一种新型冠状病毒SARS-CoV-2中和性抗体及应用

文档序号：2604 发布日期：2021-09-17 浏览：49次英文

技术领域

本发明涉及生物医学领域，尤其涉及一种新型冠状病毒SARS-CoV-2中和性抗体及应用。

背景技术

新型冠状病毒(SARS-CoV-2)肺炎平均潜伏期3-7天，感染的上呼吸道症状并不突出。部分新型冠状病毒感染患者仅表现为低热、轻微乏力等，且无肺炎表现。而在重型、危重型患者病程中可以表现为中低热，甚至无明显发热。这些非特异的临床表现给疫情防控带来了更大的挑战。有效的疫苗和治疗性药物对控制病毒的传播和改善病人的预后起到关键性的作用。然而截止目前，仍无针对冠状病毒的相关疫苗。药物治疗方面，针对新型冠状病毒感染的抗病毒治疗主要采用广谱的干扰素和洛匹那韦/利托那韦，疗效不显著，除此之外并无特异性抗病毒药物，因而急待开发相应的治疗药物。

在恢复期病人体内存在能有效中和病毒感染的抗体，利用这种中和抗体能特异、有效地预防与治疗病毒的感染。然而，由于获取具有高亲和力抗病原体的人血浆和/或免疫球蛋白，需要康复期患者的大量捐献，且存在其它潜在感染的风险，从而限制这些人衍生产品的广泛利用。随着对冠状病毒的研究，目前已经清楚地知道，冠状病毒表面的Spike蛋白在病毒入侵宿主时起到关键作用，该蛋白的S1亚基中存在一个与宿主细胞表面结合的受体结合区域(RBD)，负责识别细胞受体。因而能特异性结合RBD区域的抗体将会有很好的病毒中和作用。通过对SARS-CoV-2、SARS-CoV、MERS-CoV的Spike蛋白RBD序列比对可发现， SARS-CoV-2与SARS-CoV的RBD区域有73.5％的序列相似性。SARS-CoV可通过该区域与宿主细胞膜表面受体ACE2结合从而进入细胞，因而同SARS-CoV 一样，开发针对新型冠状病毒SARS-CoV-2RBD区域的抗体亦或有中和病毒的作用。研究表明，与SARS-CoV不同，SARS-CoV-2新型冠状病毒的Spike蛋白 RBD区域与ACE2结合的几个关键氨基酸发生了突变，导致以往开发的针对 SARS-CoV的中和抗体可能不具有中和该病毒的作用。因而，需要开发一些新的针对SARS-CoV-2新型冠状病毒的中和性抗体。

发明内容

为了克服现有技术中所存在的缺陷，本发明提供一种新型冠状病毒 SARS-CoV-2中和性抗体及其制备方法和应用。

为实现上述目的，本发明采用如下技术方案：

本发明的第一个方面是提供一种抗体，所述抗体能结合至新型冠状病毒 SARS-CoV-2的Spike蛋白S1亚基中的RBD区域，从而阻断宿主细胞膜表面受体ACE2与Spike蛋白的结合活性。

为了进一步优化上述技术方案，本发明采取的技术措施还包括：

进一步地，所述抗体为中和性全人源抗体。

进一步地，所述抗体包括重链VH和轻链VL，所述VH和VL均包括可变区CDR1、CDR2和CDR3；其中，

所述VH的CDR1的氨基酸序列选自SEQ ID NO.63-SEQ ID NO.76、SEQ ID NO.303-SEQ ID NO.305中的一种；

和/或，所述VH的CDR2的氨基酸序列选自SEQ ID NO.77-SEQ ID NO.86、 SEQ IDNO.306-SEQ ID NO.308中的一种；

和/或，所述VH的CDR3的氨基酸序列选自SEQ ID NO.87-SEQ ID NO. 104、SEQ IDNO.309-SEQ ID NO.312中的一种；

和/或，所述VL的CDR1的氨基酸序列选自SEQ ID NO.105-SEQ ID NO. 119、SEQ IDNO.313-SEQ ID NO.315中的一种；

和/或，所述VL的CDR2的氨基酸序列选自SEQ ID NO.120-SEQ ID NO. 126、SEQ IDNO.316中的一种；

和/或，所述VL的CDR3的氨基酸序列选自SEQ ID NO.127-SEQ ID NO. 152、SEQ IDNO.317-SEQ ID NO.327中的一种。

进一步地，所述抗体的VH的氨基酸序列选自SEQ ID NO.1-SEQ ID NO. 30、SEQ IDNO.279-SEQ ID NO.289中的一种；和/或，所述抗体的VL的氨基酸序列选自SEQ ID NO.31-SEQ ID NO.62、SEQ ID NO.290-SEQ ID NO.302 中的一种。

更进一步地，所述抗体的VH的氨基酸序列选自SEQ ID NO.2-SEQ ID NO. 4、SEQID NO.14中的一种；和/或，所述抗体的VL的氨基酸序列选自SEQ ID NO.32-SEQ ID NO.34、SEQ ID NO.44中的一种。

本发明的第二个方面是提供一种任一上述抗体的衍生抗体，其选自下述(1) ～(4)中的一种：

(1)由上述任一所述抗体的VH和VL连接得到的单链抗体；

(2)含有(1)中所述单链抗体的融合抗体；

(3)含有任一上述抗体的VH和VL的Fab；

(4)含有任一上述抗体的VH和VL的完整抗体。

进一步地，所述衍生抗体为scFv单链抗体，所述scFv单链抗体的氨基酸序列选自SEQ ID NO.215-SEQ ID NO.246、SEQ ID NO.356-SEQ ID NO.368中的一种。

更进一步地，所述scFv单链抗体的氨基酸序列为SEQ ID NO.216-SEQ ID NO.218、SEQ ID NO.228中的一种。更具体地，所述scFv单链抗体为下表1中的HTS0422、HTS0433、HTS0446以及HTS0483，其重链、轻链及其可变区序列也如表1中所示。

可理解的是，上述scFv单链抗体是全人源性抗体，可以直接开发为人用的抗体药物。将编码该人源性scFv抗体的基因构建、表达，可得到多种形式的小分子基因工程抗体，如Fab抗体、F(ab)₂、单链抗体、纳米抗体、抗体融合蛋白和IgG全抗体等。

进一步地，所述衍生抗体为完整IgG抗体；其中，所述完整IgG抗体的制备步骤包括：将编码所述VH和VL的基因片段分别亚克隆入人IgG1 CH载体与轻链CL表达载体，同时转染至细胞中表达并进行亲和纯化。更进一步地，人IgG1 CH载体为pTT5-hIgG1，轻链CL表达载体为pTT5-hKappa，转染细胞为293F 细胞，其采用蛋白G进行亲和纯化。

本发明的第三个方面是提供一种任一上述抗体相关的生物材料，其选自下述 (A)～(B)中的一种：

(A)编码任一上述抗体或衍生抗体的核酸分子；

(B)含有(A)中所述核酸分子的表达盒、重组载体、重组微生物、重组细胞系。

可理解的是，表达盒、重组载体、重组微生物、重组细胞系均可采用本领域常规方法制备。

进一步地，在上述生物材料中，编码所述VH的核酸的序列选自SEQ ID NO. 153-SEQ ID NO.182、SEQ ID NO.328-SEQ ID NO.342中的一种；和/或，编码所述VL的核酸的序列选自SEQ ID NO.183-SEQ ID NO.214、SEQ ID NO.343- SEQ ID NO.355中的一种；和/或，编码所述scFv单链抗体的核酸的序列选自SEQ ID NO.247-SEQ ID NO.278、SEQ IDNO.369-SEQ ID NO.381中的一种。

更进一步地，在上述生物材料中，编码所述VH的核酸的序列选自SEQ ID NO.154-SEQ ID NO.156、SEQ ID NO.166中的一种；和/或，编码所述VL的核酸的序列选自SEQ IDNO.184-SEQ ID NO.186、SEQ ID NO.196中的一种；和/或，编码所述scFv单链抗体的核酸的序列选自SEQ ID NO.248-SEQ ID NO. 250、SEQ ID NO.260中的一种。

本领域技术人员可以很容易地采用已知的方法，例如定向进化和点突变的方法，对上述抗体或衍生抗体的核苷酸序列进行突变。经过人工修饰的，具有与本发明所述抗体或所述衍生抗体的核苷酸序列75％或75％以上同一性的核苷酸，只要编码所述抗体或所述衍生抗体且具有所述抗体或所述衍生抗体活性，均是衍生于本发明的核苷酸序列并且等同于本发明的序列。

进一步地，所述scFv单链抗体数量为45个，其中，抗体重链用VH所示，其中重链可变区用VH CDR1、VH CDR2和VH CDR3表示；抗体轻链用VL所示，其中轻链可变区用VL CDR1、VL CDR2和VL CDR3表示，且对所述抗体重链及抗体轻链的可变区基因序列进行了胚系基因片段的研究，分别以 VH_Germline和VL Germline表示。

所述45个scFv单链抗体的相关序列如下表1所示：

表1-scFv单链抗体的相关序列

续表1-scFv单链抗体的相关序列

本发明的第四个方面是提供一种亲和力成熟抗体，其由任一上述的抗体经过亲和力成熟后获得。

进一步地，所述亲和力成熟抗体的VH CDR1的氨基酸序列为SEQ ID NO.64 或SEQID NO.69，VH CDR2的氨基酸序列为SEQ ID NO.77、SEQ ID NO.382 或SEQ ID NO.383，VHCDR3的氨基酸序列为SEQ ID NO.88或SEQ ID NO.95；所述亲和力成熟抗体的VL CDR1的氨基酸序列为SEQ ID NO.106或SEQ ID NO. 107，VL CDR2的氨基酸序列为SEQ ID NO.120或SEQ ID NO.123，VL CDR3 的氨基酸序列为SEQ ID NO.129或SEQ ID NO.392-SEQ IDNO.396中的一种。

进一步地，所述亲和力成熟抗体的VH的氨基酸序列选自SEQ ID NO.384～ SEQ IDNO.387中的一种；所述亲和力成熟抗体的VL的氨基酸序列选自SEQ ID NO.397～SEQ IDNO.402中的一种。

进一步地，编码所述亲和力成熟抗体VH的核酸的序列选自SEQ ID NO.388- SEQID NO.391中的一种；编码所述亲和力成熟抗体VL的核酸的序列选自SEQ ID NO.403-SEQID NO.408中的一种。

进一步地，所述亲和力成熟抗体的制备步骤包括：

步骤(1)设计点突变引物，针对任一上述抗体的CDR区，设计NNS(N 代表任意碱基，S代表碱基C或者G)；

步骤(2)根据步骤(1)中设计的突变引物进行PCR反应，环批质粒；

步骤(3)将步骤(2)中PCR反应产物进行质粒回收，并进行PCR产物的转化及质粒制备；

步骤(4)对每个定点突变的克隆诱导表达scFv并进行scFv阻断活性检测；

步骤(5)对亲和力高的突变进行单克隆化，进行鉴定测序，获得亲和力成熟抗体。

进一步地，所述PCR反应体系及其反应条件如下：

	体积(uL)
		Fn-primer(2μM)	5
Rn-primer(2μM)	5
		模板质粒(100ng/uL)	1
PrimerSRAR Max Premix	5
		水	34
总体积	50

其中，Fn与Rn是根据轻链与重链CDR1、CDR2、CDR3区域的序列为依据，每次只突变CDR区单一的位点，该位点的碱基用NNS代表，正向引物依次命名为F1-primer、F2-primer……Fn-primer，反向引物依次命名为R1-primer、 R2-primer……Rn-primer；

反应条件：95℃变性5min；95℃30S，58℃30S，72℃4min；72℃10min。

进一步地，对上表1中的HTS0422、HTS0433、HTS0446、HTS0483进行亲和力成熟；更具体地对HTS0433与HTS0483进行了亲和力成熟，其亲和力成熟后的抗体序列信息如下表2所示：

表2-亲和力成熟抗体序列

续表2-亲和力成熟抗体序列

表2-亲和力成熟抗体序列

续表2-亲和力成熟抗体序列

本发明的第五个方面是提供一种治疗和/或预防新型冠状病毒SARS-CoV-2 及其所致疾病的产品，所述产品的活性成分为任一上述抗体、衍生抗体、生物材料或亲和力成熟抗体。

本发明的第六个方面是提供一种任一上述抗体、衍生抗体、生物材料或亲和力成熟抗体在制备治疗和/或预防新型冠状病毒SARS-CoV-2及其所致疾病的产品中的应用。

进一步地，所述产品可为诊断试剂、治疗药物、疫苗等。

本发明的第七个方面是提供一种任一上述抗体的制备方法，其包括以下步骤：

步骤1)利用新型冠状病毒感染康复期病人的外周血建立全人源噬菌体抗体库；

步骤2)使用生物素化的Spike1-RBD蛋白对步骤1)中构建的所述全人源噬菌体抗体库进行淘选，获得具有RBD结合活性的潜在抗体；

步骤3)通过在细胞与蛋白水平上分析步骤2)获得的所述潜在抗体阻断 ACE2与Spike蛋白的结合活性，从而筛选出具有潜在中和活性的抗体。

为了进一步优化上述制备方法，本发明采取的技术措施还包括：

进一步地，所述制备方法具体包括：

a.使用生物素化的Spike1-RBD蛋白对全人源抗体库进行淘选

室温封闭噬菌体抗体，加入抗原，室温孵育后加入磁珠，再室温孵育，洗去未结合的噬菌体，再洗脱结合在磁珠上的噬菌体，之后中和洗脱液，取部分噬菌体侵染对数生长期的大肠杆菌，制备噬菌体用于下一轮淘选；逐渐增加每轮的筛选强度，富集度达到100倍以上时，终止淘选；

b.采用phage Elisa筛选抗Spike1-RBD的单链抗体阳性克隆

挑选淘选后的噬菌体侵染的大肠杆菌单克隆，接种培养基，过夜培养后转接至新的培养基中，培养至对数生长期后加入辅助噬菌体，静止侵染，离心，使用培养基过夜培养，离心取噬菌体上清进行克隆鉴定；用Spike1-RBD抗原包被酶标板，封闭过夜，加入噬菌体上清孵育，洗去未结合的噬菌体后加入抗体孵育，洗涤后显色，终止反应，用酶标仪于450nm读数，选择OD450>0.3的克隆进行测序，对序列进行分析，排除有潜在开发风险的分子后得到scFv单链抗体。

进一步地，上述制备方法还包括scFv单链抗体的纯化步骤，其可为本领域常规纯化方法。

与现有技术相比，本发明采用上述技术方案，具有如下技术效果：

本发明通过利用新型冠状病毒感染康复期病人的外周血建立全人源噬菌体抗体库，对病毒Spike的RBD区域蛋白和过表达该区域的细胞进行淘选，并通过在细胞与蛋白水平上分析抗体阻断ACE2与Spike蛋白的结合活性，从而筛选出具有潜在中和活性的抗体，并根据上述抗体进行了完整IgG抗体的制备以及亲和力成熟。由实施例可知，本发明所获得的全人源化scFv单链抗体及其IgG抗体均能够识别并结合Spike蛋白的RBD区域，且均能有效阻断ACE2与Spike 蛋白的结合活性，其各浓度(30、15、7.5、3.75、1.875、0.938μg/ml)的抗体均对细胞无毒性，安全可靠，一定浓度下能显著抑制病毒感染所致的细胞病变效应，能有效抑制新冠病毒，且亲和力成熟后抗体序列与原始序列相比，亲和力有一定程度的提高，对Spike1-RBD与ACE2阻断效果明显增强，上述各类抗体在治疗和/或预防新型冠状病毒SARS-CoV-2中具有应用价值。

附图说明

图1为本发明一实施例中ELISA检测淘选终止单克隆scFv与Spike1-RBD 蛋白的结合活性的示意图；

图2为本发明一实施例中scFv纯化后PAGE鉴定结果示意图；

图3为本发明一实施例中ELISA检测纯化scFv与Spike1-RBD蛋白的结合活性的示意图；

图4为本发明一实施例中ELISA检测纯化scFv阻断Spike1-RBD与ACE2 结合的示意图；

图5为本发明一实施例中FACS检测scFv阻断Spike1-RBD与ACE2结合的示意图；其中，NC(negative control)为无关序列；

图6A～6G为本发明一实施例中ELISA检测IgG形式的抗体与Spike1-RBD 蛋白的结合活性的示意图；其中，NC(negative control)为无关序列；

图7A～7F为本发明一实施例中ELISA检测IgG抗体阻断Spike1-RBD与 ACE2结合的示意图；

图8为本发明一实施例中scFv抗体中和活性检测的结果示意图；

图9为本发明一实施例中ELISA检测亲和力成熟后的序列与Spike1-RBD的结合活性的示意图；

图10为本发明一实施例中ELISA检测IgG抗体阻断Spike1-RBD与ACE2 结合的示意图。

具体实施方式

本发明涉及一种抗体，其能结合至新型冠状病毒SARS-CoV-2的Spike蛋白 S1亚基中的RBD区域，从而阻断宿主细胞膜表面受体ACE2与Spike蛋白的结合活性；上述抗体为中和性全人源抗体；其中，上述抗体包括重链VH和轻链 VL，所述VH和VL均具有可变区CDR1、CDR2和CDR3。本发明还涉及上述抗体的相关应用，具体为制备完整IgG抗体、亲和力成熟抗体，并将相应抗体应用于治疗和/或预防新型冠状病毒SARS-CoV-2。

下面结合附图和实施例，对本发明的具体实施方式作进一步描述。以下实施例仅用于更加清楚地说明本发明的技术方案，而不能以此来限制本发明的保护范围。下列实施例中未注明具体条件的实验方法，按照本领域常规方法和条件，或按照商品说明书选择。

实施例1-中和性抗体的筛选

本实施例为全人源化scFv单链抗体的筛选，其步骤包括：

(1)全人源噬菌体抗体库的建立；

收集曾感染2019-nCOV病毒并康复的患者的外周血，测定其血清效价。从中选择效价高的样本分离淋巴细胞，提取细胞的总RNA，合成cDNA，利用特异性的抗体重链引物和轻链引物，扩增抗体的可变区基因，克隆到噬菌体展示载体上，转入宿主细胞。通过NGS测序，利用库容、克隆阳性率、重轻链配对、 CDR3的分布、噬菌体展示率等质控指标评价抗体库的多样性和有效性。

(2)噬菌体库筛选：使用生物素化的Spike1-RBD蛋白对全人源抗体库进行淘选；

首先用封闭液(PBST/5％脱脂奶粉)室温封闭噬菌体抗体2h，噬菌体的投入量为10^10～12pfu，然后加入10μg抗原，室温孵育1h，孵育后加入50μl预封闭的M-280Streptavidin磁珠，室温孵育30min。先用PBST洗去未结合的噬菌体，再用0.1M的HCl-Glycine洗脱结合在磁珠上的噬菌体，之后用 Tris-HCl中和洗脱液，取部分噬菌体侵染对数生长期的大肠杆菌TG1，制备噬菌体用于下一轮淘选。逐渐增加每轮的筛选强度，富集度达到100倍以上时，终止淘选。

(3)采用phage Elisa筛选抗Spike1-RBD的单链抗体阳性克隆；

挑选四轮淘选后的噬菌体侵染的TGl单克隆，接种于96孔板中，培养基为 2YT/2％glucose/(100μg/ml Ampicilline)。37℃/250rpm过夜培养后转接至新的培养基中，培养至对数生长期后加入M13K07辅助噬菌体，37℃静止侵染1h。 4000rpm离心15min，使用2YT/(100μg/ml Ampicilline)/(70μg/ml Kanamycin) 培养基30℃过夜培养。离心取噬菌体上清进行ELISA鉴定克隆。用0.5μg/ml的 Spike1-RBD抗原包被Costar-9018酶标板，3％BSA 4℃封闭过夜，加入噬菌体上清4℃孵育2h。洗去未结合的噬菌体后加入Ml3 Bacteriophage抗体(HRP)，4℃ 孵育1h。洗涤后加入TMB显色液显色，用2M HCl终止反应，用酶标仪于450nm读数，OD450>三倍基线，即OD450>0.3的判定为阳性克隆，共470个阳性克隆。选择OD450>0.3的克隆进行测序，对序列进行Germline分析和PTMs位点分析，排除有潜在开发风险的分子后共得到了45个scFv单链抗体，ELISA检测淘选终止单克隆scFv与Spike1-RBD蛋白的结合活性结果如图1所示。

所得的45个抗Spike1-RBD单链抗体的抗体重链用VH所示，其中重链可变区用CDR1、CDR2和CDR3表示；抗体轻链用VL所示，其中轻链可变区用CDR1、 CDR2和CDR3，其对应的抗Spike1-RBD单链抗体的编号及相关序列信息如发明内容部分的表1所示。

实施例2-scFv的表达纯化

本实施例对实施例1中筛选所得的45个scFv单链抗体进行表达纯化，其包括下述步骤：

取小摇之后的大肠杆菌TGl菌液，按照1:100的比例接种，37℃，220rpm 培养。当OD在0.5左右时，室温，8000rpm离心5分钟，获得菌液沉淀，IPTG 诱导，30℃培养12小时左右后收表达上清进行纯化。纯化步骤如下：

1)轻轻颠倒翻转瓶子几次，使介质混合均匀；

2)吸取一定量的介质加入到柱子中，柱高约3-4厘米，等介质沉降至底部时加上封口；

3)放干储存液，加入10mL平衡缓冲液平衡层析介质；

4)使用离心瓶离心，4000rpm，4℃离心10min，将上清转移到新的离心瓶中，12000rpm，4℃，离心30min；

5)上样，流速控制为1mL/min；

6)25mL 10mM咪唑洗涤缓冲液洗涤柱子，流速控制为1mL/min；

7)25mL 20mM咪唑洗涤缓冲液洗涤柱子，流速控制为1mL/min；

8)5mL 250mM咪唑洗脱缓冲液洗涤柱子，流速控制为1mL/min，收集洗脱液；

9)浓缩，将洗脱液加入到超滤管中，1500rpm，4℃离心10min，浓缩scFv；

10)PAGE鉴定及浓度测定。

对上述45个样品的scFv进行纯化，其纯化后检测结果如图2所示，各样品均得到了0.5mg以上的样品，后续相关活性验证以HTS0422、HTS0433、HTS0446 以及HTS0483为例进行说明。

实施例3-ELISA检测scFv的结合活性

本实施例以抗体HTS0422、HTS0433、HTS0446以及HTS0483为例运用 ELISA检测已纯化scFv与Spike1-RBD抗原的结合力。具体步骤如下：

1)384-well plate包被抗原，每孔加入25μL 1μg/mL浓度的Spike1-RBD抗原，密封，4℃包被过夜；

2)弃去上清，每孔100μL Wash Buffer洗涤3次；

3)每孔25μL封闭液，室温封闭1小时，封闭后的酶标板弃液体，每孔100μL WashBuffer洗3次；

4)稀释scFv抗体，最高浓度为200μg/ml，四倍梯度稀释，共8个点；

5)将稀释好的抗体25μL/孔加入适当的孔中，室温孵育2小时；

6)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤3次；

7)每孔加入稀释后的25μL Anti-C-myc-HRP，室温孵育1小时；

8)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤5次；

9)每孔加入25μL 1X TMB，避光室温摇动显色10min；

10)每孔加入25μL终止液；

11)使用酶标仪读取450nm的吸光值；

上述scFv抗体的检测结果如图3所示，抗体HTS0422、HTS0433、HTS0446 以及HTS0483均能与Spike1-RBD抗原特异性结合，并呈现出剂量效应关系。

实施例4-ELISA检测scFv阻断Spike1-RBD与ACE2受体的结合

本实施例以抗体HTS0422、HTS0433、HTS0446以及HTS0483为例运用 ELISA检测已纯化scFv阻断Spike1-RBD与ACE2受体的结合。具体步骤如下：

1)384-well plate包被抗原，每孔加入25μL 1μg/mL浓度的ACE2抗原，密封，4℃包被过夜；

2)弃去上清，每孔100μL Wash Buffer洗涤3次；

3)每孔25μL封闭液，室温封闭1小时，封闭后的酶标板弃液体，每孔100μL WashBuffer洗3次；

4)稀释scFv抗体，最高浓度为200μg/ml，四倍梯度稀释，共8个点，与 Spike-RBD蛋白混匀，室温共孵育1小时；

5)将预处理的scFv以及Spike-RBD混合物每孔加入25μl，室温孵育2小时；

6)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤3次；

7)每孔加入稀释后的25μL Anti-mFC-HRP，室温孵育1小时；

8)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤5次；

9)每孔加入25μL 1X TMB，避光室温摇动显色10min；

10)每孔加入25μL终止液；

11)使用酶标仪读取450nm的吸光值。

上述scFv抗体的检测结果如图4所示，抗体HTS0422、HTS0433、HTS0446 以及HTS0483均能阻断Spike1-RBD与AEC2结合，并呈现出剂量效应关系。

实施例5-FACS检测scFv阻断Spike1-RBD与ACE2受体的结合

本实施例以抗体HTS0422、HTS0433、HTS0446以及HTS0483为例运用FACS 检测已纯化scFv阻断Spike1-RBD与ACE2受体的结合。具体步骤如下：

1)梯度稀释抗体，最高浓度为100μg/ml，四倍梯度稀释；

2)稀释抗体30μL与0.1μg/ml的Spike1-RBD蛋白30μL混合，冰上孵育 30min；

3)消化细胞，96-well plate每个孔铺3×10⁵细胞；

4)4℃，1500rpm离心1min，弃上清；

5)每个孔加入50μL预处理的抗原抗体混合液，冰上孵育30min；

6)每孔加入150μL DPBS，4℃，1500rpm离心1min，弃上清；

7)DPBS 1:800稀释二抗，50μL重悬，冰上孵育30-60min；

8)每孔加入150μL DPBS，4℃，1500rpm离心1min，弃上清；

9)每孔加入200μL DPBS，4℃，1500rpm离心1min，弃上清；

10)每孔加入100μL DPBS重悬细胞，流式检测。

上述scFv抗体的检测结果如图5所示，抗体HTS0422、HTS0433、HTS0446 以及HTS0483均阻断Spike1-RBD与AEC2结合，并呈现出剂量效应关系。

实施例6-完整IgG抗体的表达纯化

本实施例为根据实施例1中scFv单链抗体的VH和VL基因片段来制备完整IgG抗体，其步骤包括：将scFv的VH和VL基因片段分别亚克隆入人IgG1 CH 载体pTT5-hIgG1与kappa轻链CL表达载体pTT5-hKappa，同时转染至293F细胞中表达并由蛋白G亲和纯化。

在所有45个阳性克隆中，选择表达了37个完整IgG抗体，分别是HTS0390、HTS0414、HTS0422、HTS0433、HTS0446、HTS0448、HTS0460、HTS0461、 HTS0471、HTS0472、HTS0476、HTS0477、HTS0478、HTS0483、HTS0777、 HTS0778、HTS0829、HTS0842、HTS0888、HTS0889、HTS0895、HTS0896、 HTS0910、HTS0916、HTS0917、HTS0921、HTS0922、HTS0936、HTS0943、 HTS0944、HTS0948、HTS1021、HTS1049、HTS1072、HTS1099、HTS1125、 HTS1128。

实施例7-ELISA检测IgG抗体的结合活性

本实施例为运用ELISA检测实施例6中已纯化的完整IgG抗体与 Spike1-RBD抗原的结合力。具体步骤如下：

1)384-well plate包被抗原，每孔加入25μL 1μg/mL浓度的Spike1-RBD抗原，密封，4℃包被过夜；

2)弃去上清，每孔100μL Wash Buffer洗涤3次；

3)每孔25μL封闭液，室温封闭1小时，封闭后的酶标板弃液体，每孔100μL WashBuffer洗3次；

4)稀释IgG抗体，最高浓度为50μg/ml，三倍梯度稀释，共12个点；

5)将稀释好的抗体25μL/孔加入适当的孔中，室温孵育2小时；

6)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤3次；

7)每孔加入稀释后的25μL Anti-human-FC-HRP，室温孵育1小时；

8)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤5次；

9)每孔加入25μL 1X TMB，避光室温摇动显色10min；

10)每孔加入25μL终止液；

11)使用酶标仪读取450nm的吸光值；

上述IgG抗体的检测结果如图6A～6G所示，IgG抗体均能与Spike1-RBD抗原特异性结合，并呈现出剂量效应关系。

实施例8-ELISA检测IgG抗体阻断Spike1-RBD与ACE2受体的结合

本实施例运用ELISA检测实施例6中已纯化的完整IgG抗体阻断 Spike1-RBD与ACE2受体的结合。具体步骤如下：

1)384-well plate包被抗原，每孔加入25μL 1.5μg/mL浓度的ACE2抗原，密封，4℃包被过夜；

2)弃去上清，每孔100μL Wash Buffer洗涤3次；

3)每孔25μL封闭液，室温封闭1小时，封闭后的酶标板弃液体，每孔100μL WashBuffer洗3次；

4)稀释IgG抗体，最高浓度为100μg/ml，三倍梯度稀释，共11个点，与 Spike-RBD蛋白混匀，室温共孵育1小时；

5)将预处理的IgG抗体以及Spike-RBD混合物每孔加入25μl，室温孵育2 小时；

6)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤3次；

7)每孔加入稀释后的25μL Anti-mFC-HRP，室温孵育1小时；

8)弃上清，使用吸水纸吸干上清，100μL Wash Buffer洗涤5次；

9)每孔加入25μL 1X TMB，避光室温摇动显色10min；

10)每孔加入25μL终止液；

11)使用酶标仪读取450nm的吸光值。

上述IgG抗体的检测结果如图7A～7F所示，IgG抗体均能阻断Spike1-RBD 与AEC2结合，并呈现出剂量效应关系，其中HTS0422、HTS0433、HTS0483、 HTS0446以及HTS0778效果最好。

实施例9-抗体毒性试验

本实施例通过CCK8实验，验证抗体HTS0422、HTS0433、HTS0483、 HTS0446、HTS0390的抗体毒性作用，具体步骤如下：

(1)使用无血清培养基稀释抗新冠病毒的抗体HTS0422、HTS0433l、 HTS0446、HTS0390、HTS0483，起始抗体浓度为60μg/ml，2倍梯度稀释，共稀释6个稀释度，即配制的抗体浓度为60、30、15、7.5、3.75、1.875μg/ml。

(2)在96孔细胞培养板中，每孔加入各个浓度(60、30、15、7.5、3.75、 1.875μg/ml)的抗体液100μl。随后加入Vero-E6细胞(1×10⁵/ml细胞浓度悬浮在含10％FBS的MEM培养基中)100μl，抗体终浓度为：30、15、7.5、3.75、 1.875、0.938μg/ml。细胞培养板震荡混匀后置于5％CO₂培养箱中，设置4个复孔。

(3)培养6天后，每孔加入CCK-8试剂(美国MCE公司产品)20μl/孔，孵育3小时后用酶标仪测定在450nm处的OD值，分析抗体对细胞的剂量毒性效应，结果见下表：

由上述CCK-8检测结果显示，与未处理的细胞对照比较，抗体各测试浓度 (30、15、7.5、3.75、1.875、0.938μg/ml)对Vero-E6细胞均无毒性作用。

实施例10-抗体中和活性检测

本实施例通过真病毒阻断实验，检测HTS0422、HTS0433、HTS0446、 HTS0483以及HTS0390抗体的中和活性，具体步骤如下：

(1)使用无血清培养基稀释抗新冠病毒抗体HTS0422、HTS0433、HTS0446、 HTS0483以及HTS0390，起始抗体浓度为60μg/ml，2倍梯度稀释，共稀释12 个稀释度，即配制的抗体浓度为60、30、15、7.5、3.75、1.875、0.938、0.469、 0.235、0.118、0.059、0.029μg/ml。

(2)在96孔板中，每孔加入各个浓度的抗体液50μl，随后加入等体积50μl 含有100TCID50的新冠病毒，抗体终浓度为30、15、7.5、3.75、1.875、0.938、 0.469、0.235、0.118、0.059、0.029、0.0145μg/ml，混匀后置于35℃培养箱中孵育60min。每孔加入新鲜配制的Vero-E6细胞悬液(2×10⁵/ml in 10％FBS-MEM)100μl并混匀，放置于35℃含5％CO2的细胞培养箱中继续培养6天。每个测试的抗体浓度设4个复孔。

(3)接种后的第2天起显微镜下观察细胞生长情况，第4天观察细胞病变 (CPE)情况，并录。第6天根据细胞病变效应最终判定结果。计算抗体的中和效率，即能够保护50％细胞不受100TCID50病毒液感染的抗体最低浓度。

(4)通过显微镜观察各浓度抗体处理的病毒对Vero E6细胞的病变效应，分析抗体对新冠病毒的抑制作用，其结果如下表及图8所示。

由上述结果可知，HTS0422≥1.875ug/ml、HTS0433≥1.875ug/ml、HTS0446 ≥7.5ug/ml、HTS0483≥1.875ug/ml即能显著抑制病毒感染所致的细胞病变效应。但HTS0390在测试的所有浓度均无显著的抗病毒作用。

实施例11–抗体的亲和力成熟

通过上述实施例验证可知HTS0422、HTS0433、HTS0446、HTS0483的结合效果与阻断效果最好，选择了对HTS0433与HTS0483进行了亲和力成熟，具体步骤如下：

(1)设计点突变引物，针对HTS0433与HTS0483的CDR区，设计NNS (N代表任意碱基，S代表碱基C或者G)

(2)以HTS0433或者HTS0483为模板，环批质粒。

	体积(uL)
		Fn-primer(2μM)	5
Rn-primer(2μM)	5
		模板质粒(100ng/uL)	1
PrimerSRAR Max Premix	5
		水	34
总体积	50

备注：Fn与Rn是根据HTS0433或者HTS0483轻链与重链CDR1、CDR2、CDR3区域的序列为依据，每次只突变CDR区单一的位点，该位点的碱基用NNS代表，正向引物依次命名为F1-primer、F2-primer……Fn-primer，反向引物依次命名为R1-primer、 R2-primer……Rn-primer。

按上表将反应溶液加入到PCR管中，混合均匀。将PCR反应管置于PCR 仪中，设置反应条件：95℃变性5min；95℃30S，58℃30S，72℃4min；72℃ 10min；产物可4℃短暂保存，用于后续实验。

(3)使用PCR产物回收试剂盒回收质粒，按照常规方法进行PCR产物的转化及质粒制备。

(4)对每个定点突变的克隆诱导表达scFv并进行scFv阻断活性检测，具体步骤见实施例2与实施例5。

(5)对亲和力高的突变进行单克隆化，同步骤4，进行鉴定。高亲和力的克隆进行测序。亲和力成熟后的序列如发明内容部分的表2所示。

实施例12-ELISA检测亲和力成熟后抗体的结合活性

本实施例运用ELISA检测实施例11中制备的亲和力成熟后抗体与 Spike1-RBD抗原的结合力，其具体步骤同实施例7，其结果如图9所示。由实验结果可知，亲和力成熟后抗体序列，与原始序列相比，亲和力均有提高。

实施例13-ELISA检测亲和力成熟后抗体阻断Spike1-RBD与ACE2受体的结合

本实施例运用ELISA检测实施例11中制备的亲和力成熟后抗体阻断 Spike1-RBD与ACE2的结合活性，其具体步骤同实施例8，其结果如图10所示。由实验结果可知，亲和力成熟后抗体序列，与原始序列相比，AGE0003与 AGE0004的阻断效果明显增强。

由上述实施例可知，本发明筛选所获得的全人源化scFv单链抗体及其IgG 抗体能够识别并结合Spike蛋白的RBD区域，且能有效阻断ACE2与Spike蛋白的结合活性，对细胞无毒性，能显著抑制病毒感染所致的细胞病变效应，且亲和力成熟后抗体序列的亲和力以及对Spike1-RBD与ACE2的阻断效果均明显增强，其在治疗和/或预防新型冠状病毒SARS-CoV-2中具有应用价值。

以上对本发明的具体实施例进行了详细描述，但其只作为范例，本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言，任何对本发明进行的等同修改和替代也都在本发明的范畴之中。因此，在不脱离本发明的精神和范围下所作的均等变换和修改，都应涵盖在本发明的范围内。

序列表

<110> 上海祥耀生物科技有限责任公司

浙江祥耀生物医药有限公司

<120> 一种新型冠状病毒SARS-CoV-2中和性抗体及应用

<150> 202010188367.6

<151> 2020-03-17

<160> 408

<170> SIPOSequenceListing 1.0

<210> 1

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 1

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 2

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 2

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Met Val

115 120 125

Thr Val Ser Ser

130

<210> 3

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 3

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Asp Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser

130

<210> 4

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 4

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser

130

<210> 5

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 5

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 6

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 6

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 7

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 7

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Phe Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 8

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 8

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

Met Glu Met Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

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

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 9

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 9

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 10

<211> 128

<212> PRT

<213> VH(Artificial Sequence)

<400> 10

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Ala Tyr His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

Ala Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 11

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 11

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 12

<211> 128

<212> PRT

<213> VH(Artificial Sequence)

<400> 12

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Gly Phe His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

Ala Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 13

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 13

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

Ser Leu Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 14

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 14

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Thr Val Thr Val Ser Ser

115

<210> 15

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 15

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 16

<211> 123

<212> PRT

<213> VH(Artificial Sequence)

<400> 16

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 Ser Tyr

20 25 30

Ala 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 Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

100 105 110

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 17

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 17

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

Met Glu Met Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

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

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 18

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 18

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Asp Phe Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Arg Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser

115

<210> 19

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 19

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 Thr Tyr

20 25 30

Ala 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 Glu Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 20

<211> 121

<212> PRT

<213> VH(Artificial Sequence)

<400> 20

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Thr Gln Ile

20 25 30

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

35 40 45

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

85 90 95

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

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 21

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 21

Glu Val Gln Leu Leu 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 Thr Tyr

20 25 30

Ala 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 Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 22

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 22

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gly Pro Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 23

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 23

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 24

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 24

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

1 5 10 15

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

20 25 30

Ala Met 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 Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 25

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 25

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser

115

<210> 26

<211> 130

<212> PRT

<213> VH(Artificial Sequence)

<400> 26

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 Glu Phe Thr Phe Ser Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

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 Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser

130

<210> 27

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 27

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Leu Tyr Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser

115

<210> 28

<211> 130

<212> PRT

<213> VH(Artificial Sequence)

<400> 28

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 Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

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 Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser

130

<210> 29

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 29

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Ala Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 30

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 30

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 31

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 31

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr 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 Ala Asn Ser Phe Pro Pro

85 90 95

Ala Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 32

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 32

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

1 5 10 15

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

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe 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 His Ser Thr Pro Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 33

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 33

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

1 5 10 15

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 34

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 34

Ala Ile Arg 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 Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 35

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 35

Ala Ile Arg 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 Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 36

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 36

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Ser

85 90 95

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

100 105

<210> 37

<211> 103

<212> PRT

<213> VL(Artificial Sequence)

<400> 37

Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

Tyr 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 Ala Glu Ala Phe Gly Gly

85 90 95

Gly Thr Lys Val Glu Ile Lys

100

<210> 38

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 38

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Ser Trp

20 25 30

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

35 40 45

Tyr Lys Ala Ser His 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

Asp Asp Phe Ala Ile Tyr Tyr Cys Gln Gln His Asn Ser Tyr Pro Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 39

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 39

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 40

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 40

Asp Ile Gln Leu 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 Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 41

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 41

Ala Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

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

85 90 95

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

100 105

<210> 42

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 42

Ala Ile Gln Leu 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 Leu Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 43

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 43

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

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

85 90 95

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

100 105

<210> 44

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 44

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 Gly Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

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

35 40 45

Ile Tyr Asp Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 45

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 45

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ala Ile Ser Asn Trp

20 25 30

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

35 40 45

Tyr Glu Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gly Asn Tyr Trp Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 46

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 46

Asp Ile Gln Leu 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 Leu

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 47

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 47

Asp Ile Val Met Thr Gln Ser Ser 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 Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 48

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 48

Ala Ile Arg Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Lys Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Trp

85 90 95

Ala Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 49

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 49

Ala Ile Arg Met Thr Gln Phe Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser His

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 50

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 50

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu

85 90 95

Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 51

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 51

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

1 5 10 15

Glu Ser Ala Ser Leu Ser Cys Arg Ser Ser Gln Ser Leu Leu His Arg

20 25 30

Ser Gly His 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 Ile 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 Gly

85 90 95

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

100 105 110

<210> 52

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 52

Asp Ile Gln Leu 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 Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 53

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 53

Asp Ile Val Met Thr Gln Pro Pro Leu 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 Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 54

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 54

Ala Ile Arg Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Lys Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Asp Ser Gly

85 90 95

His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Arg

100 105

<210> 55

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 55

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Gly 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 Ala Asn Ser Phe Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 56

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 56

Asp Ile Val Met Thr Gln Pro Pro Leu 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 Gly Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105 110

<210> 57

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 57

Glu Ile Val Met Thr Gln Ser Pro Asp Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Glu Ser Val Ser Ser Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

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

100 105

<210> 58

<211> 113

<212> PRT

<213> VL(Artificial Sequence)

<400> 58

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

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp 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 Gly

85 90 95

Thr His Trp Pro Pro Asn Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 59

<211> 109

<212> PRT

<213> VL(Artificial Sequence)

<400> 59

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

1 5 10 15

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

20 25 30

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

35 40 45

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Asp

85 90 95

Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 60

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 60

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

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp 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 Gly

85 90 95

Thr His Trp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 61

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 61

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 62

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 62

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Glu Gln Leu Lys Ser Tyr Pro Pro

85 90 95

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

100 105

<210> 63

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 63

Gly Val Thr Val Ser Ser Asn Tyr

1 5

<210> 64

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 64

Gly Phe Thr Phe Asp Asp Tyr Ala

1 5

<210> 65

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 65

Gly Phe Thr Val Ser Ser Asn Tyr

1 5

<210> 66

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 66

Gly Tyr Thr Phe Thr Gly Tyr Tyr

1 5

<210> 67

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 67

Gly Tyr Thr Phe Thr Ser Tyr Gly

1 5

<210> 68

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 68

Gly Phe Thr Val Gly Ser Asn Tyr

1 5

<210> 69

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 69

Gly Ile Thr Val Ser Ser Asn Tyr

1 5

<210> 70

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 70

Gly Phe Thr Phe Ser Ser Tyr Ala

1 5

<210> 71

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 71

Asp Phe Thr Val Ser Ser Asn Tyr

1 5

<210> 72

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 72

Gly Phe Thr Phe Ser Thr Tyr Ala

1 5

<210> 73

<211> 10

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 73

Gly Gly Ser Ile Thr Gln Ile Ile Tyr Tyr

1 5 10

<210> 74

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 74

Gly Phe Thr Val Ser Arg Asn Tyr

1 5

<210> 75

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 75

Glu Phe Thr Phe Ser Asn Ala Trp

1 5

<210> 76

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 76

Gly Phe Thr Phe Ser Asn Ala Trp

1 5

<210> 77

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 77

Ile Tyr Ser Gly Gly Ser Thr

1 5

<210> 78

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 78

Ile Ser Trp Asn Ser Gly Ser Ile

1 5

<210> 79

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 79

Ile Asn Pro Asn Ser Gly Ala Thr

1 5

<210> 80

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 80

Ile Ser Ala Tyr His Gly Asn Thr

1 5

<210> 81

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 81

Ile Ser Gly Phe His Gly Asn Thr

1 5

<210> 82

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 82

Ile Ser Tyr Asp Gly Ser Asn Lys

1 5

<210> 83

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 83

Ile Tyr Pro Gly Gly Ser Thr

1 5

<210> 84

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 84

Ile Tyr Tyr Arg Gly Ser Thr

1 5

<210> 85

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 85

Ile Tyr Ser Gly Gly Thr Thr

1 5

<210> 86

<211> 10

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 86

Ile Lys Ser Lys Thr Asp Gly Gly Thr Thr

1 5 10

<210> 87

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 87

Ala Arg Asp Leu Val Ser Ser Gly Met Asp Val

1 5 10

<210> 88

<211> 25

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 88

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

1 5 10 15

Pro Lys Ala His Trp Tyr Phe Asp Leu

20 25

<210> 89

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 89

Ala Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val

1 5 10

<210> 90

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 90

Ala Arg Asp Leu Val Val Tyr Gly Met Asp Val

1 5 10

<210> 91

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 91

Ala Arg Asp Leu Val Val Phe Gly Met Asp Val

1 5 10

<210> 92

<211> 15

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 92

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val

1 5 10 15

<210> 93

<211> 21

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 93

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

1 5 10 15

Ala Pro Phe Asp Tyr

<210> 94

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 94

Ala Arg Asp Leu Val Tyr Tyr Gly Met Asp Val

1 5 10

<210> 95

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 95

Ala Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val

1 5 10

<210> 96

<211> 16

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 96

Ala Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

1 5 10 15

<210> 97

<211> 10

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 97

Ala Arg Asp Arg Gly Asp Ala Phe Asp Ile

1 5 10

<210> 98

<211> 15

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 98

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val

1 5 10 15

<210> 99

<211> 13

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 99

Ala Arg Ala Val Arg His Asp Tyr Asn Tyr Phe Asp Tyr

1 5 10

<210> 100

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 100

Ala Arg Asp Leu Gly Pro Tyr Gly Met Asp Val

1 5 10

<210> 101

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 101

Ala Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val

1 5 10

<210> 102

<211> 21

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 102

Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val Tyr Tyr

1 5 10 15

Tyr Gly Met Asp Val

<210> 103

<211> 10

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 103

Ala Arg Thr Leu Tyr Asp Ala Phe Asp Ile

1 5 10

<210> 104

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 104

Ala Arg Asp Leu Val Ala Tyr Gly Met Asp Val

1 5 10

<210> 105

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 105

Gln Gly Ile Ser Ser Trp

1 5

<210> 106

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 106

Gln Ser Ile Ser Ser Tyr

1 5

<210> 107

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 107

Gln Ser Val Ser Ser Ser Tyr

1 5

<210> 108

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 108

Gln Ser Ile Asn Ser Trp

1 5

<210> 109

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 109

Gln Gly Ile Ser Ser Tyr

1 5

<210> 110

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 110

Gln Ala Ile Ser Asn Trp

1 5

<210> 111

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 111

Gln Thr Ile Thr Asp Trp

1 5

<210> 112

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 112

Gln Ser Ile Gly Ser Trp

1 5

<210> 113

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 113

Gln Asp Ile Ser Asn Tyr

1 5

<210> 114

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 114

Gln Ser Leu Leu His Arg Ser Gly His Asn Tyr

1 5 10

<210> 115

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 115

Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

1 5 10

<210> 116

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 116

Gln Ile Ile Ser Asp Trp

1 5

<210> 117

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 117

Glu Ser Val Ser Ser Ser Tyr

1 5

<210> 118

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 118

Gln Ser Leu Val His Ser Asp Gly Asn Thr Tyr

1 5 10

<210> 119

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 119

Gln Ser Ile Ser Ser Trp

1 5

<210> 120

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 120

Ala Ala Ser

<210> 121

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 121

Gly Ala Ser

<210> 122

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 122

Lys Ala Ser

<210> 123

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 123

Asp Ala Ser

<210> 124

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 124

Glu Ala Ser

<210> 125

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 125

Leu Gly Ser

<210> 126

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 126

Lys Val Ser

<210> 127

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 127

Gln Gln Ala Asn Ser Phe Pro Pro Ala

1 5

<210> 128

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 128

Gln Gln Ser His Ser Thr Pro Tyr Thr

1 5

<210> 129

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 129

Gln Gln Ser Tyr Ser Thr Pro Arg Thr

1 5

<210> 130

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 130

Gln Gln Ser Tyr Ser Thr Pro Tyr Thr

1 5

<210> 131

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 131

Gln Gln Tyr Gly Ser Ser Ser Tyr Thr

1 5

<210> 132

<211> 5

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 132

Gln Gln Ala Glu Ala

1 5

<210> 133

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 133

Gln Gln His Asn Ser Tyr Pro Thr

1 5

<210> 134

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 134

Gln Gln Leu Asn Ser Tyr Pro Phe Thr

1 5

<210> 135

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 135

Gln Gln Leu Asn Ser Tyr Pro Pro Tyr Thr

1 5 10

<210> 136

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 136

Gln Gln Ser Tyr Ser Thr Leu Leu Thr

1 5

<210> 137

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 137

Gln Gln Tyr Gly Ser Ser Pro Leu Thr

1 5

<210> 138

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 138

Gln Gln Tyr Gly Asn Tyr Trp Thr

1 5

<210> 139

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 139

Gln Gln Ser Tyr Ser Thr Pro Leu Thr

1 5

<210> 140

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 140

Gln Gln Tyr Asn Ser Tyr Ser Trp Ala

1 5

<210> 141

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 141

Gln Gln Tyr Asn Ser Tyr Ser His Thr

1 5

<210> 142

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 142

Gln Gln Tyr Asp Asn Leu Pro Leu Phe Thr

1 5 10

<210> 143

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 143

Met Gln Gly Leu Gln Pro Pro Tyr Thr

1 5

<210> 144

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 144

Met Gln Ala Leu Gln Thr Pro Tyr Thr

1 5

<210> 145

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 145

Gln Gln Tyr Asn Ser Asp Ser Gly His Thr

1 5 10

<210> 146

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 146

Gln Gln Ala Asn Ser Phe Pro Pro Thr

1 5

<210> 147

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 147

Met Gln Ala Leu Gln Thr Pro Phe Thr

1 5

<210> 148

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 148

Gln Gln Tyr Gly Ser Ser Pro Tyr Thr

1 5

<210> 149

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 149

Met Gln Gly Thr His Trp Pro Pro Asn Thr

1 5 10

<210> 150

<211> 11

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 150

Gln Gln Tyr Asn Ser Tyr Ser Asp Met Tyr Thr

1 5 10

<210> 151

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 151

Met Gln Gly Thr His Trp Pro Tyr Thr

1 5

<210> 152

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 152

Glu Gln Leu Lys Ser Tyr Pro Pro Tyr Thr

1 5 10

<210> 153

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 153

caggttcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 154

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 154

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcacaat ggtcaccgtc tcgagt 396

<210> 155

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 155

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatt tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatgg acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcactgtc tcgagt 396

<210> 156

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 156

caggttcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagt 396

<210> 157

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 157

gaggtgcaac tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctggat 300

atagccgggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 158

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 158

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctagta 300

gtctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 159

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 159

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtattcggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 160

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 160

gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 161

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 161

gaggtgcagc tggtggagac tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 162

<211> 384

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 162

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcgctt accatggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagt 384

<210> 163

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 163

gaggtgcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accctggtca ccgtctcgag t 351

<210> 164

<211> 384

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 164

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcggtt tccacggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagt 384

<210> 165

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 165

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcggt agcaactaca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacttagtc 300

tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 166

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 166

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc gagt 354

<210> 167

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 167

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 168

<211> 369

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 168

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagccgatcc 300

cccagtatag cagcagccgc taatgctttt gatatctggg gccaagggac cacggtcacc 360

gtctcgagt 369

<210> 169

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 169

caggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 170

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 170

caggtccagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtacag cctctgactt caccgtcagt agcaactaca tgacctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcactt atttatcccg gtggtagcac atactacgca 180

gactccctga agggccgatt caccatctcc agagacaatt ccaagaacac gctatacctt 240

caaatgaaca gcctgagagt tgaggacacg gctgtgtatt actgtgcgag agaccggggc 300

gatgcatttg atatctgggg ccaagggacc acggtcaccg tctcgagt 348

<210> 171

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 171

gaggtgcagc tggtggagtc cgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccgagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aaggcaccct ggtcaccgtc 360

tcgagt 366

<210> 172

<211> 363

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 172

caggtgcagc tacaacagtg gggcccagga ctggtgaagc cttcggagac cctgtccctc 60

acctgtagcg tctctggtgg ctccatcacg cagattattt actactgggc ctggatccgc 120

cagcccccag ggagggggct ggagtggatt gggagtatct actatagggg gagcacctcc 180

tccaacccgt ccctcaagag tcgagtcacc atatccgtag acacgtccaa gaaccagttc 240

tccctgaacc taacctctgt gaccgccgca gacacggctg tgtattactg tgcgagggcg 300

gttagacatg actacaacta ttttgactac tggggccagg gaaccctggt caccgtctcg 360

agt 363

<210> 173

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 173

gaggtgcagc tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagt 366

<210> 174

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 174

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggagt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gcggtaccac atactacgca 180

gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatctgggg 300

ccatacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 175

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 175

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 176

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 176

gaagtgcagc tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagt 366

<210> 177

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 177

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggacaatgg tcaccgtctc gagt 354

<210> 178

<211> 390

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 178

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctgagtt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt 390

<210> 179

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 179

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcttgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaatac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag gactttatat 300

gatgcttttg atatctgggg ccaagggacc acggtcaccg tctcgagt 348

<210> 180

<211> 390

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 180

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctggatt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt 390

<210> 181

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 181

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctcgtt 300

gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 182

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 182

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 183

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 183

gacatcgtga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctaacagtt tccctccggc tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 184

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 184

gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagttcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agtcacagta ccccgtacac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 185

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 185

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcggac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 186

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 186

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcggac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 187

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 187

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 188

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 188

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcctcgta cacttttggc 300

caggggacca agctggagat caaa 324

<210> 189

<211> 309

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 189

gccatccgga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctgaggctt tcggcggagg gaccaaggtg 300

gagatcaaa 309

<210> 190

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 190

gccatccagt tgacccagtc tccttccacc ctgtctgcat ctgtcggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattaat tcctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaaactcct gatctataag gcgtctcatt tacaaagtgg cgtcccttca 180

aggttcagcg gcagtggatc tgggacagat ttcactctta ccatcagtag cctgcagcct 240

gatgattttg caatttatta ctgccaacag cataattctt atccgacctt cggccaaggg 300

accaaggtgg aaatcaaa 318

<210> 191

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 191

gaaattgtgt tgacgcagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaagaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaggtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctttcac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 192

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 192

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 193

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 193

gccatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tggggcagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctccgta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 194

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 194

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cactcctcac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 195

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 195

gacatcgtga tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctccgta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 196

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 196

gaaattgtgt tgacgcagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgcg gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggcctgg cgcccaggct cctcatctat gatgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300

ggagggacca aggtggagat caaa 324

<210> 197

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 197

gacatccagt tgacccagtc tccctccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca ggctattagt aactggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgag gcgtctaatt tagaaagtgg ggtcccatcg 180

aggttcagcg gcagtggttc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tatggtaatt attggacgtt cggccaaggg 300

accaaggtgg aaatcaaa 318

<210> 198

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 198

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctctgac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 199

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 199

gacatcgtga tgacccagtc ttcatcctcc ctgtctgcat ctgtaggaga cagggtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 200

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 200

gccatccgga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gactattact gactggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctactt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgatttcg caacttatta ctgccaacaa tataatagtt attcttgggc gttcggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 201

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 201

gccatccgga tgacccagtt tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattggt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attctcacac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 202

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 202

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tccccttatt cactttcggc 300

cctgggacca aagtggatat caaa 324

<210> 203

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 203

gatattgtga tgacccagac tccactctcc ctgcccgtca cccctggaga gtcggcctcc 60

ctctcctgca ggtctagtca gagcctcctg cataggagtg gacacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgattt atttgggttc tattcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagactttac actgaaaata 240

agtagagtgg aggctgagga tgttggggtt tattactgca tgcaaggtct acaacctccg 300

tacacttttg gccaagggac caaggtggaa atcaaa 336

<210> 204

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 204

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcgcac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 205

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 205

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctc catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgagga tgttggggtt tattactgca tgcaagctct acaaactccg 300

tacacttttg gccaggggac caagctggag atcaaa 336

<210> 206

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 206

gccatccgga tgacccagtc tccttccacc ctgtctgcat ctgtgggcga cagagtcacc 60

atcacttgcc gggccagtca gattattagt gactggttgg cctggtatca gcagagacca 120

ggggaagccc ctaagctcct catctataag gcatctaatt tacaaagtgg ggtcccatca 180

aggttcagcg gcagtgtatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg cgacttatta ctgccaacaa tataatagtg attctgggca cacttttggc 300

caagggacca aggtggaaat caga 324

<210> 207

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 207

gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatggt gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctaacagtt tccctcccac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 208

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 208

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgggga tgttggggtt tattactgca tgcaagctct acaaacccct 300

ttcactttcg gccctgggac caaagtggat atcaaa 336

<210> 209

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 209

gaaatagtga tgacgcagtc tccagacacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtga gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gtagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacccta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 210

<211> 339

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 210

gatattgtga tgactcagtc tccactctcc ctgcccgtca cccttggaca gccggcctcc 60

atctcctgca ggtctagtca aagcctcgta cacagtgatg gaaacaccta cttgaattgg 120

tttcagcaga ggccaggcca atctccaagg cgcctaattt ataaggtttc taaccgggac 180

tctggggtcc cagacagatt cagcggcagt gggtcaggca ctgatttcac actgaaaatc 240

agcagggtgg aggctgaaga tgttggggtt tattactgca tgcaaggtac acactggcct 300

ccgaacactt ttggccaagg gaccaaggtg gaaatcaaa 339

<210> 211

<211> 327

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 211

gccatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attctgacat gtacactttt 300

ggccaaggga ccaaggtgga aatcaaa 327

<210> 212

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 212

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccttggaca gccggcctcc 60

atctcctgca ggtctagtca aagcctcgta cacagtgatg gaaacaccta cttgaattgg 120

tttcagcaga ggccaggcca atctccaagg cgcctaattt ataaggtttc taaccgggac 180

tctggggtcc cagacagatt cagcggcagt gggtcaggca ctgatttcac actgaaaatc 240

agcagggtgg aggctgagga tgttggggtt tattactgca tgcaaggtac acactggcct 300

tacacttttg gccaagggac caaggtggaa atcaaa 336

<210> 213

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 213

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accccttcac tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 214

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 214

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtgaacag cttaagagtt accctccgta cacttttggc 300

caggggacca agctggagat caaa 324

<210> 215

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 215

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

<210> 216

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 216

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Met Val

115 120 125

Thr Val Ser Ser Ala Ile Gln Met 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 Phe 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 His

210 215 220

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

225 230 235

<210> 217

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 217

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Asp Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser Asp Ile Val Met 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 Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 218

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 218

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser Ala Ile Arg Met 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 Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 219

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 219

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 220

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 220

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

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

115 120 125

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

130 135 140

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

145 150 155 160

Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile

165 170 175

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

180 185 190

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln

195 200 205

Tyr Gly Ser Ser Ser Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile

210 215 220

Lys

225

<210> 221

<211> 220

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 221

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Phe Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Glu Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 222

<211> 228

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 222

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

Met Glu Met Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

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

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ile Gln Leu Thr Gln

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Cys Gln Gln His Asn Ser Tyr Pro Thr Phe Gly Gln Gly Thr Lys

210 215 220

Val Glu Ile Lys

225

<210> 223

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 223

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser Glu Ile Val Leu Thr Gln Ser Pro Ser Phe Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

<210> 224

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 224

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Ala Tyr His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

Ala Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 225

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 225

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser Ala Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Ala Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 226

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 226

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Gly Phe His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

Ala Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 227

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 227

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

Ser Leu Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Val Met Thr Gln Ser Pro Ser Phe Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 228

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 228

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 229

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 229

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Thr

115 120 125

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

130 135 140

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

145 150 155 160

Ala Pro Lys Leu Leu Ile Tyr Glu Ala Ser Asn Leu Glu Ser Gly Val

165 170 175

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr

180 185 190

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

195 200 205

Tyr Gly Asn Tyr Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 230

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 230

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile 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 Leu Tyr Tyr Cys

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser Asp Ile Gln 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 Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 231

<211> 230

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 231

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 Ser Tyr

20 25 30

Ala 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 Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

100 105 110

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Asp Ile Val Met Thr

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Thr Lys Leu Glu Ile Lys

225 230

<210> 232

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 232

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

Met Glu Met Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

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

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln

115 120 125

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

130 135 140

Cys Arg Ala Ser Gln Thr Ile Thr Asp Trp Leu Ala Trp Tyr Gln Gln

145 150 155 160

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

165 170 175

Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu

180 185 190

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

195 200 205

Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Trp Ala Phe Gly Gln Gly Thr

210 215 220

Lys Val Glu Ile Lys

225

<210> 233

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 233

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

Met Glu Met Ser Arg Leu Ile Ser Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

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

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu

180 185 190

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

195 200 205

Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser His Thr Phe Gly Gln Gly Thr

210 215 220

Lys Val Glu Ile Lys

225

<210> 234

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 234

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Asp Phe Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Arg Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser

115 120 125

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

130 135 140

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

145 150 155 160

Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser

165 170 175

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

180 185 190

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

195 200 205

Asn Leu Pro Leu Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

210 215 220

<210> 235

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 235

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 Thr Tyr

20 25 30

Ala 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 Glu Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Val Met Thr Gln

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Arg Ser Gly His Asn Tyr Leu

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asp Val Gly Val Tyr Tyr Cys Met Gln Gly Leu Gln Pro Pro Tyr Thr

210 215 220

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230

<210> 236

<211> 228

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 236

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Thr Gln Ile

20 25 30

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

35 40 45

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

85 90 95

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

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Leu Glu Ile Lys

225

<210> 237

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 237

Glu Val Gln Leu Leu 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 Thr Tyr

20 25 30

Ala 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 Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Val Met Thr Gln

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu

145 150 155 160

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

165 170 175

Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Tyr Thr

210 215 220

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230

<210> 238

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 238

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gly Pro Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Thr Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Val Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

Asn Ser Asp Ser Gly His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

210 215 220

Arg

225

<210> 239

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 239

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Phe Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 240

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 240

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

1 5 10 15

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

20 25 30

Ala Met 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 Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Val Met Thr Gln

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu

145 150 155 160

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

165 170 175

Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Phe Thr

210 215 220

Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

225 230

<210> 241

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 241

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser Glu Ile Val Met Thr Gln Ser Pro Asp Thr

115 120 125

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

130 135 140

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

145 150 155 160

Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 242

<211> 243

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 242

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 Glu Phe Thr Phe Ser Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

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 Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr

130 135 140

Leu Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val

145 150 155 160

His Ser Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly

165 170 175

Gln Ser Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly

180 185 190

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

195 200 205

Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met

210 215 220

Gln Gly Thr His Trp Pro Pro Asn Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

Glu Ile Lys

<210> 243

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 243

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Leu Tyr Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser Ala Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser

180 185 190

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

195 200 205

Ser Tyr Ser Asp Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

210 215 220

Lys

225

<210> 244

<211> 242

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 244

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 Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

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 Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser Asp Ile Val Met Thr Gln Pro Pro Leu Ser Leu Pro Val Thr

130 135 140

Leu Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val

145 150 155 160

His Ser Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly

165 170 175

Gln Ser Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly

180 185 190

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

195 200 205

Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met

210 215 220

Gln Gly Thr His Trp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu

225 230 235 240

Ile Lys

<210> 245

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 245

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Ala Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Tyr Pro Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

210 215 220

<210> 246

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 246

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Leu Lys Ser Tyr Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

210 215 220

Ile Lys

225

<210> 247

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 247

caggttcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatcgtg 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctaacagt ttccctccgg ctttcggccc tgggaccaaa 660

gtggatatca aa 672

<210> 248

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 248

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcacaat ggtcaccgtc tcgagtgcca tccagatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gttcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtc acagtacccc gtacactttt ggccaaggga ccaaggtgga aatcaaa 717

<210> 249

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 249

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatt tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatgg acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcactgtc tcgagtgaca tcgtgatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gctcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtt acagtacccc tcggacgttc ggccagggga ccaagctgga gatcaaa 717

<210> 250

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 250

caggttcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagtgcca tccggatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gctcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtt acagtacccc tcggactttt ggccaaggga ccaaggtgga aatcaaa 717

<210> 251

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 251

gaggtgcaac tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctggat 300

atagccgggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgccatc 360

cggatgaccc agtctccatc ctccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcaa gtcagagcat tagcagctat ttaaattggt atcagcagaa accagggaaa 480

gcccctaagc tcctgatcta tgctgcatcc agtttgcaaa gtggggtccc atcaaggttc 540

agtggcagtg gatctgggac agatttcact ctcaccatca gcagtctgca acctgaagat 600

tttgcaactt actactgtca acagagttac agtaccccgt acacttttgg ccaggggacc 660

aagctggaga tcaaa 675

<210> 252

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 252

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctagta 300

gtctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacacagt ctccaggcac cctgtctttg tctccagggg aaagagccac cctctcctgc 420

agggccagtc agagtgttag cagcagctac ttagcctggt accagcagaa acctggccag 480

gctcccaggc tcctcatcta tggtgcatcc agcagggcca ctggcatccc agacaggttc 540

agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 600

tttgcagtgt attactgtca gcagtatggt agctcctcgt acacttttgg ccaggggacc 660

aagctggaga tcaaa 675

<210> 253

<211> 660

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 253

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtattcggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgccatccgg 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctgaggct ttcggcggag ggaccaaggt ggagatcaaa 660

<210> 254

<211> 684

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 254

gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccagttgac ccagtctcct tccaccctgt ctgcatctgt cggagacaga 420

gtcaccatca cttgccgggc cagtcagagt attaattcct ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa actcctgatc tataaggcgt ctcatttaca aagtggcgtc 540

ccttcaaggt tcagcggcag tggatctggg acagatttca ctcttaccat cagtagcctg 600

cagcctgatg attttgcaat ttattactgc caacagcata attcttatcc gaccttcggc 660

caagggacca aggtggaaat caaa 684

<210> 255

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 255

gaggtgcagc tggtggagac tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacgcagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaagaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaggtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctttca ctttcggcgg agggaccaag 660

gtggagatca aa 672

<210> 256

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 256

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcgctt accatggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagtgacatc cagttgaccc agtctccatc ctccctgtct 420

gcatctgtag gagacagagt caccatcact tgccgggcaa gtcagagcat tagcagctat 480

ttaaattggt atcagcagaa accagggaaa gcccctaagc tcctgatcta tgctgcatcc 540

agtttgcaaa gtggggtccc atcaaggttc agtggcagtg gatctgggac agatttcact 600

ctcaccatca gcagtctgca acctgaagat tttgcaactt actactgtca acagagttac 660

agtaccccgt acacttttgg ccaggggacc aagctggaga tcaaa 705

<210> 257

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 257

gaggtgcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accctggtca ccgtctcgag tgccatccag 360

ttgacccagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctggggcaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctccgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 258

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 258

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcggtt tccacggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagtgccatc cagttgaccc agtctccatc ctccctgtct 420

gcatctgtag gagacagagt caccatcact tgccgggcaa gtcagagcat tagcagctat 480

ttaaattggt atcagcagaa accagggaaa gcccctaagc tcctgatcta tgctgcatcc 540

agtttgcaaa gtggggtccc atcaaggttc agtggcagtg gatctgggac agatttcact 600

ctcaccatca gcagtctgca acctgaagat tttgcaactt actactgtca acagagttac 660

agtacactcc tcactttcgg cggagggacc aaggtggaga tcaaa 705

<210> 259

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 259

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcggt agcaactaca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacttagtc 300

tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatcgtg 360

atgacccagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctccgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 260

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 260

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagc caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcggggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

ctggcgccca ggctcctcat ctatgatgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cgctcacttt cggcggaggg 660

accaaggtgg agatcaaa 678

<210> 261

<211> 673

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 261

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgacatc 360

cagttgaccc agtctccctc caccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcca gtcaggctat tagtaactgg ttggcctggt atcagcagaa accagggaaa 480

gcccctaagc tcctgatcta tgaggcgtct aatttagaaa gtggggtccc atcgaggttc 540

agcggcagtg gttctgggac agaattcact ctcaccatca gcagcctgca gcctgatgat 600

tttgcaactt attactgcca acagtatggt aattattgga cgttcggcca agggaccaag 660

gtggaaatca aag 673

<210> 262

<211> 719

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 262

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagtggac atccagttga cccagtctcc 420

atcctccctg tctgcatctg taggagacag agtcaccatc acttgccggg caagtcagag 480

cattagcagc tatttaaatt ggtatcagca gaaaccaggg aaagccccta agctcctgat 540

ctatgctgca tccagtttgc aaagtggggt cccatcaagg ttcagtggca gtggatctgg 600

gacagatttc actctcacca tcagcagtct gcaacctgaa gattttgcaa cttactactg 660

tcaacagagt tacagtaccc ctctgacgtt cggccagggg accaagctgg agatcaaag 719

<210> 263

<211> 692

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 263

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagccgatcc 300

cccagtatag cagcagccgc taatgctttt gatatctggg gccaagggac cacggtcacc 360

gtctcgagtg gacatcgtga tgacccagtc ttcatcctcc ctgtctgcat ctgtaggaga 420

cagggtcacc atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca 480

gcagaaacca gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg 540

ggtcccatca aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag 600

tctgcaacct gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac 660

ttttggccag gggaccaagc tggagatcaa ag 692

<210> 264

<211> 688

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 264

caggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccggatgac ccagtctcct tccaccctgt ctgcatctgt aggagacaga 420

gtcaccatca cttgccgggc cagtcagact attactgact ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa gctcctgatc tataaggcgt ctactttaga aagtggggtc 540

ccatcaaggt tcagcggcag tggatctggg acagaattca ctctcaccat cagcagcctg 600

cagcctgatg atttcgcaac ttattactgc caacaatata atagttattc ttgggcgttc 660

ggccaaggga ccaaggtgga aatcaaag 688

<210> 265

<211> 688

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 265

gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccggatgac ccagtttcct tccaccctgt ctgcatctgt aggagacaga 420

gtcaccatca cttgccgggc cagtcagagt attggtagct ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa gctcctgatc tataaggcgt ctagtttaga aagtggggtc 540

ccatcaaggt tcagcggcag tggatctggg acagaattca ctctcaccat cagcagcctg 600

cagcctgatg attttgcaac ttattactgc caacagtata atagttattc tcacactttt 660

ggccaaggga ccaaggtgga aatcaaag 688

<210> 266

<211> 674

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 266

caggtccagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtacag cctctgactt caccgtcagt agcaactaca tgacctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcactt atttatcccg gtggtagcac atactacgca 180

gactccctga agggccgatt caccatctcc agagacaatt ccaagaacac gctatacctt 240

caaatgaaca gcctgagagt tgaggacacg gctgtgtatt actgtgcgag agaccggggc 300

gatgcatttg atatctgggg ccaagggacc acggtcaccg tctcgagtgg acatcgtgat 360

gacccagtct ccatcctccc tgtctgcatc tgtaggagac agagtcacca tcacttgcca 420

ggcgagtcag gacattagca actatttaaa ttggtatcag cagaaaccag ggaaagcccc 480

taagctcctg atctacgatg catccaattt ggaaacaggg gtcccatcaa ggttcagtgg 540

aagtggatct gggacagatt ttactttcac catcagcagc ctgcagcctg aagatattgc 600

aacatattac tgtcaacagt atgataatct ccccttattc actttcggcc ctgggaccaa 660

agtggatatc aaag 674

<210> 267

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 267

gaggtgcagc tggtggagtc cgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccgagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aaggcaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac ccagactcca ctctccctgc ccgtcacccc tggagagtcg 420

gcctccctct cctgcaggtc tagtcagagc ctcctgcata ggagtggaca caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatttattt gggttctatt 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ctttacactg 600

aaaataagta gagtggaggc tgaggatgtt ggggtttatt actgcatgca aggtctacaa 660

cctccgtaca cttttggcca agggaccaag gtggaaatca aa 702

<210> 268

<211> 684

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 268

caggtgcagc tacaacagtg gggcccagga ctggtgaagc cttcggagac cctgtccctc 60

acctgtagcg tctctggtgg ctccatcacg cagattattt actactgggc ctggatccgc 120

cagcccccag ggagggggct ggagtggatt gggagtatct actatagggg gagcacctcc 180

tccaacccgt ccctcaagag tcgagtcacc atatccgtag acacgtccaa gaaccagttc 240

tccctgaacc taacctctgt gaccgccgca gacacggctg tgtattactg tgcgagggcg 300

gttagacatg actacaacta ttttgactac tggggccagg gaaccctggt caccgtctcg 360

agtgacatcc agttgaccca gtctccatcc tccctgtctg catctgtagg agacagagtc 420

accatcactt gccgggcaag tcagagcatt agcagctatt taaattggta tcagcagaaa 480

ccagggaaag cccctaagct cctgatctat gctgcatcca gtttgcaaag tggggtccca 540

tcaaggttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa 600

cctgaagatt ttgcaactta ctactgtcaa cagagttaca gtacccctcg cacttttggc 660

caggggacca agctggagat caaa 684

<210> 269

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 269

gaggtgcagc tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac tcagcctcca ctctccctgc ccgtcacccc tggagagccg 420

gcctccatct cctgcaggtc tagtcagagc ctcctccata gtaatggata caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatctattt gggttctaat 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ttttacactg 600

aaaatcagca gagtggaggc tgaggatgtt ggggtttatt actgcatgca agctctacaa 660

actccgtaca cttttggcca ggggaccaag ctggagatca aa 702

<210> 270

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 270

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggagt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gcggtaccac atactacgca 180

gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatctgggg 300

ccatacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgccatccgg 360

atgacccagt ctccttccac cctgtctgca tctgtgggcg acagagtcac catcacttgc 420

cgggccagtc agattattag tgactggttg gcctggtatc agcagagacc aggggaagcc 480

cctaagctcc tcatctataa ggcatctaat ttacaaagtg gggtcccatc aaggttcagc 540

ggcagtgtat ctgggacaga attcactctc accatcagca gcctgcagcc tgatgatttt 600

gcgacttatt actgccaaca atataatagt gattctgggc acacttttgg ccaagggacc 660

aaggtggaaa tcaga 675

<210> 271

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 271

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatccag 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgg tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctaacagt ttccctccca ctttcggcgg agggaccaag 660

gtggagatca aa 672

<210> 272

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 272

gaagtgcagc tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac tcagcctcca ctctccctgc ccgtcacccc tggagagccg 420

gcctccatct cctgcaggtc tagtcagagc ctcctgcata gtaatggata caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatctattt gggttctaat 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ttttacactg 600

aaaatcagca gagtggaggc tggggatgtt ggggtttatt actgcatgca agctctacaa 660

acccctttca ctttcggccc tgggaccaaa gtggatatca aa 702

<210> 273

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 273

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggacaatgg tcaccgtctc gagtgaaata 360

gtgatgacgc agtctccaga caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtgagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggtgca tccagtaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cctacacttt tggccaaggg 660

accaaggtgg aaatcaaa 678

<210> 274

<211> 729

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 274

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctgagtt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt gatattgtga tgactcagtc tccactctcc 420

ctgcccgtca cccttggaca gccggcctcc atctcctgca ggtctagtca aagcctcgta 480

cacagtgatg gaaacaccta cttgaattgg tttcagcaga ggccaggcca atctccaagg 540

cgcctaattt ataaggtttc taaccgggac tctggggtcc cagacagatt cagcggcagt 600

gggtcaggca ctgatttcac actgaaaatc agcagggtgg aggctgaaga tgttggggtt 660

tattactgca tgcaaggtac acactggcct ccgaacactt ttggccaagg gaccaaggtg 720

gaaatcaaa 729

<210> 275

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 275

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcttgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaatac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag gactttatat 300

gatgcttttg atatctgggg ccaagggacc acggtcaccg tctcgagtgc catccagatg 360

acccagtctc cttccaccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 420

gccagtcaga gtattagtag ctggttggcc tggtatcagc agaaaccagg gaaagcccct 480

aagctcctga tctataaggc gtctagttta gaaagtgggg tcccatcaag gttcagcggc 540

agtggatctg ggacagaatt cactctcacc atcagcagcc tgcagcctga tgattttgca 600

acttattact gccaacagta taatagttat tctgacatgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 276

<211> 726

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 276

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctggatt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt gatattgtga tgactcagcc tccactctcc 420

ctgcccgtca cccttggaca gccggcctcc atctcctgca ggtctagtca aagcctcgta 480

cacagtgatg gaaacaccta cttgaattgg tttcagcaga ggccaggcca atctccaagg 540

cgcctaattt ataaggtttc taaccgggac tctggggtcc cagacagatt cagcggcagt 600

gggtcaggca ctgatttcac actgaaaatc agcagggtgg aggctgagga tgttggggtt 660

tattactgca tgcaaggtac acactggcct tacacttttg gccaagggac caaggtggaa 720

atcaaa 726

<210> 277

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 277

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctcgtt 300

gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatccag 360

ttgacccagt ctccatcctc cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccccttca ctttcggccc tgggaccaaa 660

gtggatatca aa 672

<210> 278

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 278

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgacatc 360

cagatgaccc agtctccatc ctccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcca gtcagggcat tagcagttat ttagcctggt atcagcaaaa accagggaaa 480

gcccctaagc tcctgatcta tgctgcatcc actttgcaaa gtggggtccc atcaaggttc 540

agcggcagtg gatctgggac agatttcact ctcaccatca gcagcctgca gcctgaagat 600

tttgcaactt attactgtga acagcttaag agttaccctc cgtacacttt tggccagggg 660

accaagctgg agatcaaa 678

<210> 279

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 279

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Thr Val Thr Val Ser Ser

115

<210> 280

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 280

Gln Val Gln Leu Val Gln Ser Gly Gly 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

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr 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 Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser

115

<210> 281

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 281

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 282

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 282

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Arg 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

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr 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 Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser

115

<210> 283

<211> 123

<212> PRT

<213> VH(Artificial Sequence)

<400> 283

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

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

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

35 40 45

Gly Arg Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

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

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 284

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 284

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 285

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 285

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 286

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 286

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 287

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 287

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Ile Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 288

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 288

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 289

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 289

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Val Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 290

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 290

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

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

100 105

<210> 291

<211> 113

<212> PRT

<213> VL(Artificial Sequence)

<400> 291

Asp Ile Val Met Thr Gln Thr Pro Leu 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 Asp Ser

20 25 30

Asp Asp Gly Asn Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln

35 40 45

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

50 55 60

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

65 70 75 80

Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln

85 90 95

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

100 105 110

Lys

<210> 292

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 292

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

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

100 105

<210> 293

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 293

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Trp

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 294

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 294

Asp Ile Val Met Thr Gln Pro Pro Leu 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 Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 295

<211> 110

<212> PRT

<213> VL(Artificial Sequence)

<400> 295

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Arg Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 296

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 296

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 297

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 297

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Gly

85 90 95

Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 298

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 298

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 299

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 299

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Gln

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 300

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 300

Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Val Ala Thr Tyr Tyr Cys Gln Asn Tyr Asn Ser Ala Pro Phe

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 301

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 301

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

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

100 105

<210> 302

<211> 109

<212> PRT

<213> VL(Artificial Sequence)

<400> 302

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser

20 25 30

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

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

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

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

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

100 105

<210> 303

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 303

Gly Phe Thr Phe Ser Ser Tyr Glu

1 5

<210> 304

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 304

Gly Tyr Ser Phe Thr Ser Tyr Trp

1 5

<210> 305

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 305

Gly Phe Thr Val Ser Arg Asn Tyr

1 5

<210> 306

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 306

Ile Ser Ser Ser Gly Ser Thr Ile

1 5

<210> 307

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 307

Ile Asp Pro Ser Asp Ser Tyr Thr

1 5

<210> 308

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 308

Ile Tyr Pro Gly Asp Ser Asp Thr

1 5

<210> 309

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 309

Ala Arg Asp Leu His Val Val Gly Ala Phe Asp Ile

1 5 10

<210> 310

<211> 9

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 310

Ala Thr Ser Arg Arg Gly Arg Asp Tyr

1 5

<210> 311

<211> 16

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 311

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

1 5 10 15

<210> 312

<211> 19

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 312

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

1 5 10 15

Phe Asp Ile

<210> 313

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 313

Gln Ser Val Ser Ser Ser Tyr

1 5

<210> 314

<211> 12

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 314

Gln Ser Leu Leu Asp Ser Asp Asp Gly Asn Thr Tyr

1 5 10

<210> 315

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 315

Gln Gly Ile Ser Asn Tyr

1 5

<210> 316

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 316

Thr Leu Ser

<210> 317

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 317

Gln Gln Tyr Gly Ser Ser Pro Asp Thr

1 5

<210> 318

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 318

Met Gln Arg Ile Glu Phe Pro Tyr Thr

1 5

<210> 319

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 319

Leu Gln Asp Tyr Asn Tyr Pro Trp Thr

1 5

<210> 320

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 320

Met Gln Ala Leu Gln Thr Pro Trp Thr

1 5

<210> 321

<211> 11

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 321

Gln Gln Tyr Gly Ser Ser Pro Arg Met Tyr Thr

1 5 10

<210> 322

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 322

Gln Gln Leu Asn Ser Tyr Pro Tyr Thr

1 5

<210> 323

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 323

Gln Gln Leu Asn Ser Tyr Pro Gly

1 5

<210> 324

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 324

Gln Gln Leu Asn Ser Tyr Pro Gln Thr

1 5

<210> 325

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 325

Gln Asn Tyr Asn Ser Ala Pro Phe Thr

1 5

<210> 326

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 326

Gln Gln Tyr Gly Ser Ser Pro Arg Thr

1 5

<210> 327

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 327

Gln Gln Tyr Gly Ser Ser Pro Pro Phe Thr

1 5 10

<210> 328

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 328

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagt 396

<210> 329

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 329

gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 330

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 330

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccacgg tcaccgtctc gagt 354

<210> 331

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 331

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcaca atggtcaccg tctcgagt 348

<210> 332

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 332

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 333

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 333

gaggtgcagc tggtggagtc tgggggaggc ttggtacggc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagcac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaaaaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcacc ctggtcaccg tctcgagt 348

<210> 334

<211> 369

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 334

gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaggatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcagctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggagg attgatccta gtgactctta taccaactac 180

agcccgtcct tccaaggcca cgtcaccatc tcagctgaca agtccatcag cactgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagaatttta 300

ggggtggata cagctccctc ttggggtatg gacgtctggg gccaagggac cctggtcacc 360

gtctcgagt 369

<210> 335

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 335

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 336

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 336

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 337

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 337

caggtgcagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 338

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 338

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggtcaaggg accacggtca ccgtctcgag t 351

<210> 339

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 339

gaggtgcagc tgttggagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 340

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 340

caggtgcagc tggtgcaatc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcatcatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaagggaca 360

atggtcaccg tctcgagt 378

<210> 341

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 341

caaatgcagc tggtgcagtc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaggggaca 360

atggtcaccg tctcgagt 378

<210> 342

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 342

caggtccagc tggtacagtc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatgggggtc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaagggacc 360

ctggtcaccg tctcgagt 378

<210> 343

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 343

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggcgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccaga cacttttggc 300

caggggacca agctggagat caaa 324

<210> 344

<211> 339

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 344

gatattgtga tgacccagac tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcttg gatagtgatg atggaaacac ctatttggac 120

tggtacctgc agaagccagg gcagtctcca cagctcctga tctatacgct ttcctatcgg 180

gcctctggag tcccagacag gttcagtggc agtgggtcag gcactgattt cacactgaaa 240

atcagcaggg tggaggctga ggatgttgga gtttattact gcatgcaacg tatagagttt 300

ccctacactt ttggccaggg gaccaagctg gagatcaaa 339

<210> 345

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 345

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 346

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 346

gatattgtga tgacccagac tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtctacaa gattacaatt acccgtggac gttcggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 347

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 347

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgagga tgttggggtt tattactgca tgcaagctct acaaactccg 300

tggacgttcg gccaggggac caagctggag atcaaa 336

<210> 348

<211> 330

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 348

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccacg aatgtacact 300

tttggccaag ggaccaaggt ggaaatcaaa 330

<210> 349

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 349

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt acccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 350

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 350

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accccggttt cggccctggg 300

accaaagtgg atatcaaa 318

<210> 351

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 351

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctttcac tttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 352

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 352

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctcaaac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 353

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 353

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcgagtca gggcattagc aattatttag cctggtatca gcagaaacca 120

gggaaagttc ctaagctcct gatctatgct gcatccactt tgcaatcagg ggtcccatct 180

cggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagatgttg caacttatta ctgtcaaaac tataacagtg cccccttcac tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 354

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 354

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgag aacgttcggc 300

caggggacca agctggagat caaa 324

<210> 355

<211> 327

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 355

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcc attcactttc 300

ggccagggga ccaagctgga gatcaaa 327

<210> 356

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 356

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly

165 170 175

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

180 185 190

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

195 200 205

Gln Tyr Gly Ser Ser Pro Asp Thr Phe Gly Gln Gly Thr Lys Leu Glu

210 215 220

Ile Lys

225

<210> 357

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 357

Gln Val Gln Leu Val Gln Ser Gly Gly 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

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr 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 Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro

115 120 125

Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser

130 135 140

Leu Leu Asp Ser Asp Asp Gly Asn Thr Tyr Leu Asp Trp Tyr Leu Gln

145 150 155 160

Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Thr Leu Ser Tyr Arg

165 170 175

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

180 185 190

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

195 200 205

Tyr Cys Met Gln Arg Ile Glu Phe Pro Tyr Thr Phe Gly Gln Gly Thr

210 215 220

Lys Leu Glu Ile Lys

225

<210> 358

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 358

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 359

<211> 223

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 359

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Arg 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

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr 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 Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Asp Ile Val Met Thr Gln Thr Pro Ser Ser Leu Ser

115 120 125

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

130 135 140

Ile Arg Asn Asp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 360

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 360

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

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

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

35 40 45

Gly Arg Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

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

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Val Met Thr

115 120 125

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

130 135 140

Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

145 150 155 160

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

165 170 175

Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly

180 185 190

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

195 200 205

Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Trp

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 361

<211> 227

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 361

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

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

115 120 125

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

130 135 140

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

145 150 155 160

Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile

165 170 175

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

180 185 190

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln

195 200 205

Tyr Gly Ser Ser Pro Arg Met Tyr Thr Phe Gly Gln Gly Thr Lys Val

210 215 220

Glu Ile Lys

225

<210> 362

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 362

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 363

<211> 223

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 363

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Tyr Pro Gly Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

210 215 220

<210> 364

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 364

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 365

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 365

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Tyr Pro Gln Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 366

<211> 233

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 366

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Ile Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ile

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Gly Pro Gly Thr Lys Val Asp Ile Lys

225 230

<210> 367

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 367

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Ile

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr

210 215 220

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230

<210> 368

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 368

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Val Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ile

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Pro Phe

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 369

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 369

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccacgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagg caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggcgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cagacacttt tggccagggg 660

accaagctgg agatcaaa 678

<210> 370

<211> 687

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 370

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcaca atggtcaccg tctcgagtga tattgtgatg 360

acccagactc cactctccct gcccgtcacc cctggagagc cggcctccat ctcctgcagg 420

tctagtcaga gcctcttgga tagtgatgat ggaaacacct atttggactg gtacctgcag 480

aagccagggc agtctccaca gctcctgatc tatacgcttt cctatcgggc ctctggagtc 540

ccagacaggt tcagtggcag tgggtcaggc actgatttca cactgaaaat cagcagggtg 600

gaggctgagg atgttggagt ttattactgc atgcaacgta tagagtttcc ctacactttt 660

ggccagggga ccaagctgga gatcaaa 687

<210> 371

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 371

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccctgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagg caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggtgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cttacacttt tggccaaggg 660

accaaggtgg aaatcaaa 678

<210> 372

<211> 669

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 372

gaggtgcagc tggtggagtc tgggggaggc ttggtacggc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagcac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaaaaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcacc ctggtcaccg tctcgagtga tattgtgatg 360

acccagactc catcctccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 420

gcaagtcagg gcattagaaa tgatttaggc tggtatcagc agaaaccagg gaaagcccct 480

aagctcctga tctatgctgc atccagttta caaagtgggg tcccatcaag gttcagcggc 540

agtggatctg gcacagattt cactctcacc atcagcagcc tgcagcctga agattttgca 600

acttattact gtctacaaga ttacaattac ccgtggacgt tcggccaagg gaccaaggtg 660

gaaatcaaa 669

<210> 373

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 373

gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaggatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcagctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggagg attgatccta gtgactctta taccaactac 180

agcccgtcct tccaaggcca cgtcaccatc tcagctgaca agtccatcag cactgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagaatttta 300

ggggtggata cagctccctc ttggggtatg gacgtctggg gccaagggac cctggtcacc 360

gtctcgagtg atattgtgat gactcagcct ccactctccc tgcccgtcac ccctggagag 420

ccggcctcca tctcctgcag gtctagtcag agcctcctgc atagtaatgg atacaactat 480

ttggattggt acctgcagaa gccagggcag tctccacagc tcctgatcta tttgggttct 540

aatcgggcct ccggggtccc tgacaggttc agtggcagtg gatcaggcac agattttaca 600

ctgaaaatca gcagagtgga ggctgaggat gttggggttt attactgcat gcaagctcta 660

caaactccgt ggacgttcgg ccaggggacc aagctggaga tcaaa 705

<210> 374

<211> 681

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 374

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacacagt ctccaggcac cctgtctttg tctccagggg aaagagccac cctctcctgc 420

agggccagtc agagtgttag cagcagctac ttagcctggt accagcagaa acctggccag 480

gctcccaggc tcctcatcta tggtgcatcc agcagggcca ctggcatccc agacaggttc 540

agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 600

tttgcagtgt attactgtca gcagtatggt agctcaccac gaatgtacac ttttggccaa 660

gggaccaagg tggaaatcaa a 681

<210> 375

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 375