CN110869389B - 抗ror1抗体及其制备和使用方法 - Google Patents

抗ror1抗体及其制备和使用方法 Download PDF

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CN110869389B
CN110869389B CN201880038332.5A CN201880038332A CN110869389B CN 110869389 B CN110869389 B CN 110869389B CN 201880038332 A CN201880038332 A CN 201880038332A CN 110869389 B CN110869389 B CN 110869389B
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欧勒·奥尔森
菲尔·谭
夏冬
戴维·耶利曼
布莱恩·科瓦切维奇
比尔·布雷迪
布莱尔·伦肖
高泽人
朱义
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Chengdu Bailidote Biological Pharmaceutical Co ltd
Seattle Immunization Co
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Seattle Immunization Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/75—Agonist effect on antigen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

本申请提供了抗ROR1单克隆抗体、其抗原结合部分、其治疗组合物和/或编码其的核酸，以及它们在治疗癌症和其他T细胞功能障碍中上调T细胞功能以增强细胞介导的免疫应答的用途。

Description

抗ROR1抗体及其制备和使用方法
相关申请的交叉引用
本申请要求2017年8月28日提交的美国临时专利申请No.62551035、2017年8月28日提交的美国临时专利申请No.62551032、2017年6月25日提交的美国临时专利申请No.62524554、2017年6月25日提交的美国临时专利申请No.62524557、2017年6月25日提交的临时专利申请No.62524558、2017年8月15日提交的美国临时专利申请No.62545603、2017年8月28日提交的美国临时专利申请No.62551032和2017年8月28日提交的美国临时专利申请No.62551065的优先权，其全部公开内容通过引用明确地并入本文。
技术领域
本申请一般涉及抗体技术领域，更具体地涉及抗ROR1抗体的制备和使用。
背景技术
癌症是全世界的主要健康问题。仅在美国，据估计，2016年就诊断出了1,685,210例新癌症病例，并有595,690例死亡(http:/www.cancer.gov)。因此，任何可降低癌症严重性或死亡率的药剂都是理想的。
在免疫系统中，通过由抗原呈递细胞(APC)呈递的外源抗原肽通过T细胞受体(TCR)递送的初级信号，可以活化静息T细胞以应答抗原。除了该初级信号之外，还存在进一步影响T细胞应答的次级正、负共刺激信号。完整的T细胞激活需要次级正信号(Lafferty等人，Ausl.J.Exp.Biol.Med.Sci.5327-42(1975))。负的次级信号可导致T细胞抑制和耐受。
酪氨酸蛋白激酶跨膜受体ROR1，也称为神经营养酪氨酸激酶受体相关1(NTRKR1)，是一种在人类中由ROR1基因编码的酶。(参见Masiakowski P和Carroll RD，J.Bio.Chem.267(36):26181-90.1992；Reddy UR,et al,癌基因(Oncogene)。13(7):1555-9(1996))。ROR1是受体酪氨酸激酶样孤儿受体(ROR)家族的成员。最近已证明ROR1在卵巢癌干细胞上表达，在卵巢癌干细胞上它似乎在体外促进迁移/侵袭或球体形成和免疫缺陷小鼠的肿瘤移植中发挥功能作用。用ROR1(UC-961)特异性人源化mAb治疗可以抑制卵巢癌细胞迁移、形成球体或移植免疫缺陷小鼠的能力。此外，这种治疗抑制肿瘤异种移植物的生长，反之，肿瘤异种移植物移植免疫缺陷小鼠的能力降低，并且相对缺乏具有CSC特征的细胞，表明UC-961治疗可损害CSC更新。总之，这些研究表明卵巢CSCs表达ROR1，其可以作为抗CSC治疗的靶。(参见Zhang S等人，PNAS.111(48):17266-71(2014))。
ROR1在正常成人组织中低水平表达的许多恶性肿瘤中表达。与ROR1的生理功能非常相似，ROR1在癌症中可具有激酶活性依赖性或非依赖性功能，这可能是共受体或效应蛋白的组织特异性表达的结果。ROR1基因敲除、EGFR信号增强和ROR1介导的EMT基因上调诱导细胞凋亡支持了ROR1在癌症进展中起重要作用的观点。需要进一步研究以阐明ROR1过表达的肿瘤特异性机制和ROR1对癌症的起始和进展的贡献。
发明内容
一方面，本公开尤其提供了抗ROR1单克隆抗体、其抗原结合部分、其治疗组合物和/或编码其的核酸。
在一个实施方案中，本公开提供特异性结合人ROR1的一种或多种分离的单克隆抗体(mAb)或其抗原结合片段。在一个实施方案中，分离的一种或多种mAb或抗原结合片段包括具有本文公开的序列的抗原肽序列。在一个实施方案中，分离的mAb或抗原结合片段选自本文公开的序列。
在一个实施方案中，分离的单克隆抗体(mAb)或抗原结合片段具有与SEQ ID NO:4、SEQ ID NO:8、SEQ ID NO:12、SEQ ID NO:16、SEQ ID NO:20、SEQ ID NO:24、SEQ ID NO:28、SEQ ID NO:32、SEQ ID NO:36、SEQ ID NO:40、SEQ ID NO:44、SEQ ID NO:48、SEQ IDNO:52、SEQ ID NO:56、SEQ ID NO:60、SEQ ID NO:64、SEQ ID NO:68、SEQ ID NO:72、SEQ IDNO:76、SEQ ID NO:80、SEQ ID NO:84、SEQ ID NO:88、SEQ ID NO:88、SEQ ID NO:92、SEQ IDNO:96、SEQ ID NO:100、SEQ ID NO:104、SEQ ID NO:108、SEQ ID NO:112、SEQ ID NO:116、SEQ ID NO:120、SEQ ID NO:124、SEQ ID NO:128或SEQ ID NO:132具有同源性百分比的氨基酸序列。在一个实施方案中，同源性百分比不小于70％、80％、90％、95％、98％、99％。
在一个实施方案中，分离的mAb或抗原结合片段对ROR1的结合亲和力Kd不大于30nM、40nM，50nM、60nM、70nM、80nM、90nM或100nM。在一个实施方案中，ROR1是人ROR1。
在一个实施方案中，分离的mAb或抗原结合片段可以表现出一种或多种功能特性。功能特性的实例包括但不限于与ROR1的高亲和力结合、增强T细胞活化、刺激抗体应答的能力和/或逆转免疫抑制细胞如T调节细胞的抑制功能的能力。在一个实施方案中，增强T细胞活化包括T细胞增殖、IFN-γ和/或IL-2分泌、或其组合。在一个实施方案中，免疫抑制细胞包括调节细胞。
在一些实施方案中，分离的mAb或抗原结合片段可包括人构架区。在一个实施方案中，分离的mAb或抗原结合片段可包括人源化抗体、嵌合抗体或重组抗体。
在一个实施方案中，分离的mAb或抗原结合片段是IgG。在一个实施方案中，抗原结合片段可包括Fv、Fab、F(ab')2、scFV或scFV2片段。在一个实施方案中，分离的mAb可以是双特异性抗体、三特异性抗体或多特异性抗体。
在一个实施方案中，本申请提供了对ROR1和IgG1重链具有结合特异性的分离的mAb或抗原结合片段。IgG重链包含与SEQ ID NO:7、SEQ ID NO:15、SEQ ID NO:23、SEQ IDNO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55、SEQ ID NO:63、SEQ ID NO:71、SEQ IDNO:79、SEQ ID NO:87、SEQ ID NO:91、SEQ ID NO:99、SEQ ID NO:107、SEQ IDNO:115、SEQID NO:123或SEQ ID NO:131具有同源性百分比的氨基酸序列。该同源性百分比不小于70％、80％、90％、95％、98％或99％。
在一个实施方案中，本申请提供了对ROR1和κ轻链具有结合特异性的分离的mAb或抗原结合片段。在一个实施方案中，κ轻链包含与SEQ ID NO:3、SEQ ID NO:11、SEQ ID NO:19、SEQ ID NO:27、SEQ ID NO:35、SEQ ID NO:43、SEQ ID NO:51、SEQ ID NO:59、SEQ IDNO:67、SEQ ID NO:75、SEQ ID NO:83、SEQ ID NO:95、SEQ ID NO:103、SEQ ID NO:111、SEQID NO:119或SEQ ID NO:127有同源性百分比的氨基酸序列。该同源性百分比不小于70％、80％、90％、95％、98％或99％。
在一个实施方案中，本申请提供了对ROR1和可变轻链具有结合特异性的分离的mAb或抗原结合片段。可变轻链包含与SEQ ID NO：4、SEQ ID NO： 12、SEQ ID NO： 20、SEQID NO： 28、SEQ ID NO： 36、SEQ ID NO：44、SEQ ID NO： 52、SEQ ID NO： 60、SEQ ID NO：68、SEQ ID NO： 76、SEQ ID NO： 84、SEQ ID NO： 96、SEQ ID NO： 104、SEQ ID NO：112、SEQID NO： 120或SEQ ID NO： 128具有同源性百分比的氨基酸序列。该百分比同源性不小于70％、80％、90％、95％、98％或99％。
在一个实施方案中，本申请提供了对ROR1和可变重链具有结合特异性的分离的mAb或抗原结合片段。可变重链包含与SEQ ID NO:8、SEQ ID NO:16、SEQ ID NO:24、SEQ IDNO:32、SEQ ID NO:40、SEQ ID NO:48、SEQ ID NO:56、SEQ ID NO:64、SEQ ID NO:72、SEQ IDNO:80、SEQ ID NO:88、SEQ ID NO:92、SEQ ID NO:100、SEQ ID NO:108、SEQ ID NO:116、SEQID NO:124或SEQ ID NO:132具有同源性百分比的氨基酸序列。 同源性百分比不小于70％、80％、90％、95％、98％或99％。
本申请还提供了编码本文公开的分离的mAb或抗原结合片段的至少一部分的分离的核酸。在一个实施方案中，分离的mAb或抗原结合片段与IgG1重链SEQ ID NO:7、SEQ IDNO:15、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55、SEQ IDNO:63、SEQ ID NO:71、SEQ ID NO:79、SEQ ID NO:87、SEQ ID NO:91、SEQ ID NO:99、SEQ IDNO:107、SEQ ID NO:115、SEQ ID NO:123或SEQ ID NO:131具有同源性百分比。在一个实施方案中，分离的mAb或抗原结合片段与κ轻链：SEQ ID NO:3、SEQ ID NO:11、SEQ ID NO:19、SEQ ID NO:27、SEQ ID NO:35、SEQ ID NO:43、SEQ ID NO:51、SEQ ID NO:59、SEQ ID NO:67、SEQ ID NO:75、SEQ ID NO:83、SEQ ID NO:95、SEQ ID NO:103、SEQ ID NO:111、SEQ IDNO： 119或SEQ ID NO： 127具有同源性百分比。在一个实施方案中，分离的mAb或抗原结合片段与可变轻链： SEQ ID NO:4、SEQ ID NO:12、SEQ ID NO:20、SEQ ID NO:28、SEQ ID NO:36、SEQ ID NO:44、SEQ ID NO:52、SEQ ID NO:60、SEQ ID NO:68、SEQ ID NO:76、SEQ IDNO:84、SEQ ID NO:96、SEQ ID NO:104、SEQ ID NO:112、SEQ ID NO:120或SEQ ID NO： 128具有同源性百分比。在一个实施方案中，分离的mAb或抗原结合片段与可变重链： SEQ IDNO:8、SEQ ID NO:16、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ ID NO:48、SEQ IDNO:56、SEQ ID NO:64、SEQ ID NO:72、SEQ ID NO:80、SEQ ID NO:88、SEQ ID NO:92、SEQ IDNO:100、SEQ ID NO:108、SEQ ID NO:116、SEQ IDNO:124或SEQ ID NO:132具有同源性百分比。该同源性百分比不小于70％、80％、90％、95％、98％或99％。
本申请还提供了含有编码与本文公开的氨基酸序列具有同源性百分比的氨基酸序列的分离的核酸的表达载体。同源性百分比不小于70％、80％、90％、95％、98％或99％。在一个实施方案中，载体可在细胞中表达。
本申请还提供了包含编码与本文公开的氨基酸序列具有同源性百分比的氨基酸序列的核酸的宿主细胞。该同源性百分比不小于70％、80％、90％、95％、98％或99％。在一个实施方案中，宿主细胞可以是原核细胞或真核细胞。
另一方面，本申请提供了生产对人ROR1具有结合特异性的抗体或其抗原结合片段的方法。在一个实施方案中，该方法包括以下步骤：提供含有可在宿主细胞中表达的表达载体的宿主细胞，该表达载体包含编码分离的mAb或抗原结合片段的至少一部分、或与所述mAb或抗原结合片段具有至少70％、80％、90％、95％、98％或99％同一性的肽的核酸；以通过表达上述核酸产生抗体。
本申请还提供了免疫缀合物。在一个实施方案中，免疫缀合物包含通过接头与分离mAb或抗原结合片段连接的药物单元或显像剂。
接头可以是可切割的或不可切割的。在一个实施方案中，接头是化学接头。在一个实施方案中，接头包含共价键，例如酯键、醚键、胺键、酰胺键、二硫键、酰亚胺键、砜键、磷酸键(phosphate bond)、磷酸酯键(phosphorus ester bond)、肽键、腙键或其组合。在一个实施方案中，接头包含疏水性聚(乙二醇)接头。在一个实施方案中，接头包含肽键。
在一个实施方案中，免疫缀合物中的药物单元包括化疗剂、生长抑制剂、卡利奇霉素类药物单元、抗有丝分裂剂、毒素、放射性同位素、治疗剂或其组合。在一个实施方案中，药物单元包含卡利奇霉素、奥佐米星(ozogamicin)、单甲基澳瑞他汀E、美坦新(emtansine)、其衍生物或组合。在一个实施方案中，药物单元包含卡利奇霉素、奥佐米星(ozogamicin)、单甲基澳瑞他汀E、美坦新(emtansine)、其衍生物或组合。
在一个实施方案中，药物单元选自细胞毒性剂、免疫调节剂、显像剂或其组合。在一个实施方案中，细胞毒性剂选自生长抑制剂或来自一类微管蛋白结合剂、DNA嵌入剂、DNA烷化剂、酶抑制剂、免疫调节剂、抗代谢剂、放射性同位素或其组合的化疗剂。在一个实施方案中，细胞毒性剂选自卡利奇霉素、奥佐米星、单甲基澳瑞他汀E、美坦新(emtansine)、其衍生物或组合。在一个实施方案中，免疫调节试剂激活或抑制免疫细胞、T细胞、NK细胞、B细胞、巨噬细胞或树突细胞。
在一个实施方案中，成像剂可以是放射性核素、荧光剂、量子点或其组合。
本申请还提供了药物组合物。在一个实施方案中，药物组合物包括本文公开的分离的mAb或抗原结合片段以及药学上可接受的载体。在一个实施方案中，药物组合物包括本文公开的免疫缀合物和药学上可接受的载体。在一个实施方案中，药物单元还可以包括化疗剂、生长抑制剂、卡利奇霉素类药物单元、抗有丝分裂剂、毒素、放射性同位素、治疗剂或其组合。
在另一方面，本申请提供了使用本文公开的分离的mAb或其抗原结合片段治疗患有癌症的受试者的方法。在一个实施方案中，该方法包括向受试者施用有效量的本文公开的分离的mAb或抗原结合片段的步骤。
在一个实施方案中，该方法包括将有效量的单克隆抗体、其抗原结合片段和本文公开的免疫缀合物直接注射到肿瘤部位。
可以使用所公开的mAB、其抗原结合片段或组合物来治疗多种癌症。在一些实施方案中，癌症具有表达ROR-1的细胞。癌症的实例包括但不限于乳腺癌、结肠直肠癌、胰腺癌、头颈癌、黑色素瘤、卵巢癌、前列腺癌、非小细胞肺癌、神经胶质瘤、食管癌、鼻咽癌、肛门癌、直肠癌、胃癌、膀胱癌、宫颈癌或脑癌。
在一个实施方案中，该方法还包括共同施用有效量的治疗剂。治疗剂的实例包括化疗剂、生长抑制剂，卡利奇霉素类药物单元、抗有丝分裂剂、毒素、放射性同位素、抗体、酶或其组合。在一个实施方案中，治疗剂可以是卡培他滨、顺铂、环磷酰胺、甲氨蝶呤、5-氟尿嘧啶、阿霉素、环磷酰胺、氮芥、长春新碱、丙卡巴肼、泼尼松龙、博来霉素、长春碱、达卡巴嗪、依托泊苷、表柔比星、培美曲塞、叶酸、吉西他滨、奥沙利铂、伊立替康、托泊替康、喜树碱、多西他赛、紫杉醇、氟维司群、他莫昔芬、来曲唑、依西美坦、阿那曲唑、氨鲁米特、睾内酯、伏氯唑、福美司坦、法倔唑、来曲唑、埃罗替尼、拉法替尼、达沙替尼、吉非替尼、奥希替尼、凡德他尼、阿法替尼、伊马替尼、帕唑帕尼(pazopanib)、拉帕替尼、舒尼替尼、尼洛替尼、索拉非尼、nab-紫杉醇、依维莫司、替西罗莫司、达帕菲尼、维莫非尼、曲美替尼、叶酸-去乙酰长春碱单酰肼缀合物(vintafolide)、阿帕替尼、克立唑替尼、哌福辛(periforsine)、奥拉帕利、硼替佐米、托法替尼、或其衍生物或组合。
接受治疗的受试者可以是人。在一个实施方案中，本申请提供了包含有效浓度的分离的mAb或抗原结合片段的溶液，其中该溶液是受试者的血浆。
通过下面的详细描述，其他实施方案对于本领域技术人员将变得显而易见，其中，通过示出预期的最佳模式来描述实施方案。如将认识到的，其他和不同的实施方案是可能的，并且实施方案的若干细节能够在各种显而易见的方面进行修改，所有这些都不脱离它们的精神和范围。因此，附图和详细描述应被认为本质上是说明性的而非限制性的。
附图说明
结合附图，根据以下描述和所附权利要求书，本发明的前述和其他特征将变得更加完全显而易见。应理解，这些附图仅描绘了根据本公开安排的多个实施方案，并且因此不应被认为是对其范围的限制，将通过使用附图以附加的特性和细节来描述本公开，在附图中：
图1提供了用人或小鼠ROR1免疫NZW兔的策略；图2提供了免疫时间表；
图3显示从ROR1免疫的兔子收获脾和淋巴组织；
图4显示B细胞培养物筛选ROR1特异性IgG和筛选嵌合兔/人IgG的总结；
图5显示不同ROR1特异性人源化兔抗体的结合和解离速率分析；以及
图6是显示根据一个实施方案，在免疫前后人和小鼠ROR1特异性IgG的兔血清分析结果的图。
具体实施方式
在以下详细说明中，参考形成本文一部分的附图。在附图中，除非上下文另有说明，否则类似的符号通常标识类似的部件。在具体实施方案、附图和权利要求中描述的说明性实施方案并不意味着是限制性的。可利用其他实施方案，且可作出其他改变，而不背离本文所呈现的标的物的精神或范围。容易理解的是，如本文一般描述的，本公开的各方面，以及可以以各种不同的配置来布置、替换、组合、分离和设计在附图中示出的本公开的各方面，所有这些均在本文中明确考虑。
本公开尤其提供了针对ROR1具有特异性的分离的抗体及其抗原结合片段、制备此类抗体、双特异性或多特异性分子、由此类抗体或抗原结合片段组成的抗体-药物缀合物和/或免疫缀合物、含有此类抗体或抗原结合片段、双特异性或多特异性分子、抗体-药物缀合物和/或免疫缀合物的药物组合物的方法，以及使用所公开的抗体、抗原结合片段和组合物来治疗癌症的方法。
在一方面，本申请提供了特异性结合人或小鼠ROR1的单克隆抗体。在一个实施方案中，抗体表现出一种或多种期望的功能特性，例如与ROR1的高亲和力结合。在一个实施方案中，抗体来源于特定的重链和轻链氨基酸序列和/或结构特征，例如由特定氨基酸序列组成的兔/人嵌合抗体。
单克隆抗体可以使用各种方法产生，包括小鼠杂交瘤或噬菌体展示(参见Siegel.Transfus.Clin.Biol.9:15-22(2002)综述)或直接来自原代B细胞的抗体的分子克隆(参见Tiller.新型生物技术(New Biotechnol).28:453-7(2011))。在一个实施方案中，通过用人或小鼠ROR1胞外结构域(ECD)或用小鼠或人ROR1瞬时转染的HEK293细胞免疫兔子产生抗体。已知兔子可产生高亲和力、多样性和特异性的抗体(Weber等人，Exp.Mol.Med.49:e305)。体外培养来自免疫动物的B细胞并筛选产生抗ROR1抗体。使用重组DNA技术分离抗体可变基因并重组表达所得抗体。这种抗体发现的一般方法类似于Seeber等人，PLOS One.9:e86184(2014)。
术语“抗体”以最广泛的含义使用，并且特别涵盖单一单克隆抗体(包括激动剂和拮抗剂抗体)，具有多表位特异性的抗体组合物，以及抗体片段(例如Fab，F(ab')2和Fv)，只要它们表现出所需的生物活性即可。在一些实施方案中，抗体可以是单克隆抗体、多克隆抗体、嵌合抗体、单链抗体、双特异性抗体或双效抗体、猿抗体、人抗体和人源化抗体及其活性片段。与已知抗原结合的分子的活性片段的实例包括Fab、F(ab')2、scFv和Fv片段，以及Fab免疫球蛋白表达文库的产物和任何上述抗体和片段的表位结合片段。在一些实施方案中，抗体可以包括免疫球蛋白分子和免疫球蛋白分子的免疫活性部分，即含有免疫特异性结合抗原的结合位点的分子。免疫球蛋白可以是任何类型(IgG、IgM、IgD、IgE、IgA和IgY)或类(IgG1、IgG2、IgG3、IgG4、IgA1和IgA2)或免疫球蛋白分子的亚类。在一个实施方案中，抗体可以是完整抗体和衍生自该完整抗体的任何抗原结合片段。典型的抗体是指典型地包含两条重(H)链和两条轻链(L)的异四聚体蛋白链。每条重链由重链可变结构域(缩写为VH)和重链恒定结构域组成。每条轻链由轻链可变区(缩写为VL)和轻链恒定区组成。VH和VL区可进一步细分为超变互补决定区(CDR)的结构域和称为构架区(FR)的更为保守的区域。每个可变区(VH或VL)通常由三个CDR和四个FR组成，按以下顺序排列：从氨基末端到羧基末端为FR1、CDR1、FR2、CDR2、FR3、CDR3、FR4。在轻链和重链的可变区内存在与抗原相互作用的结合区。
如本文所用，术语“单克隆抗体”是指从基本上同质的抗体群体获得的抗体，即除了可能以少量存在的天然存在的突变之外，包含该群体的单个抗体是相同的。
单克隆抗体针对单个抗原位点具有高度特异性。此外，与通常包括针对不同决定簇(表位)的不同抗体的常规(多克隆)抗体制剂相反，每种单克隆抗体针对抗原上的单一决定簇。除了它们的特异性之外，单克隆抗体的优点在于它们由杂交瘤培养物合成，不被其他免疫球蛋白污染。修饰语“单克隆”表示从基本上同质的抗体群体获得的抗体的特征，并且不应被解释为需要通过任何特定方法生产抗体。例如，根据本公开内容使用的单克隆抗体可以通过首先由Kohler&Milstein,Nature,256:495(1975)描述的杂交瘤方法制备，或者可以通过重组DNA方法制备(参见，例如，美国专利No.4,816,567)。
单克隆抗体可包括“嵌合”抗体(免疫球蛋白)，其中重链和/或轻链的一部分与衍生自特定种类或属于特定抗体类别或亚类的抗体中的相应序列相同或同源，而所述链的剩余部分与衍生自另一种类或属于另一抗体类别或亚类的抗体以及这些抗体的片段中的相应序列相同或同源，只要它们表现出所需的生物活性即可(美国专利No.4,816,567；和Morrison等人，Proc.Natl.Acad.Sci.USA,81:6851-6855)。
单克隆抗体可以使用各种方法产生，包括小鼠杂交瘤或噬菌体展示(参见Siegel.Transfus.Clin.Biol.9:15-22(2002)综述)或直接来自原代B细胞的抗体的分子克隆(参见Tiller.新型生物技术(New Biotechnol).28:453-7(2011))。在本公开中，通过用人PD-L1蛋白和在细胞表面瞬时表达人PD-L1的细胞免疫兔产生抗体。已知兔子可产生高亲和力、多样性和特异性的抗体(Weber等人，Exp.Mol.Med.49:e305)。体外培养来自免疫动物的B细胞并筛选产生抗PD-L1抗体。使用重组DNA技术分离抗体可变基因，重组表达所得抗体，并进一步筛选所需特征，例如抑制PD-L1与PD-1结合的能力，与非人灵长类PD-L1结合的能力和增强人T细胞活化的能力。这种抗体发现的一般方法类似于Seeber等人，PLOSOne.9:e86184(2014)。
术语“抗原或表位结合部分或片段”是指能够结合抗原(在这种情况下是ROR1)的抗体片段。这些片段可以具有完整抗体的抗原结合功能和附加功能。结合片段的实例包括但不限于单链Fv片段(scFv)或Fab片段，所述单链Fv片段(scFv)由通过合成接头连接的单多肽链中的抗体的单臂的VL和VH结构域组成，所述Fab片段是由VL、恒定轻链(CL)、VH和恒定重链1(CH1)结构域组成的单价片段。抗体片段可以是甚至更小的亚片段并且可以由与单个CDR结构域一样小的结构域组成，特别是来自VL和/或VH结构域的CDR3区(例如参见Beiboer等人，J.Mol.Biol.296:833-49(2000))。使用本领域技术人员已知的常规方法产生抗体片段。可以使用与完整抗体相同的技术筛选抗体片段的效用。
“抗原或表位结合片段”可以通过许多本领域已知的技术衍生自本公开的抗体。例如，可以用酶如胃蛋白酶切割纯化的单克隆抗体，并进行HPLC凝胶过滤。然后可收集含有Fab片段的适当级分并通过膜过滤等浓缩。关于分离抗体活性片段的一般技术的进一步描述，参见例如Khaw,B.A.等.J.nucl.Med.23:1011-1019(1982)；Rousseaux等人，酶学方法(Methods Enzymology)，121:663-69,学术出版社(Academic Press)，1986。
抗体的木瓜蛋白酶消化产生两个相同的抗原结合片段，称为“Fab”片段，每个片段具有单个抗原结合位点，和残余的“Fc”片段，其名称反映其易于结晶的能力。胃蛋白酶处理产生具有两个抗原结合位点并且仍然能够交联抗原的F(ab')2片段。
Fab片段可含有轻链的恒定结构域和重链的第一恒定结构域(CH1)。Fab'片段与Fab片段的不同之处在于在重链CH1结构域的羧基末端添加了一些残基，包括来自抗体铰链区的一个或多个半胱氨酸。Fab'-SH在本文中是指Fab’，其中恒定结构域的半胱氨酸残基带有游离巯基。F(ab')2抗体片段最初产生为Fab'片段对，它们之间具有铰链半胱氨酸。另外，抗体片段的化学偶联也是已知的。
“Fv”是含有完整抗原识别和结合位点的最小抗体片段。该区域由紧密非共价结合的一个重链和一个轻链可变域的二聚体组成。在这种构型中，每个可变域的三个CDR相互作用以限定VH-VL二聚体表面上的抗原结合位点。总起来说，六个CDR赋予抗体抗原结合特异性。然而，即使单个可变结构域(或仅包含对抗原特异的三个CDR的Fv的一半)也具有识别和结合抗原的能力，尽管亲和力低于整个结合位点。
基于其恒定结构域的氨基酸序列，来自任何脊椎动物物种的抗体(免疫球蛋白)的“轻链”可以归属于两种明显不同的类型之一，称为kappa(κ)和lambda(λ)。
根据其重链恒定域的氨基酸序列，免疫球蛋白可分为不同的类别。免疫球蛋白有五大类别：IgA、IgD、IgE、IgG和IgM，其中一些可以进一步分为亚类(同种型)，例如IgG-1、IgG-2、IgG-3和IgG-4；IgA-1和IgA-2。对应于不同类免疫球蛋白的重链恒定区分别称为α、δ、ε、γ和μ。不同类免疫球蛋白的亚基结构和三维构型是众所周知的。
“人源化抗体”是指一类工程化抗体，其CDR衍生自非人供体免疫球蛋白，分子的剩余免疫球蛋白衍生部分衍生自一种(或多种)人免疫球蛋白。此外，可以改变框架支持残基以保持结合亲和力。获得“人源化抗体”的方法是本领域技术人员熟知的。(参见例如Queen等人，Proc.Natl Acad Sci USA，86：10029-10032(1989)，Hodgson等人，Bio/Technology，9：421(1991))。
如本文所用，术语“多肽”、“肽”和“蛋白质”是可互换的，并且定义为意指由通过肽键连接的氨基酸组成的生物分子。
如本文所用的术语“一个(a、an)”和“该(the)”被定义为意指“一个或多个”并且包括复数，除非上下文不适当。
“分离的”是指不含其天然存在的至少一些组分的生物分子。“分离的”当用于描述本文公开的各种多肽时，是指已经从其表达的细胞或细胞培养物中鉴定和分离和/或回收的多肽。通常，通过至少一个纯化步骤制备分离的多肽。“分离的抗体”是指基本上不含具有不同抗原特异性的其他抗体的抗体。
“重组”是指使用重组核酸技术在外源宿主细胞中产生抗体。
术语“抗原”是指可以在生物体、特别是动物、更特别是包括人在内的哺乳动物中诱导免疫应答的实体或其片段。该术语包括免疫原及其负责抗原性或抗原决定簇的区域。
“特异性结合(specific binding、specifically binds to)”或“特异性针对(specific for)”特定抗原或表位是指与非特异性相互作用显著不同的结合。特异性结合可以例如通过测定与对照分子的结合相比的分子的结合来测量，所述对照分子通常是具有不具有结合活性的类似结构的分子。例如，特异性结合可以通过与类似于靶的对照分子竞争来确定。
对特定抗原或表位的特异性结合可以例如通过抗体对抗原或表位的KD来表示，所述KD至少约10-4M、至少约10-5M、至少约10-6M、至少约10-6M、至少约10-7M、至少约10-8M、至少约10-9M、或者至少约10-10M、至少约10-11M、至少约10-12M或更高，其中KD是指特定抗体-抗原相互作用的解离速率。典型地，特异性结合抗原的抗体相对于抗原或表位对于对照分子将具有20、50、100、500、1000、5,000、10,000或更多倍的KD。
两个序列之间的“同源性”由序列同一性决定。如果相互比较的两个序列长度不同，则序列同一性优选涉及与较长序列的核苷酸残基相同的较短序列的核苷酸残基的百分比。可以使用计算机程序常规地确定序列同一性。在给定序列与本公开的上述序列之间的比较中出现的偏差可以由例如添加、缺失、取代、插入或重组引起。
本申请还提供了免疫缀合物，其包括通过接头与本文公开的抗体和抗原结合片段连接的药物单元。接头可以是可切割的或不可切割的。在一个实施方案中，接头是化学接头。在一个实施方案中，接头包含共价键，例如酯键、醚键、酰胺键、二硫键、酰亚胺键、砜键、磷酸键(phosphate bond)、磷酸酯键(phosphorus ester bond)、肽键或其组合。在一个实施方案中，接头包含疏水性聚(乙二醇)接头。在一个实施方案中，接头包含肽键。
药物单元还可以是化疗剂、生长抑制剂、卡利奇霉素类药物单元、抗有丝分裂剂、毒素、放射性同位素、治疗剂或其组合。在一个实施方案中，治疗剂包括抗体、化疗剂、酶或其组合。
在另一方面，本申请提供了药物组合物。在一个实施方案中，药物组合物可包括本文公开的分离的抗体或抗原结合片段和药学上可接受的载体。在一个实施方案中，药物组合物包括本文公开的免疫缀合物和药学上可接受的载体。
抗体及其片段或免疫缀合物可以使用已知技术以生理上可接受的制剂形式制备，并且其可以包含药学上可接受的载体、稀释剂和/或赋形剂。例如，本文公开的抗体可包括任何功能等效抗体或其功能部分，特别地，包括任何功能等效抗体或其功能部分的单克隆抗体与药学上可接受的载体、稀释剂和/或赋形剂组合以形成治疗组合物。
合适的药物载体、稀释剂和/或赋形剂是本领域熟知的，包括例如磷酸盐缓冲盐溶液、水、乳剂如油/水乳剂。
药物组合物可进一步包含蛋白质载体，例如血清白蛋白或免疫球蛋白，特别是人源的。在一个实施方案中，蛋白质药物活性物质可以每剂量1ng至10mg的量存在。
在一些实施方案中，施用方案可以在根据本公开的抗体的0.1μg至10mg的范围内，特别地在1.0μg至1.0mg的范围内，并且更特别地在1.0μg至100μg的范围内，落入这些范围内的所有个体数也是本公开的一部分。如果通过连续输注进行施用，则更合适的剂量可以在0.01μg至10mg单位/千克体重/小时的范围内，并且落入这些范围内的所有单个数值也是本公开的一部分。
“药学上可接受的”是指那些化合物、材料、组合物和剂型，它们在合理的医学判断范围内适合用于与人或动物的组织接触而没有过度的毒性、刺激或其他问题或并发症，与合理的益处/风险比相称。可以根据本领域普通技术人员已知的标准方法得到根据本公开的药物组合物的制剂。
根据预期用途，其他生物活性剂可以存在于本公开的药物组合物中。在一个实施方案中，本文公开的组合物可以与包含生物活性/治疗性物质或化合物，特别是选自由治疗剂组成的组的至少一种化合物的其他组合物组合施用，所述治疗剂包括卡培他滨、顺铂、曲妥珠单抗、氟维司群、他莫昔芬、来曲唑、依西美坦、阿那曲唑、氨鲁米特、睾内酯、伏氯唑、福美坦、法倔唑、来曲唑、埃罗替尼、拉法替尼、达沙替尼、吉非替尼、伊马替尼、帕唑帕尼(pazopanib)、拉帕替尼、舒尼替尼、尼洛替尼、索拉非尼、nab-紫杉醇、卡利奇霉素、抗有丝分裂剂、单甲基奥瑞他汀E、美坦新(emtansine)、奥佐米星、其衍生物或组合。
在另一方面，本申请提供了使用抗ROR1抗体或含有抗ROR1抗体的抗原结合部分的其他分子来治疗受试者的方法。在一个实施方案中，该方法抑制肿瘤细胞的生长。在一些实施方案中，该方法使用所公开的抗体或组合物来刺激保护性自身免疫应答、修饰免疫应答或刺激抗原特异性免疫应答。
在一个实施方案中，该法包括向需要这种治疗的受试者施用有效量的本文公开的抗ROR1抗体或其他分子或组合物的步骤。
组合物可以以固体、液体或气雾剂的形式以合适的药学有效剂量施用于受试者。固体组合物的实例包括丸剂、乳膏和可植入的剂量单位。丸剂可以口服施用。治疗乳膏可以局部施用。
可植入的剂量单位可以例如在肿瘤部位局部施用，或者可以例如皮下施用植入以系统释放治疗组合物。液体组合物的实例包括适于肌内注射、皮下注射、静脉内注射、动脉内注射的制剂以及用于局部和眼内施用的制剂。气溶胶制剂的实例包括用于向肺部施用的吸入剂制剂。
组合物可以通过标准给药途径给药。通常，组合物可以通过局部、口服、直肠、鼻、皮内、腹膜内或肠胃外(例如静脉内、皮下或肌内)途径施用。此外，可以将组合物掺入诸如生物可降解聚合物的缓释基质中，将聚合物植入需要递送的部位附近，例如肿瘤部位。该方法包括给予单一剂量、以预定时间间隔给予重复剂量和持续给予预定时间。
在一个实施方案中，施用可以是肠胃外施用，例如静脉内施用。用于肠胃外施用的制剂包括无菌水性或非水性溶液、悬浮液和乳液。非水性溶剂包括但不限于丙二醇、聚乙二醇、植物油如橄榄油以及可注射有机酯如油酸乙酯。水性溶剂可以选自水、醇/水溶液、乳液或悬浮液(包括盐水和缓冲介质)。肠胃外载体包括氯化钠溶液、林格氏葡萄糖、葡萄糖和氯化钠、乳酸化林格氏或不挥发性油。静脉内载体包括流体和营养补充剂、电解质补充剂(例如基于林格氏葡萄糖的那些)等。
还可以存在防腐剂，例如抗菌剂、抗氧化剂、螯合剂、惰性气体等。
本领域普通技术人员众所周知，组合物的剂量将取决于各种因素，例如所治疗的病症、所使用的特定组合物和其他临床因素，例如患者的体重、大小、性别和一般健康状况、体表面积、待施用的特定化合物或组合物、同时施用的其他药物和施用途径。
术语“治疗有效量”是指当施用于人或动物时引起足以在所述人或动物中产生治疗效果的应答的抗体的量。有效量易于由本领域普通技术人员按照常规方法确定。
可以使用所公开的mAb、抗原结合片段或组合物来治疗各种癌症。包括乳腺癌、结肠直肠癌、胰腺癌、头颈癌、黑素瘤、卵巢癌、前列腺癌、非小细胞肺癌、神经胶质瘤、食管癌、鼻咽癌、肛门癌、直肠癌、胃癌、膀胱癌、宫颈癌或脑癌的癌症可表达ROR1基因。在一个实施方案中，施用治疗有效量的包含抗ROR1单克隆抗体或其抗原结合片段或其免疫缀合物的组合物用于治愈、预防、改善和延迟癌症的发展或转移。
通过参考以下包括在此的具体实施方案的详细描述，可以更容易地理解本公开。尽管已经参考本发明的某些实施例的具体细节描述了本发明，但是并不意味着这些细节应当被认为是对本发明范围的限制。
实施例
实施例1：抗ROR1抗体的产生
通过免疫新西兰白兔开发抗人ROR1的单克隆抗体。如图1所示，用重组人或小鼠ROR1胞外结构域(ECD)或HEK293细胞免疫动物并通过皮下注射进行，其中所述HEK293细胞用小鼠或人ROR1瞬时转染，小鼠或人ROR1以1：1v/v与完全或不完全弗氏佐剂(第1组)或TiterMax Gold(第2组)混合，并交替添加铝胶2％(Alum)加CpG2007。随后在第7、14、21、28和37天进行加强，如图2所示。
在第5周，通过ELISA测试来自动物血清的抗ROR1滴度。免疫前，从每只兔获得的血清作为阴性对照。免疫后，再次从每只动物收集血清，并与来自相同动物的免疫前血清比较ROR1特异性IgG抗体的存在。如图6所示，所有用人和小鼠ROR1免疫的动物都产生了可检测滴度的人或小鼠ROR1特异性IgG抗体。
如图3所示，在最终免疫后第4、13和21天分别从2只动物收获脾和淋巴结。将ROR1特异性IgG+B细胞以每孔1个分选到多个96孔组织培养板中，并培养9天以使它们分化成浆细胞并分泌抗体。在如下列出的一系列结合测定中，通过ELISA和流式细胞术(FACS)筛选了来自这些浆细胞培养物的上清液中ROR1特异性抗体的存在：
人ROR1直接包被在平板上——检测ROR1特异性IgG ELISA
小鼠ROR1直接包被在平板上——检测ROR1特异性IgG ELISA
人ROR2直接包被在平板上——检测ROR1特异性IgG ELISA
生物素化人ROR1加入抗生物素蛋白包被的平板-检测ROR1特异性IgG ELISA
生物素化人ROR1“Kringle结构域”加入抗生物素蛋白包被的平板-检测ROR1-Kringle特异性IgG ELISA
生物素化人ROR1“Frizzled-Kringle结构域”加入抗生物素蛋白包被的平板-检测ROR1-Frizzled-Kringle特异性IgG ELISA
生物素化人ROR1“Ig-Frizzled结构域”加入抗生物素蛋白包被的平板-检测ROR1-Ig-Frizzled特异性IgG ELISA
人ROR1“Frizzled-Kringle结构域”直接包被在平板上-检测ROR1-Frizzled-Kringle特异性IgG ELISA
人ROR1“Ig-Frizzled结构域”直接包被在平板上-检测ROR1-Ig-Frizzled特异性IgG ELISA
人ROR1-CHO细胞-通过FACS检测ROR1特异性IgG
在B细胞培养的第9天，将上清液从B细胞中分离并储存在单独的平板中用于以后的分析。将RNAlater组织储存试剂加入到B细胞培养板中的每个孔中，以保存B细胞中的RNA，用于抗体可变区的RT-PCR扩增。
通过ELISA和FACS筛选鉴定B细胞培养孔具有所需抗体，我们进行了抗体可变区的分子“拯救”。使用简并引物通过多重RT-PCR扩增轻链和重链可变区序列，所述简并引物设计为与兔IgG和兔κ序列的前导序列和恒定区退火。使用含有限制性位点的嵌套引物分别对轻链和重链进行第二次PCR。将来自可变重链PCR的扩增子克隆到含有人IgG1的表达载体中。将轻链扩增子克隆到含有人IgK的表达载体中。测序并分析所得克隆。
将从各孔产生的重链和轻链表达质粒瞬时共转染以产生兔/人嵌合抗体。在FortebioOctt Red 96仪器上使用生物层干涉测量法分析证实重组抗体上清液含有抗ROR1抗体。使用抗人Fc生物传感器(Pall Fortebio)捕获上清液中的抗体。通过将生物传感器置于含有重组人ROR1胞外域蛋白的孔中，通过实时干涉测量法观察与ROR1的缔合。在将生物传感器转移到含有10X动力学缓冲液(PallFortebio)的孔中之后测量解离。制造商提供的软件用于分析干涉测量数据。
表4a和4b显示了27种重组嵌合兔/人IgG抗体的初级BCC筛选数据和相应筛选数据的总结。
图4中列举的上述27种嵌合兔/人IgG抗体中的8种的重链可变区和轻链可变区是人源化的。27种抗体中的8种人源化变体通过八位位组分析显示出与人ROR1相似的结合动力学，总结于图5。
虽然已经参照本发明的实施方案具体示出和描述了本公开，但是本领域技术人员将理解，在不脱离本发明的精神和范围的情况下，可以在形式和细节上进行前述和其他改变。本公开中引用或提及的所有参考文献在此全文引入作为参考。
序列表
抗ROR1抗体序列
SEQ ID NO:1
226E12嵌合轻链全长核苷酸序列
GCCTATGATATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATGTTCGGCGGAGGGACCGAGGTGGTGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:2
226E12嵌合轻链可变轻链核苷酸序列
GCCTATGATATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATGTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
SEQ ID NO:3
226E12嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
AYDMTQTPSSVSAAVGGTVTIKCQASQRIYSYLAWYQQKPGQPPKLLIYRASTLASGVPSRFKGSGSGTEYTLTISDLECADAATYYCQQGASMVDVENMFGGGTEVVVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:4
226E12嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
AYDMTQTPSSVSAAVGGTVTIKCQASQRIYSYLAWYQQKPGQPPKLLIYRASTLASGVPSRFKGSGSGTEYTLTISDLECADAATYYCQQGASMVDVENMFGGGTEVVVKSEQ ID NO:5
226E12嵌合重链全长核苷酸序列
CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGAATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAGTGGATCGGAGCCATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGGATCTGAAGATCACCAGTCCGACAATTGAGGACACGGCCACCTATTTCTGTGCCAGAAGTGTGAGTAATAATTTCGCCGAATATAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:6
226E12嵌合重链可变重链核苷酸序列
CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGAATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAGTGGATCGGAGCCATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGGATCTGAAGATCACCAGTCCGACAATTGAGGACACGGCCACCTATTTCTGTGCCAGAAGTGTGAGTAATAATTTCGCCGAATATAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGC
SEQ ID NO:7
226E12嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSLEESGGRLVTPGTPLTLTCTASEFSLSNYYMSWVRQAPGEGLEWIGAINADSDNTWYPSWVKGRFTISKTSSTTVDLKITSPTIEDTATYFCARSVSNNFAEYNIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:8
226E12嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSLEESGGRLVTPGTPLTLTCTASEFSLSNYYMSWVRQAPGEGLEWIGAINADSDNTWYPSWVKGRFTISKTSSTTVDLKITSPTIEDTATYFCARSVSNNFAEYNIWGPGTLVTVSS
SEQ ID NO:9
323H7嵌合轻链全长核苷酸序列
CAAGCCGTGGTGACCCAGACTCCATCGTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCCAGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACTATGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCGCCATCAGCGACCTGGAGTGTGACGATTCTGCCACTTACTACTGTGCAGGCGGTTATGATACGGATGGTCTTGATACGTTTGCTTTCGGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:10
323H7嵌合轻链可变轻链核苷酸序列
CAAGCCGTGGTGACCCAGACTCCATCGTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCCAGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACTATGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCGCCATCAGCGACCTGGAGTGTGACGATTCTGCCACTTACTACTGTGCAGGCGGTTATGATACGGATGGTCTTGATACGTTTGCTTTCGGCGGAGGCACCGAGGTGGAGGTCAAA
SEQ ID NO:11
323H7嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
QAVVTQTPSSVSAAVGGTVTISCQSSQSVYNNNDLAWYQQKPGQPPKLLIYYASTLASGVSSRFKGSGSGTQFTLAISDLECDDSATYYCAGGYDTDGLDTFAFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:12
323H7嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
QAVVTQTPSSVSAAVGGTVTISCQSSQSVYNNNDLAWYQQKPGQPPKLLIYYASTLASGVSSRFKGSGSGTQFTLAISDLECDDSATYYCAGGYDTDGLDTFAFGGGTEVEVK
SEQ ID NO:13
323H7嵌合重链全长核苷酸序列
CAGGAGCAGCTGAAGGAGTCCGGAGGAGGCCTGGTAACGCCTGGAGGAACCCTGACACTCACCTGCACAGCCTCTGGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGTCATATTTATGTTAATAATGATGACACAGACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAGATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATTGGATGTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:14
323H7嵌合重链可变重链核苷酸序列
CAGGAGCAGCTGAAGGAGTCCGGAGGAGGCCTGGTAACGCCTGGAGGAACCCTGACACTCACCTGCACAGCCTCTGGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGTCATATTTATGTTAATAATGATGACACAGACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAGATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATTGGATGTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGC
SEQ ID NO:15
323H7嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QEQLKESGGGLVTPGGTLTLTCTASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASWAKGRFTISKTSTTVDLKITSPTTEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:16
323H7嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QEQLKESGGGLVTPGGTLTLTCTASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASWAKGRFTISKTSTTVDLKITSPTTEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSS
SEQ ID NO:17
324C7嵌合轻链全长核苷酸序列
GACATTGTGATGACCCAGACTCCAGCCTCTGTGGAGGTCGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACTACATCCAATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGGTTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCAGTTACTGCTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGGAATGCTTTCGGCGGAGGCACCGAGGTGGTGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:18
324C7嵌合轻链可变轻链核苷酸序列
GACATTGTGATGACCCAGACTCCAGCCTCTGTGGAGGTCGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACTACATCCAATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGGTTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCAGTTACTGCTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGGAATGCTTTCGGCGGAGGCACCGAGGTGGTGGTCAAA
SEQ ID NO:19
324C7嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIVMTQTPASVEVAVGGTVTIKCQASQNIGSDLAWYQQKPGQPPKLLIYTTSNLASGVPSRFKGSGSGTGFTLTISDLECADAASYCCQGGYFSGRNIYGNAFGGGTEVVVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:20
324C7嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
DIVMTQTPASVEVAVGGTVTIKCQASQNIGSDLAWYQQKPGQPPKLLIYTTSNLASGVPSRFKGSGSGTGFTLTISDLECADAASYCCQGGYFSGRNIYGNAFGGGTEVVVK
SEQ ID NO:21
324C7嵌合重链全长核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATACATTGATAGTGGTGCTACCACATACTACGCGAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAGCCTCGACCACGGTGGATCTGAAAATCGCCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGATACTACGGCATGGACCCCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:22
324C7嵌合重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATACATTGATAGTGGTGCTACCACATACTACGCGAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAGCCTCGACCACGGTGGATCTGAAAATCGCCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGATACTACGGCATGGACCCCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGC
SEQ ID NO:23
324C7嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASWAKGRFTISKASTTVDLKIASPTTEDTATYFCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:24
324C7嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASWAKGRFTISKASTTVDLKIASPTTEDTATYFCARGYYGMDPWGQGTLVTVSS
SEQ ID NO:25
323D10嵌合轻链全长核苷酸序列
GCCATCGATTTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACGAAACATCCAAACTGGCATCTGGGGTCCCACCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAGTTATTATCGTATTAATAATATTGGTTACGATAATGCTTTCGGCGGAGGCACCGAGGTGGAGTTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:26
323D10嵌合轻链可变轻链核苷酸序列
GCCATCGATTTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACGAAACATCCAAACTGGCATCTGGGGTCCCACCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAGTTATTATCGTATTAATAATATTGGTTACGATAATGCTTTCGGCGGAGGCACCGAGGTGGAGTTCAAA
SEQ ID NO:27
323D10嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
AIDLTQTPASVEAAVGGTITINCQASESISSWLAWYQQKPGQRPKLLIYETSKLASGVPPRFSGSGSGTQFTLTISGVQCDDAATYYCQSYYRINNIGYDNAFGGGTEVEFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:28
323D10嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
AIDLTQTPASVEAAVGGTITINCQASESISSWLAWYQQKPGQRPKLLIYETSKLASGVPPRFSGSGSGTQFTLTISGVQCDDAATYYCQSYYRINNIGYDNAFGGGTEVEFK
SEQ ID NO:29
323D10嵌合重链全长核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGATACATTAGCACTAGTGGTACCACATTCTACGCGAACTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGACTATAACTACGCCATGGACATCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:30
323D10嵌合重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGATACATTAGCACTAGTGGTACCACATTCTACGCGAACTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGACTATAACTACGCCATGGACATCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGC
SEQ ID NO:31
323D10嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANWVKGRFTISKTSTTVDLKMTSLTTEDTATYFCARDYNYAMDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS VLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:32
323D10嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANWVKGRFTISKTSTTVDLKMTSLTTEDTATYFCARDYNYAMDIWGQGTLVTVSS
SEQ ID NO:33
324E2嵌合轻链全长核苷酸序列
GCTCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGTCCAGTCAGAGTGTTAATAACAACGACTTAGCCTGGTTTCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTACTGGGCATCCAAACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCATTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTCGGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:34
324E2嵌合轻链可变轻链核苷酸序列
GCTCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGTCCAGTCAGAGTGTTAATAACAACGACTTAGCCTGGTTTCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTACTGGGCATCCAAACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCATTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTCGGCGGAGGCACCGAGGTGGAGGTCAAA
SEQ ID NO:35
324E2嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
AQVLTQTPSSVSAAVGGTVTINCQSSQSVNNNDLAWFQQKPGQPPKRLIYWASKLASGVPSRFKGSGSGTQFILTISDLECDDAATYYCAGGYSGNIYGFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:36
324E2嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
AQVLTQTPSSVSAAVGGTVTINCQSSQSVNNNDLAWFQQKPGQPPKRLIYWASKLASGVPSRFKGSGSGTQFILTISDLECDDAATYYCAGGYSGNIYGFGGGTEVEVK
SEQ ID NO:37
324E2嵌合重链全长核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGAATCATTAGTAGTAGTGGTACCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCGGAGCATTTAGCGTCTGGGGCCCGGGCACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:38
324E2嵌合重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGAATCATTAGTAGTAGTGGTACCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCGGAGCATTTAGCGTCTGGGGCCCGGGCACCCTCGTCACCGTCTCGAGC
SEQ ID NO:39
324E2嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSNNAITWVRQAPGKGLEYIGI ISSSGTTYYASWAKGRFTISKTSSTTVDLKMTSLTTEDTATYFCAGAFSVWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:40
324E2嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASWAKGRFTISKTSSTTVDLKMTSLTTEDTATYFCAGAFSVWGPGTLVTVSS
SEQ ID NO:41
324C6嵌合轻链全长核苷酸序列
GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAACAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACCAGGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGCGCTTATGGTGTTAGTGGTACTAGTAGTTATTTATATACTTTCGGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:42
324C6嵌合轻链可变轻链核苷酸序列
GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAACAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACCAGGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGCGCTTATGGTGTTAGTGGTACTAGTAGTTATTTATATACTTTCGGCGGAGGCACCGAGGTGGAGGTCAAA
SEQ ID NO:43
324C6嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线部分标出
DVVMTQTPASVEAAVGGTVTIKCQASQSIDSWLSWYQQKPGQPPKLLIYQASTLASGVSSRFKGSGSGTEFTLTISDLECADAATYYCQCAYGVSGTSSYLYTFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:44
324C6嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
DVVMTQTPASVEAAVGGTVTIKCQASQSIDSWLSWYQQKPGQPPKLLIYQASTLASGVSSRFKGSGSGTEFTLTISDLECADAATYYCQCAYGVSGTSSYLYTFGGGTEVEVK
SEQ ID NO:45
324C6嵌合重链全长核苷酸序列
CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATTGGAACCATTTATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACTAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATCCTATTATGGCGGTGATAAGACTGGTTTAGGCATCTGGGGCCCAGGCACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:46
324C6嵌合重链可变重链核苷酸序列
CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATTGGAACCATTTATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACTAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATCCTATTATGGCGGTGATAAGACTGGTTTAGGCATCTGGGGCCCAGGCACCCTCGTCACCGTCTCGAGC
SEQ ID NO:47
324C6嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSLEESGGRLVTPGTPLTLTCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKTSTTVDLKITSPTTEDTATYFCARSYYGGDKTGLGIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:48
324C6嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSLEESGGRLVTPGTPLTLTCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKTSTTVDLKITSPTTEDTATYFCARSYYGGDKTGLGIWGPGTLVTVSS
SEQ ID NO:49
338H4嵌合轻链全长核苷酸序列
GACATTGTGATGACCCAGACTCCAGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCCAGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTATCTGGCATCTACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAAGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGAGGGACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:50
338H4嵌合轻链可变轻链核苷酸序列
GACATTGTGATGACCCAGACTCCAGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCCAGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTATCTGGCATCTACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAAGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGAGGGACCGAGGTGGAGGTCAAA
SEQ ID NO:51
338H4嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIVMTQTPASVSAAVGGTVTINCQASQNIYSYLSWYQQKPGQPPKRLIYLASTLASGVPSRFKSSGSGTEYTLTISDLECDDAATYYCQSNYNGNYGFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:52
338H4嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
DIVMTQTPASVSAAVGGTVTINCQASQNIYSYLSWYQQKPGQPPKRLIYLASTLASGVPSRFKSSGSGTEYTLTISDLECDDAATYYCQSNYNGNYGFGGGTEVEVK
SEQ ID NO:53
338H4嵌合重链全长核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAATGGATCGGAATCATTTATGCTAGTGGTAGCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAATTTATGACGGCATGGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:54
338H4嵌合重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAATGGATCGGAATCATTTATGCTAGTGGTAGCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAATTTATGACGGCATGGACCTCTGGGGCCCAGGGACCCTCGTCACCGTCTCGAGC
SEQ ID NO:55
338H4嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASWAKGRFTISKTSTTVDLKITSPTTEDTATYFCARIYDGMDLWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:56
338H4嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASWAKGRFTISKTSTTVDLKITSPTTEDTATYFCARIYDGMDLWGPGTLVTVSS
SEQ ID NO:57
330F11嵌合轻链全长核苷酸序列
GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTATTGTCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGCGGAGGGACCGAGGTGGAGTTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:58
330F11嵌合轻链可变轻链核苷酸序列
GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTATTGTCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGCGGAGGGACCGAGGTGGAGTTCAAA
SEQ ID NO:59
330F11嵌合轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DVVMTQTPASVEAAVGGTVTIKCQASQSINNYLAWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTQFTLTISDLECADAATYYCQSYNGVGRTAFGGGTEVEFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:60
330F11嵌合轻链可变轻链氨基酸序列。互补决定区用下划线标出
DVVMTQTPASVEAAVGGTVTIKCQASQSINNYLAWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTQFTLTISDLECADAATYYCQSYNGVGRTAFGGGTEVEFK
SEQ ID NO:61
330F11嵌合重链全长核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAATGGATCGGAACCATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAGCATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATATTCTTCTACTACTGATTGGACCTACTTTAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:62
330F11嵌合重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAATGGATCGGAACCATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAGCATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATATTCTTCTACTACTGATTGGACCTACTTTAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGC
SEQ ID NO:63
330F11嵌合重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLNNYWMSWVRQAPGEGLEWIGTISSGAYTWFATWATGRFTISKTSTTVDLSITSPTTEDTATYFCARYSSTTDWTYFNIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:64
330F11嵌合重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGRLVTPGTPLTLTCTVSGFSLNNYWMSWVRQAPGEGLEWIGTISSGAYTWFATWATGRFTISKTSTTVDLSITSPTTEDTATYFCARYSSTTDWTYFNIWGPGTLVTVSS
SEQ ID NO:65
226E12人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATGTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:66
226E12人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATGTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:67
226E12人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSSLSASVGDRVTITCQASQRIYSYLAWYQQKPGKVPKLLIYRASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGASMVDVENMFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPRE AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:68
226E12人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSSLSASVGDRVTITCQASQRIYSYLAWYQQKPGKVPKLLIYRASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGASMVDVENMFGGGTKVEIK
SEQ ID NO:69
226E12人源化重链全长核苷酸序列
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGCCATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAAGTGTGAGTAATAATTTCGCCGAATATAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:70
226E12人源化重链可变重链核苷酸序列
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGCCATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAAGTGTGAGTAATAATTTCGCCGAATATAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:71
226E12人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
EVQLLESGGGLVQPGGSLRLSCAASGFSLSNYYMSWVRQAPGKGLEWIGAINADSDNTWYPSWVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSVSNNFAEYNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:72
226E12人源化重链可变重链氨基酸序列。互补决定区用下划线标出
EVQLLESGGGLVQPGGSLRLSCAASGFSLSNYYMSWVRQAPGKGLEWIGAINADSDNTWYPSWVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSVSNNFAEYNIWGQGTLVTVSS
SEQ ID NO:73
323H7人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATGATACGGATGGTCTTGATACGTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:74
323H7人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATGATACGGATGGTCTTGATACGTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:75
323H7人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSSLSASVGDRVTITCQSSQSVYNNNDLAWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCAGGYDTDGLDTFAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:76
323H7人源化轻链可变轻链氨基酸序列。互补决定区用下划线标出
DIQMTQSPSSLSASVGDRVTITCQSSQSVYNNNDLAWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCAGGYDTDGLDTFAFGGGTKVEIK
SEQ ID NO:77
323H7人源化重链全长核苷酸序列
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGACATATTTATGTTAATAATGATGACACAGACTACGCGAGCTCCGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCACCTATTTCTGTGCGAGATTGGATGTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:78
323H7人源化重链可变重链核苷酸序列
GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGACATATTTATGTTAATAATGATGACACAGACTACGCGAGCTCCGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCACCTATTTCTGTGCGAGATTGGATGTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:79
323H7人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
EVQLLESGGGLVQPGGSLRLSCAASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASSAKGRFTISRDNSKNTLYLQMNSLRAEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPK SCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:80
323H7人源化重链可变重链氨基酸序列。互补决定区用下划线标出
EVQLLESGGGLVQPGGSLRLSCAASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASSAKGRFTISRDNSKNTLYLQMNSLRAEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSS
SEQ ID NO:81
324C7人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCAGGCCAGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATACTACATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGGAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:82
324C7人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCAGGCCAGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATACTACATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGGAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:83
324C7人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSSVSASVGDRVTITCQASQNIGSDLAWYQQKPGKAPKLLIYTTSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQGGYFSGRNIYGNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:84
324C7人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSSVSASVGDRVTITCQASQNIGSDLAWYQQKPGKAPKLLIYTTSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQGGYFSGRNIYGNAFGGGTKVEIK
SEQ ID NO:85
324C7人源化重链全长核苷酸序列-变体1
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTACATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTACGGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:86
324C7人源化重链可变重链核苷酸序列-变体1
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTACATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTACGGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:87
324C7人源化重链全长氨基酸序列-变体1。人γ-1恒定结构域用下划线标出
EVQLVESGGGLVQPGGSLRLSCAASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:88
324C7人源化重链可变重链氨基酸序列-变体1。互补决定区用下划线标出
EVQLVESGGGLVQPGGSLRLSCAASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSS
SEQ ID NO:89
324C7人源化重链全长核苷酸序列-变体2
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTACATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAAAGACAATGCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTACGGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:90
324C7人源化重链可变重链核苷酸序列-变体2
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTACATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAAAGACAATGCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTACGGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:91
324C7人源化重链全长氨基酸序列-变体2。人γ-1恒定结构域用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISKDNAKNTVDLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:92
324C7人源化重链可变重链氨基酸序列-变体2。互补决定区用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISKDNAKNTVDLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSS
SEQ ID NO:93
323D10人源化轻链全长核苷酸序列
GCCATCGATTTGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGGCACAATCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGTTATTATCGTATTAATAATATTGGTTACGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:94
323D10人源化轻链可变轻链核苷酸序列
GCCATCGATTTGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGGCACAATCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGTTATTATCGTATTAATAATATTGGTTACGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:95
323D10人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
AIDLTQSPSTLSASVGGTITINCQASESISSWLAWYQQKPGKAPKLLIYETSKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSYYRINNIGYDNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:96
323D10人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
AIDLTQSPSTLSASVGGTITINCQASESISSWLAWYQQKPGKAPKLLIYETSKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSYYRINNIGYDNAFGGGTKVEIK
SEQ ID NO:97
323D10人源化重链全长核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGATACATTAGCACTAGTGGTACCACATTCTACGCGAACAGCGTGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTATAACTACGCCATGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:98
323D10人源化重链可变重链核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGATACATTAGCACTAGTGGTACCACATTCTACGCGAACAGCGTGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTATAACTACGCCATGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:99
323D10人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANSVKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARDYNYAMDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:100
323D10人源化重链可变重链氨基酸序列。互补决定区用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANSVKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARDYNYAMDIWGQGTLVTVSS
SEQ ID NO:101
324E2人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATTGGGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAACCTGCAGCCTGAAGATTTTGCAACTTATTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:102
324E2人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTATTGGGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAACCTGCAGCCTGAAGATTTTGCAACTTATTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:103
324E2人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSSLSASVGDRVTITCQSSQSVNNNDLAWYQQKPGKAPKRLIYWASKLASGVPSRFSGSGSGTEFTLTISNLQPEDFATYYCAGGYSGNIYGFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:104
324E2人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSSLSASVGDRVTITCQSSQSVNNNDLAWYQQKPGKAPKRLIYWASKLASGVPSRFSGSGSGTEFTLTISNLQPEDFATYYCAGGYSGNIYGFGGGTKVEIK
SEQ ID NO:105
324E2人源化重链全长核苷酸序列
CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGATTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAATCATTAGTAGTAGTGGTACCACATACTACGCGAGCTCCGCGAAAGGCAGATTCACCATCTCCAAAGACACCTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGGGAGCATTTAGCGTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:106
324E2人源化重链可变重链核苷酸序列
CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGATTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAATCATTAGTAGTAGTGGTACCACATACTACGCGAGCTCCGCGAAAGGCAGATTCACCATCTCCAAAGACACCTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGGGAGCATTTAGCGTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:107
324E2人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSVEESGGGLVQPGGSLRLSCTASGFSLSNNAITWVRQAPGKGLEYIGI ISSSGTTYYASSAKGRFTISKDTSKNTVDLQMNSLRAEDTAVYYCAGAFSVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS VLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:108
324E2人源化重链可变重链氨基酸序列。互补决定区用下划线标出
QSVEESGGGLVQPGGSLRLSCTASGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASSAKGRFTISKDTSKNTVDLQMNSLRAEDTAVYYCAGAFSVWGQGTLVTVSS
SEQ ID NO:109
324C6人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTGCTTATGGTGTTAGTGGTACTAGTAGTTATTTATATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:110
324C6人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTGCTTATGGTGTTAGTGGTACTAGTAGTTATTTATATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:111
324C6人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSTLSASVGDRVTITCQASQSIDSWLSWYQQKPGKAPKLLIYQASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSAYGVSGTSSYLYTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:112
324C6人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSTLSASVGDRVTITCQASQSIDSWLSWYQQKPGKAPKLLIYQASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSAYGVSGTSSYLYTFGGGTKVEIK
SEQ ID NO:113
324C6人源化重链全长核苷酸序列
CAGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATTTATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCCTATTATGGCGGTGATAAGACTGGTTTAGGCATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:114
324C6人源化重链可变重链核苷酸序列
CAGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATTTATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCCTATTATGGCGGTGATAAGACTGGTTTAGGCATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:115
324C6人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
QSLVESGGGLVQPGGSLRLSCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARSYYGGDKTGLGIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCD KTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:116
324C6人源化重链可变重链氨基酸序列。互补决定区用下划线标出
QSLVESGGGLVQPGGSLRLSCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARSYYGGDKTGLGIWGQGTLVTVSS
SEQ ID NO:117
338H4人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAGGCCAGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCGCCTGATCTATCTGGCATCTACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:118
338H4人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAGGCCAGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCGCCTGATCTATCTGGCATCTACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTACACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO： 119
338H4人源化轻链全长氨基酸序列。人κ恒定结构域用下划线标出
DIQMTQSPSSLSASVGDRVTINCQASQNIYSYLSWYQQKPGKVPKRLIYLASTLASGVPSRFSGSGSGTDYTLTISSLQPEDVATYYCQSNYNGNYGFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:120
338H4人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSSLSASVGDRVTINCQASQNIYSYLSWYQQKPGKVPKRLIYLASTLASGVPSRFSGSGSGTDYTLTISSLQPEDVATYYCQSNYNGNYGFGGGTKVEIK
SEQ ID NO:121
338H4人源化重链全长核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGATCGGAATCATTTATGCTAGTGGTAGCACATACTACGCGAGCTCGGCGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAATTTATGACGGCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:122
338H4人源化重链可变重链核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGATCGGAATCATTTATGCTAGTGGTAGCACATACTACGCGAGCTCGGCGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAATTTATGACGGCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:123
338H4人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGRGLEWIGI IYASGSTYYASSAKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARIYDGMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:124
338H4人源化重链可变重链氨基酸序列。互补决定区用下划线标出
EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASSAKGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARIYDGMDLWGQGTLVTVSS
SEQ ID NO： 125
330F11人源化轻链全长核苷酸序列
GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGGGCATCCACTCTGGAATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
SEQ ID NO:126
330F11人源化轻链可变轻链核苷酸序列
GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGGGCATCCACTCTGGAATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA
SEQ ID NO:127
330F11人源化轻链全长氨基酸序列。人κ恒定结构域用下划线部分标出
DIQMTQSPSTLSASVGDRVTITCQASQSINNYLAWYQQKPGKAPKLLIYRASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSYNGVGRTAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:128
330F11人源化轻链可变轻链氨基酸序列。复杂度确定区域用下划线标出
DIQMTQSPSTLSASVGDRVTITCQASQSINNYLAWYQQKPGKAPKLLIYRASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSYNGVGRTAFGGGTKVEIK
SEQ ID NO:129
330F11人源化重链全长核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATATTCTTCTACTACTGATTGGACCTACTTTAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT
SEQ ID NO:130
330F11人源化重链可变重链核苷酸序列
GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATATTCTTCTACTACTGATTGGACCTACTTTAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC
SEQ ID NO:131
330F11人源化重链全长氨基酸序列。人γ-1恒定结构域用下划线标出
EVQLVESGGGLVQPGGSLRLSCAASGFSLNNYWMSWVRQAPGKGLEWIGTISSGAYTWFATWATGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSSTTDWTYFNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:132
330F11人源化重链可变重链氨基酸序列。互补决定区用下划线标出
EVQLVESGGGLVQPGGSLRLSCAASGFSLNNYWMSWVRQAPGKGLEWIGTISSGAYTWFATWATGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYSSTTDWTYFNIWGQGTLVTVSS
序列表
<110> 西雅图免疫公司
成都百利多特生物药业有限责任公司
<120> 抗ROR1抗体及其制备和使用方法
<130> SIBA013PCT
<140> 2018800383325
<141> 2018-06-22
<150> US62551035
<151> 2017-08-28
<150> US62551032
<151> 2017-08-28
<150> US62524554
<151> 2017-06-25
<150> US62524557
<151> 2017-06-25
<150> US62524558
<151> 2017-06-25
<150> US62545603
<151> 2017-08-15
<150> US62551032
<151> 2017-08-28
<150> US62551065
<151> 2017-08-28
<160> 132
<170> SIPOSequenceListing 1.0
<210> 1
<211> 651
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 1
gcctatgata tgacccagac tccatcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagaatttac agctacttag cctggtatca gcagaaacca 120
gggcagcctc ccaagctcct gatctacagg gcatccactc tggcatctgg ggtcccatcg 180
cggttcaaag gcagtggatc tgggacagag tacactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ctgtcaacag ggtgctagta tggttgatgt tgagaatatg 300
ttcggcggag ggaccgaggt ggtggtcaaa cgtacggtgg ctgcaccatc tgtcttcatc 360
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651
<210> 2
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 2
gcctatgata tgacccagac tccatcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagaatttac agctacttag cctggtatca gcagaaacca 120
gggcagcctc ccaagctcct gatctacagg gcatccactc tggcatctgg ggtcccatcg 180
cggttcaaag gcagtggatc tgggacagag tacactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ctgtcaacag ggtgctagta tggttgatgt tgagaatatg 300
ttcggcggag ggaccgaggt ggtggtcaaa 330
<210> 3
<211> 217
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 3
Ala Tyr Asp Met Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Arg Ile Tyr Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Gly Ala Ser Met Val Asp
85 90 95
Val Glu Asn Met Phe Gly Gly Gly Thr Glu Val Val Val Lys Arg Thr
100 105 110
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
115 120 125
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
130 135 140
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
145 150 155 160
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
180 185 190
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
195 200 205
Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 4
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 4
Ala Tyr Asp Met Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Arg Ile Tyr Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Gly Ala Ser Met Val Asp
85 90 95
Val Glu Asn Met Phe Gly Gly Gly Thr Glu Val Val Val Lys
100 105 110
<210> 5
<211> 1341
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 5
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctgaattctc cctcagtaac tactacatga gctgggtccg ccaggctcca 120
ggggaggggc tggagtggat cggagccatt aatgctgaca gtgataatac atggtacccg 180
agctgggtga aaggccgatt caccatctcc aaaacctcgt cgaccacggt ggatctgaag 240
atcaccagtc cgacaattga ggacacggcc acctatttct gtgccagaag tgtgagtaat 300
aatttcgccg aatataacat ctggggcccg ggcaccctgg tcaccgtctc gagcgctagc 360
accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 420
gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 600
tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct 660
tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aagccgcggg ggcaccgtca 720
gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 780
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 840
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 900
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 960
aagtgcgcgg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1020
aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1080
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1140
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200
tccgacggct ccttcttcct ctatagcaag ctcaccgtgg acaagagcag gtggcagcag 1260
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1320
agcctctccc tgtctccggg t 1341
<210> 6
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 6
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctgaattctc cctcagtaac tactacatga gctgggtccg ccaggctcca 120
ggggaggggc tggagtggat cggagccatt aatgctgaca gtgataatac atggtacccg 180
agctgggtga aaggccgatt caccatctcc aaaacctcgt cgaccacggt ggatctgaag 240
atcaccagtc cgacaattga ggacacggcc acctatttct gtgccagaag tgtgagtaat 300
aatttcgccg aatataacat ctggggcccg ggcaccctgg tcaccgtctc gagc 354
<210> 7
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 7
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Glu Phe Ser Leu Ser Asn Tyr Tyr
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Ala Ile Asn Ala Asp Ser Asp Asn Thr Trp Tyr Pro Ser Trp Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp Leu Lys
65 70 75 80
Ile Thr Ser Pro Thr Ile Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
85 90 95
Ser Val Ser Asn Asn Phe Ala Glu Tyr Asn Ile Trp Gly Pro Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
260 265 270
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 8
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 8
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Glu Phe Ser Leu Ser Asn Tyr Tyr
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Ala Ile Asn Ala Asp Ser Asp Asn Thr Trp Tyr Pro Ser Trp Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp Leu Lys
65 70 75 80
Ile Thr Ser Pro Thr Ile Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
85 90 95
Ser Val Ser Asn Asn Phe Ala Glu Tyr Asn Ile Trp Gly Pro Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 9
<211> 660
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 9
caagccgtgg tgacccagac tccatcgtcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcagttgcc agtccagtca gagtgtttat aacaacaacg acttagcctg gtatcagcag 120
aaaccagggc agcctcccaa gctcctgatc tactatgcat ccactctggc atctggggtc 180
tcatcgcggt tcaaaggcag tggatctggg acacagttca ctctcgccat cagcgacctg 240
gagtgtgacg attctgccac ttactactgt gcaggcggtt atgatacgga tggtcttgat 300
acgtttgctt tcggcggagg caccgaggtg gaggtcaaac gtacggtggc tgcaccatct 360
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 420
ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 480
caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 540
ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 600
gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 660
<210> 10
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 10
caagccgtgg tgacccagac tccatcgtcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcagttgcc agtccagtca gagtgtttat aacaacaacg acttagcctg gtatcagcag 120
aaaccagggc agcctcccaa gctcctgatc tactatgcat ccactctggc atctggggtc 180
tcatcgcggt tcaaaggcag tggatctggg acacagttca ctctcgccat cagcgacctg 240
gagtgtgacg attctgccac ttactactgt gcaggcggtt atgatacgga tggtcttgat 300
acgtttgctt tcggcggagg caccgaggtg gaggtcaaa 339
<210> 11
<211> 220
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 11
Gln Ala Val Val Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Ser Cys Gln Ser Ser Gln Ser Val Tyr Asn Asn
20 25 30
Asn Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu
35 40 45
Leu Ile Tyr Tyr Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Ala Ile Ser Asp Leu
65 70 75 80
Glu Cys Asp Asp Ser Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Asp Thr
85 90 95
Asp Gly Leu Asp Thr Phe Ala Phe Gly Gly Gly Thr Glu Val Glu Val
100 105 110
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
115 120 125
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
130 135 140
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
145 150 155 160
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
165 170 175
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
180 185 190
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
195 200 205
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215 220
<210> 12
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 12
Gln Ala Val Val Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Ser Cys Gln Ser Ser Gln Ser Val Tyr Asn Asn
20 25 30
Asn Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu
35 40 45
Leu Ile Tyr Tyr Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe
50 55 60
Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Ala Ile Ser Asp Leu
65 70 75 80
Glu Cys Asp Asp Ser Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Asp Thr
85 90 95
Asp Gly Leu Asp Thr Phe Ala Phe Gly Gly Gly Thr Glu Val Glu Val
100 105 110
Lys
<210> 13
<211> 1347
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 13
caggagcagc tgaaggagtc cggaggaggc ctggtaacgc ctggaggaac cctgacactc 60
acctgcacag cctctggatt caccatcagt cgctaccaca tgacttgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggtcat atttatgtta ataatgatga cacagactac 180
gcgagctggg cgaaaggccg attcaccatc tccaaaacct cgaccacggt ggatctgaag 240
atcaccagtc cgacaaccga ggacacggcc acctatttct gtgccagatt ggatgttggt 300
ggtggtggtg cttatattgg ggacatctgg ggccaaggga ccctggtcac cgtctcgagc 360
gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 660
aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc cgcgggggca 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcgcggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggt 1347
<210> 14
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 14
caggagcagc tgaaggagtc cggaggaggc ctggtaacgc ctggaggaac cctgacactc 60
acctgcacag cctctggatt caccatcagt cgctaccaca tgacttgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggtcat atttatgtta ataatgatga cacagactac 180
gcgagctggg cgaaaggccg attcaccatc tccaaaacct cgaccacggt ggatctgaag 240
atcaccagtc cgacaaccga ggacacggcc acctatttct gtgccagatt ggatgttggt 300
ggtggtggtg cttatattgg ggacatctgg ggccaaggga ccctggtcac cgtctcgagc 360
<210> 15
<211> 449
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 15
Gln Glu Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Thr Pro Gly Gly
1 5 10 15
Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Thr Ile Ser Arg Tyr
20 25 30
His Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly His Ile Tyr Val Asn Asn Asp Asp Thr Asp Tyr Ala Ser Trp Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys
65 70 75 80
Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
85 90 95
Leu Asp Val Gly Gly Gly Gly Ala Tyr Ile Gly Asp Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<210> 16
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 16
Gln Glu Gln Leu Lys Glu Ser Gly Gly Gly Leu Val Thr Pro Gly Gly
1 5 10 15
Thr Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Thr Ile Ser Arg Tyr
20 25 30
His Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly His Ile Tyr Val Asn Asn Asp Asp Thr Asp Tyr Ala Ser Trp Ala
50 55 60
Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys
65 70 75 80
Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
85 90 95
Leu Asp Val Gly Gly Gly Gly Ala Tyr Ile Gly Asp Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 17
<211> 657
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 17
gacattgtga tgacccagac tccagcctct gtggaggtcg ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gaacattggt agtgatttag cctggtatca gcagaaacca 120
gggcagcctc ccaagctcct gatctatact acatccaatc tggcatctgg ggtcccatcg 180
cggttcaaag gcagtggatc tgggacaggt ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccagttactg ctgtcaaggc ggttatttta gtggtcgtaa tatttatggg 300
aatgctttcg gcggaggcac cgaggtggtg gtcaaacgta cggtggctgc accatctgtc 360
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420
ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480
tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540
agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600
gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657
<210> 18
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 18
gacattgtga tgacccagac tccagcctct gtggaggtcg ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gaacattggt agtgatttag cctggtatca gcagaaacca 120
gggcagcctc ccaagctcct gatctatact acatccaatc tggcatctgg ggtcccatcg 180
cggttcaaag gcagtggatc tgggacaggt ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccagttactg ctgtcaaggc ggttatttta gtggtcgtaa tatttatggg 300
aatgctttcg gcggaggcac cgaggtggtg gtcaaa 336
<210> 19
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 19
Asp Ile Val Met Thr Gln Thr Pro Ala Ser Val Glu Val Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Asn Ile Gly Ser Asp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Thr Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Gly Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Ser Tyr Cys Cys Gln Gly Gly Tyr Phe Ser Gly Arg
85 90 95
Asn Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 20
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 20
Asp Ile Val Met Thr Gln Thr Pro Ala Ser Val Glu Val Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Asn Ile Gly Ser Asp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Thr Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Gly Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Ser Tyr Cys Cys Gln Gly Gly Tyr Phe Ser Gly Arg
85 90 95
Asn Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys
100 105 110
<210> 21
<211> 1323
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 21
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagtct ctggattctc cctcagtggc gctggagtga gctgggtccg ccaggctcca 120
gggaaggggc tggagtggat cggatacatt gatagtggtg ctaccacata ctacgcgagc 180
tgggcaaaag gccgattcac catctccaaa gcctcgacca cggtggatct gaaaatcgcc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gaggatacta cggcatggac 300
ccctggggcc aaggcaccct ggtcaccgtc tcgagcgcta gcaccaaggg cccatcggtc 360
ttccccctgg caccctcctc caagagcacc tctgggggca cagcggccct gggctgcctg 420
gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 480
ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 540
gtgaccgtgc cctccagcag cttgggcacc cagacctaca tctgcaacgt gaatcacaag 600
cccagcaaca ccaaggtgga caagagagtt gagcccaaat cttgtgacaa aactcacaca 660
tgcccaccgt gcccagcacc tgaagccgcg ggggcaccgt cagtcttcct cttcccccca 720
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacatgcgt ggtggtggac 780
gtgagccacg aagaccctga ggtcaagttc aactggtacg tggacggcgt ggaggtgcat 840
aatgccaaga caaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc 900
ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcgc ggtctccaac 960
aaagccctcc cagcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1020
ccacaggtgt acaccctgcc cccatcccgg gatgagctga ccaagaacca ggtcagcctg 1080
acctgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1140
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1200
ctctatagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1260
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1320
ggt 1323
<210> 22
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 22
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagtct ctggattctc cctcagtggc gctggagtga gctgggtccg ccaggctcca 120
gggaaggggc tggagtggat cggatacatt gatagtggtg ctaccacata ctacgcgagc 180
tgggcaaaag gccgattcac catctccaaa gcctcgacca cggtggatct gaaaatcgcc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gaggatacta cggcatggac 300
ccctggggcc aaggcaccct ggtcaccgtc tcgagc 336
<210> 23
<211> 441
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 23
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Gly Ala Gly
20 25 30
Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Ala Ser Thr Thr Val Asp Leu Lys Ile Ala
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr
85 90 95
Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
100 105 110
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
115 120 125
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
130 135 140
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
145 150 155 160
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
165 170 175
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
180 185 190
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
195 200 205
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
210 215 220
Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro
225 230 235 240
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
245 250 255
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
260 265 270
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
275 280 285
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
290 295 300
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn
305 310 315 320
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
325 330 335
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
340 345 350
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
355 360 365
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
370 375 380
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
385 390 395 400
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
405 410 415
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
420 425 430
Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 24
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 24
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Gly Ala Gly
20 25 30
Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Ala Ser Thr Thr Val Asp Leu Lys Ile Ala
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr
85 90 95
Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
100 105 110
<210> 25
<211> 657
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 25
gccatcgatt tgacccagac tccagcctcc gtggaggcag ctgtgggagg cacaatcacc 60
atcaattgcc aagccagtga gagcattagc agttggttag cctggtatca gcagaaacca 120
gggcagcgtc ccaagctcct gatctacgaa acatccaaac tggcatctgg ggtcccaccg 180
cggttcagcg gcagtggatc tgggacacag ttcactctca ccatcagcgg cgtgcagtgt 240
gacgatgctg ccacttacta ctgtcaaagt tattatcgta ttaataatat tggttacgat 300
aatgctttcg gcggaggcac cgaggtggag ttcaaacgta cggtggctgc accatctgtc 360
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420
ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480
tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540
agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600
gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657
<210> 26
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 26
gccatcgatt tgacccagac tccagcctcc gtggaggcag ctgtgggagg cacaatcacc 60
atcaattgcc aagccagtga gagcattagc agttggttag cctggtatca gcagaaacca 120
gggcagcgtc ccaagctcct gatctacgaa acatccaaac tggcatctgg ggtcccaccg 180
cggttcagcg gcagtggatc tgggacacag ttcactctca ccatcagcgg cgtgcagtgt 240
gacgatgctg ccacttacta ctgtcaaagt tattatcgta ttaataatat tggttacgat 300
aatgctttcg gcggaggcac cgaggtggag ttcaaa 336
<210> 27
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 27
Ala Ile Asp Leu Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Ile Thr Ile Asn Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile
35 40 45
Tyr Glu Thr Ser Lys Leu Ala Ser Gly Val Pro Pro Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Gly Val Gln Cys
65 70 75 80
Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Arg Ile Asn Asn
85 90 95
Ile Gly Tyr Asp Asn Ala Phe Gly Gly Gly Thr Glu Val Glu Phe Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 28
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 28
Ala Ile Asp Leu Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Ile Thr Ile Asn Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Arg Pro Lys Leu Leu Ile
35 40 45
Tyr Glu Thr Ser Lys Leu Ala Ser Gly Val Pro Pro Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Gly Val Gln Cys
65 70 75 80
Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Arg Ile Asn Asn
85 90 95
Ile Gly Tyr Asp Asn Ala Phe Gly Gly Gly Thr Glu Val Glu Phe Lys
100 105 110
<210> 29
<211> 1326
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 29
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtagg aatgcaatga actgggtccg ccaggctcca 120
gggaaggggc tggaatacat cggatacatt agcactagtg gtaccacatt ctacgcgaac 180
tgggtgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatgacc 240
agtctgacaa ccgaggacac ggccacctat ttctgtgcca gagactataa ctacgccatg 300
gacatctggg gccaaggcac cctggtcacc gtctcgagcg ctagcaccaa gggcccatcg 360
gtcttccccc tggcaccctc ctccaagagc acctctgggg gcacagcggc cctgggctgc 420
ctggtcaagg actacttccc cgaaccggtg acggtgtcgt ggaactcagg cgccctgacc 480
agcggcgtgc acaccttccc ggctgtccta cagtcctcag gactctactc cctcagcagc 540
gtggtgaccg tgccctccag cagcttgggc acccagacct acatctgcaa cgtgaatcac 600
aagcccagca acaccaaggt ggacaagaga gttgagccca aatcttgtga caaaactcac 660
acatgcccac cgtgcccagc acctgaagcc gcgggggcac cgtcagtctt cctcttcccc 720
ccaaaaccca aggacaccct catgatctcc cggacccctg aggtcacatg cgtggtggtg 780
gacgtgagcc acgaagaccc tgaggtcaag ttcaactggt acgtggacgg cgtggaggtg 840
cataatgcca agacaaagcc gcgggaggag cagtacaaca gcacgtaccg tgtggtcagc 900
gtcctcaccg tcctgcacca ggactggctg aatggcaagg agtacaagtg cgcggtctcc 960
aacaaagccc tcccagcccc catcgagaaa accatctcca aagccaaagg gcagccccga 1020
gaaccacagg tgtacaccct gcccccatcc cgggatgagc tgaccaagaa ccaggtcagc 1080
ctgacctgcc tggtcaaagg cttctatccc agcgacatcg ccgtggagtg ggagagcaat 1140
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200
ttcctctata gcaagctcac cgtggacaag agcaggtggc agcaggggaa cgtcttctca 1260
tgctccgtga tgcatgaggc tctgcacaac cactacacgc agaagagcct ctccctgtct 1320
ccgggt 1326
<210> 30
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 30
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtagg aatgcaatga actgggtccg ccaggctcca 120
gggaaggggc tggaatacat cggatacatt agcactagtg gtaccacatt ctacgcgaac 180
tgggtgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatgacc 240
agtctgacaa ccgaggacac ggccacctat ttctgtgcca gagactataa ctacgccatg 300
gacatctggg gccaaggcac cctggtcacc gtctcgagc 339
<210> 31
<211> 442
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 31
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Asn Ala
20 25 30
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Tyr Ile Ser Thr Ser Gly Thr Thr Phe Tyr Ala Asn Trp Val Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Met Thr
65 70 75 80
Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Tyr
85 90 95
Asn Tyr Ala Met Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
115 120 125
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
180 185 190
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
210 215 220
Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe Pro
225 230 235 240
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
245 250 255
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
260 265 270
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
275 280 285
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
290 295 300
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser
305 310 315 320
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
325 330 335
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
340 345 350
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
355 360 365
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
370 375 380
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
385 390 395 400
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
405 410 415
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
420 425 430
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 32
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 32
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Arg Asn Ala
20 25 30
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Tyr Ile Ser Thr Ser Gly Thr Thr Phe Tyr Ala Asn Trp Val Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Met Thr
65 70 75 80
Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp Tyr
85 90 95
Asn Tyr Ala Met Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser
<210> 33
<211> 648
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 33
gctcaagtgc tgacccagac tccatcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc agtccagtca gagtgttaat aacaacgact tagcctggtt tcagcagaaa 120
ccagggcagc ctcccaagcg cctgatctac tgggcatcca aactggcatc tggggtccca 180
tcgcggttca aaggcagtgg atctgggaca cagttcattc tcaccatcag cgacctggag 240
tgtgacgatg ctgccactta ctactgtgca ggcggttata gtggtaatat ttatggtttc 300
ggcggaggca ccgaggtgga ggtcaaacgt acggtggctg caccatctgt cttcatcttc 360
ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 420
ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 480
tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 540
ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 600
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgt 648
<210> 34
<211> 327
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 34
gctcaagtgc tgacccagac tccatcctcc gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc agtccagtca gagtgttaat aacaacgact tagcctggtt tcagcagaaa 120
ccagggcagc ctcccaagcg cctgatctac tgggcatcca aactggcatc tggggtccca 180
tcgcggttca aaggcagtgg atctgggaca cagttcattc tcaccatcag cgacctggag 240
tgtgacgatg ctgccactta ctactgtgca ggcggttata gtggtaatat ttatggtttc 300
ggcggaggca ccgaggtgga ggtcaaa 327
<210> 35
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 35
Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ser Ser Gln Ser Val Asn Asn Asn
20 25 30
Asp Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu
35 40 45
Ile Tyr Trp Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Lys
50 55 60
Gly Ser Gly Ser Gly Thr Gln Phe Ile Leu Thr Ile Ser Asp Leu Glu
65 70 75 80
Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Ser Gly Asn
85 90 95
Ile Tyr Gly Phe Gly Gly Gly Thr Glu Val Glu Val Lys Arg Thr Val
100 105 110
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
115 120 125
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
130 135 140
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
145 150 155 160
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
165 170 175
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
180 185 190
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
195 200 205
Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 36
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 36
Ala Gln Val Leu Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ser Ser Gln Ser Val Asn Asn Asn
20 25 30
Asp Leu Ala Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu
35 40 45
Ile Tyr Trp Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Lys
50 55 60
Gly Ser Gly Ser Gly Thr Gln Phe Ile Leu Thr Ile Ser Asp Leu Glu
65 70 75 80
Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Ser Gly Asn
85 90 95
Ile Tyr Gly Phe Gly Gly Gly Thr Glu Val Glu Val Lys
100 105
<210> 37
<211> 1317
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 37
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtaac aatgcaataa cctgggtccg ccaggctcca 120
gggaaggggc tggaatacat cggaatcatt agtagtagtg gtaccacata ctacgcgagc 180
tgggcgaaag gccgattcac catctccaaa acctcgtcga ccacggtgga tctgaaaatg 240
accagtctga caaccgagga cacggccacc tatttctgtg ccggagcatt tagcgtctgg 300
ggcccgggca ccctcgtcac cgtctcgagc gctagcacca agggcccatc ggtcttcccc 360
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 420
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 480
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgacc 540
gtgccctcca gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 600
aacaccaagg tggacaagag agttgagccc aaatcttgtg acaaaactca cacatgccca 660
ccgtgcccag cacctgaagc cgcgggggca ccgtcagtct tcctcttccc cccaaaaccc 720
aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 780
cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 840
aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 900
gtcctgcacc aggactggct gaatggcaag gagtacaagt gcgcggtctc caacaaagcc 960
ctcccagccc ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1020
gtgtacaccc tgcccccatc ccgggatgag ctgaccaaga accaggtcag cctgacctgc 1080
ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1140
gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctat 1200
agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1260
atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc tccgggt 1317
<210> 38
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 38
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtaac aatgcaataa cctgggtccg ccaggctcca 120
gggaaggggc tggaatacat cggaatcatt agtagtagtg gtaccacata ctacgcgagc 180
tgggcgaaag gccgattcac catctccaaa acctcgtcga ccacggtgga tctgaaaatg 240
accagtctga caaccgagga cacggccacc tatttctgtg ccggagcatt tagcgtctgg 300
ggcccgggca ccctcgtcac cgtctcgagc 330
<210> 39
<211> 439
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 39
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Asn Ala
20 25 30
Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Ile Ile Ser Ser Ser Gly Thr Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp Leu Lys Met
65 70 75 80
Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Gly Ala
85 90 95
Phe Ser Val Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Ala Ser
100 105 110
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr
115 120 125
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro
130 135 140
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val
145 150 155 160
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser
165 170 175
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile
180 185 190
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val
195 200 205
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala
305 310 315 320
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Pro Gly
435
<210> 40
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 40
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Asn Ala
20 25 30
Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Ile Ile Ser Ser Ser Gly Thr Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr Val Asp Leu Lys Met
65 70 75 80
Thr Ser Leu Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Gly Ala
85 90 95
Phe Ser Val Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
100 105 110
<210> 41
<211> 660
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 41
gatgttgtga tgacccagac tccagcctcc gtggaggcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagcattgat agttggttat cctggtatca acagaaacca 120
gggcagcctc ccaagctcct gatctaccag gcatccactc tggcatctgg ggtctcatcg 180
cggttcaaag gcagtggatc tgggacagag ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ctgtcaatgc gcttatggtg ttagtggtac tagtagttat 300
ttatatactt tcggcggagg caccgaggtg gaggtcaaac gtacggtggc tgcaccatct 360
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 420
ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 480
caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 540
ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 600
gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 660
<210> 42
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 42
gatgttgtga tgacccagac tccagcctcc gtggaggcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagcattgat agttggttat cctggtatca acagaaacca 120
gggcagcctc ccaagctcct gatctaccag gcatccactc tggcatctgg ggtctcatcg 180
cggttcaaag gcagtggatc tgggacagag ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ctgtcaatgc gcttatggtg ttagtggtac tagtagttat 300
ttatatactt tcggcggagg caccgaggtg gaggtcaaa 339
<210> 43
<211> 220
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 43
Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Asp Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Ala Tyr Gly Val Ser Gly
85 90 95
Thr Ser Ser Tyr Leu Tyr Thr Phe Gly Gly Gly Thr Glu Val Glu Val
100 105 110
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
115 120 125
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
130 135 140
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
145 150 155 160
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
165 170 175
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
180 185 190
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
195 200 205
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215 220
<210> 44
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 44
Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Asp Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Ser Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Ala Tyr Gly Val Ser Gly
85 90 95
Thr Ser Ser Tyr Leu Tyr Thr Phe Gly Gly Gly Thr Glu Val Glu Val
100 105 110
Lys
<210> 45
<211> 1338
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 45
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctggattctc cctcagtagg tactacatga cctgggtccg ccaggctcca 120
gggaaggggc tggagtggat tggaaccatt tatactagtg gtagtacatg gtacgcgagc 180
tggacaaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcact 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gatcctatta tggcggtgat 300
aagactggtt taggcatctg gggcccaggc accctcgtca ccgtctcgag cgctagcacc 360
aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420
gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480
ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540
tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600
aacgtgaatc acaagcccag caacaccaag gtggacaaga gagttgagcc caaatcttgt 660
gacaaaactc acacatgccc accgtgccca gcacctgaag ccgcgggggc accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780
tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960
tgcgcggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200
gacggctcct tcttcctcta tagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggt 1338
<210> 46
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 46
cagtcgctgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagcct ctggattctc cctcagtagg tactacatga cctgggtccg ccaggctcca 120
gggaaggggc tggagtggat tggaaccatt tatactagtg gtagtacatg gtacgcgagc 180
tggacaaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcact 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gatcctatta tggcggtgat 300
aagactggtt taggcatctg gggcccaggc accctcgtca ccgtctcgag c 351
<210> 47
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 47
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Tyr Tyr
20 25 30
Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Tyr Thr Ser Gly Ser Thr Trp Tyr Ala Ser Trp Thr Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ser Tyr
85 90 95
Tyr Gly Gly Asp Lys Thr Gly Leu Gly Ile Trp Gly Pro Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys
130 135 140
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
180 185 190
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
195 200 205
Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His
210 215 220
Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 48
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 48
Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Tyr Tyr
20 25 30
Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Tyr Thr Ser Gly Ser Thr Trp Tyr Ala Ser Trp Thr Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ser Tyr
85 90 95
Tyr Gly Gly Asp Lys Thr Gly Leu Gly Ile Trp Gly Pro Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 49
<211> 642
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 49
gacattgtga tgacccagac tccagcctcg gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc aggccagtca gaacatttac agctacttat cctggtatca gcagaaacca 120
gggcagcctc ccaagcgcct gatctatctg gcatctactc tggcatctgg ggtcccatcg 180
cggttcaaaa gcagtggatc tgggacagag tacactctca ccatcagcga cctggagtgt 240
gacgatgctg ccacttacta ctgtcaaagc aattataacg gtaattatgg tttcggcgga 300
gggaccgagg tggaggtcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 50
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 50
gacattgtga tgacccagac tccagcctcg gtgtctgcag ctgtgggagg cacagtcacc 60
atcaattgcc aggccagtca gaacatttac agctacttat cctggtatca gcagaaacca 120
gggcagcctc ccaagcgcct gatctatctg gcatctactc tggcatctgg ggtcccatcg 180
cggttcaaaa gcagtggatc tgggacagag tacactctca ccatcagcga cctggagtgt 240
gacgatgctg ccacttacta ctgtcaaagc aattataacg gtaattatgg tttcggcgga 300
gggaccgagg tggaggtcaa a 321
<210> 51
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 51
Asp Ile Val Met Thr Gln Thr Pro Ala Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Asn Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile
35 40 45
Tyr Leu Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Ser
50 55 60
Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Asn Tyr Asn Gly Asn Tyr
85 90 95
Gly Phe Gly Gly Gly Thr Glu Val Glu Val Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 52
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 52
Asp Ile Val Met Thr Gln Thr Pro Ala Ser Val Ser Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Asn Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile
35 40 45
Tyr Leu Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Ser
50 55 60
Ser Gly Ser Gly Thr Glu Tyr Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Asn Tyr Asn Gly Asn Tyr
85 90 95
Gly Phe Gly Gly Gly Thr Glu Val Glu Val Lys
100 105
<210> 53
<211> 1323
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 53
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtagc tatgcaatga gctgggtccg ccaggctcca 120
gggagggggc tggaatggat cggaatcatt tatgctagtg gtagcacata ctacgcgagc 180
tgggcgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcacc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gaatttatga cggcatggac 300
ctctggggcc cagggaccct cgtcaccgtc tcgagcgcta gcaccaaggg cccatcggtc 360
ttccccctgg caccctcctc caagagcacc tctgggggca cagcggccct gggctgcctg 420
gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 480
ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 540
gtgaccgtgc cctccagcag cttgggcacc cagacctaca tctgcaacgt gaatcacaag 600
cccagcaaca ccaaggtgga caagagagtt gagcccaaat cttgtgacaa aactcacaca 660
tgcccaccgt gcccagcacc tgaagccgcg ggggcaccgt cagtcttcct cttcccccca 720
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacatgcgt ggtggtggac 780
gtgagccacg aagaccctga ggtcaagttc aactggtacg tggacggcgt ggaggtgcat 840
aatgccaaga caaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc 900
ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcgc ggtctccaac 960
aaagccctcc cagcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1020
ccacaggtgt acaccctgcc cccatcccgg gatgagctga ccaagaacca ggtcagcctg 1080
acctgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1140
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1200
ctctatagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1260
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1320
ggt 1323
<210> 54
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 54
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcaccgtct ctggattctc cctcagtagc tatgcaatga gctgggtccg ccaggctcca 120
gggagggggc tggaatggat cggaatcatt tatgctagtg gtagcacata ctacgcgagc 180
tgggcgaaag gccgattcac catctccaaa acctcgacca cggtggatct gaaaatcacc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gaatttatga cggcatggac 300
ctctggggcc cagggaccct cgtcaccgtc tcgagc 336
<210> 55
<211> 441
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 55
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Ala
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Ile Gly
35 40 45
Ile Ile Tyr Ala Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ile Tyr
85 90 95
Asp Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
100 105 110
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
115 120 125
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
130 135 140
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
145 150 155 160
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
165 170 175
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
180 185 190
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
195 200 205
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
210 215 220
Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro
225 230 235 240
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
245 250 255
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
260 265 270
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
275 280 285
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
290 295 300
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn
305 310 315 320
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
325 330 335
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
340 345 350
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
355 360 365
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
370 375 380
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
385 390 395 400
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
405 410 415
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
420 425 430
Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 56
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 56
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr Ala
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Ile Gly
35 40 45
Ile Ile Tyr Ala Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Lys Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ile Tyr
85 90 95
Asp Gly Met Asp Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser
100 105 110
<210> 57
<211> 645
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 57
gatgttgtga tgacccagac tccagcctcc gtggaggcag ctgtgggagg cacagtcacc 60
atcaagtgcc aggccagtca gagcattaat aactacttag cctggtatca gcagaaacca 120
gggcagcctc ccaagctcct gatctacagg gcatccactc tggaatctgg ggtcccatcg 180
cggttcaaag gcagtggatc tgggacacag ttcactctca ccatcagcga cctggagtgt 240
gccgatgctg ccacttacta ttgtcaaagc tataatggtg ttggtaggac tgctttcggc 300
ggagggaccg aggtggagtt caaacgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 58
<211> 324
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 58
Gly Ala Thr Gly Thr Thr Gly Thr Gly Ala Thr Gly Ala Cys Cys Cys
1 5 10 15
Ala Gly Ala Cys Thr Cys Cys Ala Gly Cys Cys Thr Cys Cys Gly Thr
20 25 30
Gly Gly Ala Gly Gly Cys Ala Gly Cys Thr Gly Thr Gly Gly Gly Ala
35 40 45
Gly Gly Cys Ala Cys Ala Gly Thr Cys Ala Cys Cys Ala Thr Cys Ala
50 55 60
Ala Gly Thr Gly Cys Cys Ala Gly Gly Cys Cys Ala Gly Thr Cys Ala
65 70 75 80
Gly Ala Gly Cys Ala Thr Thr Ala Ala Thr Ala Ala Cys Thr Ala Cys
85 90 95
Thr Thr Ala Gly Cys Cys Thr Gly Gly Thr Ala Thr Cys Ala Gly Cys
100 105 110
Ala Gly Ala Ala Ala Cys Cys Ala Gly Gly Gly Cys Ala Gly Cys Cys
115 120 125
Thr Cys Cys Cys Ala Ala Gly Cys Thr Cys Cys Thr Gly Ala Thr Cys
130 135 140
Thr Ala Cys Ala Gly Gly Gly Cys Ala Thr Cys Cys Ala Cys Thr Cys
145 150 155 160
Thr Gly Gly Ala Ala Thr Cys Thr Gly Gly Gly Gly Thr Cys Cys Cys
165 170 175
Ala Thr Cys Gly Cys Gly Gly Thr Thr Cys Ala Ala Ala Gly Gly Cys
180 185 190
Ala Gly Thr Gly Gly Ala Thr Cys Thr Gly Gly Gly Ala Cys Ala Cys
195 200 205
Ala Gly Thr Thr Cys Ala Cys Thr Cys Thr Cys Ala Cys Cys Ala Thr
210 215 220
Cys Ala Gly Cys Gly Ala Cys Cys Thr Gly Gly Ala Gly Thr Gly Thr
225 230 235 240
Gly Cys Cys Gly Ala Thr Gly Cys Thr Gly Cys Cys Ala Cys Thr Thr
245 250 255
Ala Cys Thr Ala Thr Thr Gly Thr Cys Ala Ala Ala Gly Cys Thr Ala
260 265 270
Thr Ala Ala Thr Gly Gly Thr Gly Thr Thr Gly Gly Thr Ala Gly Gly
275 280 285
Ala Cys Thr Gly Cys Thr Thr Thr Cys Gly Gly Cys Gly Gly Ala Gly
290 295 300
Gly Gly Ala Cys Cys Gly Ala Gly Gly Thr Gly Gly Ala Gly Thr Thr
305 310 315 320
Cys Ala Ala Ala
<210> 59
<211> 215
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 59
Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Asn Gly Val Gly Arg
85 90 95
Thr Ala Phe Gly Gly Gly Thr Glu Val Glu Phe Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 60
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 60
Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly
1 5 10 15
Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Lys Gly
50 55 60
Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys
65 70 75 80
Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Asn Gly Val Gly Arg
85 90 95
Thr Ala Phe Gly Gly Gly Thr Glu Val Glu Phe Lys
100 105
<210> 61
<211> 1338
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 61
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagtct ctggattctc cctcaataac tactggatga gctgggtccg ccaggctcca 120
ggggaggggc tggaatggat cggaaccatt agtagtggtg cgtatacatg gttcgccacc 180
tgggcgacag gccgattcac catctccaaa acctcgacca cggtggatct gagcatcacc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gatattcttc tactactgat 300
tggacctact ttaacatctg gggcccgggc accctggtca ccgtctcgag cgctagcacc 360
aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420
gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480
ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540
tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600
aacgtgaatc acaagcccag caacaccaag gtggacaaga gagttgagcc caaatcttgt 660
gacaaaactc acacatgccc accgtgccca gcacctgaag ccgcgggggc accgtcagtc 720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780
tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960
tgcgcggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200
gacggctcct tcttcctcta tagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggt 1338
<210> 62
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 62
cagtcggtgg aggagtccgg gggtcgcctg gtcacgcctg ggacacccct gacactcacc 60
tgcacagtct ctggattctc cctcaataac tactggatga gctgggtccg ccaggctcca 120
ggggaggggc tggaatggat cggaaccatt agtagtggtg cgtatacatg gttcgccacc 180
tgggcgacag gccgattcac catctccaaa acctcgacca cggtggatct gagcatcacc 240
agtccgacaa ccgaggacac ggccacctat ttctgtgcca gatattcttc tactactgat 300
tggacctact ttaacatctg gggcccgggc accctggtca ccgtctcgag c 351
<210> 63
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 63
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Asn Tyr Trp
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Ser Ser Gly Ala Tyr Thr Trp Phe Ala Thr Trp Ala Thr Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Ser Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Ser
85 90 95
Ser Thr Thr Asp Trp Thr Tyr Phe Asn Ile Trp Gly Pro Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
115 120 125
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys
130 135 140
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
145 150 155 160
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
165 170 175
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
180 185 190
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
195 200 205
Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His
210 215 220
Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 64
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 64
Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro
1 5 10 15
Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Asn Tyr Trp
20 25 30
Met Ser Trp Val Arg Gln Ala Pro Gly Glu Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Ser Ser Gly Ala Tyr Thr Trp Phe Ala Thr Trp Ala Thr Gly
50 55 60
Arg Phe Thr Ile Ser Lys Thr Ser Thr Thr Val Asp Leu Ser Ile Thr
65 70 75 80
Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Tyr Ser
85 90 95
Ser Thr Thr Asp Trp Thr Tyr Phe Asn Ile Trp Gly Pro Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 65
<211> 651
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 65
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagaatttac agctacttag cctggtatca gcagaaacca 120
gggaaagttc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatct 180
cggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagatgttg caacttatta ctgtcaacag ggtgctagta tggttgatgt tgagaatatg 300
ttcggcggag ggaccaaggt ggagatcaaa cgtacggtgg ctgcaccatc tgtcttcatc 360
ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat 420
aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt 480
aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc 540
accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc 600
catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t 651
<210> 66
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 66
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagaatttac agctacttag cctggtatca gcagaaacca 120
gggaaagttc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatct 180
cggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagatgttg caacttatta ctgtcaacag ggtgctagta tggttgatgt tgagaatatg 300
ttcggcggag ggaccaaggt ggagatcaaa 330
<210> 67
<211> 217
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 67
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 Gln Ala Ser Gln Arg Ile Tyr Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Gly Ala Ser Met Val Asp
85 90 95
Val Glu Asn Met Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr
100 105 110
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
115 120 125
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
130 135 140
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
145 150 155 160
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
165 170 175
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
180 185 190
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
195 200 205
Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 68
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 68
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 Gln Ala Ser Gln Arg Ile Tyr Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Gly Ala Ser Met Val Asp
85 90 95
Val Glu Asn Met Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 69
<211> 1347
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 69
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt aactactaca tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggagcc attaatgctg acagtgataa tacatggtac 180
ccgagctggg tgaaaggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gagaagtgtg 300
agtaataatt tcgccgaata taacatctgg ggccagggaa ccctggtcac cgtctcgagc 360
gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 660
aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc cgcgggggca 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcgcggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggt 1347
<210> 70
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 70
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt aactactaca tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggagcc attaatgctg acagtgataa tacatggtac 180
ccgagctggg tgaaaggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gagaagtgtg 300
agtaataatt tcgccgaata taacatctgg ggccagggaa ccctggtcac cgtctcgagc 360
<210> 71
<211> 449
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 71
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asn Ala Asp Ser Asp Asn Thr Trp Tyr Pro Ser Trp 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 Ser Val Ser Asn Asn Phe Ala Glu Tyr Asn Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<210> 72
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 72
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asn Ala Asp Ser Asp Asn Thr Trp Tyr Pro Ser Trp 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 Ser Val Ser Asn Asn Phe Ala Glu Tyr Asn Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 73
<211> 660
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 73
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc agtccagtca gagtgtttat aacaacaacg acttagcctg gtatcagcag 120
aaaccaggga aagttcctaa gctcctgatc tattatgcat ccactctggc atctggggtc 180
ccatctcggt tcagtggcag tggatctggg acagatttca ctctcaccat cagcagcctg 240
cagcctgaag atgttgcaac ttattactgt gcaggcggtt atgatacgga tggtcttgat 300
acgtttgctt tcggcggagg gaccaaggtg gagatcaaac gtacggtggc tgcaccatct 360
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 420
ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 480
caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 540
ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 600
gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 660
<210> 74
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 74
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc agtccagtca gagtgtttat aacaacaacg acttagcctg gtatcagcag 120
aaaccaggga aagttcctaa gctcctgatc tattatgcat ccactctggc atctggggtc 180
ccatctcggt tcagtggcag tggatctggg acagatttca ctctcaccat cagcagcctg 240
cagcctgaag atgttgcaac ttattactgt gcaggcggtt atgatacgga tggtcttgat 300
acgtttgctt tcggcggagg gaccaaggtg gagatcaaa 339
<210> 75
<211> 220
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 75
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 Gln Ser Ser Gln Ser Val Tyr Asn Asn
20 25 30
Asn Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu
35 40 45
Leu Ile Tyr Tyr Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
65 70 75 80
Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Asp Thr
85 90 95
Asp Gly Leu Asp Thr Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
115 120 125
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
130 135 140
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
145 150 155 160
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
165 170 175
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
180 185 190
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
195 200 205
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215 220
<210> 76
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 76
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 Gln Ser Ser Gln Ser Val Tyr Asn Asn
20 25 30
Asn Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu
35 40 45
Leu Ile Tyr Tyr Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe
50 55 60
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
65 70 75 80
Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Asp Thr
85 90 95
Asp Gly Leu Asp Thr Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 77
<211> 1353
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 77
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt caccatcagt cgctaccaca tgacttgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggacat atttatgtta ataatgatga cacagactac 180
gcgagctccg cgaaaggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggccacct atttctgtgc gagattggat 300
gttggtggtg gtggtgctta tattggggac atctggggcc agggaaccct ggtcaccgtc 360
tcgagcgcta gcaccaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 420
tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 480
gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540
tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 600
cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagagagtt 660
gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaagccgcg 720
ggggcaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 780
acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 840
aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 900
tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 960
ggcaaggagt acaagtgcgc ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1020
atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg 1080
gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1140
gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1200
cccgtgctgg actccgacgg ctccttcttc ctctatagca agctcaccgt ggacaagagc 1260
aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1320
tacacgcaga agagcctctc cctgtctccg ggt 1353
<210> 78
<211> 366
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 78
gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt caccatcagt cgctaccaca tgacttgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggacat atttatgtta ataatgatga cacagactac 180
gcgagctccg cgaaaggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggccacct atttctgtgc gagattggat 300
gttggtggtg gtggtgctta tattggggac atctggggcc agggaaccct ggtcaccgtc 360
tcgagc 366
<210> 79
<211> 451
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 79
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Ser Arg Tyr
20 25 30
His Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly His Ile Tyr Val Asn Asn Asp Asp Thr Asp Tyr Ala Ser Ser Ala
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 Thr Tyr Phe Cys
85 90 95
Ala Arg Leu Asp Val Gly Gly Gly Gly Ala Tyr Ile Gly Asp Ile Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
225 230 235 240
Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly
450
<210> 80
<211> 122
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 80
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Ser Arg Tyr
20 25 30
His Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly His Ile Tyr Val Asn Asn Asp Asp Thr Asp Tyr Ala Ser Ser Ala
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 Thr Tyr Phe Cys
85 90 95
Ala Arg Leu Asp Val Gly Gly Gly Gly Ala Tyr Ile Gly Asp Ile Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 81
<211> 657
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 81
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc aggccagtca gaacattggt agtgatttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatact acatccaatc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaaggc ggttatttta gtggtcgtaa tatttatggg 300
aatgctttcg gcggagggac caaggtggag atcaaacgta cggtggctgc accatctgtc 360
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420
ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480
tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540
agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600
gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657
<210> 82
<211> 336
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 82
gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60
atcacttgtc aggccagtca gaacattggt agtgatttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatact acatccaatc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240
gaagattttg caacttacta ttgtcaaggc ggttatttta gtggtcgtaa tatttatggg 300
aatgctttcg gcggagggac caaggtggag atcaaa 336
<210> 83
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 83
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 Gln Ala Ser Gln Asn Ile Gly Ser Asp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Thr Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Gly Tyr Phe Ser Gly Arg
85 90 95
Asn Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 84
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 84
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 Gln Ala Ser Gln Asn Ile Gly Ser Asp
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Thr Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Gly Tyr Phe Ser Gly Arg
85 90 95
Asn Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 85
<211> 1332
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 85
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt ggcgctggag tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcgggtac attgatagtg gtgctaccac atactacgcg 180
agcagtgcaa aaggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aggatactac 300
ggcatggacc cctggggcca gggaaccctg gtcaccgtct cgagcgctag caccaagggc 360
ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600
aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 660
actcacacat gcccaccgtg cccagcacct gaagccgcgg gggcaccgtc agtcttcctc 720
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780
gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcgcg 960
gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctatagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320
ctgtctccgg gt 1332
<210> 86
<211> 345
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 86
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcagt ggcgctggag tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcgggtac attgatagtg gtgctaccac atactacgcg 180
agcagtgcaa aaggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aggatactac 300
ggcatggacc cctggggcca gggaaccctg gtcaccgtct cgagc 345
<210> 87
<211> 444
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 87
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Gly Ala
20 25 30
Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Ser Ala 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 Gly Tyr Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala
305 310 315 320
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 88
<211> 115
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 88
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Gly Ala
20 25 30
Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Ser Ala 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 Gly Tyr Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 89
<211> 1332
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 89
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtacag cctctggatt ctccctcagt ggcgctggag tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcgggtac attgatagtg gtgctaccac atactacgcg 180
agcagtgcaa aaggcagatt caccatctcc aaagacaatg ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aggatactac 300
ggcatggacc cctggggcca gggaaccctg gtcaccgtct cgagcgctag caccaagggc 360
ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600
aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 660
actcacacat gcccaccgtg cccagcacct gaagccgcgg gggcaccgtc agtcttcctc 720
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780
gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcgcg 960
gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctatagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320
ctgtctccgg gt 1332
<210> 90
<211> 345
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 90
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtacag cctctggatt ctccctcagt ggcgctggag tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcgggtac attgatagtg gtgctaccac atactacgcg 180
agcagtgcaa aaggcagatt caccatctcc aaagacaatg ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aggatactac 300
ggcatggacc cctggggcca gggaaccctg gtcaccgtct cgagc 345
<210> 91
<211> 444
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 91
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Gly Ala
20 25 30
Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Ser Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Ala Lys Asn Thr Val Asp Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Gly Tyr Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala
305 310 315 320
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 92
<211> 115
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 92
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Gly Ala
20 25 30
Gly Val Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asp Ser Gly Ala Thr Thr Tyr Tyr Ala Ser Ser Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Ala Lys Asn Thr Val Asp Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala
85 90 95
Arg Gly Tyr Tyr Gly Met Asp Pro Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 93
<211> 657
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 93
gccatcgatt tgacccagtc tccttccacc ctgtctgcat ctgtaggagg cacaatcacc 60
atcaattgcc aagccagtga gagcattagc agttggttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatgaa acatccaaac tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagag ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaaagt tattatcgta ttaataatat tggttacgat 300
aatgctttcg gcggagggac caaggtggag atcaaacgta cggtggctgc accatctgtc 360
ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 420
ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 480
tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 540
agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 600
gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt 657
<210> 94
<211> 259
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 94
tgagagcatt agcagttggt tagcctggta tcagcagaaa ccagggaaag cccctaagct 60
cctgatctat gaaacatcca aactggcatc tggggtccca tcaaggttca gcggcagtgg 120
atctgggaca gagttcactc tcaccatcag cagcctgcag cctgatgatt ttgcaactta 180
ttactgccaa agttattatc gtattaataa tattggttac gataatgctt tcggcggagg 240
gaccaaggtg gagatcaaa 259
<210> 95
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 95
Ala Ile Asp Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Gly Thr Ile Thr Ile Asn Cys Gln Ala Ser Glu 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 Glu Thr Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Arg Ile Asn Asn
85 90 95
Ile Gly Tyr Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 96
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 96
Ala Ile Asp Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Gly Thr Ile Thr Ile Asn Cys Gln Ala Ser Glu 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 Glu Thr Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Arg Ile Asn Asn
85 90 95
Ile Gly Tyr Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 97
<211> 1335
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 97
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtaccg cctctggatt ctccctcagt aggaatgcaa tgaactgggt ccgccaggct 120
ccagggaagg ggctggagta catcggatac attagcacta gtggtaccac attctacgcg 180
aacagcgtga aaggcagatt caccatctcc aaagacaata ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agactataac 300
tacgccatgg acatctgggg ccagggaacc ctggtcaccg tctcgagcgc tagcaccaag 360
ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 420
ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480
gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540
ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 600
gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 660
aaaactcaca catgcccacc gtgcccagca cctgaagccg cgggggcacc gtcagtcttc 720
ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 780
gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 840
gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 900
gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 960
gcggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1020
cagccccgag aaccacaggt gtacaccctg cccccatccc gggatgagct gaccaagaac 1080
caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1140
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200
ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1260
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 1320
tccctgtctc cgggt 1335
<210> 98
<211> 348
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 98
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtaccg cctctggatt ctccctcagt aggaatgcaa tgaactgggt ccgccaggct 120
ccagggaagg ggctggagta catcggatac attagcacta gtggtaccac attctacgcg 180
aacagcgtga aaggcagatt caccatctcc aaagacaata ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agactataac 300
tacgccatgg acatctgggg ccagggaacc ctggtcaccg tctcgagc 348
<210> 99
<211> 445
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 99
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Asn
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Tyr Ile Ser Thr Ser Gly Thr Thr Phe Tyr Ala Asn Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp 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 Tyr Asn Tyr Ala Met Asp Ile Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
115 120 125
Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu
130 135 140
Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
145 150 155 160
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser
165 170 175
Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
180 185 190
Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr
195 200 205
Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr
210 215 220
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
260 265 270
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val
290 295 300
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
325 330 335
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 100
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 100
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Asn
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Tyr Ile Ser Thr Ser Gly Thr Thr Phe Tyr Ala Asn Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp 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 Tyr Asn Tyr Ala Met Asp Ile Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 101
<211> 648
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 101
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc agtccagtca gagtgttaac aacaacgact tagcctggta tcagcagaaa 120
ccagggaaag cccctaagcg cctgatctat tgggcatcca aactggcatc tggggtccca 180
tcaaggttca gcggcagtgg atctgggaca gaattcactc tcacaatcag caacctgcag 240
cctgaagatt ttgcaactta ttactgtgca ggcggttata gtggtaatat ttatggtttc 300
ggcggaggga ccaaggtgga gatcaaacgt acggtggctg caccatctgt cttcatcttc 360
ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 420
ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 480
tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 540
ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 600
cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgt 648
<210> 102
<211> 327
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 102
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc agtccagtca gagtgttaac aacaacgact tagcctggta tcagcagaaa 120
ccagggaaag cccctaagcg cctgatctat tgggcatcca aactggcatc tggggtccca 180
tcaaggttca gcggcagtgg atctgggaca gaattcactc tcacaatcag caacctgcag 240
cctgaagatt ttgcaactta ttactgtgca ggcggttata gtggtaatat ttatggtttc 300
ggcggaggga ccaaggtgga gatcaaa 327
<210> 103
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 103
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 Gln Ser Ser Gln Ser Val Asn Asn Asn
20 25 30
Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu
35 40 45
Ile Tyr Trp Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Ser Gly Asn
85 90 95
Ile Tyr Gly Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val
100 105 110
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
115 120 125
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
130 135 140
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
145 150 155 160
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
165 170 175
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
180 185 190
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
195 200 205
Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 104
<211> 109
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 104
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 Gln Ser Ser Gln Ser Val Asn Asn Asn
20 25 30
Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu
35 40 45
Ile Tyr Trp Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu Gln
65 70 75 80
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Ala Gly Gly Tyr Ser Gly Asn
85 90 95
Ile Tyr Gly Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 105
<211> 1320
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 105
cagtcggtgg aggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 60
tgtaccgcct ctggattctc cctcagtaac aatgcaataa cctgggtccg ccaggctcca 120
gggaaggggc tggagtacat cggaatcatt agtagtagtg gtaccacata ctacgcgagc 180
tccgcgaaag gcagattcac catctccaaa gacacctcca agaacacggt ggatcttcaa 240
atgaacagcc tgagagccga ggacacggct gtgtattact gtgcgggagc atttagcgtc 300
tggggccagg gaaccctggt caccgtctcg agcgctagca ccaagggccc atcggtcttc 360
cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc 420
aaggactact tccccgaacc ggtgacggtg tcgtggaact caggcgccct gaccagcggc 480
gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg 540
accgtgccct ccagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc 600
agcaacacca aggtggacaa gagagttgag cccaaatctt gtgacaaaac tcacacatgc 660
ccaccgtgcc cagcacctga agccgcgggg gcaccgtcag tcttcctctt ccccccaaaa 720
cccaaggaca ccctcatgat ctcccggacc cctgaggtca catgcgtggt ggtggacgtg 780
agccacgaag accctgaggt caagttcaac tggtacgtgg acggcgtgga ggtgcataat 840
gccaagacaa agccgcggga ggagcagtac aacagcacgt accgtgtggt cagcgtcctc 900
accgtcctgc accaggactg gctgaatggc aaggagtaca agtgcgcggt ctccaacaaa 960
gccctcccag cccccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagaacca 1020
caggtgtaca ccctgccccc atcccgggat gagctgacca agaaccaggt cagcctgacc 1080
tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag 1140
ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1200
tatagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc 1260
gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt 1320
<210> 106
<211> 333
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 106
cagtcggtgg aggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 60
tgtaccgcct ctggattctc cctcagtaac aatgcaataa cctgggtccg ccaggctcca 120
gggaaggggc tggagtacat cggaatcatt agtagtagtg gtaccacata ctacgcgagc 180
tccgcgaaag gcagattcac catctccaaa gacacctcca agaacacggt ggatcttcaa 240
atgaacagcc tgagagccga ggacacggct gtgtattact gtgcgggagc atttagcgtc 300
tggggccagg gaaccctggt caccgtctcg agc 333
<210> 107
<211> 440
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 107
Gln Ser Val Glu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Asn Asn Ala
20 25 30
Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Ile Ile Ser Ser Ser Gly Thr Thr Tyr Tyr Ala Ser Ser Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Asp Thr Ser Lys Asn Thr Val Asp Leu Gln
65 70 75 80
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly
85 90 95
Ala Phe Ser Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala
100 105 110
Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser
115 120 125
Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe
130 135 140
Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly
145 150 155 160
Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu
165 170 175
Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr
180 185 190
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg
195 200 205
Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
210 215 220
Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys
225 230 235 240
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
245 250 255
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
260 265 270
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
275 280 285
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
290 295 300
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys
305 310 315 320
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
325 330 335
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
340 345 350
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
355 360 365
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
370 375 380
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
385 390 395 400
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
405 410 415
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
420 425 430
Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 108
<211> 111
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 108
Gln Ser Val Glu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Asn Asn Ala
20 25 30
Ile Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly
35 40 45
Ile Ile Ser Ser Ser Gly Thr Thr Tyr Tyr Ala Ser Ser Ala Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Asp Thr Ser Lys Asn Thr Val Asp Leu Gln
65 70 75 80
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly
85 90 95
Ala Phe Ser Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
100 105 110
<210> 109
<211> 660
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 109
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattgat agttggttat cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatcag gcatccactc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagag ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaatct gcttatggtg ttagtggtac tagtagttat 300
ttatatactt tcggcggagg gaccaaggtg gagatcaaac gtacggtggc tgcaccatct 360
gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc 420
ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc 480
caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc 540
ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc 600
gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt 660
<210> 110
<211> 339
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 110
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattgat agttggttat cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatcag gcatccactc tggcatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagag ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaatct gcttatggtg ttagtggtac tagtagttat 300
ttatatactt tcggcggagg gaccaaggtg gagatcaaa 339
<210> 111
<211> 220
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 111
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asp Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Ala Tyr Gly Val Ser Gly
85 90 95
Thr Ser Ser Tyr Leu Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
115 120 125
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
130 135 140
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
145 150 155 160
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
165 170 175
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
180 185 190
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
195 200 205
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215 220
<210> 112
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 112
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asp Ser Trp
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gln Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Ser Ala Tyr Gly Val Ser Gly
85 90 95
Thr Ser Ser Tyr Leu Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile
100 105 110
Lys
<210> 113
<211> 1344
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 113
cagtcgctgg tggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 60
tgtacagcct ctggattctc cctcagtagg tactacatga cctgggtccg ccaggctcca 120
gggaaggggc tggagtggat cggaaccatt tatactagtg gtagtacatg gtacgcgagc 180
tggacaaaag gcagattcac catctccaaa gacaatacca agaacacggt ggatcttcaa 240
atgaacagcc tgagagccga ggacacggct gtgtattact gtgcgagatc ctattatggc 300
ggtgataaga ctggtttagg catctggggc cagggaaccc tggtcaccgt ctcgagcgct 360
agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa 660
tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaagccgc gggggcaccg 720
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780
gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840
gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900
acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960
tacaagtgcg cggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020
gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200
gactccgacg gctccttctt cctctatagc aagctcaccg tggacaagag caggtggcag 1260
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320
aagagcctct ccctgtctcc gggt 1344
<210> 114
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 114
cagtcgctgg tggagtctgg gggaggcttg gtccagcctg gggggtccct gagactctcc 60
tgtacagcct ctggattctc cctcagtagg tactacatga cctgggtccg ccaggctcca 120
gggaaggggc tggagtggat cggaaccatt tatactagtg gtagtacatg gtacgcgagc 180
tggacaaaag gcagattcac catctccaaa gacaatacca agaacacggt ggatcttcaa 240
atgaacagcc tgagagccga ggacacggct gtgtattact gtgcgagatc ctattatggc 300
ggtgataaga ctggtttagg catctggggc cagggaaccc tggtcaccgt ctcgagc 357
<210> 115
<211> 448
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 115
Gln Ser Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Tyr Tyr
20 25 30
Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Tyr Thr Ser Gly Ser Thr Trp Tyr Ala Ser Trp Thr Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp Leu Gln
65 70 75 80
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
85 90 95
Ser Tyr Tyr Gly Gly Asp Lys Thr Gly Leu Gly Ile Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
<210> 116
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 116
Gln Ser Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
1 5 10 15
Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Arg Tyr Tyr
20 25 30
Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
35 40 45
Thr Ile Tyr Thr Ser Gly Ser Thr Trp Tyr Ala Ser Trp Thr Lys Gly
50 55 60
Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp Leu Gln
65 70 75 80
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
85 90 95
Ser Tyr Tyr Gly Gly Asp Lys Thr Gly Leu Gly Ile Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 117
<211> 642
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 117
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcaattgcc aggccagtca gaacatttac agctacttat cctggtatca gcagaaacca 120
gggaaagttc ctaagcgcct gatctatctg gcatctactc tggcatctgg ggtcccatct 180
cggttcagtg gcagtggatc tgggacagat tacactctca ccatcagcag cctgcagcct 240
gaagatgttg caacttatta ctgtcaaagc aattataacg gtaattatgg tttcggcgga 300
gggaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 118
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 118
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcaattgcc aggccagtca gaacatttac agctacttat cctggtatca gcagaaacca 120
gggaaagttc ctaagcgcct gatctatctg gcatctactc tggcatctgg ggtcccatct 180
cggttcagtg gcagtggatc tgggacagat tacactctca ccatcagcag cctgcagcct 240
gaagatgttg caacttatta ctgtcaaagc aattataacg gtaattatgg tttcggcgga 300
gggaccaagg tggagatcaa a 321
<210> 119
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 119
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 Asn Cys Gln Ala Ser Gln Asn Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
35 40 45
Tyr Leu Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Ser Asn Tyr Asn Gly Asn Tyr
85 90 95
Gly Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 120
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 120
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 Asn Cys Gln Ala Ser Gln Asn Ile Tyr Ser Tyr
20 25 30
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu Ile
35 40 45
Tyr Leu Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Ser Asn Tyr Asn Gly Asn Tyr
85 90 95
Gly Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 121
<211> 1332
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 121
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtacag cctctggatt ctccctcagt agctatgcaa tgagctgggt ccgccaggct 120
ccagggaggg ggctggagtg gatcggaatc atttatgcta gtggtagcac atactacgcg 180
agctcggcga aaggcagatt caccatctcc aaagacaata ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aatttatgac 300
ggcatggacc tctggggcca gggaaccctg gtcaccgtct cgagcgctag caccaagggc 360
ccatcggtct tccccctggc accctcctcc aagagcacct ctgggggcac agcggccctg 420
ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480
ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540
agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 600
aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 660
actcacacat gcccaccgtg cccagcacct gaagccgcgg gggcaccgtc agtcttcctc 720
ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780
gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840
gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 900
gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcgcg 960
gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1020
ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccag 1080
gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1140
agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200
tccttcttcc tctatagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260
ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 1320
ctgtctccgg gt 1332
<210> 122
<211> 345
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 122
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtacag cctctggatt ctccctcagt agctatgcaa tgagctgggt ccgccaggct 120
ccagggaggg ggctggagtg gatcggaatc atttatgcta gtggtagcac atactacgcg 180
agctcggcga aaggcagatt caccatctcc aaagacaata ccaagaacac ggtggatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag aatttatgac 300
ggcatggacc tctggggcca gggaaccctg gtcaccgtct cgagc 345
<210> 123
<211> 444
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 123
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ile Ile Tyr Ala Ser Gly Ser Thr Tyr Tyr Ala Ser Ser Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp 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 Ile Tyr Asp Gly Met Asp Leu Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
115 120 125
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
130 135 140
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
145 150 155 160
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
165 170 175
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
180 185 190
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
195 200 205
Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala
305 310 315 320
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440
<210> 124
<211> 115
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 124
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Ser Leu Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ile Ile Tyr Ala Ser Gly Ser Thr Tyr Tyr Ala Ser Ser Ala Lys
50 55 60
Gly Arg Phe Thr Ile Ser Lys Asp Asn Thr Lys Asn Thr Val Asp 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 Ile Tyr Asp Gly Met Asp Leu Trp Gly Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 125
<211> 645
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 125
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattaat aactacttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatagg gcatccactc tggaatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaaagc tataatggtg ttggtaggac tgctttcggc 300
ggagggacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 645
<210> 126
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 126
gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc aggccagtca gagcattaat aactacttag cctggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctatagg gcatccactc tggaatctgg ggtcccatca 180
aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240
gatgattttg caacttatta ctgccaaagc tataatggtg ttggtaggac tgctttcggc 300
ggagggacca aggtggagat caaa 324
<210> 127
<211> 215
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 127
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg 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 Ser Tyr Asn Gly Val Gly Arg
85 90 95
Thr Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
100 105 110
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
115 120 125
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
130 135 140
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
145 150 155 160
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
165 170 175
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
180 185 190
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
195 200 205
Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 128
<211> 108
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 128
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Arg 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 Ser Tyr Asn Gly Val Gly Arg
85 90 95
Thr Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105
<210> 129
<211> 1347
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 129
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcaat aactactgga tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggaacc attagtagtg gtgcgtatac atggttcgcc 180
acctgggcga caggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag atattcttct 300
actactgatt ggacctactt taacatctgg ggccagggaa ccctggtcac cgtctcgagc 360
gctagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc 660
aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaagc cgcgggggca 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcgcggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctat agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggt 1347
<210> 130
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> synthesized
<400> 130
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt ctccctcaat aactactgga tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg gatcggaacc attagtagtg gtgcgtatac atggttcgcc 180
acctgggcga caggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240
caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag atattcttct 300
actactgatt ggacctactt taacatctgg ggccagggaa ccctggtcac cgtctcgagc 360
<210> 131
<211> 449
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 131
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Asn Asn Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Ser Ser Gly Ala Tyr Thr Trp Phe Ala Thr Trp Ala Thr
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 Tyr Ser Ser Thr Thr Asp Trp Thr Tyr Phe Asn Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Ala Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<210> 132
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> synthesized
<400> 132
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Asn Asn Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Ser Ser Gly Ala Tyr Thr Trp Phe Ala Thr Trp Ala Thr
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 Tyr Ser Ser Thr Thr Asp Trp Thr Tyr Phe Asn Ile Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120

Claims (25)

1.一种对人ROR1具有结合特异性的分离的mAb或其抗原结合片段，其包含可变轻链氨基酸序列和可变重链氨基酸序列，其中所述可变轻链氨基酸序列包含如下互补决定区(CDR)序列：如QSSQSVYNNNDLA所示的CDR1氨基酸序列、YASTLAS所示的CDR2氨基酸序列和如GYDTDGLDTFA所示的CDR3氨基酸序列，所述可变重链氨基酸序列包含如下互补决定区序列：如RYHMT所示的CDR1氨基酸序列、如HIYVNNDDTDYASSAKG所示的CDR2氨基酸序列和如LDVGGGGAYIGDI所示的CDR3氨基酸序列。
2.根据权利要求1所述的分离的mAb或抗原结合片段，其包含SEQ ID NO:76所示的人源化轻链可变轻链氨基酸序列和SEQ ID NO:80所示的人源化重链可变重链氨基酸序列，或包含与SEQ ID NO:76具有同一性不小于98％的轻链可变轻链氨基酸序列和与SEQ ID NO:80具有同一性不小于98％的重链可变重链氨基酸序列。
3.根据权利要求2所述的分离的mAb或抗原结合片段，其包含SEQ ID NO:75所示的人源化轻链全长氨基酸序列和SEQ ID NO:79所示的人源化重链全长氨基酸序列，或包含与SEQID NO:75具有同一性不小于98％的轻链全长氨基酸序列和与SEQ ID NO:79具有同一性不小于98％的重链全长氨基酸序列。
4.根据权利要求1所述的分离的mAb或抗原结合片段，其对人ROR1具有Kd不大于70nM的结合亲和力。
5.根据权利要求1所述的分离的mAb或其抗原结合片段，其中所述分离的mAb是重组抗体。
6.根据权利要求5所述的分离的mAb或其抗原结合片段，其中所述重组抗体是人源化抗体或嵌合抗体。
7.根据权利要求1所述的分离的mAb或其抗原结合片段，其中所述分离的mAb是IgG。
8.根据权利要求1所述的分离的mAb或其抗原结合片段，其中所述抗原结合片段包含Fv、Fab、F(ab')2或scFV。
9.根据权利要求1所述的分离的mAb或其抗原结合片段，其中所述分离的mAb是双特异性抗体或三特异性抗体。
10.根据权利要求1所述的分离的mAb或其抗原结合片段，其中所述分离的mAb是多特异性抗体。
11.一种分离的核酸，其编码根据权利要求1-10任一项所述的分离的mAb或抗原结合片段。
12.一种包含根据权利要求11所述的分离的核酸的表达载体，其中所述载体可在细胞中表达。
13.一种包含根据权利要求11所述的核酸的宿主细胞，其中所述宿主细胞是原核细胞或真核细胞。
14.一种产生抗体的方法，包括培养根据权利要求13所述的宿主细胞以产生抗体。
15.一种药物组合物，其包含根据权利要求1-10任一项所述的分离的mAb或其抗原结合片段和药学上可接受的载体。
16.根据权利要求15所述的药物组合物，其还包含化疗剂、放射性同位素或其组合。
17.根据权利要求16所述的药物组合物，其中所述化疗剂为生长抑制剂。
18.根据权利要求17所述的药物组合物，其中所述生长抑制剂为细胞周期抑制剂。
19.根据权利要求18所述的药物组合物，其中所述细胞周期抑制剂为抗有丝分裂剂。
20.根据权利要求19所述的药物组合物，其中所述抗有丝分裂剂为卡利奇霉素类药物单元、DNA、RNA或蛋白质合成抑制剂、RAS抑制剂或其组合。
21.根据权利要求16所述的药物组合物，其中所述化疗剂为毒素。
22.根据权利要求16所述的药物组合物，其中所述化疗剂为激酶抑制剂。
23.根据权利要求22所述的药物组合物，其中所述激酶抑制剂为受体酪氨酸激酶抑制剂。
24.根据权利要求1-10任一项所述的分离的mAb或其抗原结合片段在制备治疗患有癌症的受试者的药物中的用途。
25.根据权利要求24所述的用途，其中所述药物还包括治疗剂，其中所述治疗剂包括抗体、化疗剂、酶或其组合。
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