>229

gcc atg gcc gaa gtg cag ctg gtg cag tct ggg gga ggc ttg gtt cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

ccg ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act cct ctc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc gca ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>230

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-029

<400>230

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

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

245 250

<210>231

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-030

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>231

gcc atg gcg gag gtc cag gtg gta cag tct gga gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Val Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctc aaa ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttt act ctc acc atc agc agt ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act cct ctg acg ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc caa ggg acc aag gtg gaa atc aaa cgt gcg gcc 756

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>232

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-030

<400>232

Ala Met Ala Glu Val Gln Val Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>233

<211>759

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-031

<220>

<221>CDS

<222>(1)..(759)

<223>

<400>233

gcc atg gcc cag gtg cag ctg gtg caa tct ggg gct gac gtg aag aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Asp Val Lys Lys

1 5 10 15

cct ggg tcc tcg gtg aag gtc tcc tgc gag gct tct gga ggc acg ttc 96

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

20 25 30

agc agc tat gct atc agc tgg gtg cga cag gcc cct gga caa ggg ctt 144

Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg atg gga agg atc atc cct atc ctt ggt ata aca aac tac gca 192

Glu Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Thr Asn Tyr Ala

50 55 60

cag aag ttc cag ggc aga gtc aca att acc gcg gac aaa tcc acg ggc 240

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Gly

65 70 75 80

aca ggc aac atg gag ctg agc agc ctg aga tct gag gac acg gcc gtg 288

Thr Gly Asn Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

tat tac tgt gcg aga gaa tcg ggt ggt ggc tac gat aac cac ttt gac 336

Tyr Tyr Cys Ala Arg Glu Ser Gly Gly Gly Tyr Asp Asn His Phe Asp

100 105 110

tac tgg ggc cag gga acc ctg gtc acc gtc tcg agc ggt acg ggc ggt 384

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

115 120 125

tca ggc gga acc ggc agc ggc act ggc ggg tcg acg cag tct gtg ctg 432

Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Gln Ser Val Leu

130 135 140

acg cag ccg ccc tca gcg tct ggg acc ccc gga cag agg gtc acc atc 480

Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln Arg Val Thr Ile

145 150 155 160

tct tgt tct gga ggc agc tcc aac atc gga agt aat act gta aac tgg 528

Ser Cys Ser Gly Gly Ser Ser Asn Ile Gly Ser Asn Thr Val Asn Trp

165 170 175

tac cag caa ctc cca gga acg gcc ccc aaa ctc gtc atc tat gct aat 576

Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Val Ile Tyr Ala Asn

180 185 190

aat cag cgg ccc tca ggg gtc cct gac cga ttc tct gcc tcc aag tct 624

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

195 200 205

ggc acc tca gcc tcc ctg gcc atc agt ggg ctc cag tct gag gat gag 672

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

210 215 220

gct gat tat tac tgt gca gct tgg gat gac agc ctg act ggt gga gtg 720

Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu Thr Gly Gly Val

225 230 235 240

ttc ggc gga ggg acc cag ctc acc gtt tta agt gcg gcc 759

Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Ser Ala Ala

245 250

<210>234

<211>253

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-031

<400>234

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Asp Val Lys Lys

1 5 10 15

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

20 25 30

Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Thr Asn Tyr Ala

50 55 60

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Gly

65 70 75 80

Thr Gly Asn Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

Tyr Tyr Cys Ala Arg Glu Ser Gly Gly Gly Tyr Asp Asn His Phe Asp

100 105 110

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

115 120 125

Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Gln Ser Val Leu

130 135 140

Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln Arg Val Thr Ile

145 150 155 160

Ser Cys Ser Gly Gly Ser Ser Asn Ile Gly Ser Asn Thr Val Asn Trp

165 170 175

Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Val Ile Tyr Ala Asn

180 185 190

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

195 200 205

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

210 215 220

Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu Thr Gly Gly Val

225 230 235 240

Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Ser Ala Ala

245 250

<210>235

<211>771

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-032

<220>

<221>CDS

<222>(1)..(771)

<223>

<400>235

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gct gag gtg aag aag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys

1 5 10 15

cct ggg tcc tcg gtg aag gtc tcc tgc aag gct tct gga ggc acc ttc 96

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

20 25 30

agc agc tat gct atc agc tgg gtg cga cag gcc cct gga caa ggg ctt 144

Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg atg gga aag atc atc cct att ctt ggt aaa gtc act tac gca 192

Glu Trp Met Gly Lys Ile Ile Pro Ile Leu Gly Lys Val Thr Tyr Ala

50 55 60

cag aag ttc cag gcc aga gtc acg att acc gcg gac gaa tcc acg agc 240

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

65 70 75 80

aca gcc tac ctg gag ctg agc agc ctg aga tct gag gac acg gcc gtt 288

Thr Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

ttt tac tgt gcg aga gac ggc tgg gat ttg act ggt tct ttt tta ggc 336

Phe Tyr Cys Ala Arg Asp Gly Trp Asp Leu Thr Gly Ser Phe Leu Gly

100 105 110

tac ggt atg gac gtc tgg ggc caa ggg acc acg gtc acc gtc tcg agc 384

Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

ggt acg ggc ggt tca ggc gga acc ggc agc ggc act ggc ggg tcg acg 432

Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr

130 135 140

cag tct gtc gtg acg cag ccg ccc tca gcg tct ggg acc ccc ggg cag 480

Gln Ser Val Val Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

145 150 155 160

agg gtc acc atc tct tgt tct gga agc agc tcc aac atc gga agt aat 528

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn

165 170 175

act gta agc tgg tac cag cag gtt cca ggg acg gcc ccc aag ctc ctc 576

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

180 185 190

atc tat agg aat aat cag cgg ccc cca ggg gtc cyt gac cga ttc tct 624

Ile Tyr Arg Asn Asn Gln Arg Pro Pro Gly Val Xaa Asp Arg Phe Ser

195 200 205

ggc tcc aag tct ggc acc tca gcc tcc ytg gcc atc agt ggg ctc cag 672

Gly Ser Lys Ser Gly Thr Ser Ala Ser Xaa Ala Ile Ser Gly Leu Gln

210 215 220

tct gac gat gag gcc ttt tat tac tgt gca gca tgg gat ggc agc mtg 720

Ser Asp Asp Glu Ala Phe Tyr Tyr Cys Ala Ala Trp Asp Gly Ser Xaa

225 230 235 240

aat ggt ctg gcc ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg 768

Asn Gly Leu Ala Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

245 250 255

gcc 771

Ala

<210>236

<211>257

<212>PRT

<213>Artificial sequence

<220>

<221>misc_feature

<222>(204)..(204)

<223>The ′Xaa′at location 204 stands for Pro，or Leu.

<220>

<221>misc_feature

<222>(218)..(218)

<223>The′Xaa′at location 218 stands for Leu.

<220>

<221>misc_feature

<222>(240)..(240)

<223>The ′Xaa′at location 240 stands for Met，or Leu.

<220>

<223>SC03-032

<400>236

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys

1 5 10 15

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

20 25 30

Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Met Gly Lys Ile Ile Pro Ile Leu Gly Lys Val Thr Tyr Ala

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

Phe Tyr Cys Ala Arg Asp Gly Trp Asp Leu Thr Gly Ser Phe Leu Gly

100 105 110

Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr

130 135 140

Gln Ser Val Val Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

145 150 155 160

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn

165 170 175

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

180 185 190

Ile Tyr Arg Asn Asn Gln Arg Pro Pro Gly Val Xaa Asp Arg Phe Ser

195 200 205

Gly Ser Lys Ser Gly Thr Ser Ala Ser Xaa Ala Ile Ser Gly Leu Gln

210 215 220

Ser Asp Asp Glu Ala Phe Tyr Tyr Cys Ala Ala Trp Asp Gly Ser Xaa

225 230 235 240

Asn Gly Leu Ala Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

245 250 255

Ala

<210>237

<211>765

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-033

<220>

<221>CDS

<222>(1)..(765)

<223>

<400>237

gcc atg gcc cag gtc cag ctg gta cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag acc agc cac aat att ttc tcc aga tcc aac aat aag gac tac 528

Cys Lys Thr Ser His Asn Ile Phe Ser Arg Ser Asn Asn Lys Asp Tyr

165 170 175

tta gct tgg tac cag cag aaa cca ggc cag cct ccc aga tta ctc att 576

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

180 185 190

tac tgg gcg tct acc cgg gca tcc ggg gtc cct gaa cga ttc agt ggc 624

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

195 200 205

agc ggc tct ggg aca gac ttc agt ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gcg gtt tat tac tgt cag caa tat tat agt tcc cct atg 720

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

225 230 235 240

tac agt ttt ggc cag ggg acc aag gtg gag atc aaa cgt gcg gcc 765

Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250 255

<210>238

<211>255

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-033

<400>238

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Thr Ser His Asn Ile Phe Ser Arg Ser Asn Asn Lys Asp Tyr

165 170 175

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

180 185 190

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

195 200 205

Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

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

225 230 235 240

Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250 255

<210>239

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-034

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>239

gcc atg gcc gag gtg cag ctg gtg cag tct gga gca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt att tta aac aga tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Ile Leu Asn Arg Ser Asn Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc aat ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Asn Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gag gat gtg gca gtt tat tac tgt cag cag tat aat aac tgg cct ctc 720

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

225 230 235 240

act ttc ggc gga ggg acc aaa gtg gat atc aaa cgt gcg gcc 762

Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>240

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-034

<400>240

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Ile Leu Asn Arg Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Asn Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

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

225 230 235 240

Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>241

<211>765

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-035

<220>

<221>CDS

<222>(1)..(765)

<223>

<400>241

gcc atg gcc gag gtg cag ctg gtg cag tct gga gca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

ccc ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agt cag agt gtt tta tac agc tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tsc tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg acs gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act ccc ctg 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu

225 230 235 240

tac agt ttt ggc cag ggg acc aag gtg gag atc aaa cct gcg gcc 765

Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Pro Ala Ala

245 250 255

<210>242

<211>255

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-035

<400>242

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu

225 230 235 240

Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Pro Ala Ala

245 250 255

<210>243

<211>759

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-036

<220>

<221>CDS

<222>(1)..(759)

<223>

<400>243

gcc atg gcc gag gtg cag ctg gtg cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt gtt tta cac agc ccc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu His Ser Pro Asn Asn Lys Asn Tyr

165 170 175

ttg gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act aac agt 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Asn Ser

225 230 235 240

ttt ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 759

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala

245 250

<210>244

<211>253

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-036

<400>244

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu His Ser Pro Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Asn Ser

225 230 235 240

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala

245 250

<210>245

<211>744

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-037

<220>

<221>CDS

<222>(1)..(744)

<223>

<400>245

gcc atg gcc aaa gtg cag ctg gtg cag tct gga gga ggc ttg atc cag 48

Ala Met Ala Lys Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc gtc 96

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

20 25 30

agt agc aac tac atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg 144

Ser Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca att gtt ttt agc ggt ggt agc aca tac tac gca gac 192

Glu Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg aac agc ctg aga gcc gag gac acg gcc gta tat 288

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

85 90 95

tat tgt gcg aga gat gcc cac cgg ggg ttc ggt atg gac gtc tgg ggc 336

Tyr Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga 384

Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly

115 120 125

acc ggc agc ggc act ggc ggg tcg acg tct tct gag ctg act cag gac 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Ser Glu Leu Thr Gln Asp

130 135 140

cct gct gtg tct gtg gcc ttg gga cag aca gtc agg atc aca tgc caa 480

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

145 150 155 160

gga gac agc ctc aga agc tat tat gca agc tgg tac cag cag aag cca 528

Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro

165 170 175

gga cag gcc cct gta ctt gtc atc tat ggc aaa aac aac cgg ccc tca 576

Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser

180 185 190

ggg atc cca gac cgg ttc tct ggc tcc agc tca gga aac aca gct tcc 624

Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser

195 200 205

ttg acc atc act ggg gct cag gcg gaa gat gag gcc gac tat tat tgt 672

Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys

210 215 220

aac ggc cgg gac agc agt ggt aac cat tgg gtg ttc ggc gga ggg acc 720

Asn Gly Arg Asp Ser Ser Gly Asn His Trp Val Phe Gly Gly Gly Thr

225 230 235 240

aag ctg acc gtc cta ggt gcg gcc 744

Lys Leu Thr Val Leu Gly Ala Ala

245

<210>246

<211>248

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-037

<400>246

Ala Met Ala Lys Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

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

20 25 30

Ser Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ile Val Phe Ser Gly Gly Ser 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 Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly

115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Ser Glu Leu Thr Gln Asp

130 135 140

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

145 150 155 160

Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser

180 185 190

Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser

195 200 205

Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys

210 215 220

Asn Gly Arg Asp Ser Ser Gly Asn His Trp Val Phe Gly Gly Gly Thr

225 230 235 240

Lys Leu Thr Val Leu Gly Ala Ala

245

<210>247

<211>744

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-038

<220>

<221>CDS

<222>(1)..(744)

<223>

<400>247

gcc atg gcc gag gtg cag ctg gtg cag tct gga gga ggc ttg atc cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct ggg ttc acc gtc 96

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

20 25 30

agt agc aac tac atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg 144

Ser Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gag tgg gtc tca att gtt ttt agc ggt ggt agc aca tac tac gca gac 192

Glu Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg aac agc ctg aga gcc gag gac acg gcc gta tat 288

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

85 90 95

tat tgt gcg aga gat gcc cat cgg ggg ttc ggt atg gac gtc tgg ggc 336

Tyr Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly

100 105 110

cag ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga 384

Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly

115 120 125

acc ggc agc ggc act ggc ggg tcg acg tct tct gag ctg act cag gac 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Ser Glu Leu Thr Gln Asp

130 135 140

cct gct gtg tct gtg qcc ttg gga cag aca gtc agg atc aca tgc caa 480

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

145 150 155 160

gga gac agc ctc aga agc tat tat gca agc tgg tac cag cag aag cca 528

Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro

165 170 175

gga cag gcc cct gta ctt gtc atc tat ggt aaa aac aac cgg ccc tca 576

Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser

180 185 190

ggg atc cca gac cga ttc tct ggc tcc agc tca gga gac aca gct tcc 624

Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asp Thr Ala Ser

195 200 205

ttg acc atc act ggg gct cag gcg gaa gat gag gct gac tat tac tgt 672

Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys

210 215 220

aac tcc cgg gac agc agt ggt aac cat tgg gtg ttc ggc gga ggg acc 720

Asn Ser Arg Asp Ser Ser Gly Asn His Trp Val Phe Gly Gly Gly Thr

225 230 235 240

aag ctg acc gtc cta ggt gcg gcc 744

Lys Leu Thr Val Leu Gly Ala Ala

245

<210>248

<211>248

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-038

<400>248

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln

1 5 10 15

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

20 25 30

Ser Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Trp Val Ser Ile Val Phe Ser Gly Gly Ser 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 Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly

115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Ser Glu Leu Thr Gln Asp

130 135 140

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

145 150 155 160

Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser

180 185 190

Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asp Thr Ala Ser

195 200 205

Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys

210 215 220

Asn Ser Arg Asp Ser Ser Gly Asn His Trp Val Phe Gly Gly Gly Thr

225 230 235 240

Lys Leu Thr Val Leu Gly Ala Ala

245

<210>249

<211>759

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-039

<220>

<221>CDS

<222>(1)..(759)

<223>

<400>249

gcc atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agc agc tat gcc atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg 144

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

35 40 45

gag tgg gtc tca gtt att tat agc ggt ggt act agt aca tac tat gca 192

Glu Trp Val Ser Val Ile Tyr Ser Gly Gly Thr Ser Thr Tyr Tyr Ala

50 55 60

gac tcc gtg aag ggc cgg ttc acc atc tcc aga gat aat tcc aag aac 240

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

65 70 75 80

aca ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gta 288

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

85 90 95

tat ttc tgt gcg aaa gga tct aaa tgg aac gac gtg ggg ggg ggt gac 336

Tyr Phe Cys Ala Lys Gly Ser Lys Trp Asn Asp Val Gly Gly Gly Asp

100 105 110

tac tgg ggc cag gga acc ctg gtc acc gtc tcg agc ggt acg ggc ggt 384

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

115 120 125

tca ggc gga acc ggc agc ggc act ggc ggg tcg acg aat ttt atg ctg 432

Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asn Phe Met Leu

130 135 140

act cag ccc cac tct gtg tcg gag tct ccg ggg aag acg gta acc atc 480

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

145 150 155 160

tcc tgc gcc ggc agc agt ggc agc att gcc agc aac tat gtg cag tgg 528

Ser Cys Ala Gly Ser Ser Gly Ser Ile Ala Ser Asn Tyr Val Gln Trp

165 170 175

tac cag caa cgc ccg ggc agt gcc ccc act act gtg atc tat gag gat 576

Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val Ile Tyr Glu Asp

180 185 190

aac caa aga ccc tct ggg gtc cct gat cgg ttc tct ggc tcc atc gac 624

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

195 200 205

agc tcc tcc aac tct gcc tcc ctc acc atc tct gga ctg aag act gag 672

Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly Leu Lys Thr Glu

210 215 220

gac gag gct gac tac tac tgt cag tct tat gat ggt tat ctt tgg att 720

Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Gly Tyr Leu Trp Ile

225 230 235 240

ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg gcc 759

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

245 250

<210>250

<211>253

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-039

<400>250

Ala Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

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

35 40 45

Glu Trp Val Ser Val Ile Tyr Ser Gly Gly Thr Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Phe Cys Ala Lys Gly Ser Lys Trp Asn Asp Val Gly Gly Gly Asp

100 105 110

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

115 120 125

Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asn Phe Met Leu

130 135 140

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

145 150 155 160

Ser Cys Ala Gly Ser Ser Gly Ser Ile Ala Ser Asn Tyr Val Gln Trp

165 170 175

Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val Ile Tyr Glu Asp

180 185 190

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

195 200 205

Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly Leu Lys Thr Glu

210 215 220

Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Gly Tyr Leu Trp Ile

225 230 235 240

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

245 250

<210>251

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-040

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>251

gcc atg gcc cag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc agg 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt agt ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Ser Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>252

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-040

<400>252

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Ser Pro Tyr Ser Phe

225 230 235 240

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

245 250

<210>253

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-041

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>253

gcc atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gat atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag cgg acc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>254

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-041

<400>254

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

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

245 250

<210>255

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-042

<220>

<221>misc_feature

<222>(153)..(154)

<223>n can be a，g，c or t

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>255

gcc atg gcc cag atg cag ctg gtg caa tct ggg gga ggc tta gtt cag 48

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctt tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtn tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac gat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asp Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agc ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>256

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-042

<220>

<221>misc_feature

<222>(153)..(154)

<223>n can be a，g，c or t

<400>256

Ala Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asp Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

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

245 250

<210>257

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-043

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>257

gcc atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agg tcc aac aat aag aac tac tta gct 528

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

165 170 175

tgg tac cag cag aag cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgt gaa tcc ggg gtc tct gag cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Ser Glu Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt acc ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>258

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-043

<400>258

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

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

145 150 155 160

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

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Ser Glu Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

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

245 250

<210>259

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-044

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>259

gcc atg gcc gag gtg cag ctg gtg gag act ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agg ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Arg Gly Ser Gly

195 200 205

tcc ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

ctg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Leu Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag ctg gag atc aaa cgt gcg gcc 756

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

245 250

<210>260

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-044

<400>260

Ala Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Arg Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Leu Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

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

245 250

<210>261

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-045

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>261

gcc atg gcc cag ctg cag ctg cag gag tcg ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Leu Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agt aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc cag 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ctg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act cca ttc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Phe Thr Phe

225 230 235 240

ggc cct ggg acc aaa gtg gat atc aaa cgt gcg gcc 756

Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>262

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-045

<400>262

Ala Met Ala Gln Leu Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Phe Thr Phe

225 230 235 240

Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Ala Ala

245 250

<210>263

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-046

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>263

gcc atg gcc gag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca ggg cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac agg ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gac ttc agt ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gcg gtt tat tac tgt cag caa tat tac agt cct ccg tac act ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Pro Pro Tyr Thr Phe

225 230 235 240

ggc ccg ggg acc aag gtg gaa atc aaa cgt gcg gcc 756

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

245 250

<210>264

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-046

<400>264

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Pro Pro Tyr Thr Phe

225 230 235 240

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

245 250

<210>265

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-047

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>265

gcc atg gcc gag gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc cag 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tat agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act cct ctc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc gga ggg acc aag gtg gaa atc aaa cgt gcg gcc 756

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>266

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-047

<400>266

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>267

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-048

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>267

gcc atg gcc gag gtg cag ctg gtg gag act ggg gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tac agt act ccg ctc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc gga ggg acc aag gtg gaa atc aaa cgt gcg gcc 756

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>268

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-048

<400>268

Ala Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>269

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-049

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>269

gcc atg gcc cag gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gac atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

tcc tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

Ser Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tat cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg ctc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc 756

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>270

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-049

<400>270

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

Ser Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>271

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-050

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>271

gcc atg gcc cag gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly GlySer Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gac atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

tcc tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

Ser Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tat cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg ctc act ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc 756

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>272

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-050

<400>272

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

Ser Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>273

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-051

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>273

gcc atg gcc cag gtg cag ctg gtg cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc ggc cag agt att tta tac agc tcc aac gat aag aac tac 528

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

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctt ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

act ttt ggc cag ggg acc aag gtg gaa atc aaa cgt gcg gcc 762

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>274

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-051

<400>274

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

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

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>275

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-052

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>275

gcc atg gcc gaa gtg cag ctg gtg cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag gtc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc acc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Thr Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

act ttt ggc cag ggg acc aag gtg gaa atc aaa cgt gcg gcc 762

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>276

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-052

<400>276

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Thr Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>277

<211>768

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-053

<220>

<221>CDS

<222>(1)..(768)

<223>

<400>277

gcc atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

cct ggg gcc tca gtg atg gtt tcc tgc aag gcc tct gga tac acc ttc 96

Pro Gly Ala Ser Val Met Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe

20 25 30

agt aac tat gct atg cat tgg gtg cgc cag ggc ccc gga caa agg ctt 144

Ser Asn Tyr Ala Met His Trp Val Arg Gln Gly Pro Gly Gln Arg Leu

35 40 45

gag tgg atg gga tgg atc aac gct gac aaa ggt cag aca aaa tat tca 192

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

50 55 60

cag aag ttc cag ggc aga gtc acc att acc ggg gac aca tcc gcc agc 240

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Gly Asp Thr Ser Ala Ser

65 70 75 80

aca gcc tac atg gac ctg agc agc ctg aga tct gaa gac acg gct gtg 288

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

85 90 95

tat tac tgt gcg aga ggg acc gga tat ttg cgg agc tac cac ggc atg 336

Tyr Tyr Cys Ala Arg Gly Thr Gly Tyr Leu Arg Ser Tyr His Gly Met

100 105 110

gac gtc tgg ggc cag ggg acc acg gtc acc gtc tcg agc ggt acg ggc 384

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly

115 120 125

ggt tca ggc gga acc ggc agc ggc act ggc ggg tcg acg gat gtt gtg 432

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val

130 135 140

atg act cag tct cca ccc tcc ctg ccc gtc acc cct ggg gag ccg gcc 480

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

145 150 155 160

tcc atc tcc tgc agg tct agt cag agc ctc ctc cat agt aat gga tac 528

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

165 170 175

aac tat ttg gat tgg tac ctg cag aag cca ggt cag tct cca cag ctc 576

Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu

180 185 190

ctg atc tat ttg ggt tct aat cgg gcc tcc ggg gtc cct gac agg ttc 624

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

195 200 205

agt ggc agt gga tca ggc aca gat ttt aca ctg aaa atc agc aga gtg 672

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

210 215 220

gag gct gag gat gtt ggg gtt tat tac tgc atg caa gct cta caa act 720

Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr

225 230 235 240

cct ctc acc ttc ggc caa ggg aca cga ctg gag att aaa cgt gcg gcc 768

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

245 250 255

<210>278

<211>256

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-053

<400>278

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

Pro Gly Ala Ser Val Met Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe

20 25 30

Ser Asn Tyr Ala Met His Trp Val Arg Gln Gly Pro Gly Gln Arg Leu

35 40 45

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

50 55 60

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Gly Asp Thr Ser Ala Ser

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Gly Thr Gly Tyr Leu Arg Ser Tyr His Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly

115 120 125

Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val

130 135 140

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

145 150 155 160

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

165 170 175

Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu

180 185 190

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

195 200 205

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

210 215 220

Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr

225 230 235 240

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

245 250 255

<210>279

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-054

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>279

gcc atg gcc gaa gtg cag ctg gtg cag tct ggg gga ggc gtg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln

1 5 10 15

cct ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc ggc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Gly Gly

195 200 205

tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac agt ttt 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

ggc cag ggg acc aag gtg gag atc aaa cgt gcg gcc 756

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>280

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-054

<400>280

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln

1 5 10 15

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gln Leu Thr Gln Ser Pro

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Gly Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Ser Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>281

<211>780

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-055

<220>

<221>CDS

<222>(1)..(780)

<223>

<400>281

gcc atg gcc cag gtg cag cta cag cag tgg ggc gca gga ctg ttg aag 48

Ala Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys

1 5 10 15

cct tcg gag acc ctg tcc ctc acc tgc gct gtc tat ggt ggg tcc ttc 96

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

20 25 30

agt ggt ttc tac tgg agc tgg atc cgc cag ccc cca ggg aag ggg ctg 144

Ser Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

35 40 45

gag tgg att ggg gaa atc aat cat agt gga agc acc aac tac aac ccg 192

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

50 55 60

tcc ctc aag agt cga gtc acc ata tca gca gac acg tcc aag aac cag 240

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

65 70 75 80

ttc tcc ctg aag ctg agc tct gtg acc gcc gcg gac acg gct gtg tat 288

Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

85 90 95

tac tgt gcg aga agg gtg gag gta gta gag tac cag ctg ctc cgt ccc 336

Tyr Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro

100 105 110

cga tat aaa agt tgg ttc gac ccc tgg ggc cag gga acc ctg gtc acc 384

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

115 120 125

gtc tcg agc ggt acg ggc ggt tca ggc gga acc ggc agc ggc act ggc 432

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly

130 135 140

ggg tcg acg cag tct gtg ttg acg cag ccg ccc tca gtg tct ggg gcc 480

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

145 150 155 160

cca ggg cag agg gtc tcc atc tcc tgc tct gga agc ggc gcc aat ggt 528

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

165 170 175

ggg act gat cct gtt tct tgg tac cag aaa ttc cca gga aca gcc ccc 576

Gly Thr Asp Pro Val Ser Trp Tyr Gln Lys Phe Pro Gly Thr Ala Pro

180 185 190

cac ctc ctc att tat gac aat aat aag cga ccc tca ggg att cct gac 624

His Leu Leu Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp

195 200 205

cga ttc tct ggc tcc aag tct ggc gcg tca gcc acc ctg gac atc acc 672

Arg Phe Ser Gly Ser Lys Ser Gly Ala Ser Ala Thr Leu Asp Ile Thr

210 215 220

gga ctc cag act ggg gac gag gcc gac tat tac tgc gga gca tgg gat 720

Gly Leu Gln Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp

225 230 235 240

ccc agt ctg agc ggt tat gtc ttc ggg act ggg acc cag ctc acc gtt 768

Pro Ser Leu Ser Gly Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val

245 250 255

tta agt gcg gcc 780

Leu Ser Ala Ala

260

<210>282

<211>260

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-055

<400>282

Ala Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys

1 5 10 15

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

20 25 30

Ser Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

35 40 45

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

50 55 60

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

65 70 75 80

Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro

100 105 110

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

115 120 125

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly

130 135 140

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

145 150 155 160

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

165 170 175

Gly Thr Asp Pro Val Ser Trp Tyr Gln Lys Phe Pro Gly Thr Ala Pro

180 185 190

His Leu Leu Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp

195 200 205

Arg Phe Ser Gly Ser Lys Ser Gly Ala Ser Ala Thr Leu Asp Ile Thr

210 215 220

Gly Leu Gln Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp

225 230 235 240

Pro Ser Leu Ser Gly Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val

245 250 255

Leu Ser Ala Ala

260

<210>283

<211>762

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-056

<220>

<221>CDS

<222>(1)..(762)

<223>

<400>283

gcc atg gcc gaa gtg cag ctg gtg cag tct gga aca gag gtg aaa aag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

ccg ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt 96

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

20 25 30

atc acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg 144

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

gag tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc 192

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

ccg tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac 240

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

65 70 75 80

acc gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata 288

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

tat tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg 336

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

ggc caa ggg acc acg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc 384

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

gga acc ggc agc ggc act ggc ggg tcg acg gat gtt gtg atg act cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

tct cca gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac 480

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

tgc aag tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac 528

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

tta gct tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att 576

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

tac tgg gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc 624

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

agc ggg tct ggg aca gat ttc act ctc acc atc agc agc ctg cag gct 672

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

gaa gat gtg gca gtt tat tac tgt cag caa tat tat agt act ccg tac 720

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

agt ttt ggc cag ggg acc aag gtg gag atc aaa cgt gcg gcc 762

Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>284

<211>254

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-056

<400>284

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys

1 5 10 15

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

20 25 30

Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu

35 40 45

Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser

50 55 60

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

65 70 75 80

Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly

115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp Val Val Met Thr Gln

130 135 140

Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn

145 150 155 160

Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

165 170 175

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

180 185 190

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly

195 200 205

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

210 215 220

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr

225 230 235 240

Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>285

<211>768

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-057

<220>

<221>CDS

<222>(1)..(768)

<223>

<400>285

gcc atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

cct ggg tcc tcg gtg aag gtc tcc tgc aag gct tct gga ggc acc ttc 96

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

20 25 30

agc aga tat gct atc agt tgg gtg cga cag gcc cct gga caa ggc ctt 144

Ser Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg atg gga agg atc aac cct atc ctt aat tta aca aac tac gca 192

Glu Trp Met Gly Arg Ile Asn Pro Ile Leu Asn Leu Thr Asn Tyr Ala

50 55 60

cag aag ttc cag ggc aga gtc acg att acc gcg gac aaa tcc acg agt 240

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser

65 70 75 80

aca gcc tac atg gag atg agt agc ctg aga tct gag gac acg gcc att 288

Thr Ala Tyr Met Glu Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile

85 90 95

tat tac tgt gcg agc ccg gat ata gta gta gcc ggt cac gct tcc ccc 336

Tyr Tyr Cys Ala Ser Pro Asp Ile Val Val Ala Gly His Ala Ser Pro

100 105 110

cca cac tac act atg gac gtc tgg ggc caa ggg acc acg gtc acc gtc 384

Pro His Tyr Thr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

tcg agc ggt acg ggc ggt tca ggc gga acc ggc agc ggc act ggc ggg 432

Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly

130 135 140

tcg acg gac atc cag atg acc cag tct cca tcc tca ctg tct gca tct 480

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

145 150 155 160

gta gga gac aga gtc acc atc act tgc cgg gca agt cag ggc att aga 528

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

165 170 175

aat gat tta ggc tgg tat cag cag aaa cca ggg aaa gcc cct aac ctc 576

Asn Asp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu

180 185 190

ctg atc tat cag gca tct gct tta cag agt ggg gtc cca tca agg ttc 624

Leu Ile Tyr Gln Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe

195 200 205

agc ggc agt gaa tct ggg gca gaa ttc act ctc acc atc agc agc ctg 672

Ser Gly Ser Glu Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu

210 215 220

cac cct gat gat ttt gca act tat tac tgc caa cag tat cat gat ttt 720

His Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr His Asp Phe

225 230 235 240

ccg atc acc ttc ggc caa ggg aca cga ctg gag att aaa cgt gcg gcc 768

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

245 250 255

<210>286

<211>256

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-057

<400>286

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

20 25 30

Ser Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Met Gly Arg Ile Asn Pro Ile Leu Asn Leu Thr Asn Tyr Ala

50 55 60

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser

65 70 75 80

Thr Ala Tyr Met Glu Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile

85 90 95

Tyr Tyr Cys Ala Ser Pro Asp Ile Val Val Ala Gly His Ala Ser Pro

100 105 110

Pro His Tyr Thr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly

130 135 140

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

145 150 155 160

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

165 170 175

Asn Asp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu

180 185 190

Leu Ile Tyr Gln Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe

195 200 205

Ser Gly Ser Glu Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu

210 215 220

His Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr His Asp Phe

225 230 235 240

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

245 250 255

<210>287

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-058

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>287

gcc atg gcc gag gtc cag ctg gta cag tct gga gga ggc ttg gtc cag 48

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

cct ggg ggg tcc ctc aaa ctc tcc tgt gca gcc tct gga ttc acc ttc 96

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

agt agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg 144

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

gaa tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca 192

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

aac tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac 240

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

65 70 75 80

acg ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg 288

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

85 90 95

tat tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa 336

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

ggg aca atg gtc acc gtc tcg agc ggt acg ggc ggt tca ggc gga acc 384

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

ggc agc ggc act ggc ggg tcg acg gac atc cag atg acc cag tct cca 432

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

130 135 140

gac tcc ctg gct gtg tct ctg ggc gag agg gcc acc atc aac tgc aag 480

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

145 150 155 160

tcc agc cag agt gtt tta tac agc tcc aac aat aag aac tac tta gct 528

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

tgg tac cag cag aaa cca gga cag cct cct aag ctg ctc att tac tgg 576

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

gca tct acc cgg gaa tcc ggg gtc cct gac cga ttc agt ggc agc ggg 624

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gat ttt act ctc acc atc agc agt ctg cag gct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

gtg gca gtt tat tac tgt cag caa tat tat agt act cct ctg acg ttc 720

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

ggc caa ggg acc aag gtg gaa atc aaa cgt gcg gcc 756

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>288

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-058

<400>288

Ala Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln

1 5 10 15

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

20 25 30

Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

35 40 45

Glu Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp

180 185 190

Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp

210 215 220

Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Leu Thr Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>289

<211>756

<212>DNA

<213>Artificial sequence

<220>

<223>SC03-059

<220>

<221>CDS

<222>(1)..(756)

<223>

<400>289

gcc atg gcc cag gtg cag ctg gtg caa tct ggg gct gag gtg aag aag 48

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

cct ggg tcc tcg gtg aag gtc tcc tgc agg gct tct ggt gga ggc gtc 96

Pro Gly Ser Ser Val Lys Val Ser Cys Arg Ala Ser Gly Gly Gly Val

20 25 30

ttc cgc aat tat gct atc aac tgg gtg cga cag gcc cct gga caa ggg 144

Phe Arg Asn Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly

35 40 45

ctt gag tgg atg gga atg atc aac cct agt ggt ggt agc aca agc tac 192

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

50 55 60

gca cag aag ttc cag ggc aga gtc acc ctg acc agg gac acg tcc acg 240

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

65 70 75 80

agc aca gtc tac atg gag ctg agc agc ctg aga tct gag gac acg gcc 288

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

85 90 95

gtg tat tac tgt gcg aga ttc cct ggt ggt acc aga agc cgc ggc tac 336

Val Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr

100 105 110

atg gac gtc tgg ggc aaa ggg acc acg gtc acc gtc tcg agc ggt acg 384

Met Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr

115 120 125

ggc ggt tca ggc gga acc ggc agc ggc act ggc ggg tcg acg gaa att 432

Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile

130 135 140

gtg ctc aca cag tct cca gcc acc ctg tct ttg tct cca ggg gaa aga 480

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

145 150 155 160

gcc acc ctc tcc tgc agg gcc agt cag agt gtt agc agc tac tta gcc 528

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala

165 170 175

tgg tac caa cag aaa cct ggc cag gct ccc agg ctc ctc atc tat gat 576

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp

180 185 190

gca tcc aac agg gcc act ggc atc cca gcc agg ttc agt ggc agt ggg 624

Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly

195 200 205

tct ggg aca gac ttc act ctc acc atc agc agc cta gag cct gaa gat 672

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp

210 215 220

ttt gca gtt tat tac tgt cag cag cgt agc aac tgg cct ccg gct ttc 720

Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe

225 230 235 240

ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc 756

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>290

<211>252

<212>PRT

<213>Artificial sequence

<220>

<223>SC03-059

<400>290

Ala Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

1 5 10 15

Pro Gly Ser Ser Val Lys Val Ser Cys Arg Ala Ser Gly Gly Gly Val

20 25 30

Phe Arg Asn Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Val Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr

100 105 110

Met Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr

115 120 125

Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile

130 135 140

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

145 150 155 160

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp

180 185 190

Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp

210 215 220

Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro Ala Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

245 250

<210>291

<211>13

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-019 and SC03-059

<400>291

Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met Asp Val

1 5 10

<210>292

<211>10

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-020，SC03-021，SC03-022，SC03-033，SC03-034，SC03-0

35，SC03-036，SC03-051.SC03-052and SC03-056

<400>292

Gly Ser Gly Ile Ser Thr Pro Met Asp Val

1 5 10

<210>293

<211>20

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-023 and SC03-055

<400>293

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

1 5 10 15

Trp Phe Asp Pro

20

<210>294

<211>10

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-024

<400>294

Lys Ser Ala Gly Ser Asn Ala Phe Asp Ile

1 5 10

<210>295

<211>8

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-025，SC03-026，SC03-027，SC03-029，SC03-030，SC03-0

40-SC03-050，SC03-054and SC03-058

<400>295

Thr Thr Asn Arg Ala Phe Asp Ile

1 5

<210>296

<211>12

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-031

<400>296

Glu Ser Gly Gly Gly Tyr Asp Asn His Phe Asp Tyr

1 5 10

<210>297

<211>16

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-032

<400>297

Asp Gly Trp Asp Leu Thr Gly Ser Phe Leu Gly Tyr Gly Met Asp Val

1 5 10 15

<210>298

<211>10

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-037 and SC03-038

<400>298

Asp Ala His Arg Gly Phe Gly Met Asp Val

1 5 10

<210>299

<211>12

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-039

<400>299

Gly Ser Lys Trp Asn Asp Val Gly Gly Gly Asp Tyr

1 5 10

<210>300

<211>13

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-053

<400>300

Gly Thr Gly Tyr Leu Arg Ser Tyr His Gly Met Asp Val

1 5 10

<210>301

<211>17

<212>PRT

<213>Artificial sequence

<220>

<223>HCDR3 of SC03-057

<400>301

Pro Asp Ile Val Val Ala Gly His Ser Pro Pro His Tyr Thr Met Asp

1 5 10 15

Val

<210>302

<211>372

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-019

<220>

<221>CDS

<222>(1)..(372)

<223>

<400>302

atg gcc cag atg cag ctg gtg cag tct ggg gga ggc gtg gtc cag cct 48

Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro

1 5 10 15

ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

ggc tat gct atg cac tgg gtc cgc cag gct cca ggc aag ggg ctg gag 144

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

35 40 45

tgg gtg gca gtt ata tca tat gat gga agc aat aaa tac tac gca gac 192

Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cga ttc gcc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gct gag gac acg gct gtg tat 288

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

85 90 95

tac tgt gcg aga ttc cct ggt ggt acc aga agc cgc ggc tac atg gac 336

Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met Asp

100 105 110

gtc tgg ggc aaa ggg acc acg gtc acc gtc tcg agc 372

Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>303

<211>124

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-019

<400>303

Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro

1 5 10 15

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

20 25 30

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

35 40 45

Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp

50 55 60

Ser Val Lys Gly Arg Phe Ala 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 Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met Asp

100 105 110

Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>304

<211>330

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-019

<220>

<221>CDS

<222>(1)..(330)

<223>

<400>304

gaa att gtg ctc aca cag tct cca gcc acc ctg tct ttg tct cca ggg 48

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

1 5 10 15

gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt agc agc tac 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

tta gcc tgg tac caa cag aaa cct ggc cag gct ccc agg ctc ctc atc 144

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

35 40 45

tat gat gca tcc aac agg gcc act ggc atc cca gcc agg ttc agt ggc 192

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

agt ggg tct ggg aca gac ttc act ctc acc atc agc agc cta gag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

gaa gat ttt gca gtt tat tac tgt cag cag cgt agc aac tgg cct ccg 288

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

gct ttc ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc 330

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

100 105 110

<210>305

<211>110

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-019

<400>305

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

100 105 110

<210>306

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-020

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>306

atg gcc gaa gtg cag ctg gtg cag tct ggg tca gag gtg aaa aag ccg 48

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

1 5 10 15

ggg gag tct ctg aag atc tct tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>307

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-020

<400>307

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

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>308

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable liqht chain of SC03-020

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>308

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag aaa att tta cac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Lys Ile Leu His Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ccg gtt ttc ggc gga ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Pro Val Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>309

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-020

<400>309

Asp Ile Gln 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 Gln Lys Ile Leu His Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Pro Val Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>310

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-021

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>310

atg gcc cag gtc cag ctg gta cag tct gga aca gag gtg aaa aag ccg 48

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

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>311

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-021

<400>311

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

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>312

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-021

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>312

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta cac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu His Ser

20 25 30

tcc aac aat aag aac tac cta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg caa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ccg acg ttc ggc caa ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>313

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-021

<400>313

Asp Val 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 Gln Ser Val Leu His Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>314

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-022

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>314

atg gcc cag atg cag ctg gtg caa tct gga aca gag gtg aaa aag ccg 48

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

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>315

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-022

<400>315

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

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>316

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-022

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>316

gac atc cag ttg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc atc aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac act ttt ggc cag ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>317

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-022

<400>317

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>318

<211>390

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-023

<220>

<221>CDS

<222>(1)..(390)

<223>

<400>318

atg gcc cag gtg cag cta cag cag tgg ggc gca gga ctg ttg aag cct 48

Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro

1 5 10 15

tcg gag acc ctg tcc ctc acc tgc gct gtc tat ggt ggg tct ttc agt 96

Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser

20 25 30

ggt ttc tac tgg agc tgg atc cgc cag ccc cca ggg aag ggg ctg gag 144

Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

tgg att ggg gaa atc aat cat agt gga agc acc aac tac aac ccg tcc 192

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

50 55 60

ctc aag agt cga gtc acc ata tca gta gac acg tcc aag aac cag ttc 240

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

tcc ctg aag ctg agc tct gtg acc gcc gcg gac acg gct gtg tat tac 288

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

tgt gcg aga agg gtg gag gta gta gag tac cag ctg ctc cgt ccc cga 336

Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro Arg

100 105 110

tat aaa agt tgg ttc gac ccc tgg ggc cag ggc acc ctg gtc acc gtc 384

Tyr Lys Ser Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val

115 120 125

tcg agc 390

Ser Ser

130

<210>319

<211>130

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-023

<400>319

Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro

1 5 10 15

Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser

20 25 30

Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

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

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro Arg

100 105 110

Tyr Lys Ser Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val

115 120 125

Ser Ser

130

<210>320

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-023

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>320

cag tct gcc ctg act cag cct cgc tca gtg tcc ggg tct cct gga cag 48

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

1 5 10 15

tca gtc acc atc tcc tgc act gga tcc agc agt act gtt ggt ggt tat 96

Ser Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Thr Val Gly Gly Tyr

20 25 30

aac tat gtc tcc tgg tac caa cag cac cca ggc aaa gcc ccc aaa ctc 144

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

atg att tat gat gtc agt aag cgg ccc tca ggg gtt tct aat cgc ttc 192

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser Asn Arg Phe

50 55 60

tct ggc tcc aag tct ggc aac acg gcc tcc ctg acc atc tct ggg ctc 240

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

cag gct gag gac gag gct gat tat tac tgc agc tca tat aca agc agc 288

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser

85 90 95

agc act tat gtc ttc gga act ggg acc aag gtc acc gtc cta ggt gcg 336

Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala

100 105 110

gcc 339

Ala

<210>321

<211>113

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-023

<400>321

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

1 5 10 15

Ser Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Thr Val Gly Gly Tyr

20 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser Asn Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser

85 90 95

Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala

100 105 110

Ala

<210>322

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-024

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>322

atg gcc cag gtg cag ctg gtg gag tct ggg tct gag ttg aag atc cct 48

Met Ala Gln Val Gln Leu Val Glu Ser Gly Ser Glu Leu Lys Ile Pro

1 5 10 15

ggg gcc tca gtg aag gtt tcc tgc aag gct act gga tac acc ttc act 96

Gly Ala Ser Val Lys Val Ser Cys Lys Ala Thr Gly Tyr Thr Phe Thr

20 25 30

cgt tat tct ctg aat tgg gtg cgg cag gcc cct gga caa ggg ctt gag 144

Arg Tyr Ser Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg gtg ggg tgg att aac acc cag act gga aac tca aac tat ggc cag 192

Trp Val Gly Trp Ile Asn Thr Gln Thr Gly Asn Ser Asn Tyr Gly Gln

50 55 60

gcc ttc tca gga cgg ttt gtc ttc tcc ttg gac acc tca gtc agc acg 240

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

65 70 75 80

gca tat ttg caa atc agc agc cta cag gcc gag gac act gcc aca tac 288

Ala Tyr Leu Gln Ile Ser Ser Leu Gln Ala Glu Asp Thr Ala Thr Tyr

85 90 95

tac tgt gcg agg aag agt gcg ggt tcg aat gct ttc gac att tgg ggc 336

Tyr Cys Ala Arg Lys Ser Ala Gly Ser Asn Ala Phe Asp Ile Trp Gly

100 105 110

caa ggg aca atg gtc acc gtc tcg agc 363

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210>323

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-024

<400>323

Met Ala Gln Val Gln Leu Val Glu Ser Gly Ser Glu Leu Lys Ile Pro

1 5 10 15

Gly Ala Ser Val Lys Val Ser Cys Lys Ala Thr Gly Tyr Thr Phe Thr

20 25 30

Arg Tyr Ser Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Val Gly Trp Ile Asn Thr Gln Thr Gly Asn Ser Asn Tyr Gly Gln

50 55 60

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

65 70 75 80

Ala Tyr Leu Gln Ile Ser Ser Leu Gln Ala Glu Asp Thr Ala Thr Tyr

85 90 95

Tyr Cys Ala Arg Lys Ser Ala Gly Ser Asn Ala Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210>324

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-024

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>324

cag tct gtc gtg acg cag ccg ccc tca gtg tct gcg gcc cca gga cag 48

Gln Ser Val Val Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln

1 5 10 15

aag gcc acc atc tcc tgc tct gga agc agc tcc aac att ggg aat aat 96

Lys Ala Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn

20 25 30

tat gta tcc tgg tac cag cag ctc cca gga aca gcc ccc aaa ctc ctc 144

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

35 40 45

att tat gac aat aat aag cga ccc tca ggg att cct aac cga ttc tct 192

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asn Arg Phe Ser

50 55 60

ggc tcc aag tct ggc acg tca gcc acc ctg ggc atc acc gga ctc cag 240

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gln

65 70 75 80

act ggg gac gag gcc gat tat tac tgc gga aca tgg gat agc agc ctg 288

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu

85 90 95

agt gct tat gtc ttc gga act ggg acc aag gtc acc gtc cta ggt gcg 336

Ser Ala Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala

100 105 110

gcc 339

Ala

<210>325

<211>113

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-024

<400>325

Gln Ser Val Val Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln

1 5 10 15

Lys Ala Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn

20 25 30

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

35 40 45

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asn Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gln

65 70 75 80

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu

85 90 95

Ser Ala Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala

100 105 110

Ala

<210>326

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-025

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>326

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

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

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

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

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>327

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-025

<400>327

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>328

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable liqht chain of SC03-025

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>328

gac atc cag ttg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct atc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Ile Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat aat att ccg tat gct ttc ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Asn Ile Pro Tyr Ala Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>329

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-025

<400>329

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Ile Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Asn Ile Pro Tyr Ala Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>330

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-026

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>330

atg gcc cag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

agt tat gcc atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

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

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

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

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>331

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-026

<400>331

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>332

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-026

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>332

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt att tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Ile Leu Tyr Ser

20 25 30

tcc aac agt aag aac tac tta ggt tgg tac cag cag aaa cca gga cag 144

Ser Asn Ser Lys Asn Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag gtg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>333

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-026

<400>333

Asp Ile Gln 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 Gln Ser Ile Leu Tyr Ser

20 25 30

Ser Asn Ser Lys Asn Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>334

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-027

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>334

atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

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

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

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

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>335

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-027

<400>335

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>336

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-027

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>336

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aaa gtg gat atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Asp Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>337

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-027

<400>337

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Asp Ile

100 105 110

Lys Arg Ala Ala

115

<210>338

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-029

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>338

atg gcc gaa gtg cag ctg gtg cag tct ggg gga ggc ttg gtt cag ccg 48

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

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

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

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

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

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>339

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-029

<400>339

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>340

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-029

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>340

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ctc act ttc ggc gca ggg acc aag ctg gag atc 336

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

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>341

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-029

<400>341

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

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

100 105 110

Lys Arg Ala Ala

115

<210>342

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-030

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>342

atg gcg gag gtc cag gtg gta cag tct gga gga ggc ttg gtc cag cct 48

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

1 5 10 15

ggg ggg tcc ctc aaa ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

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

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

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

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

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

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

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

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>343

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-030

<400>343

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>344

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-030

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>344

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

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

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

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

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttt act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agt ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ctg acg ttc ggc caa ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>345

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-030

<400>345

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

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

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>346

<211>369

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-031

<220>

<221>CDS

<222>(1)..(369)

<223>

<400>346

atg gcc cag gtg cag ctg gtg caa tct ggg gct gac gtg aag aag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Asp Val Lys Lys Pro

1 5 10 15

ggg tcc tcg gtg aag gtc tcc tgc gag gct tct gga ggc acg ttc agc 96

Gly Ser Ser Val Lys Val Ser Cys Glu Ala Ser Gly Gly Thr Phe Ser

20 25 30

agc tat gct atc agc tgg gtg cga cag gcc cct gga caa ggg ctt gag 144

Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg atg gga agg atc atc cct atc ctt ggt ata aca aac tac gca cag 192

Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Thr Asn Tyr Ala Gln

50 55 60

aag ttc cag ggc aga gtc aca att acc gcg gac aaa tcc acg ggc aca 240

Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Gly Thr

65 70 75 80

ggc aac atg gag ctg agc agc ctg aga tct gag gac acg gcc gtg tat 288

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

85 90 95

tac tgt gcg aga gaa tcg ggt ggt ggc tac gat aac cac ttt gac tac 336

Tyr Cys Ala Arg Glu Ser Gly Gly Gly Tyr Asp Asn His Phe Asp Tyr

100 105 110

tgg ggc cag gga acc ctg gtc acc gtc tcg agc 369

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>347

<211>123

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-031

<400>347

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Asp Val Lys Lys Pro

1 5 10 15

Gly Ser Ser Val Lys Val Ser Cys Glu Ala Ser Gly Gly Thr Phe Ser

20 25 30

Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Thr Asn Tyr Ala Gln

50 55 60

Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Gly Thr

65 70 75 80

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

85 90 95

Tyr Cys Ala Arg Glu Ser Gly Gly Gly Tyr Asp Asn His Phe Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>348

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-031

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>348

cag tct gtg ctg acg cag ccg ccc tca gcg tct ggg acc ccc gga cag 48

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

1 5 10 15

agg gtc acc atc tct tgt tct gga ggc agc tcc aac atc gga agt aat 96

Arg Val Thr Ile Ser Cys Ser Gly Gly Ser Ser Asn Ile Gly Ser Asn

20 25 30

act gta aac tgg tac cag caa ctc cca gga acg gcc ccc aaa ctc gtc 144

Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Val

35 40 45

atc tat gct aat aat cag cgg ccc tca ggg gtc cct gac cga ttc tct 192

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

50 55 60

gcc tcc aag tct ggc acc tca gcc tcc ctg gcc atc agt ggg ctc cag 240

Ala Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

tct gag gat gag gct gat tat tac tgt gca gct tgg gat gac agc ctg 288

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

act ggt gga gtg ttc ggc gga ggg acc cag ctc acc gtt tta agt gcg 336

Thr Gly Gly Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Ser Ala

100 105 110

gcc 339

Ala

<210>349

<211>113

<212>PRT

<213>Artificial sequence

<220>

<223>Variable liqht chain of SC03-031

<400>349

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

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Gly Ser Ser Asn Ile Gly Ser Asn

20 25 30

Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Val

35 40 45

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

50 55 60

Ala Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

Thr Gly Gly Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Ser Ala

100 105 110

Ala

<210>350

<211>381

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-032

<220>

<221>CDS

<222>(1)..(381)

<223>

<400>350

atg gcc gag gtg cag ctg gtg gag tct ggg gct gag gtg aag aag cct 48

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

1 5 10 15

ggg tcc tcg gtg aag gtc tcc tgc aag gct tct gga ggc acc ttc agc 96

Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser

20 25 30

agc tat gct atc agc tgg gtg cga cag gcc cct gga caa ggg ctt gag 144

Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg atg gga aag atc atc cct att ctt ggt aaa gtc act tac gca cag 192

Trp Met Gly Lys Ile Ile Pro Ile Leu Gly Lys Val Thr Tyr Ala Gln

50 55 60

aag ttc cag gcc aga gtc acg att acc gcg gac gaa tcc acg agc aca 240

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

65 70 75 80

gcc tac ctg gag ctg agc agc ctg aga tct gag gac acg gcc gtt ttt 288

Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Phe

85 90 95

tac tgt gcg aga gac ggc tgg gat ttg act ggt tct ttt tta ggc tac 336

Tyr Cys Ala Arg Asp Gly Trp Asp Leu Thr Gly Ser Phe Leu Gly Tyr

100 105 110

ggt atg gac gtc tgg ggc caa ggg acc acg gtc acc gtc tcg agc 381

Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210>351

<211>127

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-032

<400>351

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

1 5 10 15

Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser

20 25 30

Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Met Gly Lys Ile Ile Pro Ile Leu Gly Lys Val Thr Tyr Ala Gln

50 55 60

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

65 70 75 80

Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Phe

85 90 95

Tyr Cys Ala Arg Asp Gly Trp Asp Leu Thr Gly Ser Phe Leu Gly Tyr

100 105 110

Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210>352

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-032

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>352

cag tct gtc gtg acg cag ccg ccc tca gcg tct ggg acc ccc ggg cag 48

Gln Ser Val Val Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

agg gtc acc atc tct tgt tct gga agc agc tcc aac atc gga agt aat 96

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn

20 25 30

act gta agc tgg tac cag cag gtt cca ggg acg gcc ccc aag ctc ctc 144

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

35 40 45

atc tat agg aat aat cag cgg ccc cca ggg gtc cyt gac cga ttc tct 192

Ile Tyr Arg Asn Asn Gln Arg Pro Pro Gly Val Xaa Asp Arg Phe Ser

50 55 60

ggc tcc aag tct ggc acc tca gcc tcc ytg gcc atc agt ggg ctc cag 240

Gly Ser Lys Ser Gly Thr Ser Ala Ser Xaa Ala Ile Ser Gly Leu Gln

65 70 75 80

tct gac gat gag gcc ttt tat tac tgt gca gca tgg gat ggc agc mtg 288

Ser Asp Asp Glu Ala Phe Tyr Tyr Cys Ala Ala Trp Asp Gly Ser Xaa

85 90 95

aat ggt ctg gcc ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg 336

Asn Gly Leu Ala Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

100 105 110

gcc 339

Ala

<210>353

<211>113

<212>PRT

<213>Artificial sequence

<220>

<221>misc_feature

<222>(60)..(60)

<223>The ′Xaa′at location 60 stands for Pro，or Leu.

<220>

<221>misc_feature

<222>(74)..(74)

<223>The ′Xaa′at location 74 stands for Leu.

<220>

<221>misc_feature

<222>(96)..(96)

<223>The ′Xaa′at location 96 stands for Met，or Leu.

<220>

<223>Variable light chain of SC03-032

<400>353

Gln Ser Val Val Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn

20 25 30

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

35 40 45

Ile Tyr Arg Asn Asn Gln Arg Pro Pro Gly Val Xaa Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Xaa Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Asp Asp Glu Ala Phe Tyr Tyr Cys Ala Ala Trp Asp Gly Ser Xaa

85 90 95

Asn Gly Leu Ala Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

100 105 110

Ala

<210>354

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-033

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>354

atg gcc cag gtc cag ctg gta cag tct gga aca gag gtg aaa aag ccg 48

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

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>355

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-033

<400>355

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

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>356

<211>351

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-033

<220>

<221>CDS

<222>(1)..(351)

<223>

<400>356

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag acc agc cac aat att ttc tcc aga 96

Glu Arg Ala Thr Ile Asn Cys Lys Thr Ser His Asn Ile Phe Ser Arg

20 25 30

tcc aac aat aag gac tac tta gct tgg tac cag cag aaa cca ggc cag 144

Ser Asn Asn Lys Asp Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct ccc aga tta ctc att tac tgg gcg tct acc cgg gca tcc ggg gtc 192

Pro Pro Arg Leu Leu Ile Tyr Trp Ala Ser Thr Arg Ala Ser Gly Val

50 55 60

cct gaa cga ttc agt ggc agc ggc tct ggg aca gac ttc agt ctc acc 240

Pro Glu Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gcg gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt tcc cct atg tac agt ttt ggc cag ggg acc aag gtg gag 336

Tyr Tyr Ser Ser Pro Met Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu

100 105 110

atc aaa cgt gcg gcc 351

Ile Lys Arg Ala Ala

115

<210>357

<211>117

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-033

<400>357

Asp Val 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 Thr Ser His Asn Ile Phe Ser Arg

20 25 30

Ser Asn Asn Lys Asp Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Arg Leu Leu Ile Tyr Trp Ala Ser Thr Arg Ala Ser Gly Val

50 55 60

Pro Glu Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Ser Pro Met Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu

100 105 110

Ile Lys Arg Ala Ala

115

<210>358

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-034

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>358

atg gcc gag gtg cag ctg gtg cag tct gga gca gag gtg aaa aag ccg 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>359

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-034

<400>359

Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>360

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-034

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>360

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt att tta aac aga 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Ile Leu Asn Arg

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc aat ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Asn Leu Thr

65 70 75 80

atc agc agc ctg cag gct gag gat gtg gca gtt tat tac tgt cag cag 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat aat aac tgg cct ctc act ttc ggc gga ggg acc aaa gtg gat atc 336

Tyr Asn Asn Trp Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>361

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-034

<400>361

Asp Val 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 Gln Ser Ile Leu Asn Arg

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Asn Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Asn Asn Trp Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile

100 105 110

Lys Arg Ala Ala

115

<210>362

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-035

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>362

atg gcc gag gtg cag ctg gtg cag tct gga gca gag gtg aaa aag ccc 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>363

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-035

<400>363

Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>364

<211>351

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-035

<220>

<221>CDS

<222>(1)..(351)

<223>

<400>364

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agt cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccc ctg tac agt ttt ggc cag ggg acc aag gtg gag 336

Tyr Tyr Ser Thr Pro Leu Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu

100 105 110

atc aaa cct gcg gcc 351

Ile Lys Pro Ala Ala

115

<210>365

<211>117

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-035

<400>365

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu

100 105 110

Ile Lys Pro Ala Ala

115

<210>366

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-036

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>366

atg gcc gag gtg cag ctg gtg cag tct gga aca gag gtg aaa aag ccg 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>367

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-036

<400>367

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>368

<211>345

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-036

<220>

<221>CDS

<222>(1)..(345)

<223>

<400>368

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta cac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu His Ser

20 25 30

ccc aac aat aag aac tac ttg gct tgg tac cag cag aaa cca gga cag 144

Pro Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act aac agt ttt ggc cag ggg acc aag ctg gag atc aaa 336

Tyr Tyr Ser Thr Asn Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

cgt gcg gcc 345

Arg Ala Ala

115

<210>369

<211>115

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-036

<400>369

Asp Ile Gln 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 Gln Ser Val Leu His Ser

20 25 30

Pro Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Asn Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

Arg Ala Ala

115

<210>370

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-037

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>370

atg gcc aaa gtg cag ctg gtg cag tct gga gga ggc ttg atc cag cct 48

Met Ala Lys Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc gtc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser

20 25 30

agc aac tac atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tgg gtc tca att gtt ttt agc ggt ggt agc aca tac tac gca gac tcc 192

Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg ctg 240

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu

65 70 75 80

tat ctt caa atg aac agc ctg aga gcc gag gac acg gcc gta tat tat 288

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

tgt gcg aga gat gcc cac cgg ggg ttc ggt atg gac gtc tgg ggc caa 336

Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly Gln

100 105 110

ggg acc acg gtc acc gtc tcg agc 360

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>371

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-037

<400>371

Met Ala Lys Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser

20 25 30

Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>372

<211>333

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-037

<220>

<221>CDS

<222>(1)..(333)

<223>

<400>372

tct tct gag ctg act cag gac cct gct gtg tct gtg gcc ttg gga cag 48

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

aca gtc agg atc aca tgc caa gga gac agc ctc aga agc tat tat gca 96

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

agc tgg tac cag cag aag cca gga cag gcc cct gta ctt gtc atc tat 144

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

ggc aaa aac aac cgg ccc tca ggg atc cca gac cgg ttc tct ggc tcc 192

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

agc tca gga aac aca gct tcc ttg acc atc act ggg gct cag gcg gaa 240

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

gat gag gcc gac tat tat tgt aac ggc cgg gac agc agt ggt aac cat 288

Asp Glu Ala Asp Tyr Tyr Cys Asn Gly Arg Asp Ser Ser Gly Asn His

85 90 95

tgg gtg ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg gcc 333

Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

100 105 110

<210>373

<211>111

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-037

<400>373

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Gly Arg Asp Ser Ser Gly Asn His

85 90 95

Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

100 105 110

<210>374

<211>360

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-038

<220>

<221>CDS

<222>(1)..(360)

<223>

<400>374

atg gcc gag gtg cag ctg gtg cag tct gga gga ggc ttg atc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct ggg ttc acc gtc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser

20 25 30

agc aac tac atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tgg gtc tca att gtt ttt agc ggt ggt agc aca tac tac gca gac tcc 192

Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

gtg aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg ctg 240

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu

65 70 75 80

tat ctt caa atg aac agc ctg aga gcc gag gac acg gcc gta tat tat 288

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

tgt gcg aga gat gcc cat cgg ggg ttc ggt atg gac gtc tgg ggc cag 336

Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly Gln

100 105 110

ggg acc acg gtc acc gtc tcg agc 360

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>375

<211>120

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-038

<400>375

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser

20 25 30

Ser Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Trp Val Ser Ile Val Phe Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser

50 55 60

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Asp Ala His Arg Gly Phe Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>376

<211>333

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-038

<220>

<221>CDS

<222>(1)..(333)

<223>

<400>376

tct tct gag ctg act cag gac cct gct gtg tct gtg gcc ttg gga cag 48

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

aca gtc agg atc aca tgc caa gga gac agc ctc aga agc tat tat gca 96

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

agc tgg tac cag cag aag cca gga cag gcc cct gta ctt gtc atc tat 144

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

ggt aaa aac aac cgg ccc tca ggg atc cca gac cga ttc tct ggc tcc 192

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

agc tca gga gac aca gct tcc ttg acc atc act ggg gct cag gcg gaa 240

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

gat gag gct gac tat tac tgt aac tcc cgg gac agc agt ggt aac cat 288

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

tgg gtg ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg gcc 333

Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

100 105 110

<210>377

<211>111

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-038

<400>377

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala

100 105 110

<210>378

<211>369

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-039

<220>

<221>CDS

<222>(1)..(369)

<223>

<400>378

atg gcc gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct 48

Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agc 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agc tat gcc atg agc tgg gtc cgc cag gct cca ggg aag ggg ctg gag 144

Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tgg gtc tca gtt att tat agc ggt ggt act agt aca tac tat gca gac 192

Trp Val Ser Val Ile Tyr Ser Gly Gly Thr Ser Thr Tyr Tyr Ala Asp

50 55 60

tcc gtg aag ggc cgg ttc acc atc tcc aga gat aat tcc aag aac aca 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctg caa atg aac agc ctg aga gcc gag gac acg gcc gta tat 288

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr

85 90 95

ttc tgt gcg aaa gga tct aaa tgg aac gac gtg ggg ggg ggt gac tac 336

Phe Cys Ala Lys Gly Ser Lys Trp Asn Asp Val Gly Gly Gly Asp Tyr

100 105 110

tgg ggc cag gga acc ctg gtc acc gtc tcg agc 369

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>379

<211>123

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-039

<400>379

Met Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Trp Val Ser Val Ile Tyr Ser Gly Gly Thr Ser 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

Phe Cys Ala Lys Gly Ser Lys Trp Asn Asp Val Gly Gly Gly Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210>380

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-039

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>380

aat ttt atg ctg act cag ccc cac tct gtg tcg gag tct ccg ggg aag 48

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

acg gta acc atc tcc tgc gcc ggc agc agt ggc agc att gcc agc aac 96

Thr Val Thr Ile Ser Cys Ala Gly Ser Ser Gly Ser Ile Ala Ser Asn

20 25 30

tat gtg cag tgg tac cag caa cgc ccg ggc agt gcc ccc act act gtg 144

Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val

35 40 45

atc tat gag gat aac caa aga ccc tct ggg gtc cct gat cgg ttc tct 192

Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

ggc tcc atc gac agc tcc tcc aac tct gcc tcc ctc acc atc tct gga 240

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

ctg aag act gag gac gag gct gac tac tac tgt cag tct tat gat ggt 288

Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Gly

85 90 95

tat ctt tgg att ttc ggc gga ggg acc aag ctg acc gtc cta ggt gcg 336

Tyr Leu Trp Ile Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

100 105 110

gcc 339

Ala

<210>381

<211>113

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-039

<400>381

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

Thr Val Thr Ile Ser Cys Ala Gly Ser Ser Gly Ser Ile Ala Ser Asn

20 25 30

Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val

35 40 45

Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Gly

85 90 95

Tyr Leu Trp Ile Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala

100 105 110

Ala

<210>382

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-040

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>382

atg gcc cag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>383

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-040

<400>383

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>384

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-040

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>384

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc agg tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Arg Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt agt ccg tac agt ttt ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Ser Ser Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>385

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-040

<400>385

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Arg Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Ser Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>386

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-041

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>386

atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>387

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-041

<400>387

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>388

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-041

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>388

gat atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag cgg acc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Thr Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>389

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-041

<400>389

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Thr Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>390

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain ofSC03-042

<220>

<221>misc_feature

<222>(150)..(151)

<223>n can be a，t，c，or g

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>390

atg gcc cag atg cag ctg gtg caa tct ggg gga ggc tta gtt cag cct 48

Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctt tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtn tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>391

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-042

<220>

<221>misc_feature

<222>(150)..(151)

<223>n can be a，t，c，or g

<400>391

Met Ala Gln Met Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>392

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-042

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>392

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac gat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asp Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agc ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>393

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-042

<400>393

Asp Val 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asp Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>394

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-043

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>394

atg gcc cag gtc cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>395

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-043

<400>395

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>396

<211>348

<212>DNA

<213>Artificil sequence

<220>

<223>Variable light chain of SC03-043

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>396

gac atc cag ttg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agg 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Arg

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aag cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgt gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

tct gag cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Ser Glu Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt acc ccg tac agt ttt ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>397

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-043

<400>397

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Arg

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Ser Glu Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>398

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-044

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>398

atg gcc gag gtg cag ctg gtg gag act ggg gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>399

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-044

<400>399

Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>400

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-044

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>400

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agg ggc agc ggg tcc ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat ctg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag ctg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>401

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-044

<400>401

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Arg Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>402

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-045

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>402

atg gcc cag ctg cag ctg cag gag tcg ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Leu Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agt aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc cag ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>403

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-045

<400>403

Met Ala Gln Leu Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>404

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-045

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>404

gac atc cag ctg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cca ttc act ttc ggc cct ggg acc aaa gtg gat atc 336

Tyr Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>405

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-045

<400>405

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile

100 105 110

Lys Arg Ala Ala

115

<210>406

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-046

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>406

atg gcc gag gtc cag ctg gta cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>407

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-046

<400>407

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>408

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-046

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>408

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca ggg cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac agg ttc agt ggc agc ggg tct ggg aca gac ttc agt ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gcg gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tac agt cct ccg tac act ttt ggc ccg ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Pro Pro Tyr Thr Phe Gly Pro Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>409

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-046

<400>409

Asp Val 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Pro Pro Tyr Thr Phe Gly Pro Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>410

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-047

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>410

atg gcc gag gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc cag ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>411

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-047

<400>411

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>412

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-047

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>412

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tat agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ctc act ttc ggc gga ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>413

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-047

<400>413

Asp Val 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>414

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-048

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>414

atg gcc gag gtg cag ctg gtg gag act ggg gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>415

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-048

<400>415

Met Ala Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>416

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-048

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>416

gac atc cag ttg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tac agt act ccg ctc act ttc ggc gga ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>417

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-048

<400>417

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>418

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-049

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>418

atg gcc cag gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gac atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>419

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-049

<400>419

Met Ala Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>420

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-049

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>420

gac atc cag ttg acc cag tct cca tcc tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tat cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg ctc act ttc ggc gga ggg acc aag gtg gag atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>421

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-049

<400>421

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>422

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-050

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>422

atg gcc gaa gtg cag ctg gtg cag tct ggg gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>423

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-050

<400>423

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>424

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-050

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>424

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg ctc act ttc ggc gga ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>425

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-050

<400>425

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu LeuIle Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>426

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-051

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>426

atg gcc cag gtg cag ctg gtg cag tct gga aca gag gtg aaa aag ccg 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>427

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-051

<400>427

Met Ala Gln Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>428

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-051

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>428

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc ggc cag agt att tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Gly Gln Ser Ile Leu Tyr Ser

20 25 30

tcc aac gat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asp Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctt ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac act ttt ggc cag ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>429

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-051

<400>429

Asp Ile Gln 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 Gly Gln Ser Ile Leu Tyr Ser

20 25 30

Ser Asn Asp Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>430

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-052

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>430

atg gcc gaa gtg cag ctg gtg cag tct gga aca gag gtg aaa aag ccg 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag gtc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Val Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

acc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Thr Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>431

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-052

<400>431

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Val Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Thr Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>432

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-052

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>432

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac act ttt ggc cag ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>433

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-052

<400>433

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>434

<211>372

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-053

<220>

<221>CDS

<222>(1)..(372)

<223>

<400>434

atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

ggg gcc tca gtg atg gtt tcc tgc aag gcc tct gga tac acc ttc agt 96

Gly Ala Ser Val Met Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser

20 25 30

aac tat gct atg cat tgg gtg cgc cag ggc ccc gga caa agg ctt gag 144

Asn Tyr Ala Met His Trp Val Arg Gln Gly Pro Gly Gln Arg Leu Glu

35 40 45

tgg atg gga tgg atc aac gct gac aaa ggt cag aca aaa tat tca cag 192

Trp Met Gly Trp Ile Asn Ala Asp Lys Gly Gln Thr Lys Tyr Ser Gln

50 55 60

aag ttc cag ggc aga gtc acc att acc ggg gac aca tcc gcc agc aca 240

Lys Phe Gln Gly Arg Val Thr Ile Thr Gly Asp Thr Ser Ala Ser Thr

65 70 75 80

gcc tac atg gac ctg agc agc ctg aga tct gaa gac acg gct gtg tat 288

Ala Tyr Met Asp Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr

85 90 95

tac tgt gcg aga ggg acc gga tat ttg cgg agc tac cac ggc atg gac 336

Tyr Cys Ala Arg Gly Thr Gly Tyr Leu Arg Ser Tyr His Gly Met Asp

100 105 110

gtc tgg ggc cag ggg acc acg gtc acc gtc tcg agc 372

Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>435

<211>124

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-053

<400>435

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

Gly Ala Ser Val Met Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser

20 25 30

Asn Tyr Ala Met His Trp Val Arg Gln Gly Pro Gly Gln Arg Leu Glu

35 40 45

Trp Met Gly Trp Ile Asn Ala Asp Lys Gly Gln Thr Lys Tyr Ser Gln

50 55 60

Lys Phe Gln Gly Arg Val Thr Ile Thr Gly Asp Thr Ser Ala Ser Thr

65 70 75 80

Ala Tyr Met Asp Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Gly Thr Gly Tyr Leu Arg Ser Tyr His Gly Met Asp

100 105 110

Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>436

<211>345

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-053

<220>

<221>CDS

<222>(1)..(345)

<223>

<400>436

gat gtt gtg atg act cag tct cca ccc tcc ctg ccc gtc acc cct ggg 48

Asp Val Val Met Thr Gln Ser Pro Pro Ser Leu Pro Val Thr Pro Gly

1 5 10 15

gag ccg gcc tcc atc tcc tgc agg tct agt cag agc ctc ctc cat agt 96

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

aat gga tac aac tat ttg gat tgg tac ctg cag aag cca ggt cag tct 144

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

cca cag ctc ctg atc tat ttg ggt tct aat cgg gcc tcc ggg gtc cct 192

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

gac agg ttc agt ggc agt gga tca ggc aca gat ttt aca ctg aaa atc 240

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

agc aga gtg gag gct gag gat gtt ggg gtt tat tac tgc atg caa gct 288

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

cta caa act cct ctc acc ttc ggc caa ggg aca cga ctg gag att aaa 336

Leu Gln Thr Pro Leu Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100 105 110

cgt gcg gcc 345

Arg Ala Ala

115

<210>437

<211>115

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-053

<400>437

Asp Val Val Met Thr Gln Ser Pro Pro Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Leu Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100 105 110

Arg Ala Ala

115

<210>438

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-054

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>438

atg gcc gaa gtg cag ctg gtg cag tct ggg gga ggc gtg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro

1 5 10 15

ggg agg tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>439

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-054

<400>439

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro

1 5 10 15

Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>440

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-054

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>440

gac atc cag ttg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc ggc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag gtg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>441

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-054

<400>441

Asp Ile Gln Leu 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>442

<211>390

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-055

<220>

<221>CDS

<222>(1)..(390)

<223>

<400>442

atg gcc cag gtg cag cta cag cag tgg ggc gca gga ctg ttg aag cct 48

Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro

1 5 10 15

tcg gag acc ctg tcc ctc acc tgc gct gtc tat ggt ggg tcc ttc agt 96

Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser

20 25 30

ggt ttc tac tgg agc tgg atc cgc cag ccc cca ggg aag ggg ctg gag 144

Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

tgg att ggg gaa atc aat cat agt gga agc acc aac tac aac ccg tcc 192

Trp Ile Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn Pro Ser

50 55 60

ctc aag agt cga gtc acc ata tca gca gac acg tcc aag aac cag ttc 240

Leu Lys Ser Arg Val Thr Ile Ser Ala Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

tcc ctg aag ctg agc tct gtg acc gcc gcg gac acg gct gtg tat tac 288

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

tgt gcg aga agg gtg gag gta gta gag tac cag ctg ctc cgt ccc cga 336

Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro Arg

100 105 110

tat aaa agt tgg ttc gac ccc tgg ggc cag gga acc ctg gtc acc gtc 384

Tyr Lys Ser Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val

115 120 125

tcg agc 390

Ser Ser

130

<210>443

<211>130

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-055

<400>443

Met Ala Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro

1 5 10 15

Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Gly Ser Phe Ser

20 25 30

Gly Phe Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Glu Ile Asn His Ser Gly Ser Thr Asn Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Ala Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Arg Val Glu Val Val Glu Tyr Gln Leu Leu Arg Pro Arg

100 105 110

Tyr Lys Ser Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val

115 120 125

Ser Ser

130

<210>444

<211>339

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-055

<220>

<221>CDS

<222>(1)..(339)

<223>

<400>444

cag tct gtg ttg acg cag ccg ccc tca gtg tct ggg gcc cca ggg cag 48

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

1 5 10 15

agg gtc tcc atc tcc tgc tct gga agc ggc gcc aat ggt ggg act gat 96

Arg Val Ser Ile Ser Cys Ser Gly Ser Gly Ala Asn Gly Gly Thr Asp

20 25 30

cct gtt tct tgg tac cag aaa ttc cca gga aca gcc ccc cac ctc ctc 144

Pro Val Ser Trp Tyr Gln Lys Phe Pro Gly Thr Ala Pro His Leu Leu

35 40 45

att tat gac aat aat aag cga ccc tca ggg att cct gac cga ttc tct 192

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser

50 55 60

ggc tcc aag tct ggc gcg tca gcc acc ctg gac atc acc gga ctc cag 240

Gly Ser Lys Ser Gly Ala Ser Ala Thr Leu Asp Ile Thr Gly Leu Gln

65 70 75 80

act ggg gac gag gcc gac tat tac tgc gga gca tgg gat ccc agt ctg 288

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Pro Ser Leu

85 90 95

agc ggt tat gtc ttc ggg act ggg acc cag ctc acc gtt tta agt gcg 336

Ser Gly Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val Leu Ser Ala

100 105 110

gcc 339

Ala

<210>445

<211>113

<212>PRT

<213>Artificial sequence

<220>

<223>Variable liqht chain of SC03-055

<400>445

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

1 5 10 15

Arg Val Ser Ile Ser Cys Ser Gly Ser Gly Ala Asn Gly Gly Thr Asp

20 25 30

Pro Val Ser Trp Tyr Gln Lys Phe Pro Gly Thr Ala Pro His Leu Leu

35 40 45

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Ala Ser Ala Thr Leu Asp Ile Thr Gly Leu Gln

65 70 75 80

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Ala Trp Asp Pro Ser Leu

85 90 95

Ser Gly Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val Leu Ser Ala

100 105 110

Ala

<210>446

<211>363

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-056

<220>

<221>CDS

<222>(1)..(363)

<223>

<400>446

atg gcc gaa gtg cag ctg gtg cag tct gga aca gag gtg aaa aag ccg 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

ggg gag tct ctg aag atc tcc tgt aag ggt tct gga tac ggc ttt atc 96

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

acc tac tgg atc ggc tgg gtg cgc cag atg ccc ggg aaa ggc ctg gag 144

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

tgg atg ggg atc atc tat cct ggt gac tct gaa acc aga tac agc ccg 192

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

tcc ttc caa ggc cag gtc acc atc tca gcc gac aag tcc atc aac acc 240

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

gcc tac ctg cag tgg agc agc ctg aag gcc tcg gac acc gcc ata tat 288

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg ggg ggt tcg ggg att tct acc cct atg gac gtc tgg ggc 336

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

caa ggg acc acg gtc acc gtc tcg agc 363

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>447

<211>121

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-056

<400>447

Met Ala Glu Val Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

1 5 10 15

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

20 25 30

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

35 40 45

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

50 55 60

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

65 70 75 80

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210>448

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-056

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>448

gat gtt gtg atg act cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttc act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agc ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act ccg tac agt ttt ggc cag ggg acc aag gtg gag atc 336

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>449

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-056

<400>449

Asp Val 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>450

<211>387

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-057

<220>

<221>CDS

<222>(1)..(387)

<223>

<400>450

atg gcc cag gtg cag ctg gtg cag tct ggg gct gag gtg aag aag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

ggg tcc tcg gtg aag gtc tcc tgc aag gct tct gga ggc acc ttc agc 96

Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser

20 25 30

aga tat gct atc agt tgg gtg cga cag gcc cct gga caa ggc ctt gag 144

Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

tgg atg gga agg atc aac cct atc ctt aat tta aca aac tac gca cag 192

Trp Met Gly Arg Ile Asn Pro Ile Leu Asn Leu Thr Asn Tyr Ala Gln

50 55 60

aag ttc cag ggc aga gtc acg att acc gcg gac aaa tcc acg agt aca 240

Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr

65 70 75 80

gcc tac atg gag atg agt agc ctg aga tct gag gac acg gcc att tat 288

Ala Tyr Met Glu Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile Tyr

85 90 95

tac tgt gcg agc ccg gat ata gta gta gcc ggt cac gct tcc ccc cca 336

Tyr Cys Ala Ser Pro Asp Ile Val Val Ala Gly His Ala Ser Pro Pro

100 105 110

cac tac act atg gac gtc tgg ggc caa ggg acc acg gtc acc gtc tcg 384

His Tyr Thr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

115 120 125

agc 387

Ser

<210>451

<211>129

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-057

<400>451

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser

20 25 30

Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

35 40 45

Trp Met Gly Arg Ile Asn Pro Ile Leu Asn Leu Thr Asn Tyr Ala Gln

50 55 60

Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr

65 70 75 80

Ala Tyr Met Glu Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile Tyr

85 90 95

Tyr Cys Ala Ser Pro Asp Ile Val Val Ala Gly His Ala Ser Pro Pro

100 105 110

His Tyr Thr Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

115 120 125

Ser

<210>452

<211>330

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-057

<220>

<221>CDS

<222>(1)..(330)

<223>

<400>452

gac atc cag atg acc cag tct cca tcc tca ctg tct gca tct gta gga 48

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

gac aga gtc acc atc act tgc cgg gca agt cag ggc att aga aat gat 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp

20 25 30

tta ggc tgg tat cag cag aaa cca ggg aaa gcc cct aac ctc ctg atc 144

Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile

35 40 45

tat cag gca tct gct tta cag agt ggg gtc cca tca agg ttc agc ggc 192

Tyr Gln Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

agt gaa tct ggg gca gaa ttc act ctc acc atc agc agc ctg cac cct 240

Ser Glu Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu His Pro

65 70 75 80

gat gat ttt gca act tat tac tgc caa cag tat cat gat ttt ccg atc 288

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr His Asp Phe Pro Ile

85 90 95

acc ttc ggc caa ggg aca cga ctg gag att aaa cgt gcg gcc 330

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg Ala Ala

100 105 110

<210>453

<211>110

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-057

<400>453

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp

20 25 30

Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile

35 40 45

Tyr Gln Ala Ser Ala Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Glu Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu His Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr His Asp Phe Pro Ile

85 90 95

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg Ala Ala

100 105 110

<210>454

<211>357

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-058

<220>

<221>CDS

<222>(1)..(357)

<223>

<400>454

atg gcc gag gtc cag ctg gta cag tct gga gga ggc ttg gtc cag cct 48

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro

1 5 10 15

ggg ggg tcc ctc aaa ctc tcc tgt gca gcc tct gga ttc acc ttc agt 96

Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

agt tat gct atg cac tgg gtc cgc cag gct cca ggg aag gga ctg gaa 144

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

tat gtt tca ggt att agt agt aat ggg ggt agc aca tat tat gca aac 192

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

50 55 60

tct gtg aag ggc aga ttc acc atc tcc aga gac aat tcc aag aac acg 240

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

65 70 75 80

ctg tat ctt caa atg ggc agc ctg aga gct gag gac atg gct gtg tat 288

Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

tac tgt gcg aga act act aat cgg gct ttt gat atc tgg ggc caa ggg 336

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

aca atg gtc acc gtc tcg agc 357

Thr Met Val Thr Val Ser Ser

115

<210>455

<211>119

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-058

<400>455

Met Ala Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln pro

1 5 10 15

Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser

20 25 30

Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Tyr Val Ser Gly Ile Ser Ser Asn Gly Gly Ser Thr Tyr Tyr Ala Asn

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 Gly Ser Leu Arg Ala Glu Asp Met Ala Val Tyr

85 90 95

Tyr Cys Ala Arg Thr Thr Asn Arg Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Met Val Thr Val Ser Ser

115

<210>456

<211>348

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-058

<220>

<221>CDS

<222>(1)..(348)

<223>

<400>456

gac atc cag atg acc cag tct cca gac tcc ctg gct gtg tct ctg ggc 48

Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

gag agg gcc acc atc aac tgc aag tcc agc cag agt gtt tta tac agc 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

tcc aac aat aag aac tac tta gct tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

cct cct aag ctg ctc att tac tgg gca tct acc cgg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

cct gac cga ttc agt ggc agc ggg tct ggg aca gat ttt act ctc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

atc agc agt ctg cag gct gaa gat gtg gca gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

tat tat agt act cct ctg acg ttc ggc caa ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

aaa cgt gcg gcc 348

Lys Arg Ala Ala

115

<210>457

<211>116

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-058

<400>457

Asp Ile Gln 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 Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Ala Ala

115

<210>458

<211>375

<212>DNA

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-059

<220>

<221>CDS

<222>(1)..(375)

<223>

<400>458

atg gcc cag gtg cag ctg gtg caa tct ggg gct gag gtg aag aag cct 48

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

ggg tcc tcg gtg aag gtc tcc tgc agg gct tct ggt gga ggc gtc ttc 96

Gly Ser Ser Val Lys Val Ser Cys Arg Ala Ser Gly Gly Gly Val Phe

20 25 30

cgc aat tat gct atc aac tgg gtg cga cag gcc cct gga caa ggg ctt 144

Arg Asn Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

gag tgg atg gga atg atc aac cct agt ggt ggt agc aca agc tac gca 192

Glu Trp Met Gly Met Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala

50 55 60

cag aag ttc cag ggc aga gtc acc ctg acc agg gac acg tcc acg agc 240

Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Thr Ser

65 70 75 80

aca gtc tac atg gag ctg agc agc ctg aga tct gag gac acg gcc gtg 288

Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

tat tac tgt gcg aga ttc cct ggt ggt acc aga agc cgc ggc tac atg 336

Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met

100 105 110

gac gtc tgg ggc aaa ggg acc acg gtc acc gtc tcg agc 375

Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210>459

<211>125

<212>PRT

<213>Artificial sequence

<220>

<223>Variable heavy chain of SC03-059

<400>459

Met Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro

1 5 10 15

Gly Ser Ser Val Lys Val Ser Cys Arg Ala Ser Gly Gly Gly Val Phe

20 25 30

Arg Asn Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

35 40 45

Glu Trp Met Gly Met Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala

50 55 60

Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Thr Ser

65 70 75 80

Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

85 90 95

Tyr Tyr Cys Ala Arg Phe Pro Gly Gly Thr Arg Ser Arg Gly Tyr Met

100 105 110

Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210>460

<211>330

<212>DNA

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-059

<220>

<221>CDS

<222>(1)..(330)

<223>

<400>460

gaa att gtg ctc aca cag tct cca gcc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt agc agc tac 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

tta gcc tgg tac caa cag aaa cct ggc cag gct ccc agg ctc ctc atc 144

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

tat gat gca tcc aac agg gcc act ggc atc cca gcc agg ttc agt ggc 192

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

agt ggg tct ggg aca gac ttc act ctc acc atc agc agc cta gag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

gaa gat ttt gca gtt tat tac tgt cag cag cgt agc aac tgg cct ccg 288

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

gct ttc ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc 330

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

100 105 110

<210>461

<211>110

<212>PRT

<213>Artificial sequence

<220>

<223>Variable light chain of SC03-059

<400>461

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala

100 105 110

<210>462

<211>3789

<212>DNA

<213>Artificial sequence

<220>

<223>Codon-optimized sequence of S protein of SARS-CoV strain Frankfur

t 1

<220>

<221>CDS

<222>(10)..(3777)

<223>

<400>462

ggtaccgcc atg ttc atc ttc ctg ctg ttc ctg acc ctg acc agc ggc agc 51

Met Phe Ile Phe Leu Leu Phe Leu Thr Leu Thr Ser Gly Ser

1 5 10

gat ctg gat agg tgc acc acc ttc gac gac gtg cag gcc cct aat tac 99

Asp Leu Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn Tyr

15 20 25 30

acc cag cac acc agc tct atg cgg ggc gtg tac tac ccc gac gag atc 147

Thr Gln His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu Ile

35 40 45

ttc aga agc gac acc ctg tac ctg aca cag gac ctg ttc ctg ccc ttc 195

Phe Arg Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro Phe

50 55 60

tac agc aac gtg acc ggc ttc cac acc atc aac cac acc ttc ggc aac 243

Tyr Ser Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Gly Asn

65 70 75

ccc gtg atc cct ttc aag gac ggc atc tac ttc gcc gcc acc gag aag 291

Pro Val Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu Lys

80 85 90

agc aat gtg gtg cgg ggc tgg gtg ttc ggc agc acc atg aac aac aag 339

Ser Asn Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn Lys

95 100 105 110

agc cag agc gtg atc atc atc aac aat agc acc aac gtg gtg atc agg 387

Ser Gln Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile Arg

115 120 125

gcc tgc aac ttc gag ctg tgc gac aac cct ttc ttc gcc gtg tcc aaa 435

Ala Cys Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser Lys

130 135 140

cct atg ggc acc cag acc cac acc atg atc ttc gac aac gcc ttc aac 483

Pro Met Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe Asn

145 150 155

tgc acc ttc gag tac atc agc gac gcc ttc agc ctg gat gtg agc gag 531

Cys Thr Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser Glu

160 165 170

aag agc ggg aac ttc aag cac ctg cgg gag ttc gtg ttc aag aac aag 579

Lys Ser Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn Lys

175 180 185 190

gac ggc ttc ctg tac gtg tac aag ggc tac cag ccc atc gac gtg gtg 627

Asp Gly Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val Val

195 200 205

aga gat ctg ccc agc ggc ttc aac acc ctg aag ccc atc ttc aag ctg 675

Arg Asp Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys Leu

210 215 220

ccc ctg ggc atc aac atc acc aac ttc cgg gcc atc ctg acc gcc ttc 723

Pro Leu Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala Phe

225 230 235

agc cct gcc cag gac atc tgg ggc acc agc gcc gct gcc tac ttc gtg 771

Ser Pro Ala Gln Asp Ile Trp Gly Thr Ser Ala Ala Ala Tyr Phe Val

240 245 250

ggc tac ctg aag ccc acc acc ttc atg ctg aag tac gac gag aac ggc 819

Gly Tyr Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn Gly

255 260 265 270

acc atc acc gat gcc gtg gac tgc agc cag aac ccc ctg gcc gag ctg 867

Thr Ile Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu Leu

275 280 285

aag tgc agc gtg aag agc ttc gag atc gac aag ggc atc tac cag acc 915

Lys Cys Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln Thr

290 295 300

agc aac ttc aga gtg gtg ccc agc ggc gat gtg gtg agg ttc ccc aac 963

Ser Asn Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro Asn

305 310 315

atc acc aac ctg tgc cct ttc ggc gag gtg ttc aac gcc acc aag ttc 1011

Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe

320 325 330

cct agc gtg tac gcc tgg gag cgg aag aag atc agc aac tgc gtg gcc 1059

Pro Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala

335 340 345 350

gat tac agc gtg ctg tac aac agc acc ttc ttc agc acc ttc aag tgc 1107

Asp Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys

355 360 365

tac ggc gtg agc gcc acc aag ctg aac gac ctg tgc ttc agc aac gtg 1155

Tyr Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val

370 375 380

tac gcc gac agc ttc gtg gtg aag ggc gac gac gtg aga cag atc gcc 1203

Tyr Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala

385 390 395

cct ggc cag acc ggc gtg atc gcc gac tac aat tac aag ctg ccc gac 1251

Pro Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp

400 405 410

gac ttc atg ggc tgc gtg ctg gcc tgg aac acc aga aac atc gac gcc 1299

Asp Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala

415 420 425 430

acc tcc acc ggc aac tac aac tac aag tac cgc tac ctg agg cac ggc 1347

Thr Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly

435 440 445

aag ctg aga ccc ttc gag cgg gac atc agc aac gtg ccc ttc agc cct 1395

Lys Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro

450 455 460

gac ggc aag ccc tgc acc ccc cct gcc ctg aac tgc tac tgg ccc ctg 1443

Asp Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu

465 470 475

aac gac tac ggc ttc tac acc acc acc ggc atc ggc tac cag cct tac 1491

Asn Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr

480 485 490

aga gtg gtg gtg ctg agc ttc gag ctg ctg aac gcc cct gcc acc gtg 1539

Arg Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val

495 500 505 510

tgc ggc ccc aag ctg agc acc gac ctg atc aag aac cag tgc gtg aac 1587

Cys Gly Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val Asn

515 520 525

ttc aac ttc aac ggc ctg acc ggc acc ggc gtg ctg acc cct agc agc 1635

Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser Ser

530 535 540

aag agg ttc cag ccc ttc cag cag ttc ggc agg gac gtg agc gat ttc 1683

Lys Arg Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp Phe

545 550 555

acc gac agc gtg agg gat cct aag acc agc gag atc ctg gac atc agc 1731

Thr Asp Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile Ser

560 565 570

cct tgc agc ttc ggc ggc gtg agc gtg atc acc ccc ggc acc aac gcc 1779

Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Ala

575 580 585 590

agc tcc gag gtg gcc gtg ctg tac cag gac gtg aac tgc acc gac gtg 1827

Ser Ser Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp Val

595 600 605

agc acc gcc atc cac gcc gac cag ctg acc ccc gcc tgg aga atc tac 1875

Ser Thr Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile Tyr

610 615 620

agc acc ggc aac aac gtg ttc cag acc cag gcc ggc tgc ctg atc ggc 1923

Ser Thr Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile Gly

625 630 635

gcc gag cac gtg gac acc agc tac gag tgc gac atc ccc atc gga gcc 1971

Ala Glu His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala

640 645 650

ggc atc tgc gcc agc tac cac acc gtg agc ctg ctg aga agc acc agc 2019

Gly Ile Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr Ser

655 660 665 670

cag aag agc atc gtg gcc tac acc atg agc ctg ggc gcc gac agc agc 2067

Gln Lys Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser Ser

675 680 685

atc gcc tac agc aac aac acc atc gcc atc ccc acc aac ttc agc atc 2115

Ile Ala Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser Ile

690 695 700

agc atc acc acc gag gtg atg ccc gtg agc atg gcc aag acc agc gtg 2163

Ser Ile Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser Val

705 710 715

gac tgc aac atg tac atc tgc ggc gac agc acc gag tgc gcc aac ctg 2211

Asp Cys Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn Leu

720 725 730

ctg ctg cag tac ggc agc ttc tgc acc cag ctg aac aga gcc ctg agc 2259

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Ser

735 740 745 750

ggc atc gcc gcc gag cag gac aga aac acc agg gag gtg ttc gcc cag 2307

Gly Ile Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala Gln

755 760 765

gtg aag cag atg tat aag acc ccc acc ctg aag tac ttc ggc ggc ttc 2355

Val Lys Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly Phe

770 775 780

aac ttc agc cag atc ctg ccc gat cct ctg aag ccc acc aag cgg agc 2403

Asn Phe Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg Ser

785 790 795

ttc atc gag gac ctg ctg ttc aac aag gtg acc ctg gcc gac gcc ggc 2451

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

800 805 810

ttt atg aag cag tac ggc gag tgc ctg ggc gat atc aac gcc agg gac 2499

Phe Met Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg Asp

815 820 825 830

ctg atc tgc gcc cag aag ttc aat ggc ctg acc gtg ctg ccc ccc ctg 2547

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

835 840 845

ctg acc gac gac atg atc gcc gcc tac aca gcc gcc ctg gtg agc ggc 2595

Leu Thr Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser Gly

850 855 860

acc gcc acc gcc ggc tgg acc ttt ggc gcc gga gcc gcc ctg cag atc 2643

Thr Ala Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

865 870 875

ccc ttc gcc atg cag atg gcc tac cgg ttc aat ggc atc ggc gtg acc 2691

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

880 885 890

cag aac gtg ctg tac gag aac cag aag cag atc gcc aac cag ttc aac 2739

Gln Asn Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe Asn

895 900 905 910

aag gcc atc agc cag atc cag gag agc ctg acc acc aca agc acc gcc 2787

Lys Ala Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr Ala

915 920 925

ctg ggc aag ctg cag gac gtg gtg aac cag aac gcc cag gcc ctg aat 2835

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

930 935 940

acc ctg gtg aag cag ctg agc agc aac ttc ggc gcc atc agc tcc gtg 2883

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

945 950 955

ctg aac gac atc ctg agc cgg ctg gac aag gtg gag gcc gag gtg cag 2931

Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln

960 965 970

atc gac aga ctg atc acc ggc aga ctg cag agc ctg cag acc tac gtg 2979

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

975 980 985 990

acc cag cag ctg atc aga gcc gcc gag atc aga gcc agc gcc aac ctg 3027

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu

995 1000 1005

gcc gcc acc aag atg agc gag tgc gtg ctg ggc cag agc aag aga 3072

Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg

1010 1015 1020

gtg gac ttc tgc ggc aag ggc tac cac ctg atg agc ttc ccc cag 3117

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln

1025 1030 1035

gcc gct ccc cac ggc gtg gtg ttc ctg cac gtg acc tac gtg cct 3162

Ala Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro

1040 1045 1050

agc cag gag agg aat ttc acc acc gcc cct gcc atc tgc cac gag 3207

Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro Ala Ile Cys His Glu

1055 1060 1065

ggc aag gcc tac ttc ccc aga gag ggc gtg ttc gtg ttc aat ggc 3252

Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe Val Phe Asn Gly

1070 1075 1080

acc agc tgg ttc atc acc cag cgg aac ttc ttc agc ccc cag atc 3297

Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser Pro Gln Ile

1085 1090 1095

atc aca acc gac aac acc ttc gtg agc ggc aac tgc gac gtg gtg 3342

Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val

1100 1105 1110

atc ggc atc att aac aat acc gtg tac gac ccc ctg cag ccc gag 3387

Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu

1115 1120 1125

ctg gat agc ttc aag gag gag ctg gac aag tac ttc aag aac cac 3432

Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1130 1135 1140

acc agc ccc gat gtg gac ttc ggc gac atc agc ggc atc aat gcc 3477

Thr Ser Pro Asp Val Asp Phe Gly Asp Ile Ser Gly Ile Asn Ala

1145 1150 1155

agc gtg gtg aac atc cag aag gag atc gac cgg ctg aac gag gtg 3522

Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val

1160 1165 1170

gcc aag aac ctg aac gag agc ctg atc gac ctg cag gag ctg ggc 3567

Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly

1175 1180 1185

aag tac gag cag tac atc aag tgg ccc tgg tac gtg tgg ctg ggc 3612

Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly

1190 1195 1200

ttc atc gcc ggc ctg atc gcc atc gtg atg gtg acc atc ctg ctg 3657

Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu

1205 1210 1215

tgc tgc atg acc agc tgc tgc tcc tgc ctg aag ggc gcc tgc agc 3702

Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser

1220 1225 1230

tgt ggc agc tgc tgc aag ttc gac gag gac gat agc gag ccc gtg 3747

Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val

1235 1240 1245

ctg aag ggc gtg aag ctg cac tac acc tga tgaattctcg ag 3789

Leu Lys Gly Val Lys Leu His Tyr Thr

1250 1255

<210>463

<211>1255

<212>PRT

<213>Artificial sequence

<220>

<223>Codon-optimized sequence of S protein of SARS-CoV strain Frankfur

t 1

<400>463

Met Phe Ile Phe Leu Leu Phe Leu Thr Leu Thr Ser Gly Ser Asp Leu

1 5 10 15

Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln

20 25 30

His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg

35 40 45

Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser

50 55 60

Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Gly Asn Pro Val

65 70 75 80

Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn

85 90 95

Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln

100 105 110

Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys

115 120 125

Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met

130 135 140

Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr

145 150 155 160

Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser

165 170 175

Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly

180 185 190

Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp

195 200 205

Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu

210 215 220

Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro

225 230 235 240

Ala Gln Asp Ile Trp Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr

245 250 255

Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile

260 265 270

Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys

275 280 285

Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn

290 295 300

Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr

305 310 315 320

Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser

325 330 335

Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr

340 345 350

Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly

355 360 365

Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala

370 375 380

Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly

385 390 395 400

Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe

405 410 415

Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser

420 425 430

Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu

435 440 445

Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly

450 455 460

Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp

465 470 475 480

Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val

485 490 495

Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly

500 505 510

Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn

515 520 525

Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg

530 535 540

Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp

545 550 555 560

Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys

565 570 575

Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser

580 585 590

Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr

595 600 605

Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr

610 615 620

Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu

625 630 635 640

His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile

645 650 655

Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr Ser Gln Lys

660 665 670

Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala

675 680 685

Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile

690 695 700

Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys

705 710 715 720

Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu

725 730 735

Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile

740 745 750

Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys

755 760 765

Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe

770 775 780

Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile

785 790 795 800

Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met

805 810 815

Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile

820 825 830

Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr

835 840 845

Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala

850 855 860

Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe

865 870 875 880

Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn

885 890 895

Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala

900 905 910

Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly

915 920 925

Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu

930 935 940

Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn

945 950 955 960

Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp

965 970 975

Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln

980 985 990

Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala

995 1000 1005

Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp

1010 1015 1020

Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ala Ala

1025 1030 1035

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ser Gln

1040 1045 1050

Glu Arg Asn Phe Thr Thr Ala Pro Ala Ile Cys His Glu Gly Lys

1055 1060 1065

Ala Tyr Phe Pro Arg Glu Gly Val Phe Val Phe Asn Gly Thr Ser

1070 1075 1080

Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser Pro Gln Ile Ile Thr

1085 1090 1095

Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly

1100 1105 1110

Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp

1115 1120 1125

Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser

1130 1135 1140

Pro Asp Val Asp Phe Gly Asp Ile Ser Gly Ile Asn Ala Ser Val

1145 1150 1155

Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1160 1165 1170

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr

1175 1180 1185

Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile

1190 1195 1200

Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Cys Cys

1205 1210 1215

Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser Cys Gly

1220 1225 1230

Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys

1235 1240 1245

Gly Val Lys Leu His Tyr Thr

1250 1255

<210>464

<211>29

<212>DNA

<213>Artificial sequence

<220>

<223>Primer XhoISpikeRevC0G

<400>464

gttcctcgag gggccacttg atgtactgc 29

<210>465

<211>18

<212>DNA

<213>Artificial sequence

<220>

<223>Primer SpikeCOG seq 1

<400>465

ccaggtgaag cagatgta 18

<210>466

<211>32

<212>DNA

<213>Artificial sequence

<220>

<223>Primer KpnINCFor

<400>466

cttggtaccg ccaccatgtc tgataatgga cc 32

<210>467

<211>28

<212>DNA

<213>Artificial sequence

<220>

<223>Primer XbaINCRev

<400>467

gttctctaga tgcctgagtt gaatcagc 28

<210>468

<211>9

<212>PRT

<213>Artificial sequence

<220>

<223>Peptide

<400>468

Arg Ser Ala Pro Arg Ile Thr Phe Gly

1 5

<210>469

<211>32

<212>DNA

<213>Artificial sequence

<220>

<223>oligonucleotide primer EcoRIspikeFor318

<400>469

cctggaattc tccatggcca acatcaccaa cc 32

<210>470

<211>27

<212>DNA

<213>Artificial sequence

<220>

<223>Oligonucleotide primer XbaIspikeRev510

<400>470

gaagggccct ctagacacgg tggcagg 27

<210>471

<211>1350

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-006

<220>

<221>CDS

<222>(1)..(1350)

<223>

<400>471

gag gtg cag ctg gtg gag tct ggg gga ggc ttg gta cag cct ggg ggg 48

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agc ggc tac 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Gly Tyr

20 25 30

cct atg cac tgg gtc cgc cag gcg ccc ggg aag ggg ctg gag tgg gtg 144

Pro Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

gca gtt ata tca tat gac gga agt aat aaa tac tat gca gac tcc gtg 192

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

aag ggc cga ttc acc atc tcc aga gac aat tcc aag aac acg ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

ctg caa atg aac agc ctg aga gct gag gac aca gct gtg tat tac tgt 288

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

gct aaa gac ggc agc ccc cgc acc ccc agc ttc gat tac tgg ggc cag 336

Ala Lys Asp Gly Ser Pro Arg Thr Pro Ser Phe Asp Tyr Trp Gly Gln

100 105 110

ggc acc ctg gtg acc gtc tcc agc gct agc acc aag ggc ccc agc gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

ttc ccc ctg gcc ccc agc agc aag agc acc agc ggc ggc aca gcc gcc 432

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg agc 480

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

tgg aac agc ggc gcc ttg acc agc ggc gtg cac acc ttc ccc gcc gtg 528

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

ctg cag agc agc ggc ctg tac agc ctg agc agc gtg gtg acc gtg ccc 576

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

agc agc agc ctg ggc acc cag acc tac atc tgc aac gtg aac cac aag 624

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

ccc agc aac acc aag gtg gac aaa cgc gtg gag ccc aag agc tgc gac 672

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

210 215 220

aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga 720

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc 768

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

agc cgg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg agc cac gag 816

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac 864

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

aac gcc aag acc aag ccc cgg gag gag cag tac aac agc acc tac cgg 912

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

290 295 300

gtg gtg agc gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag 960

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

gag tac aag tgc aag gtg agc aac aag gcc ctg cct gcc ccc atc gag 1008

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

aag acc atc agc aag gcc aag ggc cag ccc cgg gag ccc cag gtg tac 1056

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

acc ctg ccc ccc agc cgg gag gag atg acc aag aac cag gtg tcc ctc 1104

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

acc tgt ctg gtg aag ggc ttc tac ccc agc gac atc gcc gtg gag tgg 1152

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

gag agc aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg 1200

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

ctg gac agc gac ggc agc ttc ttc ctg tac agc aag ctc acc gtg gac 1248

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

aag agc cgg tgg cag cag ggc aac gtg ttc agc tgc agc gtg atg cac 1296

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

gag gcc ctg cac aac cac tac acc cag aag agc ctg agc ctg agc ccc 1344

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

ggc aag 1350

Gly Lys

450

<210>472

<211>450

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-006

<400>472

Glu Val Gln Leu Val Glu Ser Gly Gly 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 Gly Tyr

20 25 30

Pro Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Asp Gly Ser Pro Arg Thr Pro Ser Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210>473

<211>1335

<212>DNA

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-015

<220>

<221>CDS

<222>(1)..(1335)

<223>

<400>473

gag gtg cag ctg gtg gag tct ggg gga ggt gtg gta cgg cct ggg ggg 48

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly

1 5 10 15

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt gat gat tat 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

ggc atg agc tgg gtc cgc caa gct cca ggg aag ggg ctg gag tgg gtc 144

Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

tct ggt att aat tgg aat ggt ggt agc aca ggt tat gca gac tct gtg 192

Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala Asp Ser Val

50 55 60

aag ggc cga ttc acc atc tcc aga gac aac gcc aag aac tcc ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

ctg caa atg aac agt ctg aga gcc gag gac acg gcc gtg tat tac tgt 288

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

gca aga ggt ttg tct ctt cgt cct tgg ggc cag ggc acc ctg gtg acc 336

Ala Arg Gly Leu Ser Leu Arg Pro Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

gtc tcc agc gct agc acc aag ggc ccc agc gtg ttc ccc ctg gcc ccc 384

Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro

115 120 125

agc agc aag agc acc agc ggc ggc aca gcc gcc ctg ggc tgc ctg gtg 432

Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val

130 135 140

aag gac tac ttc ccc gag ccc gtg acc gtg agc tgg aac agc ggc gcc 480

Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala

145 150 155 160

ttg acc agc ggc gtg cac acc ttc ccc gcc gtg ctg cag agc agc ggc 528

Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly

165 170 175

ctg tac agc ctg agc agc gtg gtg acc gtg ccc agc agc agc ctg ggc 576

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly

180 185 190

acc cag acc tac atc tgc aac gtg aac cac aag ccc agc aac acc aag 624

Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys

195 200 205

gtg gac aaa cgc gtg gag ccc aag agc tgc gac aag acc cac acc tgc 672

Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys

210 215 220

ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga ccc tcc gtg ttc ctg 720

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

225 230 235 240

ttc ccc ccc aag ccc aag gac acc ctc atg atc agc cgg acc ccc gag 768

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

gtg acc tgc gtg gtg gtg gac gtg agc cac gag gac ccc gag gtg aag 816

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

260 265 270

ttc aac tgg tac gtg gac ggc gtg gag gtg cac aac gcc aag acc aag 864

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

ccc cgg gag gag cag tac aac agc acc tac cgg gtg gtg agc gtg ctc 912

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

acc gtg ctg cac cag gac tgg ctg aac ggc aag gag tac aag tgc aag 960

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

gtg agc aac aag gcc ctg cct gcc ccc atc gag aag acc atc agc aag 1008

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

gcc aag ggc cag ccc cgg gag ccc cag gtg tac acc ctg ccc ccc agc 1056

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

cgg gag gag atg acc aag aac cag gtg tcc ctc acc tgt ctg gtg aag 1104

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

355 360 365

ggc ttc tac ccc agc gac atc gcc gtg gag tgg gag agc aac ggc cag 1152

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

370 375 380

ccc gag sac aac tac aag acc acc ccc cct gtg ctg gac agc gac ggc 1200

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

agc ttc ttc ctg tac agc aag ctc acc gtg gac aag agc cgg tgg cag 1248

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

405 410 415

cag ggc aac gtg ttc agc tgc agc gtg atg cac gag gcc ctg cac aac 1296

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

cac tac acc cag aag agc ctg agc ctg agc ccc ggc aag 1335

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445

<210>474

<211>445

<212>PRT

<213>Artificial sequence

<220>

<223>IgG heavy chain of 03-015

<400>474

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Asn Trp Asn Gly Gly Ser Thr Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser 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 Gly Leu Ser Leu Arg Pro Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro

115 120 125

Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val

130 135 140

Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala

145 150 155 160

Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly

165 170 175

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly

180 185 190

Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys

195 200 205

Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys

210 215 220

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 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 Ser 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 Gln 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 Leu Val Lys

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 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 Gln

405 410 415

Gln Gly Asn 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>475

<211>642

<212>DNA

<213>Artificial sequence

<220>

<223>IgG light chain of 03-006

<220>

<221>CDS

<222>(1)..(642)

<223>

<400>475

gac atc cag atg acc cag tct cca cac tct ctg tct gca tct gta gga 48

Asp Ile Gln Met Thr Gln Ser Pro His Ser Leu Ser Ala Ser Val Gly

1 5 10 15

gac aga gtc acc atc act tgc cgg gcg agt cag ggc att agc aat tat 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr

20 25 30

tta gcc tgg tat cag cag aaa cca ggg aaa gtt cct aag ctc ctg atc 144

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile

35 40 45

tat gct gca tcc act ttg caa tca ggg gtc cca tct cgg ttc agt ggc 192

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

agt gga tct ggg aca gat ttc act ctc acc atc agc agc ctg cag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

gaa gat gtt ggg gtt tat tac tgc cag cag agg ttc cgc acg ccg gtc 288

Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val

85 90 95

acc ttc ggc cag ggc acc aaa ctg gaa atc aaa cgg acc gtg gcc gct 336

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

ccc agc gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag agc ggc 384

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

acc gcc agc gtg gtg tgc ctg ctg aac aac ttc tac ccc cgg gag gcc 432

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

aag gtg cag tgg aag gtg gac aac gcc ctg cag agc ggc aac agc cag 480

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

gag agc gtg acc gag cag gac agc aag gac tcc acc tac agc ctg agc 528

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

agc acc ctc acc ctg agc aag gcc gac tac gag aag cac aag gtg tac 576

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

gcc tgc gag gtg acc cac cag ggc ctg agc agc ccc gtg acc aag agc 624

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

ttc aac cgg ggc gag tgt 642

Phe Asn Arg Gly Glu Cys

210

<210>476

<211>214

<212>PRT

<213>Artificial sequence

<220>

<223>IgG light chain of 03-006

<400>476

Asp Ile Gln Met Thr Gln Ser Pro His Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Arg Phe Arg Thr Pro Val

85 90 95

Thr Phe Gly Gln 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>477

<211>642

<212>DNA

<213>Artificial sequence

<220>

<223>IgG light chain of 03-015

<220>

<221>CDS

<222>(1)..(642)

<223>

<400>477

tcc tcc gag ctg acc cag gac cct gct gag tct gtg gcc ttg gga cag 48

Ser Ser Glu Leu Thr Gln Asp Pro Ala Glu Ser Val Ala Leu Gly Gln

1 5 10 15

aca gtc agg atc aca tgc caa gga gac agc ctc aga agc tat tat gca 96

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

agc tgg tac cag cag aag cca gga cag gcc cct gta ctt gtc atc tat 144

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

ggt aaa aac aac cgg ccc tca ggg atc cca gac cga ttc tct ggc tcc 192

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

agc tca gga aac aca gct tcc ttg acc atc act ggg gct cag gcg gaa 240

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

gat gag gct gac tat tac tgt aac tcc cgg gac agc agt ggt aac cat 288

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

gtg gta ttc ggc gga ggg acc aag ctt acc gtg ctg ggc cag ccc aag 336

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys

100 105 110

gcc gct ccc agc gtg acc ctg ttc ccc ccc tcc tcc gag gag ctg cag 384

Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln

115 120 125

gcc aac aag gcc acc ctg gtg tgc ctc atc agc gac ttc tac cct ggc 432

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

gcc gtg acc gtg gcc tgg aag gcc gac agc agc ccc gtg aag gcc ggc 480

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

gtg gag acc acc acc ccc agc aag cag agc aac aac aag tac gcc gcc 528

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

agc agc tac ctg agc ctc acc ccc gag cag tgg aag agc cac cgg agc 576

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

tac agc tgc cag gtg acc cac gag ggc agc acc gtg gag aag acc gtg 624

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

gcc ccc acc gag tgc agc 642

Ala Pro Thr Glu Cys Ser

210

<210>478

<211>214

<212>PRT

<213>Artificial sequence

<220>

<223>IgG light chain of 03-015

<400>478

Ser Ser Glu Leu Thr Gln Asp Pro Ala Glu Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys

100 105 110

Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln

115 120 125

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

Ala Pro Thr Glu Cys Ser

210

Claims

1.一种能够特异结合至SARS-CoV并且具有SARS-CoV中和活性的结合分子，

其中所述结合分子包括可变重链，所述可变重链包括氨基酸序列SEQ ID NO：37；以及

其中所述结合分子包括可变轻链，所述可变轻链包括氨基酸序列SEQ ID NO：41。

2.权利要求1的结合分子，其是人的结合分子。

3.一种免疫缀合物，其包括权利要求1或2的结合分子，所述免疫缀合物进一步包括至少一个标记物。

4.权利要求3的免疫缀合物，其中所述标记物选自由放射性物质、酶及其组合组成的一组。

5.一种编码权利要求1或2的结合分子的核酸分子。

6.一种载体，其包括至少一种权利要求5的核酸分子。

7.一种宿主，其包括至少一种权利要求6的载体。

8.权利要求7的宿主，其中所述宿主是衍生自人细胞的细胞。

9.一种用于生产权利要求1或2的结合分子的方法，其中所述方法包括步骤：

a)在有助于表达所述结合分子的条件下培养权利要求7或8的宿主，和任选地，

b)回收所述表达的结合分子。

10.一种结合分子，其可通过权利要求9的方法获得。

11.一种组合物，其包括权利要求1或2的结合分子、权利要求3或4的免疫缀合物、或权利要求10的结合分子。

12.一种组合物，其包括权利要求5的核酸分子。

13.一种药物组合物，其包括权利要求1或2的结合分子、权利要求3或4的免疫缀合物、权利要求10的结合分子、或权利要求11或12的组合物，所述药物组合物进一步包括至少一种药物学可接受的赋形剂。

14.权利要求13的药物组合物，其进一步包括至少一种其他的治疗剂。

15.权利要求1或2的结合分子、权利要求3或4的免疫缀合物、权利要求10的结合分子、权利要求11或12的组合物、或权利要求13或14的药物组合物，其被用作药物。

16.权利要求1或2的结合分子、权利要求3或4的免疫缀合物、权利要求10的结合分子、权利要求11或12的组合物、或权利要求13或14的药物组合物，其被用于SARS-CoV导致的疾病的诊断、预防、治疗、或其组合。

17.权利要求1或2的结合分子、权利要求3或4的免疫缀合物、权利要求10的结合分子、权利要求11或12的组合物、或权利要求13或14的药物组合物在制备用于SARS-CoV导致的疾病的诊断、预防、治疗、或其组合的药物中的应用。

18.一种试剂盒，其包括权利要求1或2的结合分子、权利要求3或4的免疫缀合物、权利要求5的核酸分子、权利要求6的载体、权利要求7或8的宿主、权利要求10的结合分子、权利要求11或12的组合物、权利要求13或14的药物组合物、或其组合。

19.诊断有效量的权利要求1、2或10任一项的结合分子、或权利要求3或4的免疫缀合物在制备用于检测样品中的SARS-CoV的组合物中的用途。

20.权利要求19的用途，其中所述样品是来自被SARS-CoV潜在感染的人对象的样品。

21.一种用于筛选特异结合至SARS-CoV的与权利要求1、2或10任一项的结合分子结合的表位相同的表位的结合分子的方法，其中所述方法包括步骤：

a)使待筛选的结合分子、权利要求1、2或10任一项的结合分子与SARS-CoV或其片段接触，

b)测量待筛选的结合分子是否能够与权利要求1、2或10任一项的结合分子竞争与SARS-CoV的特异结合。