TW201247706A - Novel vaccine adjuvants based on targeting adjuvants to antibodies directly to antigen-presenting cells - Google Patents

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201247706 六、發明說明： 【發明所屬之技術領域】 本發明大體上係關於靶向樹突狀細胞（DC)之疫苗，且更 特定言之係關於藉由直接將佐劑（例如TLR配位體/促效劑） 直接連至乾向DC之疫苗來增強疫苗功效。 序列表參考 序列表附加於且併入本文中。序列表反映如最初歸檔所 列出之序列且無新内容併入本說明書中。 【先前技術】 在不限制本發明之範疇之情況下，關於新穎佐劑、樹突 狀細胞（DC)疫苗及增強對DC疫苗之免疫反應的策略描述 其背景。 美國專利申請案第20090004194號（KecU，2007)係關於可 促進抗原特異性細胞免疫性之新穎蛋白質及DNA結合物。 使用此等多肽結合物及DNA結合物作為免疫佐劑用於治療 包括癌症、傳染性疾病、自體免疫疾病、過敏性及發炎疾 病之多種慢性疾病。Kedl之發明揭示含有TLR/CD40/促效 劑及視情況選用之抗原組合之融合蛋白質及DNA結合物。 亦教示使用此等蛋白質及DNA結合物作為免疫佐劑及疫苗 用於治療多種慢性疾病。 美國專利申請案第20080220011號（Steven，2008)提供一 種包含鞭毛蛋白佐劑及腫瘤抗原之融合蛋白質。亦提供包 含鞭毛蛋白佐劑及腫瘤抗原之組合物。該發明另外提供用 於誘導針對腫瘤抗原之免疫反應之醫藥調配物及方法以及 162948.doc 201247706 治療個體之腫瘤的方法。 美國專利申請案第20080248068號（Ljunggren等人， 2〇〇8)係有關鞭毛蛋白及其作為疫苗接種用佐劑之用途。 該發明可用於疫苗調配物以改善針對在相同位置處投與之 任何其他抗原之免疫性。抗原可以與鞭毛蛋白相同之構築 體形式投與或以在相同位置處給與之任何其他調配物形式 投與。作為替代物，鞭毛蛋白可用來刺激針對在特定位置 處所表現之抗原之免疫性。鞭毛蛋白亦可用於誘導局部發 炎以達到建立發炎模型之目的。 頒予Sotomayor及Suarez(2008)之美國專利第7 4〇4 963號 提供適用於誘發針對腫瘤抗原之免疫反應、尤其免疫反應 之佐劑、疫田及相關方法。根據S〇t〇may〇r之發明，鞭毛 蛋白能夠在其與致耐受性抗原一起投與時抑制耐受性。此 效應可能由鞭毛蛋白誘導IL-12而保持IL· 10含量較低之能 力所介導。另外，鞭毛蛋白可藉由使用表現鞭毛蛋白之細 胞以延長釋放之方式提供。表現鞭毛蛋白之細胞較佳諸如 藉由致死輻射加以處理，使得其不再能夠複製，但仍保留 表現鞭毛蛋白之能力。 【發明内容】 本發明描述用於製造以使具有抗體之佐劑直接靶向抗原 呈現細胞為基礎之新穎疫苗佐劑的組合物及方法。已發現 本發明藉由直接將佐劑（例如TLR配位體）直接連至乾向DC 之疫苗來增強疫苗功效。如本文所示，本發明之組合物及 方法可廣泛適用於所有靶向DC之疫苗且可擴展至製造具

C 162948.doc 201247706 有出乎意料之新穎性質的佐劑。 在本發明之一個實施例中揭示一種佐劑組合物。該佐劑 包含結合至Toll樣受體（TLR)促效劑之抗樹突狀細胞（DC) 特異性抗體或其片段；及醫藥學上可接受之載劑，其中結 合物及促效劑之個別含量可以使得其組合可在需要免疫刺 激之人類或動物個體令有效產生免疫反應。如本文所揭示 之DC特異性抗體或片段係選自抗DCIR、MHC I類、MHC II類、CD1、CD2、CD3、CD4、CD8、CDllb、CD14、 CD15、CD16、CD19、CD20、CD29、CD31、CD40、 CD43、CD44、CD45、CD54、CD56、CD57、CD58、 CD83、CD86、CMRF-44、CMRF-56、DCIR、DC-ASPGR、 CLEC-6、CD40、BDCA-2、MARCO、DEC-205、甘露糖 受體、蘭格素（Langerin)、DECTIN-1、B7-1、B7-2、IFN-γ 受體及 IL-2 受體、ICAM-1、Fey 受體、LOX-1 或 ASPGR。 在一相關態樣中，DC特異性抗體之核苷酸序列係選自SEQ ID NO:3至SEQ ID NO:67且DC特異性抗體之胺基酸序列係 選自 SEQ ID NO:68至 SEQ ID NO:132。 本發明之組合物另外包含選自以下之抗原肽：選自由 gag、pol及env基因、Nef蛋白質 '逆轉錄酶、HIV肽串 (Hipo5)、PSA(KLQCVDLHV)四聚體（SEQ ID NO:159)、源 自 HIVgag之 p24-PLA HIV gag p24(gag)及其他 HIV 組分組 成之群的人類免疫缺乏症病毒（human immunodeficiency virus ’ HIV)抗原及基因產物；肝炎病毒抗原（hepatitis viral antigen);選自由血球凝集素（hemagglutinin)、神經 162948.doc -6 - 201247706 胺酸酶（neuraminidase)、來自H1N1流感病毒株之流感Ajk 球凝集素HA-1、HLA-A201-FluMP(58-66)肽（GILGFVFTL) 四聚體及禽流感（Avian Flu)(HA5-l)組成之群的流感病毒抗 原（influenza viral antigen)及肽；來自熱纖梭菌（C. Mer/woce/Zw/w)之銘定結構域（dockerin domain)、麻療病毒 抗原（measles viral antigen)、風療病毒抗原（rubella viral antigen)、輪狀病毒抗原（rotaviral antigen)、細胞巨大病毒 抗原（eytomegaloviral antigen)、呼吸道融合性病毒抗原 (respiratory syncytial viral antigen)、單純癌珍病毒抗原 (herpes simplex viral antigen)、水痘帶狀范療病毒抗原 (varicella zoster viral antigen)、日本腦炎病毒抗原 (Japanese encephalitis viral antigen)、狂犬病毒抗原（rabies viral antigen)或其組合及其經修飾物。在一個態樣中，該 組合物另外包含選自癌症肽之抗原肽，該等癌症肽係選自 包含來自以下各者之抗原的腫瘤相關抗原：白血病及淋巴 瘤、諸如星形細胞瘤或神經膠母細胞瘤之神經性腫瘤、黑 色素瘤、乳癌、肺癌、頭頸部癌症、胃腸腫瘤、胃癌、結 腸癌、肝癌、胰臟癌、諸如子宮頸癌、子宮癌、卵巢癌、 陰道癌、睪丸癌、前列腺癌或陰莖癌之泌尿生殖腫瘤、骨 腫瘤、血管瘤、或唇、鼻咽、咽及口腔、食道、直腸、膽 囊、膽道（biliary tree)、喉、肺及支氣管、膀胱、腎、腦 部及神經系統其他部分之癌症、甲狀腺癌、霍奇金氏病 (Hodgkin's disease)、非霍奇金氏淋巴瘤（non-Hodgkin's lymphoma)、多發性骨趙瘤及白血病。在另一態樣中，組

C 162948.doc 201247706 合物另外包含選自腫瘤相關抗原之抗原肽，該等腫瘤相關 抗原係選自CEA、前列腺特異性抗原（PSA)、HER-2/neu、 BAGE、GAGE、MAGE 1-4、MAGE 6 及 MAGE 12、 MUC(黏蛋白）（例如MUC-1、MUC-2等）' GM2及GD2神經 節苷脂、ras、myc、酷·胺酸酶、MART(黑色素瘤抗原）、 MARCO-MART、細胞週期素B1、細胞週期素D、Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移酶 V内含子V序列）' 前列腺癌psm、前列腺血清抗原（PSA)、 PRAME(黑色素瘤抗原）、β-索烴素、MUM-1-B(黑色素瘤 遍佈突變基因產物（melanoma ubiquitous mutated gene product))、GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗 原）2-10、c-ERB2(Her2/neu)、EBNA(愛潑斯坦-巴爾病毒 (Epstein-Barr Virus)核抗原）1-6、gp75、人類乳頭狀瘤病 毒（human papilloma virus)(HPV)E6及 E7、ρ53、肺封藥蛋 白質（LRP)、Bcl-2及Ki-67。在另一態樣中，DC特異性抗 體經人類化。在另一態樣中，組合物係藉由經口途徑、經 鼻途徑、局部或以注射形式投與人類或動物個體，其中注 射係選自由皮下、靜脈内、腹膜内、肌肉内及靜脈内組成 之群。 本發明之另一實施例係關於一種疫苗組合物’其包含： 抗原；及佐劑，其中佐劑包含結合至Toll樣受體（TLR)促效 劑之抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學上 可接受之載劑，其中結合物及促效劑之個別含量可以使得 其組合可在需要免疫刺激之人類或動物個體中有效產生免 162948.doc 201247706 疫反應。在一個態樣中，DC特異性抗體或片段係選自抗 DCIR、MHC I類、MHC II類、CD1、CD2、CD3、CD4、 CD8 ' CDllb、CD14 ' CD15、CD16、CD19、CD20、 CD29、CD31、CD40、CD43、CD44、CD45、CD54、 CD56、CD57、CD58、CD83、CD86、CMRF-44、CMRF-56、 DCIR、DC-ASPGR、CLEC-6 、CD40 、BDCA-2 、 MARCO、DEC-205、甘露糖受體、蘭格素、DECTIN-1、 B7-1、B7-2、IFN-γ 受體及 IL-2 受體、ICAM-1、Fey 受體、 LOX-1或ASPGR。在另一態樣中，組合物另外包含選自以 下之抗原狀：選自由gag ' pol及env基因、Nef蛋白質、逆 轉錄酶、HIV 肽串（Hipo5)、PSA(KLQCVDLHV)四聚體 (SEQ ID NO:159)、源自 HIVgag 之 p24-PLA HIV gag p24 (gag)及其他HIV組分組成之群的人類免疫缺乏症病毒 (HIV)抗原及基因產物；肝炎病毒抗原；選自由血球凝集 素、神經胺酸酶、來自H1N1流感病毒株之流感A血球凝集 素 HA-1、HLA-A2(H-FluMP(58-66)肽（GILGFVFTL)四聚體 (SEQ ID NO:160)及禽流感（Avian Flu)(HA5-l)組成之群的 流感病毒抗原及肽；來自熱纖梭菌之錨定結構域、麻疹病 毒抗原、風療病毒抗原、輪狀病毒抗原、細胞巨大病毒抗 原、呼吸道融合性病毒抗原、單純疱疹病毒抗原、水痘帶 狀疱疹病毒抗原、日本腦炎病毒抗原、狂犬病毒抗原或其 組合及其經修飾物。在另一態樣中’組合物另外包含選自 癌症肽之抗原肽，該等癌症肽係選自包含來自以下各者之 抗原的腫瘤相關抗原：白血病及淋巴瘤、諸如星形細胞瘤 162948.doc -9- 201247706 或神經膠母細胞瘤之神經性腫瘤、黑色素瘤、乳癌、肺 癌、頭頸部癌症、胃腸腫瘤、胃癌、結腸癌、肝癌、胰臟 癌、諸如子宮頸癌、子宮癌、卵巢癌、陰道癌、睪丸癌、 前列腺癌或陰莖癌之泌尿生殖腫瘤'骨腫瘤、血管瘤、或 唇、鼻咽、咽及口腔、食道、直腸'膽囊、膽道、喉、肺 及支氣管、膀胱、腎、腦部及神經系統其他部分之癌症、 甲狀腺癌、霍奇金氏病、非霍奇金氏淋巴瘤、多發性骨髓 瘤及白血病。在另一態樣中，組合物另外包含選自腫瘤相 關抗原之抗原肽，該等腫瘤相關抗原係選自CEA、前列腺 特異 *1"生抗原（PSA)、HER-2/neu、BAGE、GAGE、MAGE Ια 、 MAGE 6 及 MAGE 12 ' MUC( 黏蛋白 ）（ 例如 MUC-1 、 MUC-2等）、GM2及GD2神經節苷脂、ras、myc、酪胺酸 酶、MART(黑色素瘤抗原）、MARCO-MART、細胞週期素 B1、細胞週期素D、Pmel 17(gpl〇〇)、GnT-V内含子V序列 (N-乙醯基葡糖胺基轉移酶v内含子v序列）、前列腺癌 Psm、前列腺血清抗原（PSA)、PRame(黑色素瘤抗原）、β_ 索烴素、MUM· 1-Β(黑色素瘤遍佈突變基因產物）、 GAGE(黑色素瘤抗原）i ' BAGE(黑色素瘤抗原）2-1〇、 c-ERB2(Her2/neU)、EBNA(愛潑斯坦·巴爾病毒核抗原） 1-6、gP75、人類乳頭狀瘤病毒（HPV)E6及E7、P53、肺耐 藥蛋白質（LRP)、Bcl-2及 Ki-67。 在其他相關態樣中’ DC特異性抗體經人類化且組合物 係藉由經口途徑、經鼻途徑、局部或以注射形式投與人類 或動物個體’其中注射係選自由皮下、靜脈内、腹膜内、 162948.doc 201247706 肌肉内及靜脈内組成之群。 在另一實施例中，本發明提供一種提高由抗原呈現細胞 呈現抗原之有效性的方法，其包含使抗原呈現細胞與組合 物接觸之步驟，該組合物包含抗原及佐劑，其中佐劑包含 結合至Toll樣受體（TLR)促效劑之抗樹突狀細胞（DC)特異 性抗體或其片段；及醫藥學上可接受之載劑，其中結合物 及促效劑之個別含量可以使得其組合可在需要免疫刺激之 人類或動物個體中有效產生免疫反應。在該方法之一個態 樣中，DC特異性抗體或片段係選自抗DCIR、MHC I類、 MHC II類、CD1、CD2、CD3、CD4、CD8、CDllb、 CD14、CD15、CD16、CD19、CD20、CD29、CD31、 CD40、CD43、CD44、CD45、CD54、CD56、CD57、 CD58、CD83、CD86、CMRF-44、CMRF-56、DCIR、 DC-ASPGR、CLEC-6 ' CD40、BDCA-2、MARCO、 DEC-205、甘露糖受體、蘭格素、DECTIN-1、B7-1、 B7-2、IFN-γ受體及 IL-2受體、ICAM-1、Fey受體、LOX-1 或ASPGR 〇

在另一態樣中，組合物另外包含選自以下之抗原肽：選 自由gag、ρ〇1及env基因、Nef蛋白質、逆轉錄酶、HIV肽 串（Hipo5)、PSA(KLQCVDLHV)四聚體（SEQ ID NO:159)、 源自 HIVgag之P24-PLA HIV gag p24(gag)及其他 HIV組分組 成之群的人類免疫缺乏症病毒（HIV)抗原及基因產物；肝 炎病毒抗原；選自由血球凝集素、神經胺酸酶、來自H1N1 流感病毒株之流感A血球凝集素HA-1、HLA-A201-FluMP 162948.doc 201247706 (58-66)肽（GILGFVFTL)四聚體（SEQ ID NO:160)及禽流感 (Avian Flu)(HA5-l)組成之群的流感病毒抗原及肽；來自熱 纖梭菌之錯定結構域、麻療病毒抗原、風瘆病毒抗原、輪 狀病毒抗原、細胞巨大病毒抗原、呼吸道融合性病毒抗 原、單純疱療病毒抗原、水痘帶狀癌療病毒抗原、日本腦 炎病毒抗原、狂犬病毒抗原或其組合及其經修飾物。在另 一態樣中，組合物另外包含選自癌症肽之抗原肽’該等癌 症肽係選自包含來自以下各者之抗原的腫瘤相關抗原：白 血病及淋巴瘤、諸如星形細胞瘤或神經膠母細胞瘤之神經 性腫瘤、黑色素瘤、乳癌、肺癌、頭頸部癌症、胃腸腫 瘤、胃癌、結腸癌、肝癌、胰臟癌、諸如子宮頸癌、子宮 癌、卵巢癌 '陰道癌' 睪丸癌、前列腺癌或陰莖癌之泌尿 生殖腫瘤、骨腫瘤、血管瘤、或唇、鼻咽、咽及口腔、食 道、直腸、膽囊、膽道、喉、肺及支氣管、膀胱、腎、腦 部及神經系統其他部分之癌症、甲狀腺癌、霍奇金氏病、 非霍奇金氏淋巴瘤、多發性骨髓瘤及白血病。在另一態樣 中，組合物另外包含選自腫瘤相關抗原之抗原肽，該等腫 瘤相關抗原係選自CEA、前列腺特異性抗原（PSA)、HER-2/neu、BAGE ' GAGE ' MAGE 1-4、MAGE 6 及 MAGE 12、MUC(黏蛋白）（例如 MUC-1、MUC-2 等）、GM2 及 GD2 神經節苦脂、ras、myc、酷胺酸酶、MART(黑色素瘤抗 原）、MARCO-MART '細胞週期素B1 '細胞週期素D、 Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯基葡糖胺基 轉移酶V内含子V序列）、前列腺癌psm、前列腺血清抗原 162948.doc -12- 201247706 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素、MUM-l-Β (黑 色素瘤遍佈突變基因產物）、GAGE(黑色素瘤抗原）1、 BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(愛 潑斯坦-巴爾病毒核抗原）1-6、gp75、人類乳頭狀瘤病毒 (HPV)E6及 E7、p53、肺耐藥蛋白質（LRP)、Bcl-2及 Ki-67。 在該方法之一特定態樣中，DC特異性抗體經人類化且組 合物係藉由經口途徑、經鼻途徑、局部或以注射形式投與 人類或動物個體。在上所述方法中所用之注射類型係選自 由以下組成之群：皮下' 靜脈内、腹膜内、肌肉内及靜脈 内。 本發明之一個實施例揭示一種治療、預防或既治療又預 防人類個體之一或多種癌症的方法，其包含以下步驟：⑴ 鑑別需要治療、預防或既治療又預防之人類個體；及（Π) 投與包含抗原及佐劑之疫苗組合物，其中佐劑包含結合至 Toll樣受體（TLR)促效劑之抗樹突狀細胞（DC)特異性抗體 或其片段；及醫藥學上可接受之載劑，其中結合物及促效 劑之個別含量可以使得其組合可在需要免疫刺激之人類或 動物個體中有效產生免疫反應。 在上文所揭示之治療方法之一個態樣中，DC特異性抗 體或片段係選自抗DCIR、MHC I類、MHC II類、CD1、 CD2、CD3、CD4、CD8、CDllb、CD14、CD15、CD16、 CD19、CD20、CD29、CD31、CD40、CD43、CD44、 CD45、CD54、CD56、CD57、CD58、CD83、CD86、 CMRF-44、CMRF-56、DCIR、DC-ASPGR、CLEC-6、 s 162948.doc 13 201247706 CD40、BDCA-2、MARCO、DEC-205、甘露糖受體、蘭格 素、DECTIN-1、B7-1、B7-2、IFN-γ 受體及 IL-2 受體、 ICAM-1、Fey受體、LOX-1或ASPGR。在另一態樣中，組 合物另外包含選自以下之抗原肽··選自由gag、pol及env基 因、Nef蛋白質、逆轉錄酶、HIV肽串（Hipo5)、 PSA(KLQCVDLHV)四聚體（SEQ ID NO:159)、源自 HIVgag 之p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人 類免疫缺乏症病毒（HIV)抗原及基因產物；肝炎病毒抗 原；選自由血球凝集素、神經胺酸酶、來自H1N1流感病 毒株之流感A血球凝集素HA-1、HLA-A201-FluMP(58-66) 肽（GILGFVFTL)四聚體（SEQ ID NO.160)及禽流感（Avian Flu)(HA5-l)組成之群的流感病毒抗原及肽；來自熱纖梭菌 之錫定結構域、麻療病毒抗原、風療病毒抗原、輪狀病毒 抗原、細胞巨大病毒抗原、呼吸道融合性病毒抗原、單純 疱疹病毒抗原、水痘帶狀疱疹病毒抗原、日本腦炎病毒抗 原、狂犬病毒抗原或其組合及其經修飾物。在另一態樣 中，組合物另外包含選自癌症肽之抗原肽，該等癌症肽係 選自包含來自以下各者之抗原的腫瘤相關抗原：白血病及 淋巴瘤、諸如星形細胞瘤或神經膠母細胞瘤之神經性腫 瘤、黑色素瘤、乳癌、肺癌、頭頸部癌症、胃腸腫瘤、胃 癌、結腸癌 '肝癌、胰臟癌、諸如子宮頸癌、子宮癌、卵 巢癌、陰道癌、睪丸癌、前列腺癌或陰莖癌之泌尿生殖腫 瘤、骨腫瘤、血管瘤、或辱、鼻咽、咽及口腔、食道、直 腸、膽囊、膽道、喉、肺及支氣管、膀胱、腎、腦部及 162948.doc -14- 201247706 神經系統其他部分之癌症、甲狀腺癌 '霍奇金氏病、非霍 奇金氏淋巴瘤、多發性骨髓瘤及白血病。在另一態樣中， 組合物另外包含選自腫瘤相關抗原之抗原肽，該等腫瘤相關 抗原係選自CEA、前列腺特異性抗原（pSA)、HER 2/neu、 BAGE、GAGE、MAGE W、MAGE 6 及 MAGE 12、 MUC(黏蛋白）（例如MUC_1、㈣⑺等）、GM2&GD2神經 節苷脂、ras、myc、酪胺酸酶、MART(黑色素瘤抗原）、 MARCO-MART、細胞週期素B1、細胞週期素D、pmd 17(gpl〇〇)、GnT-V内含子V序列（N—乙醯基葡糖胺基轉移酶 V内含子V序列）、前列腺癌psm、前列腺血清抗原（PSA)、 PRAME(黑色素瘤抗原）' β-索烴素' MUM-1-B(黑色素瘤 遍佈突變基因產物）、GAGE(黑色素瘤抗原）l、BAGE(黑色 素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(愛潑斯坦-巴爾 病毒核抗原）丨_6、gp75、人類乳頭狀瘤病毒（HPV)E6及 E7、P53、肺耐藥蛋白質（LRP)、bc1-2及Ki-67。 在治療方法之相關態樣中，DC特異性抗體經人類化且 組合物係藉由經口途徑、經鼻途徑、局部或以注射（皮 下、靜脈内、腹膜内、肌肉内或靜脈内）形式投與人類或 動物個體 在另一實施例中，本發明描述一種藉由活化一或多個樹 突狀細胞（DC)來向人類個體提供免疫刺激以預防、治療或 既預防又治療一或多種病毒、細菌、真菌、寄生蟲、原蟲 及寄生蟲疾病及過敏性病症的方法，該方法包含以下步 驟：（i)鑑別需要免疫刺激以預防、治療或既預防又治療選 162948.doc -15- 201247706 自自流感、HIV、癌症及免疫病症中選定之群的一或多種 疾病的人類個體；自人類個體分離一或多個DC ; (ii)用可 有效形成活化的DC之量的組合物來活化分離的DC，該組 合物包含：（a)抗原及（b)佐劑，其中佐劑包含結合至Toll樣 受體（TLR)促效劑之抗樹突狀細胞（DC)特異性抗體或其片 段；及醫藥學上可接受之載劑，其中結合物及促效劑之個 別含量可以使得其組合可在需要'免疫刺激之人類或動物個 體中有效產生免疫反應；及（iii)將活化的DC再引入人類個 體體内。 在上文所揭示之方法之一個態樣中，DC特異性抗體或 片段係選自抗DCIR、MHC I類、MHC II類、CD1、CD2、 CD3、CD4、CD8、CDllb、CD14、CD15、CD16、 CD19、CD20、CD29、CD31、CD40、CD43、CD44、 CD45、CD54、CD56、CD57、CD58、CD83、CD86、 CMRF-44、CMRF-56、DCIR、DC-ASPGR、CLEC-6、 CD40、BDCA-2、MARCO、DEC-205、甘露糖受體、蘭格 素、DECTIN-1、B7-1、B7-2、IFN-γ 受體及 IL-2 受體、 ICAM-1、Fey受體、LOX-1或ASPGR。在另一態樣中，組 合物另外包含選自以下之抗原肽：選自由gag、pol及env基 因、Nef蛋白質、逆轉錄酶、HIV肽串（Hipo5)、PSA (KLQCVDLHV)四聚體（SEQ ID NO:159)、源自 HIVgag之 p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人類 免疫缺乏症病毒（HIV)抗原及基因產物；肝炎病毒抗原； 選自由血球凝集素、神經胺酸酶、來自H1N1流感病毒株 162948.doc • 16 - 201247706 之流感A血球凝集素HA-l、HLA-A201-FluMP(58-66)肽 (GILGFVFTL)四聚體（SEQ ID NO: 160)及禽流感（Avian Flu)(HA5-l)組成之群的流感病毒抗原及肽；來自熱纖梭菌 之錯定結構域、麻療病毒抗原、風療病毒抗原、輪狀病毒 抗原、細胞巨大病毒抗原、呼吸道融合性病毒抗原 '單純 疮療病毒抗原、水殖帶狀癌療病毒抗原、日本腦炎病毒抗 原、狂犬病毒抗原或其組合及其經修飾物。在另一態樣 中，組合物另外包含選自癌症肽之抗原肽，該等癌症肽係 選自包含來自以下各者之抗原的腫瘤相關抗原：白血病及 淋巴瘤、諸如星形細胞瘤或神經膠母細胞瘤之神經性腫 瘤、黑色素瘤、乳癌 '肺癌、頭頸部癌症、胃腸腫瘤、胃 癌、結腸癌、肝癌、胰臟癌、諸如子宮頸癌、子宮癌、卵 巢癌、陰道癌、睪丸癌、前列腺癌或陰莖癌之泌尿生殖腫 瘤、骨腫瘤、血管瘤、或唇、鼻咽、咽及口腔、食道、直 腸、膽囊、膽道、喉、肺及支氣管、膀胱、腎、腦部及神 經系統其他部分之癌症、甲狀腺癌、霍奇金氏病 '非霍奇 金氏淋巴瘤、多發性骨髓瘤及白也病。在另一態樣中，組 合物另外包含選自腫瘤相關抗原之抗原肽，該等腫瘤相關抗 原係選自CEA、前列腺特異性抗原（PSA)、HER-2/neu、 BAGE、GAGE、MAGE 1-4、MAGE 6 及 MAGE 12、 MUC(黏蛋白）（例如MUC-1、MUC-2等）、GM2及GD2神經 節苦脂、ras、myc、酷·胺酸酶、MART(黑色素瘤抗原）、 MARCO-MART、細胞週期素B1、細胞週期素D、Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移酶 162948.doc -17- 201247706 V内含子V序列）、前列腺癌psm、前列腺血清抗原（psA)、 PRAME(黑色素瘤抗原）、β_索烴素、MUM-1-B(黑色素瘤 遍佈突變基因產物）、GAGE(黑色素瘤抗原）1、BAGE(黑色 素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(愛潑斯坦-巴爾 病毒核抗原）1-6、gp75、人類乳頭狀瘤病毒（HPV)E6及 E7、p53、肺耐藥蛋白質（LRP)、Bcl-2及 Ki-67。 在方法之一個態樣中’ DC特異性抗體經人類化。在另 一態樣中，組合物係藉由經口途徑、經鼻途徑、局部或以 注射形式投與人類或動物個體。在另一態樣中，注射係選 自由以下組成之群：皮下、靜脈内' 腹膜内、肌肉内及靜 脈内。 【實施方式】 為了更全面地理解本發明之特徵及優勢，現提及本發明 之貫施方式以及隨附圖式。 雖然下文詳細論述本發明之各種實施例之製備及使用， 但應瞭解’本發明提供許多可在多種特定情況中具體化之 適用的發明構想。本文論述之特定實施例僅說明形成及使 用本發明之特定方式，且並不限定本發明之範疇。 為了有助於理解本發明，下文定義許多術語。本文定義 之術語具有一般熟習與本發明相關之領域的技術者通常所 理解的含義。諸如「一（a/an)」及「該」之術語無意僅指 單個實體，而是包括可能利用一特定實例來說明之一般種 類使用本文之術語描述本發明之特定實施例，但除了如 申請專利範圍中所概述外，其用法並不限定本發明。 162948.doc 201247706 如本文所用，術語「抗原呈現細胞」（APC)為能夠活化Τ 細胞且包括（但不限於）某些巨噬細胞、Β細胞及樹突狀細 胞之細胞。「樹突狀細胞」（DC)係指出現於淋巴或非淋巴 組織中之各種形態學上類似之細胞類型群體中的任何成 員。此等細胞特徵在於其獨特的形態、其表面高度表現II 類 MHC(Steinman等人，Ann. Rev. Immunol. 9:271(1991); 其對該等細胞之描述以引用之方式併入本文中）。如本文 所述’此等細胞可自大量組織來源中分離，且適宜自周邊 血液中分離。樹突狀細胞結合蛋白係指其受體表現在樹突 狀細胞上之任何蛋白質。實例包括GM-CSF、IL-1、TNF、 IL-4、CD40L、CTLA4、CD28及 FLT-3 配位體。 出於本發明之目的，術語r疫苗組合物」意謂可投與人 類或動物以便誘導免疫系統反應之組合物；此免疫系統反 應可引起抗體之產生或僅僅引起某些細胞（特定言之為抗 原呈現細胞、T淋巴細胞及B淋巴細胞）的活化。疫苗組合 物可為用於預防目的或用於治療目的或兩種用途皆有之組 合物。如本文所用，術語「抗原」係指可用於疫苗中之任 何k原’無論其是否與整個微生物有關抑或與亞單元有 關’且無論其為以下何種性質：肽、蛋白質、醣蛋白、多 醣、醣脂、脂肽等。其可為病毒抗原、細菌抗原或其類似 物；術語「抗原」亦包含聚核苷酸，其序列經過選擇以便 其所編碼之抗原在稱為DNA免疫法之免疫技術下，讓接受 投與該聚核苷酸之個體產生所需之表現。其也可為一組抗 原，特定言之在包含能夠防止數種疾病之抗原的多價疫苗 162948.doc •19· 201247706 組合物情況下，且其因而通常稱為疫苗組合，或在包含數 種不同抗原以便防止單一疾病的組合物情況下，例如某些 抗百日咳或流感的疫苗例子。術語Γ抗體」係指免疫球蛋 白，無論是天然或部分或完全人工產生（例如重組）^抗體 可為單株或多株。在一些情況下抗體可為一種或組合免疫 球蛋白類別（包括：IgG、IgM、IgA、IgD及IgE)之成員之 — ο 術語「佐劑」係指增強、增加或強化宿主對疫苗抗原之 免疫反應的物質。 術語「基因」用於指功能蛋白、多肽或肽之編碼單元。 如同此項技術者所將瞭解’此功能術語包括基因組序列、 cDNA序列、或其片段或組合，以及基因產物，包括彼等 可藉助於人類而改變者。經純化之基因、核酸、蛋白質及 其類似物用於指自通常與其締合之至少一種含雜質核酸或 蛋白質中鑑別且分離之該等實體。 如本文所用，術語「核酸」或「核酸分子」係指聚核苦 酸（諸如去氧核糖核酸（DNA)或核糖核酸（RNA))、寡核普 酸、由聚合酶鏈反應（PCR)產生之片段及由接合、剪切、 核酸内切酶作用及核酸外切酶作用中之任一者產生的片 段°核酸分子可由天然存在之核苷酸（諸如DNA及RNA)或 天然存在之核苷酸之類似物（例如天然存在之核苷酸之α_ 對映異構形式）或兩者之組合的單體組成。經修飾之核苷 酸可在糖部分中及/或在嘧咬或嘌呤驗基中出現變化β糖 修飾法包括（例如）以鹵素、烷基、胺及疊氮基置換一或多 162948.doc -20- 201247706 個羥基，或糠可經官能化為醚或酯《此外，整個糖部分可 經空間上及電價上類似之結構置換，諸如氮雜糖及碳環糖 類似物。鹼基部分之修飾法實例包括烷基化嘌呤及嘧啶、 酿化嘌呤或嘧啶、或其他熟知之雜環取代法。核酸單體可 由碟酸一s旨鍵或該等鍵之類似物鍵聯。鱗酸二醋鍵之類似 物包括硫代磷酸酯、二硫代磷酸酯、硒代磷酸酯、二硒代 填酸醋、苯胺硫代磷酸酯、苯胺基磷酸酯、胺基磷酸酯及 其類似物。術語「核酸分子」亦包括所謂「肽核酸」，其 包含連接於聚醯胺主鏈之天然存在或經修飾之核酸鹼基。 核酸可為單股或雙股。 如本申請案中所用，術語「胺基酸」意謂蛋白質所包含 之天然存在之胺基羧酸中之一者。如本文所述，術語「多 狀」係指無論是天然抑或合成產生之經肽鍵接合之胺基酸 殘基的聚合物。少於約10個胺基酸殘基之多肽通常稱為 狀」。蛋白質」為包含一或多個多肽鏈之大分子。蛋白 質亦可包含非肽組分，諸如碳水化合物基團。碳水化合物 及其他非肽取代基可藉由產生蛋白質之細胞而添加至蛋白 貝中’且將視細胞類型而變化。蛋白質在本文中係根據其 胺基酸主鏈結構來定義；通常不指定諸如碳水化合物基團 之取代基，但其仍可存在。 如本文所用，術語「活體内」係指在身體内部。如本申 °月案中所用之術語「活體外」應理解為指示在無生命系統 中進行之操作。 如本文所用，術語「治療（treatment/ treating)」意謂本 c 162948.doc -21 - 201247706 發明化合物之任何投與且包括（1)抑制經歷或呈現患病者之 病狀或症狀之動物的疾病（亦即，阻止該病狀及/或症狀進 一步發展），或（2)改善經歷或呈現患病者之病狀或症狀之 動物的疾病（亦即，逆轉該病狀及/或症狀）。 本發明描述以使具有抗體之佐劑直接靶向抗原呈現細胞 為基礎之新穎疫苗佐劑。已發現本發明藉由直接將佐劑 (例如TLR配位體或促效劑）、更特定言之為TLR7配位體 (TLR7L)直接連至靶向DC之疫苗來增強疫苗功效。如本文 所示，本發明之組合物及方法可廣泛適用於所有靶向DC 之疫苗且可擴展至製造具有出乎意料之新穎性質的佐劑。 本發明為一種佐劑以及製造及使用其之方法，其中佐劑結 合於靶向DC之疫苗（例如與抗原融合之抗DC受體抗體）。 本發明之數種態樣比先前技術有優勢，包括節省劑量（藉 由直接向實際上接收抗原之抗原呈現細胞傳送佐劑），出 乎意料地，此發現提供一種使佐劑之促效劑活性嚴格取決 於所靶向之DC受體類型的方法。 製備細胞：在收集知情同意書後對健康個體進行採集程 序(apheresis procedure)。此方案由 Baylor Research Institute Institutional Review Board審核及批准。PBMC係 自採集血液樣本中純化而得且在極冷保藏後使用。自在 Cellgenix 中與 GM-CSF(100 ng/ml)及 IFNa(500 U/ml) (Salluto等人，J. Exp. Med)—起培養3天之冷束人類單核細 胞（淘析份 5，Lemarie 等人，J· Immunological Methods， 2007)製備源自單核細胞之IFNa-DC。 162948.doc -22- 201247706 細胞外細胞激素分泌分析。將PBMC或源自單核細胞之 IFNa-DC(2xl06個細胞/毫升’ 200微升/孔）在37。(：及5% C02下在含有10%人類AB血清、2 mM L-麩醯胺酸、50 U 月磁素' 5 0 pg/ml鍵徽素、lx必需胺基酸、25 mM hepes、 55 μΜ 2-巯基-乙醇之crpMI中與所關注的靶向之疫苗 及TLR配位體一起培養或保持不受刺激（陰性對照）24小 時。隨後’收集培養物上清液，且隨後使用Bi〇plex2〇〇 Luminex(Bi〇Rad)在培養物上清液中量測所分泌之細胞因 子0 本發明描述以使具有抗體之佐劑直接靶向抗原呈現細胞 為基礎之新穎疫苗佐劑。已發現本發明藉由直接將佐劑、 更特定言之為Toll樣受體（TLR)配位體直接連至靶向DC之 疫苗來增強疫苗功效。如本文所示，本發明之組合物及方 法可廣泛適用於所有把向DC之疫苗且可擴展至製造具有 出乎意料之新穎性質的佐劑。雖然佐劑與佐劑直接連接因 例如與CPG連接之Hep B疫苗（Dynavax)或與鞭毛蛋白連接 之流感抗原（Vaxigen)的研製而眾所周知，但本發明係關於 佐劑以及製造及使用其之方法，其中佐劑結合於靶向〇〇 之疫苗（例如與抗原融合之抗DC受體抗體）。 本發明之數種態樣比先前技術有優勢，包括節省劑量 (藉由直接向實際上接收抗原之抗原呈現細胞傳送佐二 出乎意料地，此發現提供-種使佐劑之促效劑活性嚴格取 決於所靶向之DC受體類型的方法。 其包含：（i)抗原、 本發明另外揭示一種疫苗組合物 162948.doc -23 201247706 (ii)包含與TLR促效劑结合之抗樹突狀細胞（DC)特異性抗體 或其片段的佐劑及（iii)醫藥學上可接受之載劑，其中結合 物及促效劑之個別含量可以使得其組合可在需要免疫刺激 之人類或動物個體中有效產生免疫反應。 本發明者描述一種與TLR7配位體或基於鞭毛蛋白之佐 劑連接及經由錨定結構域與黏連蛋白（cohesin)抗原連接的 DC靶向劑。必須注意任何所需抗原亦可經直接融合以替 代錨定結構區域。此等構築體之一些非限制性實例呈現於 以下本文中： C566大腸桿菌（E.coli)-pET28載體，其編碼[黏連蛋白-varl-FluMl-6xHis](SEQ ID ΝΟ:1)之表現

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OAYOKRMGVOMORFKLEHHHHHH 粗體為展示加下劃線之單個c至A變化的黏連蛋白區 域，該變化維持允許TLRL加合物之位點特異性順丁烯二 醯亞胺鍵的錨定結構結合及3 £殘基（加下劃線的粗體）。加 下劃線者為流感Ml抗原序列。呈粗斜體形式之AS序列為 來自表現載體之構築之接合序列。 在相關形式中，任何具有游離cys殘基之黏連蛋白-抗原 均可適宜以TLR7-L化合物修飾且與任何抗DC受體-錨定結 162948.doc • 24· 201247706 構-抗原疫苗連接。 C1450 編碼小鼠抗-DCIR—9E8_H-LV-hIgG4H-C-Flex-vl-vlC2(SEQ ID NO:2)：

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PSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRΨQEGmFSCS^mlmAL·ΉmYτQK.SLShSlJGKASQTPTNTISVTPΊmSTPmNSN

PKPNPASQQTPTNTISVTPTNNSTPTNNSNPKPgPAS 粗體為攜有位點特異性連接TLRL加合物之兩個2殘基 (加下劃線）的可撓性連接子序列《在與適當L鏈表現載體 一起共轉染至哺乳動物細胞（例如CHO-S細胞）中時，此載 體引導與基於化學物之佐劑連接的DC靶向劑之典型實施 例的有效分泌。在相關實施例中，其他載體可用任何直接 融合至C末端密碼子之所需抗原製備。呈粗斜體形式之AS 序列為來自表現載體之構築之接合序列。斜體者為可撓性 連接子（見上文）。 具有不同DC特異性抗體或片段之構築體之一些其他非 限制性實例（核苷酸及蛋白質序列）呈現於下文中： ^L_CLEC_6_9B9.2G12_Hv-V-hIgG4H-C(SEQ ID NO:3)：

ATGGGCAGGCTTACTTCTTCATTCTTGCTACTGATTGTCCCTC5CATATGTCCTGTCCC

AGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTC

TGACCTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGAGTGTAGGCTGGAT

TCGTCAGCCTTCAGGGAAGGGTCTGGAGTGGCTGGCTCACATTTGGTGGAATGATGA •25- 162948，doc 201247706

TAAGTACTATAATCCAGTCCTGAAAAGCCGGCTCACAATCTCCAAGGAGACCTCCA

ACAACCAGGTATTCCTCAAGATCGCCAGTGTGGTCTCTGCAGATACTGCCACATACT

ACTGTGCTCGATTCTATGGTAACTGTCTTGACTACTGGGGCCAAGGCACCACTCTCA

CAGTCTCCTCGGCCAAAACAaagggcccATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGA

GCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA

CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC

GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC

CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA

CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCA

GCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC

ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAG

GAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGC

CAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCC

TCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCC

AACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC

AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT

GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC

TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAG

GAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACA

CAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGATTAATTAA 抗_(：1^(：_6_989.2012_1^-¥-1118〇411-€(3£(5 ID NO:68):

MGRLTSSFLLLIVPAYVLSQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMSVGWIRQPS

GKGLEWLAHIWWNDDKYYNPVLKSRUnSKETSNNQVFLKIASWSADTATYYCARFY

GNCLDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN

SGALTSGVmTPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK

YGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDG

VEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKBSKAK

GQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗_(：1^(：_6_989.2012_1^-¥-111吕01〇(：(8£(5 ID NO:4):

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGmTCAAGGTACCAGAT

GTGATATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAG

TCACCATCAGTTGCAGGGCAAGTCAGGACATTAGCAATTAITTAAACTGGTATCAGC

AGAAACCAGATGGAACTGTTAAACTCCTGATCTACTACACATCAATATTACAATTAG

GAGTCCCATCAAGATTCAGTGGCAGTGGGTCTGAAACAGATTATTCTCTCACCATTA -26- 162948.doc 201247706

GCAACCTGGAGCAAGAAQATATTGCCACTTACTTTTGCCAACAGGGTGATTCGCTTC

CATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTGGCTGCACCA

TCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG

TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGAT

AACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGA

CAC3CACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAAC

ACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG

AGCTTCAACAGGGGAGAGTGTTAG ^_CLEC_6_9B9.2G12_Kv-V-hIgGK-C(SEQ ID NO:69)：

MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVnSCRASQDISNYLNWYQQK

PDGTVKLLIYYTSILQLGVPSRFSGSGSETDYSLTISNLEQEDIATYFCQQGDSLPFTFGSG

TKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQ

ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-ASGPR_49Cll_7H-LV-hIgG4H-C(SEQ ID NO:5):

ATGAGAGCGCTGATTCTTTTGTGCCTGTTCACAGCCTTTCCTGGTATCCTGTCTGATG

TGCAGCTTCAGGAGTCAGGACCTGACCTGGTGAAACCrrCTCAGTCACnTCACTCA

CCTGCACTGTCACTGGCTACTCCATCACCAGTGGTTATAGCTGGCACTGGATCCGGC

AGTTTCCAGGAAACAAACTGGAATGGATGGGCTACATACTCTTCAGTGGTAGCACTA

ACTACAACCCATCTCTGAAAAGTCGAATCTCTATCACTCGAGACACATCCAAGAACC

AGTTCTTCCTGCAGTTGAATTCTGTGACTACTGAGGACACAGCCACATATITCTGTGC

AAGATCTAACTATGGTTCCTTTGCTTCCTGGGGCCAAGGGACTCTGGTCACTGTCTCT

GCAGCCAAAACAACGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACC

TCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT

GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAG

CTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGG

TGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTG

AGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCA

TGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC

CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGAC

AAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG tcctgcaccaggactggctgaacggcaaggagtacaagtgcaaggtctccaacaaa

GGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA

GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCA

GCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG c 162948.doc -27- 201247706

AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA

CGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGG

GGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGA

AGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGAITAATTAA 抗-ASGPR_49Cll_7H-LV-hIgG4H-C(SEQ ID NO:70):

MRALILLCLFTAFPGILSDVQLQESGPDLVKPSQSLSLTCTVTGYSITSGYSWHWIRQFPG

NKLEWMGYILFSGSTNYNPSLKSRISITRDTSKNQFFLQLNSVTTEDTATYFCARSNYGS

FASWGQGTLVTVSAAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA

LTSGVHirPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP

CPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEV

HNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEICnSKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-ASGPR_49C11—7K-LV-hIgGK-C(SEQ ID NO:6):

ATGGATTTTCAAGTGCAGAITTTCAGCTTCCTGCTAATCAGTGCCTCAGTCATAATAT

CCAGAGGACAAATTGTTCTCACCCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGG

AGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTCACATGCACTGGTAC

CAGCAGAAGTCAGGCACTTCCCCCAAAAGATGGATTTATGACACATCCAGACTGGC ttctggagtccctgctcgcttcagtggcagtgggtctgggacctcttactctctcaca

ATCAGCAGCATGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAGTGGAGTAG

TCACCCATGGTCGTTCGGTGGAGGCACCAAACTCGAGATCAAACGAACTGTGGCTG

CACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTC tgttgtgtgcctgctgaataacttctatcccagagaggccaaagtacagtggaaggt

GGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCA

AGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAG

AAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCAC

AAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-ASGPR_49Cll_7K-LV-hIgGK-C(SEQ ID NO:71):

MDFQVQIFSFLLISASVIISRGQIVLTQSPAIMSASPGEKVTMTCSASSSVSHMHWYQQKS

GTSPKRWIYDTSRLASGVPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSHPWSFG

GGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGN

SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-ASGPR_4G2.2_Hv-V-hIgG4H-C(SEQ ID NO:7): 162948.doc -28 - 201247706

ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCA

CAGATCCAGTTGGTGCAGTCTGGACCTGAGCTGAAGAAGCCTGGAGAGACAGTCAA

GATCTCCTGCAAGGCTTCTGGGTATACCTTCACAAACTATGGAATGAACTGGGTGAA

GCAGGTTCCAGGAAAAGGTTTAAGGTGGATGGGCTGGATGGACACCTTCACTGGAG

AGCCAACATATGCTGATGACTTCAAGGGACGGTTTGCCTTCTCTTTGGAAACCTCTG

CCAGCACTGCCTATTTGCAGATCAACAGCCTCAAAAATGAGGACACGGCTACTTATT

TCTGTGCAAGAGGGGGGA1TTTACGACTCAACTACTTTGACTACTGGGGCCAAGGCA

CCACTCTCACAGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGC

CCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGAC

TACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT

GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT

GACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACA

AGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATCiC

CCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCA

AAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG

GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTG

TGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAG

TGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCC

AAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGAT

GACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACA

TCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT

CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAG

AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC

AACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGATTAATT

AA 抗-ASGPR_4G2.2_Hv-V-hIgG4H-C(SEQ ID NO:72):

MAWVWTLLFLMAAAQSAQAQIQLVQSGPELKKPGETVKISCKASGYTFTNYGMNWVK

QVPGKGLRWMGWMDIFTGEPTYADDFKGRFAFSLETSASTAYLQINSLKNEDTATYFC

ARGGILRLNYFDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKYD

KRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSI

EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY ΚΤΤΡΡνίΧ^ϋΟΒΡΗϋΥΒΚυΓνΟΚεΐΙίρΕσΝλ^^ΟΒνΜΗΕΑυίΝΗΥΤρΚΒΙ^Ι^Ι^ΚΑε 抗-ASGPR_4G2.2_Kv-V-hIgGK-C(SEQ ID NO:8): 162948.doc -29- c 201247706

：TTCTCC CACCAT

ATGAAGTTTCCTTCTCAACTTCTGCTCTTACTGCTGTTTGGAATCCCAGGCATGATAT GTGACATCCAGATGACACAATCTTCATCCTCCTTTTCTGTATCTCTAGGAGACAGAG TCACCATTACTTGCAAGGCAAGTGAGGACATATATAATCGGTTAGGCTGGTATCAGC AGAAACCAGGAAATGCTCCTAGGCTCTTAATATCTGGTGCAACCAGTTTGGAAACTG GGGTTCCITCAAGATTCAGTGCjCAGTGGATCTGGAAAGGATTACGCTCTCAGCATTA CCAGTCTTCAGACTGAAGATCTTGCTACTTATTACTGTCAACAGTGTTGGACT GTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGa CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGT GTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATA acgccctccaatcgggtaactcccaggagagtgtcacagagcaggacagcaaggac

AGCACCTACAGCCTCAGCACjCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACA

CAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTQAGCTCGCCCGTCACAAAGA

GCTTCAACAGGGGAGAGTGTTAG 抗-ASGPR_4G2.2_Kv-V-hIgGK-C(SEQ ID NO:73):

MKFPSQLLLLLLFGIPGMICDIQMTQSSSSFSVSLGDRVTITCKASEDIYNRLGWYQQKPG

NAPRLLISGATSLETGVPSRFSGSGSGKDYALSITSLQTEDLATYYCQQCWTSPYTFGGG

TiCLEIKRTVAAPSVFlFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQ

ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSBiRGEC 抗-ASGPR_5F10H_LV-hIgG4H-C(SEQ ID NO:9):

ATGGGATGGAGCTGGATCTTTCTCnTCTCTTGTCAGGAACTGGAGGTGTCCTCTCTG

AGGTCCAGCTGCAACAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAG

ATGTCCTGCAAGGCTTCTGGATACACCTTCACTGACTACTACATGAAGTGGGTGAAG

CAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAGATATTAATCCTAACTATGGTGA

TACTTTCTACAACCAGAAGTTCGAGGGCAAGGCCACATTGACTGTAGACAAATCCTC

CAGGACAGCCTACATGCAGCTCAACAGCCTGACATCTGAGGACTCTGCAGTCTATTA

TTGTGGAAGAGGGGACTATGGATACTTCGATGTCTGGGGCGCAGGGACCACGGTCA

CCGTCTCCTCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCA

GGAGCACCTCCGAGAGCACAC3CCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT

CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGIOACCGTGCC

CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA

ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGC

CCAGCACCTGAGITCGAAGGCGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAG

GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC 162948.doc -30- 201247706

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAA

TGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACACX：ACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC

TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCA

GCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGA

ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGG

AGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG

GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG

CAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC

ACACAGAAGAGCCTCTCCJCTGTCTCTGGGTAAAGCTAGCTGA 抗-ASGPR_5F10H-LV-hIgG4H-C(SEQ ID NO:74):

MGWSWIFLFLLSGTGGVLSEVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMKWVK

QSHGKSLEWIGDINPNYGDTFYNQKFEGKATLTVDKSSRTAYMQLNSLTSEDSAVYYC

GRGDYGYFDVWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT

VSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKR

VESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNW

YVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKT

ISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLLSLGKAS 抗-ASGPR_5F10K-LV-hIgGK-C(SEQ ID NO:10):

ATGGAGACACATTCTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGTTGAAG

GAGACATTGTGATGACCCAGTCTCACAAATTCATGTCCACATCAGTAGGAGACAGG

GTCAGCATCACCTGCAAGGCCAGTCAGGATGTGGGTACTGCTGTAGCCTGGTATCAA

CAGAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGGCATCCACCCGGCACACT

GGAGTCCCTGATCGCTTCACAGGCAGTGGATCIXJGGACAGATTTCACTCTCACCATT

AACAATGTGCAGTCTGAAGACTTGGCAGATTATrTCTGTCAGCAATATAGCAGCAAT

CCGTACATGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCACC

ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGA

TAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGG

ACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA

CACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA

GAGCTTCAACAGGGGAGAGTGTTAG 抗-ASGPR_5F10K-LV-hIgGK-C(SEQ ID NO:75): 162948.doc -31 - 201247706

METHSQVFVYMLLWLSGVEGDIVMTQSHKFMSTSVGDRVSITCKASQDVGTAVAWYQ

QKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLTINNVQSEDLADYFCQQYSSNPY

MFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCXLNNFYP3REAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEiCHKVYACEVTHQGLSSPVTKSFNRGEC 抗-ASGPRlHll_H-V-hIgG4H-C(SEQ ID NO:ll):

ATGGGATGGAGCTGGATCTTTCTCTTTCTCCTGTCAGGAACTGCAGGTGTCCTCTCTG

AGGTCCAGCTGCAACAGTCTGGACCTGAGTTGGTGAAGCCTGGGGCTTCAGTGAAG

ATATCCTGCAAGACTTCTGGATACACATTCACTGAATACACCATGCACTGGGTGAGG

CAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAGGTATTAATCCTATCAATGGTGG

TCCTACCTACAACCAGAAGTTCAAGCXjCAAGGCCACATTGACTGTTGACAAGTCCTC

CAGCACAGCCTACATGGAGCTCCGCAGCCTGACATCTGAGGACTCTGCAGTCTATTA

CTGTGCAAGATGGGACTATGGTAGTCGAGATGTTATGGACTACTGGGGTCAAGGAA

CCTCAGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGC

CCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGAC

TACTTCCCCGAACCGGTACCGOTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC

GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC

GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGA

TCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCC

CATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCC

CCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGG

TGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC

GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTA

CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGT

ACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCC

AAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGA

GGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTCM3TCAAAGGCTTCTACCCCA

GCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCTGGAGAACAACTACAAGAC

CACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGT

GGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGG

CTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCT

GA 抗-ASGPRlHll_H-V-hIgG4H-C(SEQ ID NO:76):

MGWSWIFLFLLSGTAGVLSEVQLQQSGPELVKPGASVKISCKTSGYTFTEYTMHWVRS

HGKSLEWIGGINPINGGPTYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARW

DYGSRDVMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVD -32- 162948.doc 201247706

KRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSI

EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY kttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkas 抗-ASGPRlHllK-LV-var2-hIgGK-C(SEQ ID NO:12):

ATGGAATCACAGACTCTGGTCTTCATATCCATACTGCTCTGGTTATATGGTGCTGATG

GGAACATTGTAATGACTCAATCTCCCAAATCCATGTCCATGTCAGTAGGGGAGAGG

GTCACCTTGAGCTGCAAGC3CCAGTGAGAATGTGGGAACTTATGTATCCrGGTATCAA

CAGAGACCAGAACAGTCTCCAAAACTC3CTGATATACGGGGCATCCAACCGGTACAC

TGGGGTCCCCGATCGCTTCACAGGCAGTGGATCTGCAACAGATTTCACTCTGACCAT

CAGCAGTGTGCAGGCTGAGGACCTTGCAGATTATCACTGTGGACAGACTTACAGCTA

TATATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTGGCTGCACC

ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGA

TAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGG

ACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA

CACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA

GAGCTTCAACAGGGGAGAGTGTTAG 抗-ASGPRlHllK-LV-var2-hIgGK-C(SEQ ID NO:77):

METHSQVFVYMLLWLSGVEGNIVMTQSPKSMSMSVGERVTLSCKASENVGTYVSWYQ

QRPEQSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQTYSYEFTF

GSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-CDld—2B5.3G10_H-V-hIgG4H-C(SEQ ID NO:13):

ATGGGATGGAGCCGGATCTTTCTCTTCCTCCTGTCAATAACTGCAGGTGTCCATTGCC

AGGTCCAGGTGCAGCAGTCGGGACCTGAGTTGGTGAAGCCTGGGGCCTCAGTGAAG

ATTTCCTGCAAAGCCTCTGGCGACGCATTCAGTAGTTCTTGGATGAACTGGGTGAAG

CAGAGGCCTGGACAGGGTCTTGAGTGGATTGGACGGATTTATCTTGOAGATGGAGA

TATTAATTACAATGGGAAGTTCAAGGGCAGGGCCACACTGACTGCAGACAAATCCT

CCAGCACAGCCTACATGCAGCTCAGCAGCCTGACCTCTGTGGACTCTGCGGTCTATT

TCTGCGCGAGGCAGCTCGGGCTATGGTATGTTATGGACTACTGGGGTCAAGGAACCT

CAGTCACCGTCTCCTCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCT

GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTAC

TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA 162948.doc -33- ε 201247706

CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC

CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC

CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA

CCCTGCCCAGCACCTGAGITCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA

CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC

GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGQAGCAGTTCAACAGCACGTACCGTGTGG

TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC

AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAA

AGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGA

CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC

GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC

CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGA

GCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA

ACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGOTAAAGCTAGCTGA 抗-CDld_2B5.3G10_H-V-hIgG4H-C(SEQ ID NO:78):

MGWSREFLFLLSITAGVHCQVQVQQSGPELVKPGASVKISCKASGDAFSSSWMNWVKQ rpgqglewigriylgdgdinyngkfkgratltadkssstaymqlssltsvdsavyfcar

QLGLWYVMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALC3CLVKDYFPEPV

WSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDK

RVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFN

WYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE

mSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-CDld_2B5.3G10_K-V-hIgGK-C(SEQ ID NO:14):

ATGAGTGTGCCCACTCAGGTCCTGGGGTTGCTGCTGCTGTGGCTTACAGGTGCCAGA

TGTGACATCCAGATGGCTCAGTCTCCAGCCTCCCTATCTGCATCTGTGGGAGAAACT

GTCACCATCACATC5TCGAGCAAGTGAGAATATTTACAGTTATTTAGCATGGTATCAG

CAGAAACAGGGAAAATCTCCTCAGCTCCTGGTCTATAA.TGCAAAAACCTTAGCAGA

AGGTGTGCCATCAAGGTTCAGTGGCAGTGGATCAGGCACACAGTTTTCTCTGAA.GAT

CAACAGCCTGCAGCCTGAAGATTTTGGGAGTTATTACTGTCAACATCATTATGGTTT

TCCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCAC

CATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT

TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGG 34- 162948.doc 201247706

ATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG

GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA

ACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAA

AGAGCTTCAACAGGGGAGAGTGTTAG 抗-CDld_2B5.3G10_K-V-hIgGK-C(SEQ ID NO:79):

MSVPTQVLGLLLLWLTGARCDIQMAQSPASLSASVGETVTITCRASENIYSYLAWYQQK

QGKSPQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGFPWTF

GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCXL>JNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-CDld_2H11.2G5_H-V-hIgG4H-C(SEQ ID NO:15):

ATGAACTTCGGGCTCAGCTTGATTTTCCTTGTCCTCATTTTAAAAGGTGTCCAGTGTG

AGGTGCAGCTGGTGGAGTCTGGGGGAGACTTAGTGAAGCCTGGAGGGTCCCTGAAA

CTCTCCTGTGCAGCCTCTGGATTCACnTCAGTAGCTATGGCATGTCTTGGGTTCGCC

AGACTCCAGACAAGAGGCTGGAGTGGGTCGCAGTCATTAGTAGTGGTGGAAGTTCC

ACCTTCTATCCAGACAGTGTGAAGGGGCGATTCACCATCTCCAGAGACAATGCCAA

GAACACCCTGTACCTGCAAATGAGCAGTCTGAAGTCTGAGGACACAGCCGTGTATT

ACTGTTCAAGAGGAGGTTACTACTTTGACTACTGGGGCCAAGGCACCACTCTCACAG

TCTCCGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGA

GCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA

CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC

GGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTC

CAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACA

CCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCA

GCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC

ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAG

GAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGC

CAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCC

TCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCC

AACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACC

AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT

GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC

TCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAC5GTGGCAG

GAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACA

CAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA s 162948.doc -35- 201247706 抗-CDld_2H11.2G5_H-V-hIgG4H-C(SEQ ID NO:80):

MNFGLSLIFLVLILKGVQCEVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQT

PDKRLEWVAVISSGGSSTFYPDSVKGRFnSRDNAKNTLYLQMSSLKSEDTAVYYCSRG

GYYFDYWGQGTTLTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWN

SGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK

YGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDG

VEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK gqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvld

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-CDld_2H11.2G5一K-V-hIgGK-C(SEQ ID NO:16):

ATGAGGTTCCAGGTTCAGGTTCTGGGGCTCCITCTGCTCTGGATATCAGGTGCCCAG

TGTGATGTCCAGATAACCCAGTCTCCATCTTATCTTGCTGCATCTCCTGGAGAAACC

ATTACTATTAATTGCAGGGCAAGCAAGACCATTAGCAAATAriTAGCCTGGTATCAA

GAGAAACCTGAGAAAACTGATAAGCTTCTTATCTACTCTGGATCCACTTTGCAATCT

GGAATTCCATCAAGGTTCAGTGGCAGTGGATCTGGTACAGATTTCACTCTCACCATC

AGTGGCCTGGAGCCTGAAGATTTTGCAATGTATTACTGTCAACAGCATAATGAATAC

CCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACC

ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGITGAAATCTGGAACTGCCTCTGTT

GTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGA

TAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGG

ACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAA

CACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAA

GAGCTTCAACAGGGGAGAGTGTTAG 抗-CDld_2H11.2G5_K-V-hIgGK-C(SEQ ID NO:81):

MRFQVQVLGLLLLWISGAQCDVQITQSPSYLAASPGETrnNCRASKJISKYLAWYQEKP

EKTDKLLIYSGSTLQSGIPSRFSGSGSGTDFTLTISGLEPEDFAMYYCQQHNEYPWTFGG

GTKLEKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNS

QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-CD40_llB6.1C3_H-LV-hIgG4H-C(SEQ ID NO:17):

ATGGGATGGAGCTGGATCTTrCTCTTTCTCCTGTCAGGAACTGCAGGTGTCCTCTCTG

AGGTCCAGCTGCAACAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAG

ATATCCTGCAAGGCITCTGGTTACTCATTCACTGGCTACTACATGCACTGGGTGAAG

CAAAGCCATGTAAAGAGCCTTGAGTGGATrGGACGTATTAATCCTTACAATGGTGCT 162948.doc -36- 201247706

ACTAGCTACAACCAGAATTTCAAGGACAAGGCCAGCTTGACTGTAGATAAGTCCrCC

AGCACAGCCTACATGGAGCTCCACAGCCTGACATCTGAGGACTCTGCAGTCTATTAC

TGTGCAAGAGAGGACTACGTCTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA

GCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCC

GAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC

GGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT

ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTT

GGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG

ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGT

TCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGA

TCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCC

GAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAA

GCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC

TGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC

CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCC

ACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC

TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC

AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG

CTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGA

ATGTCTTCTCATGCTGCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGA

GCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-CD40_llB6.1C3_H-LV-hIgG4H-C(SEQ ID NO:82):

MGWSWIFLFLLSGTAGVLSEVQLQQSGPELVKPGASVKISCKASGYSFTGYYMHWVKQ

SHVKSLEWIGRINPYNGATSYNQNFKDKASLTVDKSSSTAYMELHSLTSEDSAVYYCAR

EDYVYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKY

GPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFKWYVDGV

EVHNAKTKPREEQFNSTYRWSYLTVLHQDWLNGKEYKCKVSNKGLPSSIEmSKAKG

QPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-CD40_llB6.1C3_K-LV-hIgGK-C(SEQ ID NO:18):

ATGAAGTTGCCTGTTAGGCTGTTGGTGCTGATGTTCTGGATTCCTGCTTCCAGCAGTG

ATGTTGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCT

CCATCTCTTGCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTAC

ATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGnTCCA 162948.doc -37- 201247706

ACCGATTTTCTGCXjGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCG

CACTCAAGATCAGTAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAA

GTACACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACT

GTGGCTGCACCATCTGTCTTCATCTTCCCC3CCATCTGATGAGCAGTTGAAATCTGGA

ACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCA

GGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAG

ACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCG

CCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-CD40_llB6.1C3_K-LV-hIgGK-C(SEQ ID NO:83):

MKLPVRLLVLMFWIPASSSDWMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHW

YLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFALKISRVEAEDLGVYFCSQSTHVP

WTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVraQGLSSPVTKSFNRGE

C 抗-CD40_12B4.2C10_H-LV-hIgG4H-C(SEQ ID NO:19):

ATGGAATGGAGTTGGATATTTCTCTTTCTTCTGTCAGGAACTGCAGGTGTCCACTCTG

AGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGTAAAGCCTGGGGCTTCAGTGAAG

ATGTCCTGCAAGGCTTCTGGATACACATTCACTGACTATGTTTTGCACTGGGTGAAA

CAGAAGCCTGGGCAGGGCCTTGAGTGGATTGGATATATTAATCCTTACAATGATGGT

ACTAAGTACAATGAGAAGTTCAAAGGCAAGGCCACACTGACTTCAGACAAATCCTC

CAGCACAGCCTACATGGAGCTCAGCAGCCTGACCTCTGAGGACTCTGCGGTCTATTA

CTGTGCAAGGGGCTATCCGGCCTACTCTGGGTATGCTATGGACTACTGC5GGTCAAGG

AACCTCAGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGC

GCCCTGCTCCAGGAGCACCTCCGAGAGCACACJCCGCCCTGGGCTGCCTGGTCAAGG

ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC

GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG

GTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCAT

GCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG

GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGT

GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA 162948.doc • 38 - 201247706

AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTG

A 抗-CD40_12B4.2C10_H-LV-hIgG4H-C(SEQ ID NO:84):

MEWSWIFLFLLSGTAGVHSEVQLQQSGPELVKPGASVKMSCKASGYTFTDYVLHWVK

QKPGQGLEWIGYINPYNDGTKYNEKFKGKATLTSDKSSSTAYMELSSLTSEDSAVYYCA

RGYPAYSGYAMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTK

VDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEV

QFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPS

SE^SKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-CD40_12B4.2C10_K-LV-v2-hIgGK-C(SEQ ID NO:20):

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGTnTCAAGGTACCAGAT

GTGATATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAG

TCACCATCAGTTGCAGGGCAAGTCAGGACATTAGCAATTATTTAAACTGGTATCAGC

AGAAACCAGATGGAACTGTTAAACTCCTGATCTACTACACATCAAGATTACACTCAG

GAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTA

GCAACCTGGAGCAAGAAGATATTGCCACTTACriTTGCCATCATGGTAATACGCTTC

CGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCA

TCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG

TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGAT

AACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGA

CAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAAC

ACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG

AGCTTCAACAGGGGAGAGTGTTAG 抗-CD40_12B4.2C10_K-LV_v2-hIgGK-C(SEQ ID NO:85):

MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVISCRASQDISNYLNWYQQK

PDGTVKLLIYYTSRLHSGVPSRFSGSGSGTDYS^SNLEQEDIATYFCHHGNTLPWTFGG •39- 162948.doc 201247706

GTKLEIKRTVAAPSVF1FPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNS

QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-CD40—12E12.3F3_H-V-hIgG4H-C(SEQ ID NO:21):

ATGAACTTGGGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTGTCCAGTGTG

AAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAA

CTCTCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCC

AGACTCCAGAGAAGAGGCTGGAGTGGGTCGCATACATTAATTCTGGTGGTGGTAGC

ACCTATTATCCAGACACTGTAAAGGGCCGATTCACCATCTCCAGAGACAATGCCAA

GAACACCCTQTACCTGCAAATGAGCCGGCTGAAGTCTGAGGACACAGCCATGTATT

ACTGTGCAAGACGGGGGTTACCGTTCCATGCTATGGACTATTGGGGTCAAGGAACCT

CAGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCT

GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTAC

TTCCCCGAACCGQTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA

CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC

CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC

CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA

CCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA

CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC

GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGG

TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC

AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAA

AGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGA

CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC

GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC

CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGA

GCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA

ACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-CD40_12E12.3F3一H-V-hIgG4H-C(SEQ ID NO:86):

MNLGLSLIFLVLVLKGVQCEVKLVESGGGLVQPGGSLKLSCATSGFTFSDYYMYWVRQ

TPEKRLEWVAYINSGGGSTYYPDTVKGRFTISRDNAKNTLYLQMSRLKSEDTAMYYCA

RRGLPFHAMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV

TVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDK

RVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFN

WYVDGVEVHNAKTBCPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE 162948.doc -40- 201247706

mSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-CD40_12E12.3F3_K-LV-hIgGK-C(SEQ ID NO:22):

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGTTTTCAAGGTACCAGAT

GTGATATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTAGGAGACAGAG

TCACCATCAGTTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGGTATCAGC

AGAAACCAGATGGAACTGTTAAACTCCTGATCTATTACACATCAATTTTACACTCAG

GAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGGACAGATTATTCTCTCACCATCG

GCAACCTGGAACCTGAAGATATTGCCACTTACTATTGTCAGCAGTTTAATAAGCTTC

CTCCGACGTTCGGTGGAGGCACCAAACTCGAGATCAAACGAACTGTGGCTGCACCA

TCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTG

TGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGAT

AACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGA

CAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAAC

ACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG

AGCTTCAACAGGGGAGAGTGTTAG 抗-CD40_12E12.3F3_K-LV-hIgGK-C(SEQ ID NO:87): MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVIISCSASQGISNYLNWYQQK：

PDGTVKLLIYYTSILHSGVPSRFSGSGSGTDYS^GNLEPEDIATYYCQQFNKLPPTFGG

GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNS

QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_24A5.4A5_H-V-hIgG4H-C(SEQ ID NO:23):

ATGGATTGGCTGTGGAACTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCA

CAGATCCAGTTGGTGCAGTCTGGACCTGAGCTGAAGAAGCCTGGAGAGACAGTCAA

GATCTCCTGCAAGGCTTCTGGGTATTCCTTCACAAACTATGGAATGAACTGGGTGAA

ACAGGCTCCAGGAAAGGGTTTAAAGTGGATGGGCTGGATAAACACCTACACTGGAG

AGTCAACATATGCTGATGACTTCAAGGGACGGTTTGCCTTCTCTTTGGAAACCTCTG

CCAGCACTGCCTATTTGCAGATCAGTAACCTCAAAAATGAGGACATGGCTACATATT

TCTGTGCTAGAGGGGACTTTAGGTACTACTATTTTGACTACTGGGGCCAAGGCACCA

CTCTCACAGGCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCT

GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTAC

TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA

CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC

CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC 162948.doc -41 - 201247706

CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA

CCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA

CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC

GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGG

TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC

AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAA

AGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGA

CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC

GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC

CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGA

GCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA

ACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGAT 抗-DCIR_24A5.4A5—H-V-hIgG4H-C(SEQ ID NO:88):

MDWLWNLLFLMAAAQSAQAQIQLVQSGPELKKPGETVKISCKASGYSFTNYGMNWVK

QAPGKGLKWMGWINTYTGESTYADDFKGRFAFSLETSASTAYLQISNLKNEDMATYFC

ARGDFRYYYFDYWGQGTTLTGSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSI

EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNWSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_24A5.4A5一K-V-hIgGK-C(SEQ ID NO:24):

ATGAGTGTGCTCACTCAGGTCCTGGCGTTGCTGCTGCTGTGGCTTACAGGTGCCAGA

TGTGACATCCAGATGACTCAGTCTCCAGCCTCCCTATCTGCATCTGTGGGAGAAACT

GTCACCATCACGTGTCGAGCAAGTGGGAATATTCACAATTAITTAGCATGGTATCAG

CAGAAACAGGGAAAATCTCCTCAGCTCCTGGTCTATAATGCAAAAACCTTGGCAGA

TGGTGTGCCATCAAGGTTCAGTGGCAGTGGATCAGGAACACAATATTCTCTCAAGAT

CAACACCCTGCAGCCTGAAGATTTTGGGAGTTATTACTGTCAACATTTTTGGGATTCT

TGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATC

TGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTG

TGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAA

CGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACA

GCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACAC -42- 162948.doc 201247706

AAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAG

CTTCAACAGGGGAGAGTGTTAG 抗-DCIR_24A5.4A5_K-V-hIgGK-C(SEQ ID NO:89):

MSVLTQVLALLLLWLTGARCDIQMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQ

KQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINTLQPEDFGSYYCQHFWDSWTF gggtkleikrtvaapsvfifppsdeqlksgtaswcllnnfypreakvqwkvdnalqsg

NSQESVTEQDSKDSTYSLSSTLTLSiCADYEBCHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_24E7.3H9_H-V-hIgG4H-C(SEQ ID NO:25)

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCACTCCC

AGGTTCAGCTGCACTCAGTCTGGAGCTGAGCTGATGAAGCCTGGGGCCTCAGTGAAG

ATATCCTGCAAGGCTACTGGCTACACATTCAGTAGCTACTGGATAGAGTGGGTAAAG

CAGAGGCCTGGACATGGCCTTGAGTGGATTGGAGAGATTTTACCTGGAAGTGGTAG

GACTAACGACAATGAGAAGTTCAAGGGCAAGGCCACATTCACTGCAGATACATCCT

CCAAGAAAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCCGTCTATT

ATTGTGCAAGAAGGGGTGGTTACTCCTTTGCITACTGGGGCCAAGGGACTCTGGTCA

CTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCA

GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT

CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC

CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA

ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGC

CCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGITCCCCCCAAAACCCAAG

GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAA

TGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC

TCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCA

GCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGA

ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCQTGG

AGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG

GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG

CAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC

ACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-DCIR_24E7.3H9_H-V-hIgG4H-C(SEQ ID NO:90): 162948.doc -43 -

C 201247706

MEWTWVFLFLLSVTAGVHSQVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVK

QRPGHGLEWIGEILPGSGRTNDNEKFKGKATFTADTSSKKAYMQLSSLTSEDSAVYYCA

RRGGYSFAYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV

SWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRV

ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS

KAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_24E7.3H9_K-V-hIgGK-C(SEQ ID NO:26):

ATGACCATGTTCTCACTAGCTCTTCTCCTCAGTCTTCTTCTCCTCTGTGTCTCTGATTC

TAGGGCAGAAACAACTGTGACCCAGTCTATGACCATGTTCTCACTAGCTCTTCTCCT

CAGTCTTCTTCTCCTCTGTGTCTCTGATTCTAGGGCAGAAACAACTGTGACCCAGTCT

CCAGCATCCCTGTCCATGGCTATAGGGGAAAAAGTCACCATCAGATGCGTAACCAG

CACTGATATTGATGATGATGTGAACTGGTACCAGCAGAAGCCAGGGGAACCTCCTA

AACTCCTTATTTCAGAAGGCAATACTCTTCGTCCTGGAGTCCCATCCCGATTCTCCAG

CAGTGGCTATGGTACAGAmTGTTTTTACAATTGAGAACATGCTCTCAGAAGATGT

TGCAGATTACTACTGTTTGCAAAGTGGTAACTTGCCGTACACGTTCGGAGGGGGGAC

CAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATC

TGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTA

TCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT

CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAG

CACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATXjCCTGCGAAG

TCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

TAGCCAGCATCCCTGTCCATGGCTATAGGGGAAAAAGTCACCATCAGATGCGTAAC

CAGCACTGATATTGATGATGATGTGAACTGGTACCAGCAGAAGCCAGGGGAACCTC

CTAAACTCCTTATTTCAGAAGGCAATACTCTTCGTCCTGGAGTCCCATCCCGATTCTC

CAGCAGTGGCTATGGTACAGATTTTGTTTTTACAATTGAGAACATGCTCTCAGAAGA

TGTTGCAGATTACTACTGTrTGCAAAGTGGTAACTTGCCGTACACGTTCGGAGGGGG

GACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCC

ATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTT

CTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTA

ACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGC

AGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGA

AGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGT

GTTAG 抗-DCIR_24E7.3H9一K-V-hIgGK-C(SEQ ID NO:91): -44- 162948.doc 201247706

MTMFSLALLLSLLLLCVSDSRAETTVTQSPASLSMAIGEKVTIRCVTSTDIDDDVNWYQ

QKPGEPPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSGNLPYTF

GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR一29E9.2E2_H-VhIgG4H-C(SEQ ID NO:27):

ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCA

CAGATCCAGTTGGTGCAGTCTGGACCTGAGCTGAAGAAGCCTGGAGAGACAGTCAA

GATCTCCTGCAAGGCTTCTGGGTATACCTTCACAAACTATGGAATGAACTGGGTGAA

GCAGGCTCCAGGAAAGGGTTTAAAGTGGGTGGGCTGGATAAACACCTTCACTGGAG

AGCCAACATATGTTGATGACTTCAAGGGACGGTTTGCCTTCTCTTTGGAAACCTCTG

CCAGCACTGCCTATTTGCAGATCAACAACCTCAAAAATGAGGACACGGCTACATATT

TCTGTGCAAGAGGGAATTTTAGGTACTACTACTTTGACTACTGGGGCCAAGGCACCA

CTCTCACAGTCTCCTCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCT

GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTAC

TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA

CACC1TCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGAC

CGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC

CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA

CCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA

CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC

GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGG

TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGC

AAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAA

AGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGA

CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATC

GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC

CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGA

GCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGAIXjCATGAGGCTCTGCACA

ACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-DCIR_29E9.2E2_H-VhIgG4H-C(SEQ ID NO:92):

MAWVWTLLFLMAAAQSAQAQIQLVQSGPELm>GET^KISCKASGYTFTNYGMNWVK

QAPGKGLKWVGWINTIFTGEPTYVDDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCA 162948.doc •45- 201247706

RGNFRYYYFDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV

TVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDK

RVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFN

WYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE

raSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_29E9‘2E2_K-V-hIgGK-C(SEQ ID NO:28):

ATGAGTGTGCTCACTCAGGTCCTGGCGTTGCTGCTGCTGTGGCTTACAGGTGCCAGA

TGTGACATCCAGATGACTCAGTCCCCAGCCTCCCTATCTGCATCTGTGGGAGAAACT

GTCACCATCACATGTCGAACAAGTGGGAATATTCGCAATTATTTAGCATGGTATCAG

CAGAAACAGGGAAAATCTCCTCAACTCCTGGTCTATAATGCAAAAACCTTAGCAGA

TGGTGTGCCATCAAGGTTCGGTGGCAGTGGATCAGGAACACAATATTCTCTCAAGAT

CAACAGCCTGCAGCCTGAAGATTTTGGGAATTATTACTGTCAACATTTTTGGAGTAG

TCCGTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCAC

CATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT

TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGG

ATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG

GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAA

ACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAA

AGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR_29E9.2E2_K-V-hIgGK-C(SEQ ID NO:93):

MSVLTQVLALLLLWLTGARCDIQMTQSPASLSASVGETVTITCRTSGNIRNYLAWYQQK

QGKSPQLLVWAKTLADGVPSRFGGSGSGTQYSLKINSLQPEDFGNYYCQHFWSSPYTF

GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_29G10.3D9_H-V_hIgG4H-C(SEQ ID NO; 29):

ATGATGGGATGGAGCTATATCATCCTCTTTTTGGTAGCAACAGCTACAGATGTCCAC

TCCCAGGTCCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGCTTCAGT

GAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGGT

GAAGCAGAGGCCTGGAGAAGGCCTTGAGTGGATTGGAGAGATTAATCCTAGCTACG

GTCGTACTGACTACAATGAGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAAA

TCCTCCAGCACAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGTC

TATTACTGTGCAAGAGGAGATTACTACGGTAGTAGCTCGTTTGCTTACTGGGGCCAA

GGGACTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTG 162948.doc -46- 201247706

GCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAA

GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG

GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG

TGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC

ATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

- GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCG TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

- CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG GACAAGAGCAGGTC3GCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCGG ATGGAGCTATATCATCCTCTTTTTGGTAGCAACAGCTACAGATGTCCACTCCCAGGT CCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGCTTCAGTGAAGCTGT CCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGGTGAAGCAGA GGCCTGGAGAAGCjCCTTGAGTGGATTGGAGAGATTAATCCTAGCTACGGTCGTACT GACTACAATGGGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAAATCCTCCAG CACAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTG TGCAAGAGGAGATTACTACGGTAGTAGCTCGTTTGCTTACTGGGGCCAAGGGACTCT GGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTG CTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACT TCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCAC ACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCC CAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCGATGCCCAC CCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAAC

'· CCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACG

TGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGT CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCA AGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGAC CAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCG -47- 162948.doc 201247706

CCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC

GTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGC

AGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAAC

CACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA

.TSEDSAVYYC .GCXVKDYFPI

MMGWSYnLFLVATAIDVHSQVQLQQPGAELVKPGASVKLSCKASGTTFTSYWMHWV KQRPGEGLEWIGEINPSYGRTDYNEKFKNKATLTVAKSSSTAYMQLSSLTSI ARGDYYGSSSFAYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALC PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKV DKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQ FNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSS IEKnSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR一29G10.3D9一K-VaH-V-hIgGK-C(SEQ ID NO:30):

ATGGAITTTCAAGTGCAGATTTTCAGCTTCCTGCTAATGAGTGCCTCAGTCATAATGT

CCAGGGGACAAATTGTTCTCACCCAGTCTCCAGCACTCATGTCTGCATCTCCAGGGG

AGAAGGTCACCATGACCTGCAGTGCCAGCTCAAATATAAGTTACATGTACTGGTACC

AGCAGAAGCCAAGATCCTCCCCCAAACCCTGGATTTATCTCACATCCAACCTGGCIT

CTGGAGTCCCTGCTCGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAA

CCAGCAGCATGGAGGCTGAAGATGCTGCCACTTATTGCTGCCAGCAGTGGAGTAGT

AACCCACCCACGTTCGGTGCTGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGC

ACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT

GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTG

GATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA

GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGA

AACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACA

AAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR_29G10.3D9_K-Varl-V-hIgGK-C(SEQ ID NO:95):

MDFQVQIFSFLLMSASVIMSRGQIVLTQSPALMSASPGEKVTMTCSASSNISYMYWYQQ

KPRSSPKPWIYLTSNLASGVPARFSGSGSGTSYSLTTSSMEAEDAATYCCQQWSSNPPTF

GAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_29G10.3D9_K-Var2-V-hIgGK-C(SEQ ID NO:31): 162948.doc -48- 201247706

ATGGATTTTCGAGTGCAGATTTTCAGCTTCCTGCTAATGAGTGCCTCAGTCAT

AATGTCCAGGGGACAAATTGTTCTCACCCAGTCTCCAGCACTCATGTCTGCATCTCC

AGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAATATAAGTTACATGTACT

GGTACCAGCAGAAGCCAAGATCCTCCCCCAAACCCTGGATTTATCTCACATCCAACC

TGGCTTCTGGAGTCCCTGCTCGCTTCAGTGGCAGTGGGTCTGGGACCTCITACTCTCT

CACAATCAGCAGCATGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAGTGGA

GTAGTAACCCACCCACGTTCGGTGCTGGGACCAAGCTCGAGATCAAACGAACTGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACT

GCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGG

AAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGA

CAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACT

ACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCC

GTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR一29G10.3D9_K-Var2-V-hIgGK-C(SEQ ID NO:96):

MDFRVQFSFLLMSASVIMSRGQIVLTQSPALMSASPGEKVTMTCSASSN1SYMYWYQQ

KPRSSPKPWIYLTSNLASGVPARFSGSGSGTSYSmSSMEAEDAATYYCQQWSSNPPTF

GAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_2C9K-V-hIgGK-C(SEQ ID NO:32):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTCCACA

GGTGACATTGTGCTGATCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGG

GCCACCATATCCTGCAGAGCCAGTGAAAGTGTTGATAGTTATGTCAATAGTnTATG

CACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCGTGTATCC

AACCTAGAATCTGGGATCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTTC

ACCCTCACCATTAATCCTGTGGAGGCTGATGATGTTGCAACCTATTACTGTCAGCAA

AGTAATGAGGATCCATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAACGAAC

TGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGA

ACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCA

GGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAG

ACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCG

CCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR_2C9K-V-hIgGK-C(SEQ ID NO:97):

METDTLLLWVLLLWVPGSTGDIVLIQSPASLAVSLGQRATISCRASESVDSYVNS 162948.doc -49- 201247706

FMHWYQQKPGQPPKLLIYRVSNLESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQS

NEDPFTFGSGTKLEIKRTVAAPSWIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVD

NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTBCSFN RGEC. 抗-DCIR一31A6.1F5_H·var2-V-hIgG4H-C(SEQIDNO:33):

ATGGAATGTAACTGGATACTTCCTTTTATrCTGTCGGTAATTTCAGGGGTCTACTCAG

AGGTTCAGCTCCAGCAGTCTGGGACTGTGCTGGCAAGGCCTGGGGCTTCCGTGAATA

TGTCCTGTAAGGCTGCTGGCTACAGCTTTACCAGTTACTGGGTGTACTGGGTCAAAC

AGAGGCCTGGACAGGGTCTGGAATGGATTGGTGCTATTTACCCTAAAAATAGTAGA

ACTAGCTACAACCAGAAGTTCCAGGACAAGGCCACACTGACTGCAGTCACATCCGC

CAGCACTGCCTACATGGAGCTCAGCAGCCTGACAAATGAGGACTCTGCGOTCTATTA

CTGTACAAGACCTCACTATGATTCGTTTGGTTACTGGGGCCAAGGGACTCTGGTCAC

TGTCTCTGCAGCCAAAACAaagggcccATCCGICTTCCCCCTGGCGCCCTGCTCCAGGAG

CACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACC

GGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGG

CTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCA

GCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACC

AAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGC

ACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACAC

TCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGA

AGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCA

AGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTC

ACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAA

CAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCC

GAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAG

GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGG

GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTC

CGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGG

AGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACAC

AGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-DCIR_31A6.1F5_H_var2-V-hIgG4H-C(SEQIDNO:98):

MECNWILPFILSVISGVYSEVQLQQSGTVLARPGASVNMSCKAAGYSFTSYWVYWVKQ

RPGQGLEWIGAIYPKNSRTSYNQKFQDKATLTAVTSASTAYMELSSLTNEDSAVYYCTR

PHYDSFGYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS

WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVE

SKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYV -50- 162948.doc 201247706

DGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEmSK

AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_31A6.1F5_K_var2-V-hIgGK-C(SEQ ID NO:34):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTCCACA

GGTGACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGG

GCCACCATATCCTGCAGAGCCAGTGAAAGTGTAGATAGTTATGGCATTAGTTTTATG

CACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCGTGCATCC

AACCAAGAATCTGGGATCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTT

CACCCTCACCATTAATCCTGTGGAGGCTGATGATGTTGCAACCTATTACTGTCAGCA

AAGTAATGAGGATCCGCTCACGTTCGGTGCTGGGACCAAGCTCGAGATCAAACGAA

CTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGG

AACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACA

GTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGC

AGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCA

GACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTC

GCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR_31A6.1F5_K-var2-V-hIgGK-C(SEQ ID NO:99):

METDTLLLWVLLLWVPGSTGDIVLTQSPASLAVSLGQRATISCRASESVDSYGISFMHW

YQQKPGQPPKLLIYRASNQESGIPARFSGSGSRnDFTLTINPVEADDVATYYCQQSNEDP

LTFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE

C 抗-DCIR_3C2.2D9_H-LV-hIgG4H-C(SEQ ID NO:35):

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTCCC

AGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTC

TGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTGTGAGCTGGAT

TCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGGGATGATGA

CAAGCGCTATAATCCATCCCTGAAGAGCCGGCTCACAATCTTTAAGGATCCCTCCAG

CAACCAGGTATTCCTCAGGATCACCAGTGTGGACACTGCAGATACTGCCACATACTA

CTGTGCTCGAAACTCCCATTACTACGGTAGTACTTACGGGGGATACTTCGATGTCTG

GGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACAAAGGGCCCATCCGTCT

TCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCC

TGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG -51 · 162948.doc 201247706

：CAAATATG ：AGTCTTCC

ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCy GTCCCCCATGCCCA<XCTGCCCAGCACCTGAGTTCGAAGGGGGACCATC> TGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGT GCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTG GATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACA GCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCA AGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACC ATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATC CCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT ACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTA CAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCT AACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGC ATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAG CTAGCTGA 抗-DCIR_3C2.2D9_H-LV-hIgG4H-C(SEQ ID N0:100):

NRLTSSLLLLIVPAYVLSQQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPS

GKGLEWLAHIYWDDDKRYNPSLKSRLTIFKDPSSNQVFLRITSVDTADTATYYCARNSH

YYGSTYGGYFDVWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFHSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSI

EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS. 抗-DCIR一3C2.2D9_K-LV-hIgGK-C(SEQ ID NO:36):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCGGGGTTCCAGGTTCCACA

GGTAACATTGTGCTGACCCAGTCTCCAACTTCTTTCACTGTGTCTCTTGGGCAGAGG

GCCACCATATCCTGCAGAGCCAGTGAAAGTGTTCATAGTTATGGCAATAGTTTTATG

CACTGGTACCAGCAGAAACCAGGGCAGCCACCCAAACTCCTCATCTATCITGCATCC

AACGTAGAATCTGGGGTCCCTC3CCAGGTTCAGTGGTAGTGGGTCCAGGACAGACTTC

ACCCTCACCATTGATCCTGTGGAGGCTGATGATGCTGCAACCTATTACTGTCAGCAA

AATAGTGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAAC

TGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGA

ACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG -52- 162948.doc 201247706

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCA

GGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAG

ACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCG

CCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR_3C2.2D9_K-LV-hIgGK-C(SEQ ID NO:101):

METDTLLLWVLLLGVPGSTGNIVLTQSPTSfTVSLGQRATISCRASESVHSYGNSFMHW

YQQKPGQPPKLLIYLASNVESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNSEDP

WTFGGGTKLEKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE

C 抗-DCIR一6C8.1G9_H-V-hIgG4H-C(SEQ ID NO:37):

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCA

CTCCCAGGTTCAGCTGCAGCAGTCTGGAACTGAGCTGATGAAGCCTGGGGCCTCAGT

GAAGATATCCTGCAAGGCTACTGGCTACACATTCAGTACCTACTGGATAGAGTGGGT

AAAGCAGAGGCCTGGACATGGCCTTGAGTGGATTGGAGAGATTTTACCTGGAAGTG

GTAGGACTAACGACAATGAGAAGTTCAAGGGCAAGGCCACAATCACTGCAGATACA

TCCTCCAAGAAA.GCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCCGTC

TATTACTGTCSCAAGAAGGGGTGGTTACTCCTTTGCTTTCTGGGGCCAAGGGACTCTG

GTCTCTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGC

TCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT

CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA

CC1TCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCG

TGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCC

AGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACC

CTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTG1TCCCCCCAAAACC

CAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGT

GAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC

ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTC

AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAA

GGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAG

GGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC

AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC

CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC

GTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGC

AGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAAC

CACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 162948.doc -53- s 201247706 抗-DCIR_6C8.1G9_H-V-hIgG4H-C(SEQ ID NO:102):

MEWTWVFLFLLSVTAGVHSQVQLQQSGTELMKPGASVKISCKATGYTFSTYWIEWVK

QRPGHGLEWIGE1LPGSGRTNDNEKFKGKATITADTSSKKAYMQLSSLTSEDSAVYYCA

RRGGYSFAFWGQGTLVSVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPYTV

SWNSGALTSGyHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRV

ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS

KAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_6C8.1G9_K-V-hIgGK-C(SEQ ID NO:38):

ATGACCATGTTCTCACTAGCTCTTCTCCTCAGTCTTCTTCTCCTCTGTGTCTCT

GATTCTAGGGCAGAAACAACTGTGACCCAGTCTCCAGCATCCCTGTCCATGGCTATA

GGAGAAAAAGTCACCATCAGATGCGTAACCAGCACTGATATTGATGATGATGTGAA

CTGGTACCAGCAGAAGCCAGGGGAACCTCCTAAGCTCCTTATTTCAGAAGGCAATA

CrcrrCGTGCTGGAGlUCCATX：CCGArrcTTCCAGCAGTGGCrATGGTACAGATTXTGr

TTTTACAATTGAGAACATGCTCTCAGAAGATGTTGCAGATTACTACTGTTTGCAAAG

TGGTAACTTGCCGTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTG

TGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAA

CTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGT

GGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAG

GACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA

CTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGC

CCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DCIR一6C8.1G9_K-V-hIgGK-C(SEQ ID NO:103):

MTMFSLALLLSLLLLCVSDSRAETTVTQSPASLSMAIGEKVTIRCVTSTDIDDDVNWYQ

QKPGEPPKLUSEGNTLRAGVPSRFSSSGYGTDFVFTIENMLSEDVADYYCLQSGNLPYT fgggtkleikrtvaapsvfifppsdeqlksgtaswcllnnfypreakvqwkvdnalqs

GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-DCIR_9E8.1E3_H-V-hIgG4H-C(SEQ ID NO:39):

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTCCC

AGGTTACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTC

TGACTTGTTCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAGCTGGAT

TCGTCAGCCTTCAGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGGGATGATGA -54- 162948.doc 201247706

CAAGCGCTATAACCCATCCCTGAAGAGCCGGCTCACAATCTCCAAGGATACCTCCA

GCAACCAGGTTTTCCTCAAGATCACCATTGTGGACACTGCAGATGCTGCCACATACT

ACTGTGCTCGAAGCTCCCATTACTACGGTTATGGCTACGGGGGATACTTCGATGTCT

GGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTC

TTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGC

CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG

ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC

AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAA

CGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATG

GTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCC

TGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGT

GCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTG

GATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACA

GCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCA

AGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACC

ATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAC3GTGTACACCCTGCCCCCATC

CCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT

ACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTA

CAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCT

AACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGC

ATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAG

CTAGCTGA 抗-DCIR_9E8.1E3_H_V-hIgG4H-C(SEQ ID NO:104):

MNRLTSSLLLLIVPAYVLSQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPS

GKGLEWLAmYWDDDKRYNPSLKSRmSKDTSSNQVFLKmVDTADAATYYCARSSH

YYGYGYGGYFDVWGAGTTVTVSSAKTKGPSWPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSI

EKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-DCIR_9E8.1E3_K-LV-hIgGK-C(SEQ ID NO:40):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTC

CACAGGTAACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCA

GAGGGCCACCATATCCTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTT c 162948.doc -55- 201247706

TCTGCACTGGTACCAGCAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTTGC

ATCCAACCTAGAATCTGGGGTCCCTGCCAGGTTCAGCGGCAGTGGGTCTAGGACAG

ACTTCACCCTCACCATTGATCCTGTGGAGGCTGATGATGCTGCAACCTATTACTGTC

AGCAAAATAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAA

CGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAA

TCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA

GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCAC

AGAGCAGGACAGOAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGCXjGAGAGTGTTAGGCGGCCGCACTAGC

GCGGGCCGCATTCGAAGAGCTCGGTACCCGGGGATCCTCTAGAGTCGACCTGCAGG

CATGCAAGCTGGCCGCGACTCTAGATCATAATCAGC 抗-DCIR_9E8.1E3_K-LV-hIgGK-C(SEQ ID NO:105):

METDTLLLWVLLLWVPGSTGMVLTQSPASLAVSLGQRATISCRASESIHSYGNSFLHWY

QQKPGQPPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDP

WTFGGGTKLEIKRTVAAPSWIFPPSDEQLKSGTASWCLLN>iFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE

C 抗-DCIR2C9H-LV-hIgG4H-V-hIgG4H-C(SEQ ID NO:41):

ATGAAAtGCAGCTGGGTCATCTTCTTCCTGATGGCAGTGGTTACAGGGGTCAATTCA

GAGGTTCAGCTGCAGCAGTCTGGGGCTGAGCTTGTGAGGCCAGGGGCCTTAGTCAA

GTTGTCCTGCAAAGCTTCTGGCTTCAACATTAATGACTACTATATCCACTGGGTGAA

GCAGCGGCCTGAACAGGGCCTGGAGCGGATTGGATGGATTGATCCTGACAATGGTA

ATACTATATATGACCCGAAGTTCCAGGGCAAGGCCAGTATAACAGCAGACACATCC

CCCAACACAGCCTACCTGCAGCTCAGCAGCCTGACATCTGAGGACACTGCCGTCTAT

TACTGTGCTAGAACCCGATCTCCTATGGTTACGACGGGGTTTGTTTACTGGGGCCAA

GGGACTGTGGTCACTGTCTCTGCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTG

GCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAA

GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG

GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG

TGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC

ATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT 162948.doc -56- 201247706

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCG

TGGAGGTGCATAATGCCAAGACRAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA

AAGCCAAAGC3GCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAATGA 抗-DCIR2C9H-LV-hIgG4H-V_hIgG4H-C(SEQ ID NO:106):

MKCSWVIFFLMAWTGVNSEVQLQQSGAELVRPGALVKLSCKASGFNINDYYIHWVKQ

RPEQGLERIGWIDPDNGNTIYDPKFQGKASITADTSPNTAYLQLSSLTSEDTAVYYCART

RSPMVTTGFVYWGQGTWTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV

TVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDK

RVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFN

WYVDGVEVHNAKXKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE

mSKAKGQPREPQVyTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 抗-DC-SIGNL16E3H(SEQ ID NO:42):

ATGGAAAGGCACTGGATCTTTCTCTTCCTGmTCAGTAACTGCAGGTGTCCA

CTCCCAGGTCCAGCTIOAGCAGTCTGGGGCTGAGCTGGCAAAACCTGGGGCCTCAGT

GAAGATGTCCTGCAAGGCTTCTGGCTACACCTTTACTACCTACTGGATGCACTGGGT

AAAACAGAGGCCTGGACAGGGTCTGGAATGGATTGGATACATTAATCCTATCACTG

GTTATACTGAGTACAATCAGAAGTTCAAGGACAAGGCCACCTTGACTGCAGACAAA

TCCTCCAGCACAGCCTACATGCAACTGAGCAGCCTGACATCTGAGGACTCTGCAGTC

TArrACrGTGCAAGAGAGGGTTTAAGTGCTArGGACrATrGGGGTCAGGGAACCrCA

GTCACCGTCACCTCAGCCAAAACAACAGCCCCATCGGTCTATCCACTGGCCCCTGTG

TGTGGAGATACAACTGGCTCCTCGGTAACTCTAGGATGCCTGGTCAAGGGTTATTTC

CCTGAGCCAGTGACCTTGACCTGGAACTCTGGATCCCTGTCCAGTGGTGTGCACACC

TTCCCAGCTGTCCTGCAGTCTGACCTCTACACCCTCAGCAGCTCAGTGACTGTAACC

TCGAGCACCTGGCCCAGCCAGACCGTCACCTGCAGCGTTGCTCACCCAGCCAGCAG

CACCACGGTGGACAAAAAACTTGAGCCCAGCGGGCCCATTTCAACAATCAACCCCT

GTCCTCCATGCAAGGAGTGTCACAAATGCCCAGCTCCTAACCTCGAGGGTGGACCAT

CCGTCTTCATCTTCCCTCCAAATATCAAGGATGTACTCATGATCTCCCTGACACCCAA £ 162948.doc -57- 201247706

GGTCACGTGTGTGGTGGTGGATGTGAGCGAGGATGACCCAGACGTCCAGATCAGCT

GGTTTGTGAACAACGTGGAAGTACACACAGCTCAGACACAAACCCATAGAGAGGAT

TACAACAGTACTATCCGGGT(3GTCAGCACCCTCCCCATCCAGCACCAGGACTGGATG

AGTGGCAAGGAGTTCAAATGCAAGGTCAACAACAAAGACCTCCCATCACCCATCGA

GAGAACCATCTCAAAAATrAAAGGGCTAGTCAGAGCTCCACAAGTATACATCTTGC

CGCCACCAGCAGAGCAGTTGTCCAGGAAAGATGTCAGTCTCACTTGCCTGGTCGTGG

GCTTCAACCCTGGAGACATCAGTGTGGAGTGGACCAGCAATGGGCATACAGAGGAG

AACTACAAGGACACCGCACCAGTCCTGGACTCTGACGGTTCTTACTTCATATATAGC

AAGCTCAATATGAAAACAAGCAAGTGGGAGAAAACAGATTCCTTCTCATGCAACGT

GAGACACGAGGGTCTGAAAAATTACTACCTGAAGAAGACCATCTCCCGGTCTCCGG

GTAAAGCTAGCTGA 抗-DC_SIGNL16E3H(SEQ ID NO:107):

MERHWLFLFSVTAGVHSQVQLQQSGAELAKPGASVKMSCKASGYTFTTYWMHWVK

QRPGQGLEWIGYINPITGYTEYNQKFKDKATLTADKSSSTAYMQLSSLTSEDSAVYYCA

REGLSAMDYWGQGTSVTVTSAKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVT

LTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQTVTCSVAHPASSTTVDKKLE

PSGPISTINPCPPCKECHKCPAPNLEGGPSVFIFPPNIKDVLMISLTPKVTCWVDVSEDDP

DVQISWFVNNVEVHTAQTQTHREDYNSTIRVVSTLPIQHQDWMSGKEFKCKVInINKDLP

SPIERTISKIKGLVRAPQVYILPPPAEQLSRKDVSLTCLWGFNPGDISVEWTSNGHTEEN

YKDTAPVLDSDGSYFIYSKLNMKTSKWEKTDSFSCNVRHEGLKNYYLKKnSRSPGKAS 抗-DC-SIGNL16E3K(SEQ ID NO:43):

ATGGGCATCAAGATGGAGTCACGGATTCAGGCATTTGTATTCGTGTTTCTCTG

GTTGTCTGGTGTTGGCGGAGACATTGTGATGACCCAGTCTCACAAATTCATGTCCAC

ATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGGATGTGACTTCTG

CTGTAGCCTGGTATCAACAAAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGG

CATCCACCCGGCACACTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACA

GATTATACTCTCACCATCAGCAGTGGGCAGGCTGAAGACCTGGCACTTTATTACTGT

CACCAATATTATAGCGCTOCTCGGACGTTCGGTGGAGGCACCAAGCTGGAAGTCAA

ACGGGCTGATGCTGCACCAACTGTATCCATCTTCCCACCATCCAGTGAGCAGTTAAC

ATCTGGAGGTGCCTCAGTCGTGTGCTTCTTGAACAACTTCTACCCCAAAGACATCAA

TGTCAAGTGGAAGATTGATGGCAGTGAACGACAAAATGGCGTCCTGAACAGTTGGA

CTGATCAGGACAGCAAAGACAGCACCTACAGCATGAGCAGCACCCTCACGTTGACC

AAGGACGAGTATGAACGACATAACAGCTATACCTGTGAGGCCACTCACAAGACATC

AACTTCACCCATCGTCAAGAGCTTCAATAGGAATGAGTGTTAG -58 · 162948.doc 201247706 抗-DC-SIGNL16E3K(SEQ ID NO:108):

MESRIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCKASQDVTSAVAWYQ

QKPGQSPKLLIYWASTRHTGVPDRPTGSGSGTDYTLTISSGQAEDLALYYCHQYYSAPR

TFGGGTKLEVKRADAAPTVSIFPPSSEQLTSGGASWCFLNNFYPKDINVKWKIDGSERQ

NGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC 抗-DC-SIGNL16E7H-LV-hIgG4H-C(SEQ ID NO:44):

ATGGAAAGGCACTGGATCTTTCTCTTCCTGTTTTCAGTAACTGCAGGTGTCCA

CTCCCAGGTCCAGCTTCAGCAGTCTGGGGCTGAGCTGGCAAAACCTGGGGCCTCAGT

GAAGATGTCCTGCAAGGCTTCTGGCTACACCTTTACTACCTACTGGATGCACTGGGT

AAAACAGAGGCCTGGACAGGGTCTGGAATGGATTGGATACATTAATCCTATCACTG

GTTATACTGAGTACAATCAGAAGTTCAAGGACAAGGCCACCTTGACTGCAGACAAA

TCCTCCAGCACAGCCTACATGCAACTGAGCAGCCTGACATCTGAGGACTCTGCAGTC

TATTACTGTGCAAGAGAGGGTTTAAGTGCTATGGACTATTGGGGTCAGGGAACCTCA

GTCACCGTCACCTCAGCCAAAACAACGGGCCCATCCGTCTTCCCCCTGGCGCCCTGC

TCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTT

CCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA

CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCG

TGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCC

AGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACC

CTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACC

CAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGT

GAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC

ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTC

AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAA ggtctccaacaaaggcctcccgtcctccatcgagaaaaccatctccaaagccaaag

GGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC

AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGC

CGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC

GTGCTGGACTCCGACGGCTCCTTCrrcCTCTACAGCAGGCTAACCGTGGACAAGAGC

AGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAAC

CACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-DC-SIGNL16E7H-LV-hIgG4H-C(SEQ ID NO:109):

MERHWIFLFLFSVTAGVHSQVQLQQSGAELAKPGASVKMSCKASGYTFTTYWMHWVK

QRPGQGTLEWIGYINPITGYTEYNQKFKDKATLTADKSSSTAYMQLSSLTSEDSAVYYCA 162948.doc •59- £ 201247706

REGLSAMDYWGQGTSVTVTSAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV

SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRV

ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS

KAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS. 抗-DC-SIGNL16E7K-LV-hIgGK-C(SEQ ID NO:45):

A.TGGGCATCAAGATGGAGTCACAGATTCAGGCATTTGTATTCGTGTrrCTCTQ

GTTGTCTGGTGTTGGCGGAGACATTGTGATGACCCAGTCTCACAAATTCATGTCCAC

ATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGGATGTGACTTCTG

CTGTAGCCTGGTATCAACAAAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGG

CATCCACCCGGCACACTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACA

GATTATACTCTCACCATCAGCAGTGGGCAGGCTGAAGACCTGGCACTTTATTACTGT

CACCAATATTATAGCGCTCCTCGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAA

ACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAA

ATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAA

AGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA

CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGC

AAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCT

GAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-DC-SIGNL16E7K-LV-hIgGK-C(SEQ ID NO:110):

MESQIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCKASQDVTSAVAWYQ

QKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLnSSGQAEDLALYYCHQYYSAPR

TFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-Dectin一l_llB6.4_H-V-hIgG4H-C(SEQ ID NO:46):

ATGGCTGTCCTGGCACTACTCCTCTGCCTGGTGGCTTTCCCAACTTGTACCCT

GTCCCAGGTGCAACTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCACAGAGCC

TGTCCATTACCTGCTCTGTCTCTGGGTTCTCATTAAGCAACTATGATATAAGCTGGAT

TCGCCAGCCACCAGGAAA<jGGTCTGGAGTGGCTTGGA.GTAATGTGGACTGGTGGAG

GCGCAAATTATAATTCAGCTTTCATGTCCAGACTGAGCATCAACAAGGACAACTCCA

AGAGCCAAGTTTTTTTAAAAATGAACAATCTGCAAACTGATGACACAGCCATTTATT

ACTGTGTCAGAGATGCGGTGAGGTACTGGAACTTCGATGTCTGGGGCGCAGGGACC

ACGGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCC -60- 162948.doc 201247706 tgctccaggagcacctccgagagcacagccgccctgggctgcctggtcaaggacta

CTTCCCCGAACCGGTGACCKJTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGC

ACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGA

CCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAG

CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC

ACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTrCCTGTTCCCCCCAAA

ACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGA

CGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGG

TGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTG

GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGCJCAAGGAGTACAAGTG

CAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCA

AAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATG

ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACAT

CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT

CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAG

AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC

AACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-Dectin_l_llB6.4_H-V-hIgG4H-C(SEQ ID NO:lll):

MAVLALLLCLVAFPTCTLSQVQLKESGPGLVAPSQSLSITCSVSGFSLSNYDISWIRQPPG

KGLEWLGVMWTGGGANYNSAFMSRLSINKDNSKSQVFLKMNNLQTDDTArYYCVRDA

VRYWNFDVWGAGTTVTVSSAKTKGPSVEPLAPCSRSTSESTAALGCLVKDYFPEPVTVS

'WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVE

SKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEmSK

AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-Dectin_l_llB6.4_K-LV-hIgGK-C(SEQ ID NO:47):

ATGGATTTTCAAGCGCAGATTTTCAGCTTCCTGCTAATCAGTGCTTCAGTCAT

AATGTCCAGAGGACAAATTGTTCTCTCCCAGTCACCAGCAATCCTGTCTGCATCTCC

AGGGGAGAAGGTCACAATGACTTGCAGGGCCAGCTCAAGTGTAAGTTACATACACT

GGTACCAGCAGAAGCCAGGATCCTCCCCCAAACCCTGGATTTATGCCACATCCCACC

TGGCTTCTGGAGTCCCTGCTCGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCT

CACAATCAGCAGAGTGGAGGCTGAAGATACTGCCACTTATTACTGCCAGCAGTGGA

GTAGTAACCCATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTG

GCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACT s 162948.doc -61 - 201247706

GCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGG

AAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGA

CAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACT

ACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCC

GTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Dectin_l_llB6.4_K-LV-hIgGK-C(SEQ ID NO:112):

MDFQAQIFSFLLISASVIMSRGQIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWYQQKP

GSSPKPWIYATSHLASGVPARFSGSGSGTSYSmSRVEAEDTATYYCQQWSSNPFTFGS

GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNS

QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-Dectin_l_15E2.5_H-V_hIgG4H-C(SEQ ID NO:48):

ATGGAAAGGCACTGGATCTTTCTACTCCTGTTGTCAGTAACTGCAGGTGTCCACTCC

CAGGTCCAGCTGCAGCAGTCTGGGGCTGAACTGGCAAGACCTGGGGCCTCAGTGAA

GATGTCCTGCAAGGCTTCTGGCTACACCTTTACTACCTACACTATGCACTGGGTAAA

ACAGAGGCCTGGACAGGGTCTGGAATGGATTGGATACATTAATCCTAGCAGTGGTT

ATACTAATTACAATCAGAAGTTCAAGGACAAGGCCACATTGACTGCAGACAAATCC

TCCAGCACAGCCTCCATGCAACTGAGCAGCCTGACATCTGAGGACTCTGCAGTCTAT

TACTGTGCAAGAGAGAGGGCGGTATTAGTCCCCTATGCTATGGACTACTGGGGTCAA

GGAACCTCAGTCACCGTCTCCTCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTG

GCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAA

GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG

GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG

TGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC

ATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCG

TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA

AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC -62- 162948.doc 201247706

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTC3GGTAAAGCTAGCTG

A 抗-Dectin一l_15E2,5_H-V-hIgG4H-C(SEQ ID NO:113):

MERHWIFLLLLSVTAGVHSQVQLQQSGAELARPGASVKMSCKASGYTFTTYTMHWVK QRPGQGLEWIGYINPSSGYTNYNQKFKDKATLTADKSSSTASMQLSSLTSEDSAVYYCA RERAVLVPYAMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE * PVTVSWNSGALTSGVHITPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKV

. DKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQ

' FNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSS

IEmSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-Dectin—l_15E2.5_K-V-hIgGK-C(SEQ ID NO:49):

ATGCATTTTCAAGTGCAGATTTTCAGCTTCCTGCTAATCAGTGCCTCAGTCAT

AATGTCCAGAGGACAAATTGTTCTCACCCAGTCTCCAGCAGTCATGTCTGCATCTCC

AGGGGAGAAGGTCACCATAACCTGCACTGCCAGCTCAAGTTTAAGTTACATGCACT

GGTTCCAGCAGAAGCCAGGCACTTCTCCCAAACTCTGGCTTTATAGCACATCCATCC

TGGCTTCTGGAGTCCCTACTCGCTTCAGTGGCAGTGGATCTGGGACCTCTTACTCTCT

CACAATCAGCCGAATGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAAAGGA

GTAGTTCCCCATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTGG

CTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTQTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA

GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACA

GCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTAC

GAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGT

CACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Dectin丄15E2.5_K-V-hIgGK-C(SEQ ID NO:114):

MHFQVQIFSFLLISASVIMSRGQIVLTQSPAVMSASPGEKVTrTCTASSSLSYMHWFQQKP : GTSPKLWLYSTSILASGVPTRFSGSGSGTSYSLTISRMEAEDAATYYCQQRSSSPFTFGSG

IKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQ ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-Dectin丄2D8.2D4H-V-hIgG4H-C(SEQ ID NO:50):

ATGGGATGGACCTGGATCmATTTTAATCCTGTCAGTTACTACAGGTGTCCA

CTCTGAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGAGAAGCCTGGCGCTTCAGT -63- 162948.doc 201247706

GAAGATATCCTGCAAGGCTrCTGGTrACTCCTTCACTGGCTACAACATGAACTGGGT

GAAACAGAGCAATGGAAAGAGCCTTGAGTGGATTGGAAATATTGATCCTTACTATG

GTGATACTAACTACAACCAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAA

TCCTCCAGCACAGCCTACATGCACCTCAAGAGCCTGACATCTGAGGACTCTGCAGTC

TATTACTGTGCAAGACCCTACGGTAGTGAGGCCTACTTTGCTTACTGGGGCCAAGGG

ACTCTGGTCACTGTCTCTGCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCG

CCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGA

CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGT

GCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT

GACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACA

AGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGC

CCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGITCCCCCCA

AAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTG

GACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTG

TGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAG

TGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCC

AAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGAT

GACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACA

TCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT

CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAG

AGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC

AACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-Dectin—l_2D8.2D4H-V_hIgG4H-C(SEQ ID NO:115):

MGWTWIFIHLSVTTGVHSEVQLQQSGPELEKPGASVKISCKASGYSFTGYNMNWVKQS

NGKSLEWIGNIDPYYGDTNYNQKFKGKATLTVDKSSSTAYMHLKSLTSEDSAVYYCAR

PYGSEAYFAYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT

VSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKR

VESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNW

YVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKT

iNNYKTT KAS ISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE: PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG： 抗-Dectin_l_2D8.2D4K-V-hIgGK-C(SEQ ID NO:51):

ATGGTGTCCAaTCTCAGCTCCTTGGACTTTTGCTTTTCTGGACTTCAGCCTCC

AGATGTGACATTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGACTCCAGGAGAT -64- 162948.doc 201247706

TTTCCG ACCATC

AGAGTCTCTCnTCCIOCAGGGCCAGCCAGAGTATTAGCGACTACTTACACTGGTAT CAACAAAA^TCACATGAGTCTCCAAGGCTTCTCATCAAATATGCTGCCCAATCCATC TCTGGGATCCCCTCCAGGTTCAGTGGCAGTGGATCAGGGTCAGATTTCACTCTCAGT ATCAACGGTGTQGAACCTGAAGATGTTGGAGTGTATTACTGTCAAAATGGTCACAGC ：GTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGC rCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTG GATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGA AACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACA AAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Dectin丄2D8.2D4K-V-hIgGK-C(SEQ ID NO:116):

DIVMTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYAAQSISGIPSR

FSGSGSGSDFTLSINGVEPEDVGVYYCQNGHSFPYTFGGGTKLEIKRTVAAPSVFIFPPSD

EQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL

SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-蘭格素 15B10H-LV-hIgG4H-C(SEQ ID NO:52):

ATGGAATGGAGGATCTTTCTCTTCATCCTGTCAGGAACTGCAGGTGTCCACTC

CCAGGTTCAGCTGCGGCAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGA

AGATGTCCTGCAAGGCTTCTGGATACACATTTACTGACTATGTTATAAGTTGGGTGA

AGCAGAGAACTGGACAGGGCCTTGAGTGGATTGGAGATATTTATCCTGGAAGTGGT

TATTCTTTCTACAATGAGAACTTCAAGGGCAAGGCCACACTGACTGCAGACAAATCC

TCCACCACAGCCTACATGCAGCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTAT

TTCTGTGCAACCTACTATAACTACCCTTTTGCTTACTGGGGCCAAGGGACTCTGGTCA

CTGTCTCTGCAGCCAAAACAACGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCA

GGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTT

CCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC

CTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA

ACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGC

CCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAG

GACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAA

TGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTC 162948.doc -65- 201247706

TCCAACAAAGGCqTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCA

GCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGA

ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGG

AGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG

GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG

CAGGAGGGGAATGTCITCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC

ACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-籣格素 15B10H-LV-hIgG4H-C(SEQ ID NO:117):

QVQLRQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGDIYPGSGYS

FYNENFKGKATLTADKSSTTAYMQLSSLTSEDSAVYFCATYYNYPFAYWGQGTLVTVS

AAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS

SGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPS

VFLFPPKPKDTLMTSRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE

MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS. 抗-蘭格素 15B10K-LV-hIgGK-C(SEQ ID NO:53):

ATGAAGTTGCCTGTTAGGCTGTTGGTGCTGATGTTCTGGATTCCTGCTTCCAG

CAGTGATGTTGTGATGACCCAAACTCCACTCTCCCTGCCTGTCCGTCTTGGAGATCA

AGCCTCCATCTCTTGCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTA

TTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGT

TTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAAA

TTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGACITTATTTCTGCTC

TCAAAGTACACATGTTCCGTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAAC

GAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAAT

CTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAG

TACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACA

GAGCAGGACAGCAAGGACAC3CACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAA

AGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGA

GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-蘭格素 15B10K-LV-hIgGK-C(SEQ ID NO:118):

DWMTQTPLSLPVRLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNR

FSGVPDRFSGSGSGTNFTLKISRVEAEDLGLYFCSQSTHVPYTFGGGTKLEIKRTVAAPSV fifppsdeqlksgtaswcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstys 162948.doc • 66- 201247706

LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗-蘭格素2G3H-LV-hIgG4H-C(SEQ ID NO:54):

ATGACATTGAACATGCTGTTGGGGCTGAGGTGGGTTTrCTTTGTTGTTTTITAT

CAAGGTGTGCATTGTGAGGTGCAGCTTGTTGAGTCTGGTGGAGGATTGGTGCAGCCT

AAAGGGTCATTGAAACTCTCATGTGCAGCCTCTGGATTAACCTTCAATATCTACGCC

ATGAACTGGGTCCGCCAGGCTCCAGGAAAGGGTTTGGAATGGGTTGCTCGCATAAG

AAATAAAAGTAATAATTATGCAACATATTATGCCGATTCAGTGAAAGACAGGTTCA

CCATCTCCAGAGATGATTCACAAAGCTTGCTCTATCTGCAAATGAACAACTTGAAAA

CTGAGGACACAGCCATGTATTACTGTGTGGGACGGGACTGGTTTGATTACTGGGGCC

AAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCC

TGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC

AAGGACTAC1TCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG

CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG

CGTGGTGACCGTGCCCTCCAGCAGCTTC5GGCACGAAGACCTACACCTGCAACGTAG

ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC

CCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTC

CCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG

GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGG

CGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGT

ACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAG

TACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCC aaagccaaagggcagccccgagagccacaggtgtacaccctgcccccatcccagga ggagatgaccaagaaccaggtcagcctgacctgcctqgtcaaaggcttctacccca

GCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGAC

CACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGT

GGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGG

CTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCT

GA 抗-蘭格素2G3H-LV-hIgG4H-C(SEQ ID NO:119):

MTLNMLLGLRWVFFWFYQGVHCEVQLVESGGGLVQPKGSLKLSCAASGLTFN

IYAMNWVRQAPGKGLEWVARIRNKSNNYATYYADSVKDRFTISRDDSQSLLYLQMNN

LKTEDTAMYYCVGRDWFDYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCL

VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVS -67- 162948.doc 201247706

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVS

NKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN

GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLS LSLGKAS. 抗-蘭格素2G3L-LV-hIgGK-C(SEQ ID NO:55):

ATGGCCTGGATTTCACTTATACTCTCTCTCCTGGCTCTCAGCTCAGGGGCCAT

TTCCCAGGCTGTTGTGACTCAGGAATCTGCACTCACCACATCACCTGGTGAAACAGT

CACACICACTTGTCXjCTCAAGTACTGGGGCTGTTACAACTAGTAACTATGCCAACTG

GGTCCAAGAAAAACCAGATCATTTATTCACTGGTCTAATAGGTGGTACCAACAACCG

AGTTTCAGGTGTTCCTGCCAGATTCTCAGGCTCCCTGATTGGAGACAAGGCTGCCCT

CACCATCACAGGGGCACAGACTGAGGATGAGGCAATATATTTCTGTGCTCTATGGTA

CAGCAACCATTGGGTGTTCGGTGGAGGAACCAAACTCGAGATCAAACGAACTGTGG

CTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAA

GGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACA

GCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTAC

GAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGT

CACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-蘭格素 2G3L-LV-hIgGK-C(SEQ ID NO:120): mawislelsllalssgaisqawtqesalttspgetvtltcrsstgavttsnyanw

VQEKPDHLFTGLIGGTNNRVSGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNH

WVFGGGTKLEKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE

C 抗-Lox_l_10F9H-LV-hIgG4H-C(SEQ ID NO:56):

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCA

CTCCCAGGTTCAGCTGCAGCAGTCTGGAGCTGAGCTGATGAAGCCTGGGGCCTCAGT

GAAGATATCCTGCAAGGCTACTGGCTACACATTCGGTAGCTACTGGATAGAGTGGGT

AAAGCAGAGGCCTGGACATGGCCTTGAGTGGATTGGAGAGATTTTACCTGGAAGTG

GTAATACTAACTACAATGAGAACTTCAAGGGCAAGGCCACATTCACTGCAGATACA

TCCTCCAACACAGCCTACATGCAACTCACCAGTCTGACATCTGAGGACTCTGCCGTC

TATTACTGTGCTAGGGCGGGGATTTATTGGGGCCAAGGGACTCTGGTCACTGTCTCT

GCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCAC

CTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT -68 - 162948.doc 201247706

GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAG

CTTGGGCACGAAGACCTACACCTGfCAACGTAGATCACAAGCCCAGCAACACCAAGG

TGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTG

AGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCA

TGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGAC

CCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGAC

AAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG

TCCTGCACCAC3GACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA

GGCCTCCCGTCCTCCAICGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA

GCCACAGGTGTACACCCTGCCCCCATCCCACKJAGGAGATGACCAAGAACCAGGTCA

GCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG

AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA

CGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGG

GGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGA

AGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗-Lox_l_10F9H-LV-hIgG4H-C(SEQ ID NO:121):

MEWTWVFLFLLSVTAGVHSQVQLQQSGAELMKPGASVKISCKATGYTFGSYWI

EWVKQRPGHGLEWIGEILPGSGNTNYNENFKGKATFTADTSSNTAYMQLTSLTSEDSAV

YYCARAGIYWGQG1TLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP\rrV

SWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRV

ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTIS

KAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTIPP

VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-Lox_l —10F9K-LV-hIgGK-C(SEQ ID NO:57):

TGAAA 5CCAAA

ATGGAGAAAGACACACTCCTGCTATGGGTCCTGCTTCTCTGGGTTCCAGGTTC CACAGGTGACATTGTGCTGACCCAATCTCCAGCTTTTTTGGCTGTGTCTCTAGGGCA GAGGGCCACCATCTCCTGCAGAGCCAGCGAAAGTGTTGATAATTATGGCATTAGTTT TATGAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGTTGC ATCCAAGCAAGGATCCGGGGTCCCTGCCAGGTTTAGTGGCAGTGGGTCTGGGACAG ACTTCAGCCTCAACATCCATCCTATGGAGGAGGATGATACTGCAATGTATTTCTGTC AGCAAAGTAAGGAGGTTCCTCGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAA CGAACTGTGGCTGCACX：ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTC TCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGC 162948.doc -69- c 201247706

GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCAC

AGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Lox_l_10F9K-LV-hIgGK-C(SEQ ID NO:122):

MEKDTLLLWVLLLWVPGSTGDIVLTQSPAFLAVSLGQRATISCRASESVDNYGIS

FMNWFQQKPGQPPKLLIYVASKQGSGVPARFSGSGSGTDFSLNIHPMEEDDTAMYFCQ

QSKEVPRTFGGGTKLEIKRTVAAPSWIFPPSDEQLKSGTASWCLLNNFYPREAKVQWK

VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGEC 抗-LOX-lllC8H-LV-hIgG4H-C(SEQ ID NO:58):

ATGGAATGTAACTGGATACTTCCTnTATTCTGTCGGTAACTTCAGGGGTCTA

CTCAGAGGTTCAGCTCCAGCAGTCTGGGACTGTGCTGGCAAGGCCTGGGGCTTCAGT

GAAGATGTCCTGCAAGGCTTCTGGCTACACCTTTACCAGCTACTGGATGCACTGGGT aaaacagaggcctggacagggtctggaatggattggcgctatttatcctggaaata

GTGATACTACCTACAACCAGAAGTTCAAGGGCAAGGCCAAACTGACTGCAGTCACA

TCCACCAGCACTGCCTACATGGAGCTCAGCAGCCTGACAAATGAGGACTCTGCGGT

CTATTACTGTACACCTACTTACTACTTTGACTACTGGGGCCAAGGCACCTCTCTCACA

GTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGG

AGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGA

ACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC

CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT

CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAAC

ACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCC

AGCACXTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGG

ACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCC

AGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAAT gccaagacaaagccgcgggaggagcagttcaacagcacgtaccgtgtggtcagcgt

CCTCACCGI€CTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCT

CCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAG ccccgagagccacaggtgtacaccctgcccccatcccaggaggagatgaccaagaa

CCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGA

GTGGGAGAGCAATGGGCAC5CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGG

ACTCCGAajGCTCCTTCITCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGC

AGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACA

CACAGAAGAGCCTCTCCCTGTCTCTGGGT/L^iAGCTAGCTGA -70- 162948.doc 201247706 抗-LOX-lllC8H-LV-hIgG4H-C(SEQ ID NO:123):

MECNWILPFILSVTSGVYSEVQLQQSGTVLARPGASVKMSCKASGYTFTSYWMH

WVKQRPGQGLEWIGAIYPGNSDTTYNQKFKGKAKLTAVTSTSTAYMELSSLTNEDSAV

YYCTPTYYFDYWGQGTSLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT

VSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKR

VESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPKVTCWVDVSQEDPEVQFNW

YVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKT

ISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-LOX-lllC8K-LV-hIgGK-C(SEQ ID NO:59):

ATGAGTCCTGCCCAATTCCTGTTTCTGTTAGTGCTCTGGATTCGGGAAACCAA

CGGTGATGTTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACC

AGCCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAGACATA tttgaattggttcttacagaggccaggccagtctccaaagcgcctaatctatctggt gtctaaactggactctggagtccctgacaggttcactggcagtggatcagggacag

ATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCT

GGCAAGGTACACATTTTCCGTGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAA

CGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAA

TCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA

GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCAC

AGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-LOX-lllC8K-LV-hIgGK-C(SEQ ID NO:124):

MSPAQFLFLLVLWIRETNGDWMTQTPLTLSVTIGQPASISCKSSQSLLDSDGiaY

LNWFLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQG

THFPWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKV

DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGEC 抗-LOX-115C4H-LV-hIgG4H-C(SEQ ID NO:60):

ATGGGAGGGATCrGGATCTTTCTCITCCTCCTGTCAGGAACTGCAGGTGCCCA

CTCTGAGATCCAGCTGCAGCAGACTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGT

GAAGATATCCTGCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGGT 162948.doc -71 - 201247706

GAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGAAATATTAGTCCTTACTATG

GTACTACTAACTACAATCTGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAA

TCTTCCAGCACAGCCTACATGCAGCTCAACAGTCTGACATCTGAGGACTCTGCAGTC

TATTACTGTGCAAGATCCCCTAACTGGGACGGGGCCTGGTTTGCTCACTGGGGCCAA

GGGGCTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTG

GCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAA

GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG

GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG

TGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCC

ATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCG

TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA

AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTG

ATTAATTAA 抗-LOX-115C4H-LV-hIgG4H-C(SEQ ID NO:125):

MGGIWEFLFLLSGTAGAHSEIQLQQTGPELVKPGASVKISCKASGYPFTDYIMVW

VKQSHGKSLEWIGNISPYYGTTNYNLKFKGKATLTYDKSSSTAYMQLNSLTSEDSAVYY

CARSPNWDGAWFAHWGQGALVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTK

VDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEV

QFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPS

SIE^SKAKGQPREPQVYTLPPSQEEMnKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗-LOX-115C4K-LV-hIgGK_C(SEQ ID NO:61):

ATGGAGACAGACACAATCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGCT

CCACTGGTGACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCA 162948.doc -72- 201247706

GAGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTTA

TATGAACTGGTTCCAACAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGCTGC

ATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAG

ACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTC

AGCAAAGTAATGAGGATCCATTCACGTTCGGCTCGGGGACAAAGCTCGAGATCAAA

CGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAA

TCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA

GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCAC

AGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-LOX-115C4K-LV-hIgGK-C(SEQ ID NO:126):

METDmLWVLLLWVPGSTGDIVLTQSPASLAVSLGQR/mSCKASQSVDYDGDS

YMNWFQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQS nedpftfgsgtkleikrtvaapsvfifppsdeqlksgtaswcllnnfypreakvqwkvd

NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN

RGEC 抗-Marco_10B7.3G4H-LV-hIgG4H-C(SEQ ID NO:62):

ATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACGTTCCCAAGCTGTGTCCT

GTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCACCCTCACAGAGCC

TGTCCATCACATGCACTGTCTCTGGGTTCTCATTATCCAGATATAGTGTATTTTGGGT

TCGCCAGCCTCCAGGAAAGGGTCTGGAGTGGCTGGGATTGATATGGGGTGGTGGAA

GCACAGACTATAATTCAGCTCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCC

AAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGATGACACAGCCATGTA

CTACTGTGCCAGAATCTACTTTGATTACGACGGGGCTATGGACTACTGGGGTCAAGG

AACCTCAGTCACCGTCTCCTCAGCCAAAACAACGGGCCCATCCGTCTTCCCCCTGGC

GCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGG

ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC

GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG

GTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCAT

GCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG

GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGT

GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC £ 162948.doc -73- 201247706

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA

AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTG 抗-Marco_10B7.3G4H-LV-hIgG4H-C(SEQ ID NO:127):

MAVLGLLLCLVTFPSCVLSQVQLKESGPGLVAPSQSLSITCTVSGFSLSRYSVFW

VRQPPGKGLEWLGLIWGGGSTDYNSALKSRLSISKDNSKSQVFLKMNSLQTDDTAMYY

CARIYFDYDGAMDYWGQGTSVTVSSAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFP

EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTIC

VDKRA/ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEV qfnwyvdgvevhnaktkpreeqfnstyrwsvltvlhqdwlngkeykckvsnkglps

SIEKBSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCXVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗Marco_10B7.3G4K_H-V-hIgGK-C(SEQ ID NO:63):

ATGCATCGCACCAGCATGGGCATCAAGATGGAGTCACGGATTCAGGCATTTG

TATTCGTGTITCTCTGGTTGTCTGGTGTTGGCGGAGACATTGTGATGACCCAGTCTCA

CAAATTCATGTCCACATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTC

AGGATGTGACTTCTGCTGTAGCCTGGTATCAACAAAAACCAGGGCAATCTCCTAAAC

TACTGATTTACTGGGCATCCACCCGGCACACTGGAGTCCCTGATCGCTTCACAGGCA

GTGGATCTGGGACAGATTATACTCTCACCATCAGCAGTGGGCAGGCTGAAGACCTG

GCACTTTATTACTGTCACCAATATTATAGCGCTCCTCGGACGTTCGGTGGAGGCACC

AAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTAT

CCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTC

CCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGC

ACCCTOACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGT

CACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTT

AG 抗Marco_10B7.3G4K_H-V-hIgGK-C(SEQ ID NO:128):

MHRTSMGIKMESRIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCK -74- 162948.doc 201247706

ASQDVTSAVAWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLTISSGQAEDL

ALYYCHQYYSAPRTFGGGTKLEIKRTVAAPSWIFPPSDEQLKSGTASWCLLNNFYPRE

AKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEBCHKVYACEVTHQGL

SSPVTKSFNRGEC 抗·Marco_llA8:3C9_H-V-hIgG4H-C(SEQ ID ΝΟ:6·4):

ATGGAATGGAACTGGGTCGTTCTCTTCCTCCTGTCATTAACTGCAGGTGTCTA

TGCCCAGGGTCAGATGCAGCAGTCTGGAGCTGAGCTGGTGAAGCCTGGGGCTTCAG

IXjAAGCTGTCCTGCAAGACTTCTGGCTTCACCTTCAGCAGTAACTATATAAGTTGGT

TGAAGCAAAAGCCTGGACAGAGTCTTGAGTGGATTGCATGGATTTATGCTGGAACT

GGTGGTATTACCTATAATCAGAAGTTCAGAGGCAGGGCCCAACTGACTGTAGACAC

ATCCTCCAGCACAGCCTACATGCAGTTCAGCAGCCTGACAACTGATGACTCTGCCAT

CTATTACTGTGCAAGACACGTGAGGGGTTACCATCCTATGGACTACTGGGGTCAAGG

AACCTCAGTCACCGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGC

GCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGG

ACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC

GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG

GTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCAT

GCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTG

GTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGT

GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTAC

CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTA

CAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCA

AAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTG

GACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGC

TCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTG

A 抗-Marco_llA8.3C9_H-V-hIgG4H-C(SEQ ID NO:129):

MEWNWWLFLLSLTAGVYAQGQMQQSGAELVKPGASVKLSCKTSGFTFSSNYI

SWLKQKPGQSLEWIAWIYAGTGGUYNQKFRGRAQLTVDTSSSTAYMQFSSLTTDDSAI

YYCARHVRGYHPMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCXVKDY 162948.doc -75- 201247706

FPEPVTVSWNSGALTSGVHTFPAVLQSSGmSSWTVPSSSLGTKTYTCNVDHKPSNT

KVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPE

VQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG

KAS 抗-Marco_llA8.3C9_H-V-hIgGK-C(SEQ ID NO:65):

ATGGAGTCACAGACTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGT

TGATGGAGACATTGTGATGACCCAGTCTCAAAAATTCATGTCCGCATCAGTAGGGGA cagggtcagcgtcacctgcagggccagtcagaatgtggttactaatgtaggctggt

ATCAACAGAAACCAGGGCAATCTCCTAAAGTACTGATTTACTCGGCATCCTTCCGGT

ACAGTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCA

CCATCACCAATGTGCAGTCTGAAGACTTGGCAGAGTATTTCTGTCAGCAATATAACA

ACTATCCGTACACGTTCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCT

GCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT

CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGG

TGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGC

AAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA

GAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCA

CAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Marco_llA8.3C9_H-V-hIgGK-C(SEQ ID NO:130):

MESQTQVFVYMLLWLSGVDGmVMTQSQKFMSASVGDRVSVTCRASQNWTN

VGWYQQKPGQSPKVLIYSASFRYSGVPDRFTGSGSGTDFTLIITNVQSEDLAEYFCQQY

NNYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKV

DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGEC 抗-Marco_3H10.1F3_H-V-hIgG4H-C(SEQ ID NO:66):

ATGGGATGGAGCTATATCATCCTCmTTGGTAGCAACAGCTACAGATGTCCA

CTCCCAGGTCCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGCTTCAG

TGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGG

TGAAGCAGAGGCCTGGAGAAGGCCTTGAGTGGATTGGAGAGATTAATCCTAGCTAC

GGTCGTACTGACTACAATGGGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAA

ATCCTCCAGCACAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGT

CTATTACTGTGCAAGAGGAGATTACTACGGTAGTAGCTCGTTTGCTTACTGGGGCCA 162948.doc -76- 201247706

AGGGACTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCT

GGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCA

AGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC

GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC

GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGA

TCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCC

CATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCC

CCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGG

TGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGC

GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTA

CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGT

ACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCC

AAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGA

GGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCA

GCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGAC

CACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGT

GGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGG

CTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCT

GA 抗-Marco_3H10.1F3_H-V-hIgG4H-C(SEQ ID NO:131):

MGWSYIILFLVATATDVHSQVQLQQPGAELVKPGASVKLSCKASGYTFTSYWM

HWVKQRPGEGLEWIGEINPSYGRTDYNGKFKNKATLTVAKSSSTAYMQLSSLTSEDSA

VYYCARGDYYGSSSFAYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPS

NTKVDKRVESKTOPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVIX^WDVSQED

PEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNK

GLPSSIEOISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKAS 抗-Marco_3H10.1F3_K-V_hIgGK-C(SEQ ID NO:67):

ATGGAGTCACAGACTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGT

TGATGGAGACATTGTGATGACCCAGTCTCAAAAATTGATGTCCACATCATTAGGAGA

CAGGGTCAGCGTCACCTGCAAGGCCAGTCAGAATGTGGGTACTAATGTAGCCTGGT

ATCAACAGAAACCAGGGCACTCTCCTAAAGCACTGATTTACTCGGCATCCTACCGGT

ACAGTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCA c 162948.doc - 77 - 201247706

CCATCAGCAATGTGCAGTCTGAAGACITGGCAGAGTmTCTGTCAGCAATATAACA

ACTATCCGTACACGTTCGGAGGGGGGACCACGCTCGAGATCAAACGAACTGTGGCT

GCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT

CTGTTGTGTGCCTGCTGAATAACTTCTAT(XCAGAGAGGCCAAAGTACAGTGGAAGG

TGGATAACGCCCTCCAATCGGGTAACTCX：CAGGAGAGTGTCACAGAGCAGGACAGC

AAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGA

GAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCA

CAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗-Marco_3H10.1F3_K-V-hIgGK-C(SEQ ID NO:132):

MESQTQVFVYMLLWLSGVDGDIVMTQSQKFMSTSLGDRVSVTCKASQNVGTN

VAWYQQKPGHSPKALIYSASYRYSGVPDRFTGSGSGTDFTUnSNVQSEDLAEFFCQQY

NNYPYTFGGGTTLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKV

DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGEC 本發明之抗原包含一或多種來自以下各者之病毒抗原或 肽：腺病毒（adenovirus)'反轉錄病毒（retrovirus)、小核糖 核酸病毒（picornavirus)、疮療病毒（herpesvirus)、輪狀病 毒、漢坦病毒（hantaviruse)、冠狀病毒（coronavirus)、彼衣 病毒（togavirus)、黃病毒（flavirvirus)、棒狀病毒 (rhabdovirus)、副黏液病毒（paramyxovirus)、正黏液病毒 (orthomyxovirus)、崩芽病毒（bunyavirus)、沙粒狀病毒 (arenavirus)、里奥病毒（reovirus)、乳頭瘤病毒 (papilomavirus)、小病毒（parvovirus)、痘病毒（poxvirus)、 嗜肝DNA病毒（hepadnavirus)，或海綿狀病毒（spongiform virus)、HIV、CMV、A型肝炎、B型肝炎及C型肝炎、流 感；麻疹、脊髓灰質炎、天花、風疹；呼吸道融合性病 毒、單純癌療病毒、水痘帶狀癌療病毒、愛潑斯坦-巴爾 病毒、日本腦炎病毒、狂犬病毒、流感病毒或冷病毒。抗 162948.doc • 78- 201247706 原係選自：Nef(66-97) : VGFPVTPQVPLRPMTYKAAVDL SHFLKEKGGL(SEQ ID NO:154) ； Nef(116-145) ： HTQGYF PDWQNYTPGPGVRYPLTFGWLYKL(SEQ ID NO:155)； Gag pl7(17-35) ： EKIRLRPGGKKKYKLKHIV(SEQ ID NO: 156) ； Gag pl7-p24(253-284) ： NPPIPVGEIYKRWIILGLNK IVRMYSPTSILD(SEQ ID NO:157);及/或 Pol 325-355(RT 158-188)為：AIFQSSMTKILEPFRKQNPDIVIYQYMDDLY(SEQ ID NO:158)。在一個態樣中，該抗原為19至32個殘基且選 自在MHC I類分子之情況下所呈現的HIV-1 Nef、Gag及 Env蛋白質中鑑別之細胞毒性T淋巴細胞（CTL)抗原決定 基。在另一態樣中，Ag係選自HIV gpl20、gp41、Gag、 pl7、p24、p2、p7、pi、p6、Tat、Rev、PR、RT、IN、 Vif、Vpr、Vpx、Vpu及 Nef o 在另一態樣中，抗原係選自腫瘤相關抗原，該等腫瘤相關 抗原係選自CEA、前列腺特異性抗原（PSA)、HER-2/neu、 BAGE、GAGE、MAGE 1-4、MAGE 6 及 MAGE 12、 MUC(黏蛋白）（例如MUC-1、MUC_2等）、GM2及GD2神經 節苷脂、ras、myc、絡胺酸酶、MART(黑色素瘤抗原）、 MARCO-MART、細胞週期素B1、細胞週期素D、Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移酶 V内含子V序列）、前列腺癌psm、前列腺血清抗原（PSA)、 PRAME(黑色素瘤抗原）、β-索烴素、MUM-1-B(黑色素瘤 遍佈突變基因產物）、GAGE(黑色素瘤抗原）1、BAGE(黑色 素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(愛潑斯坦-巴爾 162948.doc -79- 201247706 病毒核抗原）1-6、gp75、人類乳頭狀瘤病毒（HPV)E6及 E7、p53、肺对藥蛋白質（LRP)、Bcl-2及Ki-67。在另一態 樣中、Ag係選自包含來自以下各者之抗原的腫瘤相關抗 原：白血病及淋巴瘤、諸如星形細胞瘤或神經膠母細胞瘤 之神經性腫瘤、黑色素瘤、乳癌、肺癌、頭頸部癌症、胃 腸腫瘤、胃癌、結腸癌、肝癌、胰臟癌、諸如子宮頸癌、 子宮癌、卵巢癌、陰道癌、睪丸癌、前列腺癌或陰莖癌之 泌尿生殖腫瘤、骨腫瘤' 血管瘤、或唇、鼻咽、咽及口 腔、食道、直腸、膽囊、膽道、喉、肺及支氣管、膀胱、 腎、腦部及神經系統其他部分之癌症、曱狀腺癌、霍奇金 氏病、非霍奇金氏淋巴瘤、多發性骨趙瘤及白血病。

Ag係選自以下中之至少一者： MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPW QVLVASRGRAVCGGVLVHPQWV(SEQ ID NO:133)； LTAAHCIRNKSVILLGRHSLFHPEDTGQVFQVSHSFPHPL YDMSLLKNRFLRPGDDSSHD(SEQ ID NO:134)； LMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWG SIEPEEFLTPKKLQCVDLHVIS(SEQ ID NO:135)； NDVCAQVHPQKVTKFMLCAGRWTGGKSTCSGDSGGPL VCNGVLQGITSWGSEPCALPERP(SEQ ID NO:136);或 SLYTKVVHYRKWIKDTIVANP(SEQ ID NO:137)。 在另一態樣中，Ag係選自以下中之至少一者： IMDQVPFSV(SEQ ID NO:138)； ITDQVPFSV(SEQ ID NO:139)； 162948.doc -80 * 201247706 YLEPGPVTV(SEQ ID NO:140)； YLEPGPVTA(SEQ ID NO:141)； KTWGQYWQV(SEQ ID NO:142)； DTTEPATPTTPVTTPTTTKVPRNQDWLGVSRQLRTKAW NRQLYPEWTEAQRLDCWRGGQVSLKVSNDGPTLIGANAS FSIALNFPGSQKVLPDGQVIWVNNTIINGSQVWGGQPVYP QETDDACIFPDGGPCPSGSWSQKRSFVYVWKTWGQYWQ VLGGPVSGLSIGTGRAMLGTHTMEVTVYHRRGSQSYVPL AHSSSAFTITDQVPFSVSVSQLRALDGGNKHFLRNQ(SEQ ID NO:143)； PLTFALQLHDPSGYLAEADLSYTWDFGDSSGTLISRAXV VTHTYLEPGPVTAQVVLQAAIPLTSCGSSPVPAS(SEQ ID NO: 144) ； GTTDGHRPTAEAPNTTAGQVPTTEVVGTTPGQAPTAEPS GTTSVQVPTTEVISTAPVQMPTAESTGMTPEKVPVSEVMG TTLAEMSTPEATGMTPAEVSIVVLSGTTAA(SEQ ID NO: 145) ； QVTTTEWVETTARELPIPEPEGPDASSIMSTESITGSLGP LLDGTATLRLVKRQVPLDCVLYRYGSFSVTLDIVQ(SEQ ID NO:146);及 GIESAEILQAVPSGEGDAFELTVSCQGGLPKEACMEISSP GCQPPAQRLCQPVLPSPACQLVLHQILKGGSGTYCLNVSL ADTNSLAVVSTQLIVPGILLTGQEAGLGQ(SEQ ID NO:147) 及其片段》 c 162948.doc -81- 201247706 在另一態樣中，Ag係選自以下中之至少一者：ΜΕΜΚ ILRALNFGLGRPLPLHFLRRASKIGEVDVEQHTLAKYLME LTMLDY(SEQ ID ΝΟ:148);及 DWLVQVQMKFRLLQETMYMTVSIIDRFMQNNCVPKK(S EQ ID NO:149)。 在另一態樣中，Ag係選自以下中之至少一者： MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETC APSVSYFKCV(SEQ ID NO:150)； QKEVLPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLD RFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIY TDNSIRPEELLQMELL(SEQ ID NO:151)； LVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRKH AQTFVALCATDVKFISNPPSMV(SEQ ID NO:152);及 AGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCDPDC LRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDL ACTPTDVRDVDI(SEQ ID NO:153)及其片段。 在另一態樣中，Ag為19至32個胺基酸長。在另一態樣 中，Ag為17至60個胺基酸長且選自於PSA或細胞週期素1 中鑑別之細胞毒性T淋巴細胞（CTL)抗原決定基。 在另一態樣中，癌症肽係選自腫瘤相關抗原，該等腫瘤 相關抗原係選自CEA、前列腺特異性抗原（卩3八）、1^尺-2/neu、BAGE、GAGE、MAGE 1-4、MAGE 6 及 MAGE 12、MUC(黏蛋白）（例如 MUC-1、MUC-2 等）、GM2 及 GD2 神經節苷脂、ras、myc、路胺酸酶、MART(黑色素瘤抗 162948.doc •82· 201247706 原）、MARCO-MART、細胞週期素B1、細胞週期素〇、 Pmel 17(gpl00)、GnT-V内含子V序列（N-乙酿基葡糖胺基 轉移酶V内含子V序列）、前列腺癌psm、前列腺血清抗原 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素、MUM-1-B(黑色 素瘤遍佈突變基因產物）、GAGE(黑色素瘤抗原）1、bage (黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(愛潑斯 坦-巴爾病毒核抗原）1 -6、gp75、人類乳頭狀瘤病毒（HPV) E6及 E7、p53、肺对藥蛋白質（LRP)、Bcl-2及 Ki-67。 圖1A至圖1C展示如本發明中所述之TLR7L變體之化學結 構。圖2A至圖2C展示本發明之TLRg、TLRf及TLRf變體在 1 0 nM、100 nM、1 μΜ及10 μΜ之濃度下的劑量滴定。活 性係用IL-6(圖2Α)、IL-8(圖2Β)、IL-Ιβ(圖2C)之分泌 (pg/ml)來衡量e劑量滴定曲線指示3種不同TLR7-L化合物 之活性十分相似。全部3種化合物在100 nM下仍有效； 圖2D至圖2G展示本發明之TLRg、TLRf及TLRf’變體在 12.5 nM、25 nM、50 nM及100 nM之濃度下的劑量滴定。 活性係用 IL-6(圖 2D)、IL-8(圖 2E)、IL-Ιβ(圖 2F)及 IL-12p40(圖2G)之分泌來衡量。劑量滴定曲線指示TLRf·略 微更有效且在25 nM下仍偵測到其活性； 圖3A及圖3B展示與靶向DC之mAb連接之TLR7L增強且 限制佐劑活性。與CohFluMl連接之TLR7L之活性視靶向抗 體而定。與CohFluMl連接之TLR7L或單獨CohFluMl僅在 最高30 nM劑量下有效。此外，在以與TLR7L連接之抗 DCIR及抗CD40抗體所誘導之細胞因子之效能及相對量，方 162948.doc -83 - 201247706 面存在差異。圖3C為本發明之一實施例之11<尺7配位體的 化學結構。 預期本說明書中論述之任何實施例可關於本發明之任何 方法、套組、試劑或組合物加以實施，且反之亦然。此 外，本發明之組合物可用以實現本發明之方法。 應瞭解，本文所述之特定實施例為了說明而展示，而非 限制本發明。本發明之主要特徵可在不脫離本發明範疇之 情況下用於各種實施例中。熟習此項技術者將認識到或能 夠僅僅使用常規貫驗來確定本文所述之特定程序的眾多等 效形式。該等等效形式被視為屬於本發明之範疇内且由申 請專利範圍所涵蓋。 本說明書中提及之所有公開案及專利申請案均指示熟習 本發明所屬技術者之技能水準。所有公開案及專利申請案 均以引用的方式併入本文中，該引用的程度就如同已特定 及個別地將各個別公開案或專利申請案以引用的方式併入 一般。 當在申請專利範圍及/或本說明書中與術語「包含」一 起使用時，字詞「一（a/an)」之使用可意謂「一個（種）」， 但其亦與「一或多個（種）」、「至少一個（種）」及「一個 (種）或一個（種）以上」之含義一致。除非明確指示僅係指 替代形式或替代形式互相排斥，否則在申請專利範圍中使 用術夂或」用於意謂「及/或」，不過本發明支持僅係 指替代形式及「及/或」之定義。在整個本申請案中術 語「約」用於指示值包括用以測定該值之裴置、方法固有 162948.doc • 84 - 201247706 的誤差變化或研究個體間存在之變化。 如本说明書及申請專利範圍中所使用，詞語「包含 (comprising)」（及包含之任何形式，諸如「包含 (C〇mpnSe)」及「包含（comprises)」）、「具有（having)」 (及具有之任何形式，諸如「具有（have)」及「具有 (has)」）、「包括（including)」（及包括之任何形式，諸如 「包括（includes)」及「包括（include)」）或「含有 (containing)」（及含有之任何形式，諸如「含有 (contains)」及「含有（c〇ntain)」）為包括性的或開放性的 且不排除額外、未陳述之要素或方法步驟。 如本文中所用之術語「或其組合」係指該術語前面所列 項目之所有排列及組合。舉例而言，「a、B、C或其組 合」思欲包括以下至少一者：A、b、c ' AB、AC、BC或 ABC，且若在特定情形下次序具有重要意義，則亦包括 BA、CA、CB、CBA、BCA、ACB、BAC 或 CAB。繼續關 於此實例，明確地包括含有重複出現一或多個項目或術語 的組合，諸如 BB、AAA、MB、BBC、AAABCCcc、 CBBAAA、CABABB，諸如此類。熟練技術人員應瞭解， 除非另外自上下文清楚瞭解，否則通常在任何組合中對項 目或術語之數目均無限制。 根據本發明，可形成並實施本文中所揭示並主張之所有 組合物及/或方法，而無需不適當之實驗。雖然已用較佳 貫施例來描述了本發明之組合物及方法，但熟習此項技術 者可顯而易見，在不脫離本發明之概念、精神及範疇之情 162948.doc -85 - 201247706 況下，可對本文所描述之組合物及/或方法及方法之步驟 或方法之步驟順序作出變更。認為熟習此項技術者易於瞭 解之所有該等類似替代及修改在如隨附申請專利範圍所界 定之本發明之精神、範_及概念的範圍内。 參考文獻 美國專利申請案第20090004194號：TLR Ag〇nist (Flagellin)/CD40 Agonist/Antigen Protein and DNA Conjugates and use thereof for Inducing Synergistic Enhancement in Immunity ° 美國專利申請案第 20080220011號：Use of Flagellin in

Tumor Immunotherapy 0 美國專利中請案第 20080248068號：Use of Flagellin as an Adjuvant for Vaccine。 美國專利第 7,404,963號：Flagellin-Based Adjuvants and Vaccines ° 【圖式簡單說明】 圖1A至圖1C展示如本發明中所述之TLR7L變體之化學結 構； 圖2Α至圖2C展示本發明之TLRg、TLRf及TLRf，變體在 10 πΜ、100 nM、1 μΜ及10 μΜ之濃度下的劑量滴定。活 性係用IL-6(圖2Α)、IL-8(圖2Β)、IL-Ιβ(圖2C)之分泌 (pg/ml)來衡量。劑量滴定曲線指示3種不同TLR7-L化合物 之活性十分相似。全部3種化合物在100 nM下仍有效； 圖2D至圖2G展示本發明之TLRg、TLRf及TLRf，變體在 162948.doc -86· 201247706 12.5 nM、25 nM、50 nM及100 nM之濃度下的劑量滴定。 活性係用 IL-6(圖 2D)、IL-8(圖 2Ε)、IL-Ιβ(圖 2F)及 IL-12p40(圖2G)之分泌來衡量。劑量滴定曲線指示TLRf'略微 更有效且在25 nM下仍偵測到其活性； / 圖3A及圖3B展示與靶向DC之mAb連接之TLR7L增強且 ^ 限制佐劑活性。與CohFluMl連接之TLR7L之活性視靶向抗 體而定。與CohFluMl連接之TLR7L或單獨CohFluMl僅在 最高30 nM劑量下有效。此外，在以與TLR7L連接之抗 DCIR及抗CD40抗體所誘導之細胞因子之效能及相對量方 面存在差異；且 圖3C為本發明之一實施例之TLR7配位體的化學結構。 162948.doc -87 - 201247706 序列表 <110>美商貝勒研究協會 <no>以靶向直接對抗原呈現細胞之抗體的佐劑為基礎之新穎疫苗佐劑 <130> BHCS:2477n¥ <140> 101107940 <141> 2012/03/08 <150> 61/450,480 <151> 2011-03-08 <160> 160 <170> Patcntln version 3.5 <210> 1 <211> 430 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 1

Met Asp Leu Asp Ala Val Arg lie Lys VaL Asp Thr Val Asn Ala Lys 15 10 15

Pro Gly Asp Thr Val Asn lie Pro Val Aig Phe Ser Gly lie Pro Ser 20 25 30

Lys Gly lie Ala Asn Ala Asp Phe Val Tyr Scr Tyr Asp Pro Asn Val 35 40 45

Leu G!u lie lie GIu Jlc Lys Pro Gly Glu Leu lie Va] Asp Pro Asn 50 55 60

Pro Thr Lys Ser Phe Asp Thr Ala Val Tyr Pto Asp Arg Lys Met lie 65 70 75 80

Val Phe Leu Phe Ala Glu Asp Ser Gly Thr Gly Ala Tyr Ala lie Thr 85 90 95

Lys Asp Gly Val Phe Ala Thr He Val Ala Lys Val Lys Glu Gly Ala 100 105 . 110

Pro Asn Gly Leu Ser Val lie Lys Phe Val Glu Val Gly Gly Phe Ala 115 120 125

Asn Asn Asp Leu Val Glu Gin Lys Thr Qln Phe Phe Asp Gly Gly Val 130 135 140

Asn Val Gly Asp Thr Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr 145 150 155 L60

Thr Pro Thr Thr Thr Asp Asp Leu Asp Ala Ala Ser Leu Leu Thr Glu 165 170 175

Val Glu Thr Tyr Val Leu Ser lie He Pro Ser Gly Pro Leu Lys Ala 180 185 190 162948-序列表.doc 201247706

Glu He Ala (Jin Arg Leu Glu Asp Val Phe Ala Gly Lys Asn Thr Asp 195 200 205

Leu Glu Val Leu Met Glu Trp Leu Lys Ήιγ Arg Pro lie Leu Ser Pro 210 215 220

Leu Thr Lys Cly He Leu Gly Phe Val Phe Thr Leu Thr Val Pro Ser 225 230 235 240

Glu Arg Gly Leu Gin Arg Arg Arg Phe Val Gin Asn Ala Leu Asn Gly 245 250 255

Asn Gly Asp Pro Asn Asn Met Asp Lys Ala Val Lys Leu Tyt Arg Lys 260 265 270

Leu Lys Arg Glu lie Thr Phe His Gly Ala Lys Glu lie Ala Leu Ser 275 280 285

Tyr Ser Ala Gly Ala Leu Ala Ser Cys Met Gly Leu He Tyr Asn Arg 290 295 300

Met Gly Ala Val Thr Thr Glu Val Ala Phe Gly Leu Val Cys Ala Thr 305 310 315 320

Cys Glu Gin He Ala Asp Ser Gin His Arg Ser His Arg Gin Met Val 325 330 335

Thr Thr Thr Asn Pro Leu lie Arg His Glu Asn Arg Met Val Leu Ala 340 345 350

Ser Thr Thr Ala Lys Ala Met Glu Gin Met Ala Gly Ser Ser Glu Gin 355 360 365

Ala Ala Glu Ala Met Asp lie Ala Ser Gin Ala Arg Gin Met Val Gin 370 375 380

Ala Met Arg Thr He Gly Thr His Pro Ser Ser Ser Ala Gly Leu Lys 385 390 395 400

Asp Asp Leu Leu Glu Asn Leu Gin Ala Tyr Gin Lys Arg Met Gly Val 405 410 415

Gin Met Gla Arg Phe Lys Leu Glu His His His His His His 420 425 430 <210> 2 <211> 513 <212> PRT <2】3>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 2

Gin Val Thr Leu Lys Glu Ser Gly Pro Gly lie Leu Gin Pro Ser Gin 15 10 15 -2 * 162948-序列表.doc 201247706

Thr Leu Ser Leu Thr Cys Sei Phe Scr Gly Phe Ser Leu Scr Thx Ser 20 25 30

Gly Met Gly Leu Ser Trp lie Arg Gin Pro Ser Gly Lys Gly Leu (Jlu 35 40 45

Trp Leu Ala His lie Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 50 55 60

Leu Lys Scr Arg Leu Thr lie Ser Lys Asp Thi Ser Ser Asn Gin Val 65 70 75 80

Phe Leu Lys He Thr lie Val Asp Thr Ala Asp Ala Ala Thr Tyr Tyr 85 90 95

Cys Ala Arg Ser Scr His Tyr Tyr Gly Tyr Gly Tyi Gly Gly Tyr Phe 100 105 110

Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr 115 120 125

Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Set Thr Ser 130 135 140 GIu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 ISO 155 160

Pro Val Thr Val Scr Trp Asn Ser Gly Ala Leu Thr Ser Cly Val His 165 170 175

Thr Phe Pro Ala Val Leu Gin Ser Ser Qly Leu Tyr Ser Leu Ser Ser 180 185 190

Val Val Thr Val Pro Scr Scr Ser Leu Qly Thr Lys Thr Tyr Thr Cys 195 200 205

Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 210 215 220

Ser Lys Tyr Gly Pto Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu 225 230 235 240

Gly C]y Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255

Met lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270

Gin Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285

Va】His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr 290 295 300

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn 305 310 315 320 162948·序列表.doc 201247706

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335

He Glu Lys Thr I)e Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Oln 340 345 350

Va】Tyr Thr Leu Pro Pro Ser G】n Glu Glu Met Thr Lys Asn Gin Val 355 360 365

Sei Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp IJe Ala Val 370 375 380

Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Tbi Pro 385 390 395 400

Pro Val Leu Asp Ser Asd Gly Sei Phe Phe Leu Tyr Ser Arg Leu Thr 405 410 415

Val Asp Lys Ser Arg Trp Gin Glu Gly Asn Va! Phe Ser gs Ser Val

Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu 435 440 445

Ser Leu Gly Lys Ala Sax Gin Thr Pro Thr Asn Thr He Ser Val Thr 450 455 460

Pro Thr Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Asn 465 470 475 480

Pro Ala Ser Cys Gin Thr Pro Thr Asn Thr lie Ser Val Thr Pro Thr 485 490 495

Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Cys Pro Ala 500 505 510

Ser <210> 3 <211> 1409 <212>DNA <213>人造序列 <220> <223>人造序列之猫述：合成聚核苷酸 <400> 3 atgggcaggc ttaettette attettgeta ctgattgtcc ctgcatatgt cctgtcccag gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgzcc tgttctttct ctgggttttc actgageact tctggtatga gtgta^gctg gattegteag ccttcaggga agggtctgga gtggctggct cacatttggt ggaatsatga taagtactat aatccagtcc tgaaaagccg gctcacaatc tccaaeeaga cctccaacaa ccasgtattc ctcaagatcg ccagtgtggt ctctgcagat actgccacal actactgtgc tegattetat 4- 162948-序列表.doc 201247706 ggtaactgtc Ctgactactg g££ccaag?c accactctca cagtctcctc ggccaaaaca aagggcccat ccgtcttccc cctggcgccc tgctcca^ga ecacctccga gagcacagcc gccctgggct gcctgstcaa ggactacttc cccgaaccgg tgacggigtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc cc^gctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cstgccctcc agcagcttgf； gcacgaagac ctacacctgc aacgtagato acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag ttceaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcat£atc tcccsgaccx ctgaggtcac £tgcgtgg【2 gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcetggas gtgcataatg ccaagacaaa gccgcggfag gagca^ttca acascacgta ccgtgtggtc agcgtcctoa ccgtcctgca cca£gact£g ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag asaaccatct ccaaagccaa agggcagccc cgagagccac aggtgiacac cctgccccca tcccaggagg agatgaccaa gaaccags^c agcctgacct gcccggtcaa aggcttctac ccoagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggaccc cgacggctcc ttcttcccct acagcaggct aaccgtggac aagagcagst ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga gsctctgcac aaccactaca cacagaagag cctctccctg tctctgggta aagctagctg attaattaa <2t0> 4 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷醆 <400> 4 atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gtittcaagg taccagatgt gatatcoaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc atcagttgca gggcaaetca ggacattagc aattatttaa aciggtatca gcagaaacca gatggaactg ttaaactcct gatctactac acatcaacat tacaattagg agtcccatca agattcagtg gcagtgggtc tgaaacagat tattctctca ccattagcaa cctggagcaa gaa£ataitg ccacttactt ttgccaacag ggtgattcgc ttccattcac gttcggctcg gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcucat cttcccgcca tctgatgagc agttgaaatc tggaacigcc tctgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggcg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatscct gcgaastcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <210> 5 <211> 1403 162948-序列表.doc 420 480 540 600 660 720 780 840 900 960 1020 10S0 1140 1200 1260 1320 1380 1409 60 120 ISO 240 300 360 420 m 540 600 66Q 705 201247706 <212> m <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <4〇0> 5 atgagagcgc tgattctttt gtgcctgttc acagcctttc ctggtatcct gtctgatgtg cagcttcafig agtcaggacc tgacctggtg aaaccttcic agtcactttc actcacctgc actgtcactg gctactccet caccagtggt tatagctggc actggatccg gcagtttcca ggaaacaaac tggaacggat gggctacata ctcttcagtg gtagcactaa ctacaaccca tctctgaaaa gtcgaatctc taccactcga gacacatcca asaacc&gtt cttcct£cag ttgaattctg tgactactga ggacacagcc acatatttct gtgcaagatc taactatggt tccutgctt cctggggcca agggactctg gtcactgtct ctgcagccaa aacaacgggc ccatccgtct tccccctgsc gccctgctcc aggagcacct ccgagagcac agccgcccte ggctgcctgg tcaaggacta cttccccgaa ccggtgacis t£tcgtggaa ctca^gcgcc ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacsta gatcacaagc ccagcaacac caaggtggac aagagagttg agiccaaata tggtccccca tgcccaccct gcccagcacc tgagttcgaa gggggaccat ca^tcttcct gttcccccca aaacccaag£ acactctcat gatctcccgg acc〇ctga£g tcacgtgcgt ggtggtggac gtgagcca^s aagaccccga ggtccagttc aactggtacg tg£atggc£t ggaggtgcat aacgccaaga caaagccgcg ggaggagcag Ucaacagca cgtaccgtgt ^glcagcgtc ctcaccgtcc tgcaccaiga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac aaasscctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag ccaca££tgt acaccctgcc cccatcccag gaggagatga ccaagaacca egtcagcctg acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttctcc ctccacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc tccgtgatgc atgaggctct gcacaapcac tacacacaga agagcctctc cctstctctg ggtaasgcu sctgattaat taa <210> 6 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <4〇0> 6 atggattttc aagtgcagat tttcagcttc ctgctaatca gtscctcagt cataatatcc agaggacaaa ttgttctcac ccajtctcca gcaatcatgt ctgcatctcc aggggagaag gtcaccatga cctgcagtgc cagctcaagt gtaagtcaca tgcactggta ccagcagaag tcaggcactt cccccaaaae atggatttat gacacatcca gactggcttc tggagtccct 162948-序列表.doc -6 - 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 3200 1260 1320 1380 1403 60 120 180 240 201247706 gctcgcttca gtggcagtg^ gtctgggacc tcttactctc tcacaatcag cagcatggag 300 gctgaagatg ctgccactta ttactgccag cagtggagta gtcacccatg gtcgttcggt 360 ggaggcacca aactcgagat caaacgaact gtggctgcac catctgtcu catottcccg 420 ccatctgatg agcagttgaa atcig£aact gcctctgttg tgtgcotgct gaataacttc 480 tatcccagag aggccaaagt acagt£gaag gtggataacg ccctccaatc gsgtaactcc 540 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctc$g cagcaccctg 600 acgctgagca aagcagacta csagaaacac aaastctatg cctgcgaagt cacccatcas 660 igcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708 <210> 7 <211> L415 <2J2> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 7 atggcttggg tgtggaccn gctattcccg atggcagctg cccaaa£tgc ccaagcacag 60 atccagttgg tgcagtctgg acctga^ctg aagaagcctg gagagacagt caagatctcc 120 tgcaa£gctt ctgggtatac cticacaaac tatggaatsa actgggtgaa gca£gttcca 180 g耷aaaaggtt taaggtggat gggctggatg gacaccttca ctggagagcc aacat&tgct 240 gatgacttca agggacggtt tgccttctct ttg£aaacct ctgccagcac tgcccatttg 300 cagatcaaca gcctcaaaaa tgaggacacg gctacttatt tctgtgcaag aggggggatt 360 ttacgactca actactttga ctactggggc caaggcacca ctctcacagt ctcctcagcc 420 aaaacgaagg gcccatccgt ctcccccctg gcsccctgcl ccaggagcac ctccgasagc 480 acagccgccc tgggctgcct ggtcaaggac tacctccccg aaccggtgac egtgtcgtgg 540 aactcaggcg ccctgaccag cggcgcgcac accttcccgg ctgtcctaca gtcctcaega 600 ctctactccc tcagcagcgt ggtgaccgts ccctccagca gcttgggcac gaagdcctac 660 acctgcaacg tagatcacaa gcccagcaac accaaggtg£ acaaeagagt tgagtccaaa 720 tatggtcccc catgcccacc ctgcccagca cct£asttc£ aagggggacc atcagtcttc 780 ctettccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcAcgtgc &40 gtgstggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900 gtggaggtgc ataatgccaa gacaaagccs cgggaggagc agttcaacag cacgtaccgt 960 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080 cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 1140 caggtcagcc tgacctgcct £gtcaaa££c ttctacccca gcgacatcgc cgtggagtgg 1200 gagagcaatg ggcagccgga gaacaactac aagaccacgo ctcccgtgct ggactccgac 1260 ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggagggs^t 1320 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 13&0 tccctgtctc tgggtaaagc tagctgatta attaa 1415 162948-序列表.doc c 201247706 <210> S <211> 705 <212> DMA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 8 atgaagtetc cttctcaact tctgctctta ctgctgtttg gaatcccagg catgatatgt gacatccaga tgacacaatc ttcatcctcc mtctgtal ctctafg战a cagagtcacc attacttgpa aggcaagtga ggacatatat a^tcggttag gctggtatca gcagaaacca ggaaatgccc ctaggctctt aatatctggt gcaaccagtt tggaaactgg ggttccttca agattcagtg gca^tggatc tgsaaaggat tacgctctca gcattaccag tcttcagact gaagatcttg ctacttatta ctgtcaacag tgtt£gactt ctccgtacac gctcggaggg gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ct£tctccat cttcccgcca tctsatgagc a£tt£aaatc tggaactgcc tctgttgt£t gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa etctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <210> 9 <211> 1398 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 9 atgggatgga gctggatctt tctctttctc ttgtcaggaa ctggaggtgt cctctctgag gtccagctgc aacagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatgtcc tgcaaggctt ctggatacac cttcaccgac tactacacga agtgggtgaa gcagagccat ggaaagagcc ttgagtg&at tggagatatt aatcctaact atsgtgdtac tttctacaac cagaagttcg aggscaagfic cacattgact gtagacaaat cctccaggac agcctacatg cagctcaaca gcctgacatc tgaggactct gcagtctatt attgt^aag agfggactat ggatacttcg atgtctgggg cgcagggacc acggtcaccg tctcctcagc caaaacaaag ggcccatccg tcttccccct ggcgccct^c tccaggagca cctccgagag cacagccgcc cUggctgcc tggtcaagga ctacucccc gaaccggtga cggtgtc^tg ^aactcaggc gccctgacca gcggcgtgca caccttcccg gctgtcciac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaa^accta cacctgcaac gtagatcaca a^cccagcaa caccaagstg gacaaga^ag ttgagtccas atatggtccc ccatgcccac cctgcccagc acct&agttc gaasggg^ac catcagtctt cctgttcccc ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg gacgtgagcc agiaagaccc cgaggtccag ttcaactgst acgtggatgg cgtgga^etg J62948-序列表.doc -8- 60 120 180 240 300 360 420 480 540 600 660 705 60 120 ISO 240 300 360 420 480 540 600 660 720 780 840 900 201247706 cataatscca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtsgtcagc 960 gtcctcaccs tcctgcacca ggactggctg aacggcaagg agtacaagtg caasgtctcc 1020 aacaaaggcc tcccgtcctc categagaaa accatctcca aagccaaagg gcagccccga 1080 gagccacagg tgtacaccct gcccccatcc caggags^ tgaccaagaa ccaggtcagc 1140 ctgacctgcc tggtcaaagg cttctacccc agcgacatci ccgtsgagts ggagagcaat 1200 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cgsctccttc 1260 tccctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 <210> 10 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 10 atggagacac attctcaggt ctttgtatac atgttgct£t ggttgtctgg tgttgaagga 60 sacattgtga teacccagtc icacaaattc atgtccacat cagtasgaga cagggtcagc 120 atcacctgca aggccagtca ggatgtgggt actgctgtag cctggtatca acasaaaccd 180 gggcaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat 240 cgcttcacas gcagt^gatc tgggacagat Itcactctca ccattaacaa tgtgcagtct 300 gaagacttg£ cagattattt ctgtcagcaa tatascagca atccgiacat gttcggaggg 360 gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tctfittgtgt gcctgctgaa taacttccat 480 cccagaga^g ccaaagtaca gtggaag^te gataacgccc tccaatcggg taactcccag 540 gaia£tgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagsgc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagigt gttag 705 <210> 11 <211> 1413 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 11 atgggatgga gctggatctt tccctttctc ct£tcaggaa ctgcasgtgt cctctctgag 60 gtccagctgc aacagtctgg acctgagttg gtgaagcctg gggcttcagt gaagatatcc 120 tgcaagactt ctggatacac attcactgaa tacaccatgc actgggtgag gcagagccat 180 ggaaagdgcc ttgagtggat tggaggcatt aatcctatca atggtggtcc tacctacaac 240 cagaagttca agggcaaggc cacatteact gltgacaagt cctccagcac agcctacatg 300 c 162948·序列表.doc -9- 201247706 gagctccgca gcctgacatc tgaggactct gcagtctatt actgt£caag atgggactat 360 £gtagtC£ag atgtcatgga ctactggggt c^aggaacct cagccaccgt ctcctca^cc 420 aaaacgaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480 acagccgccc tgggctgcct ggtcaaggac tacttccccs aaccggtacc g£tgacggtg 540 icgtg£aaci caggcgccct gaccagcggc gtgcacacct tcccggctet cctaca£tcc 600 tcaggactct actccctcag cagcgtggte accgt^ccct ccagcaictt gggcacsaag 660 acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gagagttgag 720 tccaaataig gtcccccatg cccaccctgc ccagcaccig agttcgaag^ ge^accatca 780 ^tcttcctgt tccccccaaa acccaaggac actctcatga tctcccggac ccctgaggtc 840 acgtgcgtgg tggtggacgt gagccaggaa gaccccgagg tccagttcaa ctgstacgtg 900 £atggc£tgg aggt£cataa tgccaagaca aagccgcgge aggagcagtt caacagcacg 960 taccgtgtgg tca£C£tcct caccgtcctg caccaggact gsctgaacgg caaggagtac 1020 aagtgcaagg (ctccaacaa aggcctcccg tcctccatcg a财a&accat ctccaaagcc 10S0 aaagggcagc cccgagagcc acaggtgtac accctgcccc catcccagga ggagatgacc 1140 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1200 gagtggga^a ^caalgggca gccggagaac aactacaa£3 ccac£c：ctcc cgt£ct££ac 1260 tccgacggct ccttcttcct ctacagcagg ctaaccgtgg acaagagcag gtggcagsag 1320 gggaatgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacacagaag 1380 agcctctccc tgtctctggg taaagcugc tga 1413 <210> 12 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 12 atggaatcac agactctggt cttcatatcc atactgctct ggttatatgg tgctgatggg 60 aacatt^taa tgactcaatc tcccaaatcc atgiccatgt castaggegd gagggtcacc 120 ttgagctgca aggccagtga gaatgt^gga acttatgtat cctggtatca acasagacca 180 gaacagtctc caaaactgct gatatacggg gc^ttccaacc ggtacactgg ggtccccgat 240 cgcttcacag gcagtgg&u tgcaacagat ttcactctga ccatcagcag tgtgcaggct 300 gaggaccttg cagauatca ctgtggacag actiacagct autatlcac sttcggctcg 360 gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tclgttgtgt gcctgctgaa taacttctat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540

gagagtgtca cagagcagga cagcaaggac aecacctaca gcctcagcag caccctgacg · 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct scgaagtcac ccatcagggc 660 ctgagctcsc ccgtcacaaa ^agcttcaac agggsagagt £ttag 70S <210> Π •10- 162948-序列表.doc 201247706 <211> 1404 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 13 atgggatgga gccggatctt tctcttcctc ctgtcaaua ctgcaggtgt ccattgccag gtccagglgc agcagtcggg acctgagttg gtgaagcctg gggcctcagt saagatttcc tgcaaagcct ctggcgacgc attcagtagt tcttggatga actgggtgaa gcagaggcct ggacagggtc ttgagtggat tggacggatt tatcttggag a^gagatai taattacaat gggaagttca agggcagggc cacactgact gcagacaaat octccagcac agoctacatg cagctcagca gcctgacctc tgtggactct gcggtctatt tctgcgcgag gcagctcggg ctatggtatg ttatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagcQaaa acaaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc ttc^ccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc (gcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg gtggtggacg tgagcca.g^a agaccccgag gtccagttca actggtacgt ggatggcstg gaggtgcata atgccaagac aaagccgcse gaggagcagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag gtctccaaoa aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta cacccdccc ccatcccagg a^gagatgac caagaaccag gtcagcctga cctgcctggt caaaggcctc taccccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcag gctaaccgtg gacaagagca g£tg£cagga ggggaatgtc ttctcatgct ccgtgatsca tgaggctctg cacaaccact acacacagaa gagcctctcc ctgtctctgg gtaaagctag ctga <210> 14 <2I1> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 14 atgagtgtgc ccactcaggt cctggggtts ctgctgctgt ggctt^cagg tgccagatgt £acatccaga tggctcagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc atcacatgtc gagcaagtga gaatatttac agttatttag catggtatca gcagaaacag ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tagcagaass tgtgccatca 60 120 m 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1404 60 120 180 240 162948·序列表,doc -11 · c 201247706 aggttcagtg £cagt£gatc aggcacacag ttttctctga agatcaacag cctgcagcct 300 gaagattttg egagttatta ctgtcaacat cattatggtt ttccgtggac gtlcggtgga 360 ggcaccaagc tcgagatcaa acgaactetg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 cccagagaeg ccaaagtaca gtfigaaggcg galaacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga ca^caaggac agcacctaca gcctcagcag cacccigacg 600 ctgagcaaag cagactacsa gaaacacaaa £tctatgcct gc^aagtcac ccatcagg^c 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <210> 15 <211> 1395 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 15 atgaacttcg ggctca£ctt gattttccU gtcctcattt taaaaggtgt ccagtgtgag 60 gcgcagctgg t££agtccgg gggasactta gtgaagcctg gagggtccct gaaactctcc 120 tgtgcagcct ctggattcac tttcagtagc tatggcatgt cttgggttcg ccagactcca 180 gacaagaggc tggastgggt cgcagtcatt agtagtggtg gaagttccac cttctatcca 240 gacagtgtea aggggcsatt caccatctcc agagacaatg ccaagaacac cctgtacctg 300 caaatga£ca gtctgaagtc tgaggacaca gccgtftatt actgttcaag aggaggttac 360 tactttgact actggggc^a aggcaccact ctcacsgtct ccgcagocaa aacaaagggc 420 ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccotc 600 agcagcgtEg tgaccgtgcc ccccagcagc ttgggcacga agacctacac ctgcaacgta 660 gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720 tgcccacccc gcccagcacc tgagttcgaa ssgggaccat cagtcttcct gttcccccca 780 aaacccaagg acactctcat gatctcccgg acccctgaga tcacgtgcgt ggtggtggac 840 gtgascca^g aagaccccga ggtccagttc aactggtacg tggatggcgc gsaggtgcat 900 aat£〇caa£a caaagccgcg ggaggagcag Ucaacagca cgtaccgtgt ggtcagcgtc 960 ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020 aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1080 ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140 acct£cctgg icaaaggctt ctaccccasc sacatcgccg tggagtgesa gagcaatggg 1200 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260 ctctacagca g£daaccgt ggacaagagc aigtggcagg aggggaatgt cttctcatgc 1320 tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg 1380 £gtaaagcta gctga 1395 -12- 162948-序列表.doc 201247706 <210> 16 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <40Q> 16 atgaggttcc aggttcaggt tctemctc cttctgctct ggatatcagg tgcccagtgC gatgtccaga taacccagtc tccatctlat cttgctgcat ctcctggaga aaccattact attaattgca gg^caagcaa gaccattagc aaatattt^g cctggtatca agagaaacct gagaaaactg ataagcttct tatctactct ggatccactt tgcaatctgg aattccatca aggttcagtg gcagtggatc tggtacagat itcactctca ccatcagtgg cctggagcct gaagattttg caatgtatta ctgtcaacag cataatgaat acccgtggac gttcggtgga ggcaccaagc tcgagatcaa acgaactgtg gctgcacca! ctgtcttcat cttcccgcca tctgatgagc agttgaaatc tggaactgcc Ictgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagt^ca gtggaaggtg gataacgccc tccaatcggs taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcas caccctgacg ctgagcaaag cagact^cga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <210> 17 <211389 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸

60 120 180 240 300 360 420 480 540 600 660 70S <400> 17 atgggatgga gtccagctgc tgcaaggctt gtaaagagcc cagaatttca gagctccaca gtcUctggg gtcttccccc ctggtcaagg agcggcgtgc gtggtgaccg aagcccagca ccctgcccag aaggacactc gctggatctt aacagtctsg ctggttactc ttgagtggat aggacaaggc gcctgacatc gccaaggcac tggcgccctg actacttccc acaccttccc tgccctccag acaccaaggt cacctgagtt tcatgatctc tctctttctc acctgagctg attcactggc tggacgxatt cagctcgact tgagaaccct cactctcaca ctccaggagc c^aaccggts g^ctgtccta cagcttgggc ggacaagaga cgaaggggga ccggacccct ctgtcaggaa gtgaagcctg tactacatec aatccttaca gtagataagt gcastctatt gtctcctcag acctccgaga acg£tgtcgt cagtcctcag acgaagacct £tt£agtcca ccatcagtct gag£tcacgi ctgcaggtgt gggcttcagt actgggtgaa atggtgctac cctccagcac actgtgcaag ccaaaacgaa gcacagccgc ggaactca£g gactctactc acacctgcaa aatatggccc tcctgttccc gcgtggteet cctctctgag gaagatatcc gcaaagccat tagctacaac agcctacatg agaggactac gggcccatcc cctgggctgc cgccctgacc cctcagcagc cgtagatcac cccatgccca cccaaaaccc ggacgtgagc 60 120 180 240 300 360 420 480 540 600 660 720 780 840 ! 62948-序列表.doc -】3· c 201247706 caggaagacc ccgaggtcca gttcaactgg tacgtggatg gcgtggaggt gcataatgcc MO aagacaaagc cgcgggagga gcagttcaac agcacgtacc gtgtggtcag cgtcctcacc 960 gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc caacaaaggc 1020 ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agagccacag 10S0 gtgtacaccc tgcccccatc ccaggagsag atgaccaaga accaggtcag cctgacctgc 1140 ct££tcaaag scttctaccc cagcgacatc sccgtggagt ggs^sagcaa tgggcagccg 1200 gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1260 agcaggctaa ccgtggacaa gagcaggtgg caggagggga atgtcttctc atgctccgtg 1320 atgcatgagg ctctgcacaa ccactacaca cagaagagcc tctccctgtc tctgggtaaa 1380 gctagctga 1389 <210> 18 <211> 717 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 18 atgaagttgc ctgttaggct sttggtgctg atgUcigga ttcctgcttc cagcagtgat 60 gttgtgatga cccaaactcc actctccctg cctgtcagtc tt£gagatca agcctccatc 120 tcttfic&gat ctagtcagag ccttgtacac agtaatggaa acacctattt acattggtac 180 ctgcagaagc caggccagtc tccaaa^ctc ctgatctaca aagtttccaa ccgattttct 240 ggggtcccag acaggttcag tggcagtgga tcagggacag atttcgcact caagatcagt 300 ag&£tggagg ctgaggatct gggagtttat ttctsctctc aaagtacaca tgttccgtee 360 acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccgc catctgatga gcasttgaaa tctggaactg cctctgttgt gtgcctgctg 480 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctc^gc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgc^aagtc 660 acccatcd^g gcctgagctc gcccgtcaca aagascttca acaggtsaga stgttag 717 <210> 19 <211> 1410 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 19 atggaatgga gttggatatt cctctttctt ctgtcaggaa ctecaggtgt ccactctgag 60 gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120 tgcaaggctt ctigatacac attcactgac tatgtttt^c actgggtgaa acagaagcct 180 gggca£g£cc ttgagtggat t££atatatt daiccttaca atgatggtac taastacaat 240 gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300 -14· 162948·序列表.doc 201247706 gafictcagca gcctiacctc tgaggactct gcggtctatt actgtgcaag gggctatccg 360 gcctactctg ggtatgctat ggactactg£ ggtcaaggaa cctcagtcac cgtctcctca 420 gccaaaacga agg£cccatc cgtcttcccc ct£gc£ccct gctccaggag cacctccgag 480 a^cacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acastcctca 600 ggactctact ccctcagcag cgtggtsacc gtgccctcca £cagcttggg cac^aaiacc 660 tacacctgca acgtag^tca caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840 tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggac 900 SScgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960 cgtgt££tca gcgtcctcac cgtcct£cac caggactggc tsaacggcaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgtacacc ctgcccccal ccca££ag2a gatsaccaag 1140 aaccagstca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtigag 1200 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 gacggctcct tcttcctcta cagcaggcta accgtgi&ca agagcaggts gcasgagggs 1320 aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acasaagagc 1380 ctctccctgt ccctgggtaa agccagctga 1410 <210> 20 <211> 705 <212> DMA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 20 atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60 gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc 120 atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca 180 gatggaactg ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca 240 aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctgga^caa 300 gaasacattg ccacttactt ttgccatcat ggt&atacgc ttccgtggac gttcgftgga 360 gscaccaagc tcgagatcaa acgaactgtg gctgcacc&c ctgtcttcat.cttcccgcca 420 tctgatsagc agttgaaatc tggaactgcc tatgttgtgc gcctgctgaa taacttctat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 162948·序列表.doc -15- c 201247706 <21Q> 21 <211> 1404 <212> \m <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 21 atgaacttgg ggclcagctt gattttcctt ctccttgttt taaaasstgt ccagtgtgaa 60 gtgaagctgg tggagtctgg mflsgcua gtgcagcctg gagggtccct saaactctcc 120 tgtgcaacct ctggattcac tttcagtgac tattacatgt attsggttcg ccagactcca 180 gagaagaggc tggagtgggt cgcatacatt aattctggtg gtggtagcac ctattatcca 240 gacactgtaa agggccgatt caccatctcc agagacaatg ccaagaacac cctgtacctg 300 caaatgagcc fgctgaagtc tgaggacaca gccatgtatt actstgcaag acgggggtta 360 ccgttccatg ctatggacta ttggggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420 acgaagggcc catccgtcit ccccctg£〇g ccctgctcca ggascacctc cgagagcacs 480 gccgccct£S £dgcctg£t caasgactac ttccccgaac cggtgac^gt gtcgtggaac 540 tca££〇gccc tgaccagcgg cgtgcacacc ttcccgectg tcctacagtc ctcaggactc 600 tactccctca gcagcgtggt gaccgtgccc tccagca£Gt t£££cacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca aga£agttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaocatc agtcttcctg 780 ttccccccaa aacccaagsa cactctcatg atctcccgga cccctgaggt cacgt£cgt£ &40 gtgglggacg tgagcca战a agaccccgag gtccagttca actggtacgt ggatggcgU ^00 gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaac&gcac gtaccgtgu 960 gtca^cgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaaf 1020 gtccccaaca aaggcctccc stcctccatc gagaaaacca tctccaaagc caaagggcag 1080 ccccfagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140 gtcascctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200 » agcaatgg£c agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260 tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtsgcagga ggggaatgtc 1320 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380 ctgtctctgg gtaaagccag ctga 1404 <210> 22 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <4〇〇> 22 atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60 gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctaggaga cagagtcacc 120 atcagttgca gtgcaagtca gggcattagc aattatttaa actggtatca gcagaaaccd 180 -16· 162948-序列表.doc 201247706 gaiggaactg ttaaacccct gatctattac acatcaattt tacactcagg agtcccatca aggttcagtg gcagtgggtc tgggacagat tattctctca ccaccggcaa cctgsaacct gaagatattg ccacttacta ttgtcaecag tttaataagc ttcctccgac gttcggtgga ggcaccaaac tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca tctgatsagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat cccagaiagg ccaaagtaca gtggaaigtg gataacgccc tccaatcggg taactcccag gagagt£tca cagagcagga cagcaa^gac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcEaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac ag£ggagagt gttag <210> 23 <211> 1405 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 23 atggattggc tgtggaactc gctattcctg atggcagctg cocaaagtgc ccaagcacag atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagt caagatctcc tgcaaggctt ctgggtattc cttcacaaac tatggaatga actgggtgaa acaggctcca ggaaagggtt taaagtggat gggctggata aacacctaca ctggagagtc aacatatgct gatgacttca agggacggtt tgccttctot ttggaaacct ctgccagcac tgcctatttg cagatcagta acctcaaaaa tgaggacatg gctacatatt tctgtgctag aggggacttt aggtactact attttgacta ctggggccaa ggcaccactc tcacaggctc ctcagccaaa ac£aag£gcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccctgs gctgcctg£t caaggactac ttccccgaac cggt£acg£t gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacaoc ttcccggctg tcctacagtc ctcaggactc tactccctca gcascgtggt gaccgtgccc tccagcasci t£ggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttcgaag ££ggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg gtgstssacg tgagccagga agaccccgag giccagttca actggtacgt ggacggcgtg gaggtgcata atgccaagac aaagccgcgg gaggagcast tcaacagcac gcaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctsaacg gcaaggagta caagtgcaag gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc taccccagcg acatceccgt £&agtgg£ag agcaatgg£C agccggagaa caactacaag accacgcctc ccgtsctgga ctccgacggc tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacac&gaa gagcctctcc

240 300 360 420 480 540 600 660 70S 60 120 180 240 300 360 420 480 540 600 660 720 780 «40 900 960 1020 1080 1140 1200 1260 1320 1380 162948-序列表.doc •17- £ 201247706 ct£tctct£g gtaaagctag ctgat 1405 <210> 24 <211> 702 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 24 atgagt^tgc tcactcaggt cct£gcgttg ctgctgctgt ggctcacagg tgccagatgc 60 gacatccaga tgactcagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc ]20 atcacgtgic gagcaagtgg gaacattcac aattatttag catggtatca gcagaaacag 180 ggaaaatctc ctcagctcct g£tctataat gcaaaaacct tggcagatgg tgtgccatca 240 aggttcagtg gcagtggatc aggaacacaa tattctctca agaccaacac cctgcagccc 300 gaagatttte ggagttatta ctgtcaacat ttttg£gatt cttsgac£tt cggtgsaggc 360 accaagctcg agatcaaa〇£ aactgtggct gcaccatctg tcttcatctt cccgccatct 420 gatgagcagt tgaaatcteg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgcts 600 agcaaagcag actacgagaa acacaaastc tatgcctgcg aaglcaccca tcagggcctg 660 agctcgcccg tcacaaagag cttca&cagg ggagagtgtt a£ 702 <210> 25 <211> 1398 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 25 atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60 gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120 tgcaaggcta ctggctacac attcagtagc tactgfalag a£t£ggtaaa gcaga£gcct 180 ggacacggcc ttgagtggat tggagagatt ttacctggaa gtggtaggac taacgacaat 240 gagaagttca agggcaaggc cacattcact gcagatacat cctccaagaa agcctacatg 300 caactcagca gcctgacatc tgaggactcc gccgtctatt att£tgcaag aaggg£tg^t 360 tactcctttg cttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccag^agca cctccga£ag cacaicogcc 480 ctgg£Ct£〇c tggtcaag£a ciacticccc gaacc^gtga cggigicgxg gaactcaggc 540 gccctgacca gcggcstgca caccttcccg gctgtcctac agtccicagg actctactcc 600 ctcagcagcg tggtgaccgt gccctccagc agctt£ggca cgaagaccta cacctgcaac 660 gtagatcaca agcccagcaa caccaagstg gacaaiagag ttgagiccaa atat£gtccc 720 ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780 ccaaaaccca aggacactct catgatctcc cggacccctg a££tcac£tg cgtggtggtg 840 -18 * 162948-序列表.doc 201247706 gacgtgagcc aggaagaccc cgaggtccag ttQaaccggt acgtggatgg cgtsgaggtg cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc aacaaaggcc tcccgtcctc catcgagaaa acoatctcca aagccaaagg gcagccccsa gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc ctsacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat ssecagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc ttcctctaca scagsctaac cgtggacaag agoaggtggc aggaggggaa tgtctcctca tgctcc^tga tgcatgaggc (ctgcacaac cactacacac agaaga^cct ctccctgtct ctgggtaaag ctagctga <210> 26 <211> 1422 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 26 atgaccatgt tctcactagc tcttctcctc agtcttcttc tcctctgtgt ctctgattct agggcagaaa caactgtgac ccagtctatg accatgttct cactagctct tctcctcagt cttcttctcc tctgtgtctc tgattctagg ica^aaacaa ctgtgaccca gtctccagca tccctgtcca tggctatagg ggaaaaagtc accatcagat gcgtaaccag cactgatatt gatgatgatg tgaactggta ccagcagaag ccaggggaac ctcctaaact ccttatttca gaaggcaata ctcttcgtcc tggagtccca tcccgattct ccagcagtgg ctatggtaca gattttgttt ttacaattga gaacatgctc tcagaagatg ttgcagatta ctactgtttg caaagtggta acttgccgta cacgttcgga ggggggacca agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtsgaag gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac aeagtctatg cctgcgaagt c&cccatcag ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttagcc agcatccctg tccatggcta taggggaaaa agtcaccatc agatgcgtaa ccagcactga tattgatgat gatgtgaact ggtaccagca gaagccaggg gaacctecta aactccttat ttcagaaggc aatactcttc gtcctggagt cccatcccga ttctccagca gtggctatgg tacagatttt gtttttacaa ttgagaacat gctctcagaa gatgttgcag attaccactg tttgcaaagt ggtaactt^c cgtacacgtt cggagggggg accaagctcg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct gatgageagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 162948-序列表.doc •19- 900 960 1020 1080 1140 1200 1260 1320 1380 1398 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 201247706 agcaaagcag actacsagaa acacaaagtc tatgcctgc£ aagtcaccca tcagsgcctg 1380 agctcgcccg tcacaaagag cttcaacagg ggasagtgtt ag 1422 <210> 27 <211> 1404 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 27 atggcttggg t£tg£acctt gctattcctg atggca£ct£ cccdaagtgo ccaagcacag 60 atccagttgg tscagtctgg acctgagctg aagaa^cctg gagagacagt caagatctcc 120 tgcaaggctt ctgggtatac cttcacaaac tatggaatga actgggtgaa gcaggctcca 180 ggaaagffgU taaagtgggt gggctggata aacaccttca ctggagagcc aacatalgtt 240 gatgacttca agggacggtt tgccttctct ttggaaacct ctgccagcac igcctatttfi 300 cagatcaaca accccaaaaa tgaggacacg gctacatatt tctstgcaag agggaatttt 360 aggtactact actttgacta ccg£ggccaa ggcaccactc tcacagtctc ctcagccaaa 420 acaaagggcc catccgtctt ccccctg£cg ccctgctcca g£agcacctc cgagagcaca 480 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540 tcaggcgccc tgaccagces cstscacacc ttcccggctg tcctacastc cxcaggactc 600 tactccctca gcascgtggt gaccgtgccc tccagcagct t£ggcacaaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttcgaag g£ggaccatc agtcttcct^ 780 ttccccccaa aacccaagga cactctcatg atc(cccgga cccctgaggt cacgtgcgtg 840 gtggtgffacg tgagccagga agaccccgag gtccagltca actggtacgt ggalggcgts 900 gaggtgcata atgccaagac aaegccgcgg gaggaicagt tcaacagcac gtaccgtgtg 960 Stcagcgtcc tcacc^tcct gcaccaggac tggctgaacg gcaaggagta caagtgcaaf 1020 gtctccaaca aaggcctccc gccctccatc gagaaaacca cctccaaagc caaagggcag 1080 ccccgagagc cacaggtgta caccctgccc ccaccccagg a£gagac^ac caagaaccag 1140 gtcagcctga cctgcctggt caaaggctlc taccccagcg acatcgccgt ggagtgggag L200 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc L260 tccttcttcc tctacagcag gctaaccgtg gacaasagca g£tggca£ga gggg-aatgtc L320 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc L380 ctgtctctgg gtaaagctag ctga 1404 <210> 2S <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 28 20- 162948-序列表 _doc 201247706 atga£tgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tgccagatgt gacatccaga tgactca^tc cccagcctcc ctatctgcat ctgtfggaga aactgtcacc atcacatgcc gaacaagtgg gaatattcgc aattatttag catggtatca gcagaaacag ggaaaatctc ctcaactcct ggtctataat gcaaaaacct tagcagat^g tgtgccatca aggttcggtg gcagtggatc aggaacacaa tattctctca agatcaacag ccrgcagcct gaagattttg ggaattatta ctgtcaacat ttttgga^ta gtccgtacac gttcsgaggg gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg gata^cgccc tccaatcggg taactcccag £a£astgtca ca£a£ca£ga cagcaa£gac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gasacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac ag^ggagagt gttag <210> 29 <21l> 2811 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 29 atgatgsgat ggagctatat catcctcttt ttggtagcaa cagctacaga tgtccactcc caggtccaac tgcagcagcc tggggctgaa ctggtgaagc ctggggcttc agtgaagctg tcctgcaagg cttctggcta caccttcacc agctactgga tgcactgggt gaagcagagg cctggagaae gcctteagtg gattggagae atuatccta gctacsgtcg tactgactac aatgagaagt tcaagaacaa ggccacactg actgtagcca aatcctccag cacagcctac atgcaactca gcagcctgac atctgaggac tctgcggtct attactgtgc aagaggagat tactacggta gtagctcgtt tgcttactgg egccaaggga ctctggtcac tgtctctgca gccaaaacaa agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag agcacagccs ccctsggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg tseaactcag gcgccctgac cagcgscgtg cacaccttcc cggct£(cct acagicctca ggactctact ccctcagcag c^tggtgacc gtgccctcca gcagcttg£e cacgaagacc tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agtteagtcc aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat g£Cgtgsa£g tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac cgtgtggtca gcgtcctcac c^tcctgcac caggactggc t2aac£gcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccgtcc tccatc£aga aaaccflictc caaagccaaa ££gcagcccc gagagccaca e£tgiacacc ctgcccccat; cccaggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 60 120 180 240 300 360 420 480 540 600 660 705 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 162948·序列表.doc •21 - c 201247706 tgg£agagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc gac^sctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg adtgtctict catgctccgt gatgcatgag gctctscaca accactacac acagaasa^c ctctccctgt ctctgggtaa agctagcgga tggagctata tcatcctcit utgstagca acagctacag atgtccactc ccaggtccaa ctgcagcagc ctggggctga actgstgaag cctggggctt cagtgaagct gtcctgcaag gcttciggct acaccttcac cagctactgg atgcactggg tgaagcagag gcctggagaa g^ccttgagt ggattggaga gactaatcct agctacggtc gtactgacta caatgggaag ttcaagaaca aggccacact gactgtagcc aaatccicca gcacagccta catgcaactc agcagcctga catctgasga ctctgcggtc tattactgtg caagaggaga ttactacggt a^tagctcgt ttgcttactg fggccaaigg actctggtca ctgtctctgc agccaaaaca aaggscccat ccstcttccc cccggcgccc tgctccagga gcacctccga gagcacagcc gccctgsgci gcctggtcaa ggactacitc cccgaaccgg tgacggtgtc gtggaactca g^cgccctga ccascggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc agcascttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaas gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcgggas gagcagttca acagcacgta ccgtgtggtc ascgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa glgcaaggtc tccaacaaag gcctcccgtc ctccatcgaf aaaaccatct ccaaagccaa agg^cagccc c^agagccac aggt£tacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc a^cctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc ac^cctcccg tgctggactc cgacfigctcc ttcttcctct acascaggct aacc£tggac aagagcaggt ggcaggaggg gaatgtcttc tcat^ctccg tgatgcacga ggctctgcac aaccactaca cacagaagag cctctccctg tctctgggta aagctagctg a <210> 30 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2D40 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2811 60 120 180 240 300 <400> 30 atggattttc aagtgcagat tttcagcttc agggs^caaa ttgttctcac ccagtctcca gtcaccatga cctgcagtgc cagctcaaat ccaagatcct cccccaaacc ctggatttat gctcgcttca gtgscagtgg gtctgggacc ctsctaac£a gtgcctcagt cataatgtcc gcactcatgt ctgcatctcc aggg|agaag ataagttaca tgtactggta ccagcagaag ctcacatcca acctggcttc tgga^tccct tcitactctc tcaoaaccag cagcatggag -22- 162948-序列表.doc 201247706 gctgaagatg ctgccactta ttgctgccag cagtggagta gtaacccacc cacattcggt 360 gctgggacca agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 tatcccagag aggccaaagt acagcggaag gtggataacg ccctccaatc gggtaactcc 540 casgagagt£ tcacagagca ggacagcaag gacascacct acagcctcag cagcaccctg 600 acgctgagca ^agcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag 660 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708 <210> 31 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 31 atggattttc gagtgcagat tttcagcttc ccgctaatga gtgcctcagt cataacgicc 60 ageggacaaa ttgttctcac ccagtctcca gcactcatgt ctgcatctcc aggggagaag 120 gtcaccatga cccgcagtgc cagctcaaat ataagttaca tgtactggta ccagcagaag 180 ccaagatcct cccccaaacc ctggacttat ctcacatcca acctggcttc tggagtccct 240 gctcgcitca gtggcagtgg gtctggsacc tcttactctc tcacaatcag cagcatggag 300 gctgaagacg ctgccactca ttactgccag cagtggagta gtaacccacc cacgttcggt 360 gctgggacca agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg t£tgcctect gaataacttc 480 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcac^gagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta cgagaaacac aaagtctatg cclgcgaagt cacccatcag 660 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708 <210> 32 <211> 717 <212> DNA c213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 32 atggagacag acacactcct gctatgggcg ctgctgctct gggttccagg ttccacaggc 6〇 gacattstgc tgacccaatc tccagcttct ttggct£tst ctctagggca gagggccacc 120 atatcctgca gagccagtga aagtgttgat agttat£tca atagttttat gcactggtac 180 cagcasaaac caggacagcc acccaaactc ctcatctatc gtgtatccaa cctagaatct 240 gggatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccatt&at 300 cctgtggagg ctgatgatgt tgcaacctat iactgtcagc aaagtaatga ggatccattc 360 acgttc^gct cggggacaaa gctcgagatc aaacgaactg tggctgcacc atctgccttc 420 atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480 162948-序列表.doc •23- c 201247706 aataacttct atcccagaga ggccaaagta casts^aagg tggataacgc cccccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac £agaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aasagcttca acaggggaga £tgtta£ 717 <210> 33 <211> 1398 <212> m <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 33 at£gaatgta actggatact tccttttatt ctgtcggtaa ctactcagag 60 gttcagctcc agcagtctgg gactgtgctg gcaaggcctg gsgcttccgt gaataigtcc 120 tgtaaggctg ctggctacag ctttaccagt tactgggtgt actgggtcaa acagaggcct 180 ggacagggtc tggaatggai t£gtgctatt taccciaaaa atagt&geac tagctacaac 240 cagaagttcc aggacaaggc cacactgact gcagtcacai ccgccagcac tgcctacacg 300 gagctcagca gcctgacaaa tgaggactct gcggcctatt actgtacaag acctcacut 360 gattcgtttg gttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgaiag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgic^tg gaactcaggc 540 gccctgacca 芨cggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 ctcagcagcs tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660 gtagatcaca agcccagcaa caccaaggtg gacaagagag tt£d£tccaa atat£gtccc 720 ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtg£tggtg S40 gac£tga£cc aggaagaccc cgaggtccag ttcaactg£t acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc gcgggag^ag casttcaaca gcac£iacc£ t£tg£tcagc 960 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020 aacaaaggcc tcccgtcccc catcgagaaa accatclcca aagccaaagg gcagccccga 1080 gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140 ctgacct^cc tggtcaaagg cttctacccc ascgacatcg ccgtggdigig gga^a^caat 1200 gggcagcc£g agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctaca gcaggctaac cgtggacaag agcaggig^c aggaggggaa tgtcttctca L320 tgctccgtga tgcatgaggc tcigcacaac cactacacac agaagagcct ctccctgtct 1380 cCg££taaag ctagctga 1398 <210> 34 <211> 717 <212> DNA <213>人造序列 <220> 24- 162948-序列表.doc 201247706 <223>人造序列之描述：合成聚核苷酸 <400> 34 atggagacag acacactcct gctatg^gtg ctgctgctct gggttcoagg ttccacaggt gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctotagsgca gagggccacc atatcctgca gagccagtga aagtgtagat agttatggcfl ttagttttat gcactgstac cagcagaaac caggacagcc acccaaactc ctcatctatc gtgcatccaa ccaa£aatct gggatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattaat cctgtggagg ctgatgatgt t£caacctat tactgtca£c aaagtaatga ggatccgctc acgttcggtg ctgggaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga ^cagttgaaa tct£gaactg cctct£ttgt gtgcctgctg aataacttct atcccag^ga aeccaaagta cagt£gaa£g tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gaca£caa^8 acagcaccta cagcctcagc agcaccctga cgctgagcaa^agcagactac gagaaacaca aagtctatgc ctgcgaagtc ^cccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag <210> 35 <21l> 1422 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 35 atgaacaggc ttacttcctc attgccgctg ctgattgtcc ctgcatatgt cct£tcccag gttactctga aagagtctgg cccteseata ttscagccct ccca^accct cagtctgact tgttctttct ctgggctttc actgagcact tctggtat££ ststgagctg aattcgtcag ccttcaggaa agggtctgga gtggctggca cacatttact gggatgatga caagcgctat aatccatccc tgaagagccg gctcacaatc tltaaggatc cctccagcaa cca£gtattc ctcaggatca ccagtgtgga cactgcagat actgccacat actaccgtgc tcgaaactcc cattactacg gtagtactta cgggggatac tlcgatgtct ggggcgcass gaccacggtc accgtctcct cagccaaaac aaagggccca tccgtcttcc ccctggcgcc ctsctccagg agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccs gtgacsgtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt ccc^gctgtc ctacagtcct caggactcta ctccctcagc agcgtggtga ccgt^ccctc cagcagcttg ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggt£gacaag agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcgaaggg ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc cctgaggcca cgtgcgtggt eitggscgtg agccaggaag accccgaggt ccagtccaac t£gtacgtg£ atgicgt£ga ggtgcataat gccaagacaa agccgcgiga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc accgxcctgc accassactg gct£aacggc aagsagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatc^a gaaaaccatc 60 120 180 240 300 360 420 480 540 600 660 717 60 120 180 240 300 .360 420 480 540 600 660 720 780 S40 900 960 1020 1080 162948·序列表.doc -25- s 201247706 tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1140 gagatgacca agaaccaggt cagcctgacc tKCCtggtoa aaggcttcta ccccagcgac 1200 atc^ccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1260 gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1320 tggca£gagg ssaatgtctt ctcatgctcc gtgatgcats asgcictgca caaccactac 13S0 acacagaaga gcctctccct gtctctgggt aaasctasct ga H22 列 序 0>1>2>3> •l «1 <2<2<2<2 <220> <223>人造序列之描述：合成聚核苷酸 <400> 36 atggagacag acacactcct gctatgggtg ctgctgctcg eeettccagg ttccacaggt 60 aacattgtgc tgacccagtc cccaacttct ttcactgtgt ctctcgggca gagggccacc 120 atatcctgca sagccagtga aagtgttcat agttat£gca ataEttttat gcactggtac 180 cagcagaaac c^gggcagcc acccaaactc ctcatctatc ttgcatccaa cgtagaatct 240 ggggtccctg ccaggttcag tegtagtggg tccaggacag acttcaccct caccattgat 300 cctgtggagg ctgatgatgc tgcaacctat tactgtcagc aaaatagtga ggatccgtgg 360 acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccfic catctgatfia gca£tt£aaa tct^gaactg cctctgttgt gtgcctgcts 480 aataacttct atcccagaga ggccaaa^ta ca£t^aa££ tggataacgc cctccaatc^ 540 ggtaactccc aggagagtgt cacagagcag gacagcaag^ acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcag&ctac gagaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 <21fl> 37 <211> 1398 <212> DNA <213>人造序列 <220> 人造序列之描述：合成聚核苷酸 <400> 37 atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60 gttcagctgc agcagtctgg aactgagctg atgaagcctg gggcctcagt gaagatatcc 120 tgcaaggcta ctggctacac attcagtacc tactgsaiag agtsggtaaa gcagasgcct 180 ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagsac taacgacaat 240 gagaagttca a£ggc&ag£C cacaatcact gcagatacat cctccaa^aa agcctacatg 300 caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcaag aaggggtggt 360 tactcctttg cttcctgg£g ccaagggact ctggtctctg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgasag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccsgtga cggtgtcgtg gaactcaggc 540 • 26- 162948-序列表.doc 201247706 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 ctcagcagcg tggtgaccgt gccctccagc agcttggfca cgaagaccta cacctgcaac 660 gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa aiatggtccc 720 ccatgcccac cctgcccagc acctgagttc gaagggggdc catcagtctt cct£tccccc 780 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggcggtg 840 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc icgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080 gagccacagg tgtacaccct gcccccatcc caggaggafa tgaccaagaa ccaggtcagc 1140 ctgacctgcc tggtcaaa£g cttctacccc agcgacatcg ccgtgga£tg ggagagcaat 1200 gggcagccgg agaacaacta caagaccacg cctcccgl^c tggactccga cggctccttc 1260 ttccictaca gcaggctaac cgtggacaag agca£gtg£c aggaggggaa tgtcttctca 1320 tgctccgtga tgcatgagsc tctgcacaac cactacacac a^aagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 <210> 38 <211> 711 <2】2>腿 <213>人造序列 <220> <Ώ3>人造序列之描述：合成聚核苷酸 <400> 38 atgaccatgt tctcactagc tcttctcctc agtcttcttc tcctctgtgt ctctgattct 60 agggcagaaa caactgtgac ccagtctcca gcatccctgt ccatggctat aggagaaaaa 120 gtcaccatca gatgcgtaac cagcactgat attgatgatg atgtgaactg gtaccagcag 180 aagccagggg aacctcctaa gctccttatt tcagaaggca atactcttcg tgctggagjtc 240 ccatcccgat tctccagcag tggctatggt acagattttg tttttacaat tgagaacatg 300 ctctcagaag atgttgcaga ttactactgt ttgcaaagtg gtaacttgcc giacacgttc 360 ggagggggga ccaagctcga gatcaaacga actgtggctg caccatctgt cttcatcttc 420 ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 480 ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 540 tcccaggaga glgtcacaga gcaggacagc aaggacagca cctacagccl cagcagcacc 600 ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct atgcctgcga agtcacccat 660 cagggcctga gctcgcccgt cacaaagagc Itcaacaggg gagagtgtta g 711 <210> 39 <211> 1422 <212> mk <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 162948·序列表.doc •27· £ 201247706 <400> 39 atgaacaggc ttacttcctc attgctgctg ctgattgtcc ctgcaiatgt cctgtcccag 6〇 gttactctga aagagtctgg ccctgggata ttgcasccct cccagacccl cagtctgact 120 t£ttctttct ctgggttttc actsagcact tctggtatgs gtctgagctg gattcgtcag is〇 ccttcaegaa asggtctgsa gtggccggca cacatttact gggatgatga caagcgctat 240 aacccatccc tgaagagccg gctcacaatc tccaaggata cctccagcaa ccaggttttc 3〇〇 ctcaagatca ccatt^tgga cactgcaiat gctgccacat actactgtsc tcgaagctcc 360 cattactacg gttatggcta cgggggatac ttcgatgtct ggggcscags eaccacgstc 420 accgtcicct cagccaaaac gaagggccca tccstcttcc ccctggcgcc ctgctccagg 480 agcacclccg agagcacagc cgccctg£gc tgcctggtca aggactactt ccccgaaccg 540 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacclt cccggctgtc 600 ctacagtcct caggactcta ctccctcagc agcgtsgtga ccgtgccctc cagcagcttg 660 ggcacgaaga cctacacctg caacgcagat cacaagccca gcaacaccaa £gtggacaag 720 agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga ^ttcgaaggg 780 ggaccatcag tcttcct£tt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 840 cctgaggtca cgtgc£tggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 900 tggtacgtgg atg^cgtgga ggtgcataat gccaagaaaa agccgcggga ^gagcagttc 960 aacagcacgt accgtgtggt cagcgccctc accgtcctgc accaggactg gctgaacggc 1020 aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga saaaaccatc 1080 tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggas 1140 gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1200 atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1260 gtgctggact ccgacsgctc cttcttcctc tacagcaggc taaccgtsga caagagcags 1320 t^caggagg gsaatgtctt ctcatgctcc gtgatscatf aggctctgca caaccactac 1380 acacagaaga gcctctccct gtctctgggt aaagctagct ga 1422 <210> 40 <211> 823 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 40 atggagacag acacactcct gctatg££tg ctgct£ctct gg£ttccagg ttccacag£t 60 aacattgtgc tgacccaatc tccagcttct ttggctgt£t ctctagggca £a££gccacc 120 atatcclgca gagccagtga aagtattcat agttatggca atagttttct ^cactggtac 180 cagcagaaac caggacagcc acccaaactc ctcatctatc ttgcatccaa cctagaatct 240 ggggtccctg ccaggttcag cggcagtggg tctaggacag acttcaccct caccattgat 300 cctgtgsagg ctgatgatgc tgcaacctat tactgtcagc aaaataatga sgatccgtgg 360 acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tg^ctgcacc atctgtcttc 420 • 28 - 162948-序列表-doc 201247706 atcttcccgc catctgatga gc^gtt^aaa tctggaactg cctctgttgt gcgcctgccg 480 aataacttct atcccagaga ggccaaagta cagtgg&agg tggataacgc cctccaatcg 540 ggtaactccc aggagagtgt cacaga^cag gacagcaa^g acagcaccta cagcctcagc 6〇〇 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aamcttca acagggga^a gtgttag£Cg 720 gccgcactag cgceggccgc attcgaagag ctcggtaccc gsggatcctc lagagtcgac 780 ctgcaggcat scaagctggc cgcgactcta gatcataatc a£C 823 <210> 41 <211> 1404 <212> DMA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 41 atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttacaggggt caattcaeag 60 gitcagctgc agcagtctgg ggctgagctt gtgaggccag gggccttagt caagttgtcc 120 tgcaaa^ctt ctggcttcaa cattaatgac tactatatcc actgg£tgaa gaagcggcct 180 gaacagggcc tggagcggat tggatggatt gatcct£aca atggtaatac tataiat£ac 240 ccgaagttcc agggcaaggc cagtataaca gcagacacat cccccaacac agcctacctg 300 cagctcagca gcctgacatc tgaggacact gccgtctatc actgtgctag aacccgatct 360 cctatggtta cgacggggtt t£tttactgg ggccaaggga ctgtggtcac tgtctctgca 420 gccaaaacga aggficccatc cgicxtcccc ctggcgccci gctccaggag cacctccgag 480 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag scgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 ggacictact ccctcagcag c£tggtgacc gtgccctcca gcagcttges cacgaagacc 660 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggg££ accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 240 t^cgtggcgg tggacgtgag ccaggaagac ccciaggtcc agttcaacts stacgtggat 900 ggcgtggagg tgcataatgc caagacraag ccgcsssagg agcagttcaa cagcacgtac 960 cgtgtggcca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tacatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca g£tgtacacc ctgcccccat cccas^agga gatgaccaag 1140 aaccagstca gcctgacctg cctggtcaaa ggcttctacc ccagcsacat cgccgtggag 1200 tgggasagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 gacggctccc tcttcctcta cagcaegcta accgtggaca agagcaggtg gcaggagggg 1320 aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380 ctctccctgc ctctgggtaa atga 1404 <210> 42 162948-序列表.doc • 29· c 201247706 <211> 1425 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 42 atggaaaggc actggatctt tctcttccig ttttcagtaa ctgcaggtgt ccactcccag 60 gtccagcttc agcagtctgg gectgagctg gcaaaacctg gggcctcagt gaagatgtcc 120 tgcaaggctt ctggctacac ctttactacc tactggatgc act^ggtaaa acagaggcct 180 ggacag£2tc iggaatggat tggatacatt aatcctatca ctesttatac tgagtacaat 240 casaagttca dgsacaagge caccttgact scagacaaat cctccagcac agcctacat£ 300 caactgagca gcctgacatc tgaggactct gcagtctatt actftgcaag agaggsttta 360 agtgctatgg actattgggg tcagggaacc tcagtcaccg tcacctcagc caaaacaaca 4-20 gccccatcgg tctatccact ggcccctgtg tgtggagata caactggctc ctcggtaact ctaggatgcc tggtcaageg ttatttccct eagccagtga ccttgacctg eaactctiga 540 tccctgtcca gtggtgtgca caccttccca gccgtcctgc agtctgacct ctacaccctc 如〇 agcasctcag tgactgtaac ctcgagcacc tggcccagcc agaccgtcac ctgcagcgtt gctcacccag ccagcagcac cacggtggac aaaaaacttg agcccagcgg gcccatttca 720 acaatcaacc cctgtcctcc atgcaaggag t^tcacaaat gcccagctcc taacctc£ag 780 ggtg£accat ccgtcttcac cttccctcca &atatcaagg atgtactcat gatctccctg 糾〇 acacccaa£g tcacgtgtgt ggtgstggat gtgagcgagg atgacccaga cgtccagatc 900 agctggtttg tgaacaa〇£t ggaagtacac acagctcaga cacaaaccca tagagaggat 960 tacaacagta ctatccgggt ggtcsgcacc ctccccatcc a^caccagga ctggatgagt 1020 ggcasggagt tcaaatgc^a ggtcaacaac aaagacctcc ca.tcacccat cgagagaacc 1 ⑽〇 atctcaaaaa ttaaagggct agtcagagct ccacaagtat acatctt^cc gccaccagca Π40 gagcagttgt ccaggaaaga tgtcagtctc &cttgcctgg tcgtgggctt caaccctgga 12〇〇 gacatcagtg tggagtggac cagcaatggg catacagagg agaactacaa ggacaccgca 126〇 ccagtcctgg actctgacgg ttcttacttc atatatagca agctcaatat gaaaacaagc 1320 aagtgggaga aaacagattc cttctcatgc aacgtgagac acgagggtct gaaaaattac 1380 tacctgaaga agaccatctc ccggtctccg ggtaaagcta gct^a 1425 <210> 43 <211> 717 <212> WA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 43 atgggcatca agatggagtc acggattcag gcatttgtat tcgtgtttct ctggttgtct . ggtgttggcg gAgacattgt gatgacccag tctcacaaat tcatgtccac atcagtagga 120 gacagggtca gcgtcacctg caaggccagt caggatstga cttctgct£t agcct££tat 180 caacaaaaac cagggcaatc tcctaaacta ctgaittact g£gcatccac ccggcacact 240 -30- 162948-序列表.doc 201247706 ggagtccctg atcgcttcac aggcagtgga tctgggacag attatactct caccatcagc 300 agtggscagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg 360 acgttcggtg gaggcaccaa gctggaagtc aaacgggctg atgctgcacc aactgtatcc 420 atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg 480 aacaacttct accccaaasa catcaatgtc aagtggaaga ttgatggcag tgaacgacaa 540 aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc 600 agcaccctca cgttgaccaa ggacga^tat gaacgacata acagctalac ctgtgaggcc 660 actcacaaga catcaacttc acccatcgtc aagagcttca ataggaaiga gtgttag 717 <210> 44 <211> 1398 <212>DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <40〇> 44 atggaaaggc actggatctt tctcttcctg ttttcagtaa ctgcaggtgt ccactcccag 60 gtccagcttc aecagtctgg egctgagctg gcaaaacctg gggcctcagt gaagatgtcc 120 tgcaassett ctggctacac ctttactacc tactggatgc actsggtaaa acagaggcct 180 ggacagsgtc tggaatggat tggatacatt aatcctatca ctggttatac igagtacaat 240 cagaagttea aggacaaggc caccttgact gcagacadAt cctccagcac ascctdC4tg 300 caactgagca gcctgaeatc tgaggactct gcagtctatt actgtgcaag agagggttta 360 agtgctatgg actattgggg tcagggaacc tcagtcaccg tcacctcagc caaaacaacg 420 ggcocatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660 gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720 ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg S40 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca dgacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080 gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctacsi gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 162948-序列表.doc -31 - £ 201247706 <210> 45 <211> 717 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> i5 atgggcatca agatggagtc acagattcag gcatttgtat tcgtstttct ctsgttgtct g£tgttggcg gagacattgt gatgacccag tctcacaaat tcatgtccac atcastagfa gacagggtca gcgtcacctg caaggccagt cag^atgtga cttctgctgt agcctggtat caacaaaaac cagggcaatc tcctaaacta ctgatttact gggcatccac ccggcacact ggagtccclg atcgcttcac aggcagtgga tctgg^acag attatactct caccatcagc agtgggcagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgat^a gcagttgaaa tctggaactg cctctgttgt gtgcctgctg aataacttct atcccagaga s^ccaaagta cagtgiaagg tggataacgc cctccaatcg ggta^ictccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg scctgagctc gcccgtcaca aagagcttca acag£ggaga gtgttag <210> 46 <211> 1401 <212> IWA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 46 atggctgtcc tggcactact cctctgcctg gtggctttcc caacttgtac cctgtcccag gtgcaactga aggagtcagg acctggcctg gtggcgccct cacagagcct gtccattacc tgctctgtct ctgggttctc attaagcaac tatgatataa gctggattcg ccagccacca ggaaasggtc tggagtggct tggagtaatg tggactggtg gaggcgcaaa ttataattca gctttcatgt ccagactgag catcaacaag gacaactcca agagccaagl ttttttaaaa atgaacaatc tgcaaactga tgacacagcc atttattact gtgtcagaga tgcggtgagg tactggaact tcgatgtctg gggcgcaggg accacggtca ccgtctcctc agccaaaacg aagggcccat ccgtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtstc gtggaactca ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtg£tg3c cgtgccctcc agcagcttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg 162948·序列表.doc •32- 60 120 180 240 300 360 420 480 540 600 660 717 60 120 180 240 300 360 420 480 540 600 660 720 780 840 201247706 gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga iggcgtggag 900 gtgcataatg ccaa^acaaa gccgcgggag gagcagttca acagcacgta ccgtetggtc 960 agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc 1020 tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc 1080 cgagagccac aggtgtacac cctgccccca tcccaggagg agatgacca.a gaaccaggtc 1140 agcctgacct gcct£gtcaa a£gcttctac cccagcgaca tcgccgtgga gtgggagagc 1200 aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1260 ttcttcccct acagcaggct aaccgtggac aagagcag^t egcaggaggg gaatgtcttc 1320 tcat^ctccg tgatgcatga ggctctgcac aaccactaca cacagaagag cctctccctg 1380 tctctgggta aagctagctg a 1401 <210> 47 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 47 atggattttc aagcgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60 a^aggacaaa ttgttctctc ccagtcacca gcaatcctst ctgcatcicc aggggagaag 120 gtcacaatga cLt£cagg£c cagctcaagt gtaagttaca tacactggta ccagcagaag 180 ccaggatcct cccccaaacc ctggatttat gccacatccc acctggcttc tggagtccct 240 gctcgcttca gtggcagtgg etctgggacc tcttactctc tcacaatcag cag^gtggag 300 gctgaagata ctgccactta ttactgccag cagtggagta gtaacccatt cacfittcggc 360 tcggggacaa agctcgagat caaacgaact gt£gctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttEaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacagagca g£acagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta c卵gaaacac aaagKUtg cctgcgaagt cacccatcag 660 gscctsagct cgcccgtcac aaagagcttc aacaggggag agigttag 708 <210> 48 <211> 1410 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 48 atggaaaggc actggatctt tctactcctg ttgtcagtaa ctgcaggtgt ccactcccag 60 gtccagctgc agcagtctgg ggctgaaccg gcaagacctg gggcctcagt gaagatgtcc 120 tgcaaggctt ctggctacac ctttactacc tacactatsc actgggtaaa acagaggcct 180 ggacagggtc tggaatggat t£gatacact aatcctagca gtggttatac laattacaat 240 cagaagttca aggacaaggc cacattgact gcagacaaat cctccagcac agcctccatg 300 162948-序列表.doc -33- s 201247706 oaactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagagggcg 360 gtattagtcc cctatgctat ggactactgg g£tcaag£aa cctcaetcac cgtctcctca 420 gccaaaacaa agggcccatc cgtcttcccc ctgfceccct gctccaggag cacctccgag 480 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccg£t gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660 tacacctgca acgtagatca caagcccagc aacaccaagg tg^acaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatsatct cccggacccc tgaggtcacg 840 tgcgtggtgg tggacgtgag ccasgaagac ccc^aggtcc agttcaactg giacgtgeat 900 ggcgtggagg tgcataatgc caagacaaag ccgcgggagf agcagttcaa cagcacgtac 960 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc ceaaceecaa seagtacaag 1020 tgcaaggtct ccaacaaagg cctcccstcc tccatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140 aaccaggtca gcctgacctg cct£gtcaaa ggcttctacc ccagcgacat cgccgtggag 1200 tgggagagca atgggcagcc gga£aacaac tacaagacca cgcctcccgt gctggactcc 1260 gacggctcct tcttcctcta cagcaggcta accgtggaca agagcagstg gcaggagggg 1320 aatgtcttct cat£ctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380 ctctccct£t ctctgggtaa agctagctga 1410 <210> 49 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 49 atgcattltc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt cataatgtcc 60 agaggacaaa ttgttctcac cca^tctcca gca^tcatgt ct^catctcc aggggagaas 120 gtcaccataa cctgcactgc cagctcaagt ttaagttaca tgcactggtt ccagcagaag 180 ccaggcactt ctcccaaact ctggctttat aficacatcca (cciggcttc tggagtccct 240 actcgcttca gtg£cagtgg atctgggacc tcttactctc tcacaatcag ccgaatggag 300 gctgaagatg ctgccactta ttactgccdg caaa^gagta gttccccatt cacgttcggc 360 tcggggacaa agctcgagat caaacgaact gtgictgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgtts (gtgcctgct gaataacttc 480 tatcccagag aggcc^aagt acagt££aag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta cgagaaacac aaagtctats cctgcgaagt cacccatcag 660 gscct^agct cgcccgtcac aaagagcttc aacag£gga£ a£tgttag 708 -34· 162948-序列表.doc 201247706 <210> 50 <211> 1404 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 50 atgggatgga cctggatctt tattttaatc ccgtcagtta ctacaggtgt ccactctgag ^tccagctgc agcagtctgg acctgagctg gagaagcctg gcgcttcagt gaagatatcc tgcaaggctt ctggttactc cttcactggc tacaacatga actgggtgaa acagagcaat ggaaagagcc ttgagtggat tg^aaatatt gatccttact atggtgatac taactacaac cagaagttca agggcaaggc cacattgact gtflgacaaat cctccagcac agcctacatg cacctcaaga gcct£acatc tgaggactct gcagtctatt actgtgcaag accctacggt agtgaggcct actttgctta ctggggccaa gggactctgg tcactgtctc tgcagccaaa acgaagggcc catccgtctt ccccctggcg ccctgctcca £gagcacctc cgagagcaca gccgccctgg gctgcctggt caaggactac ttccccg^ac cggtgacggt gtcgtggaac tcaggc^ccc tgaccagcgg cgtgcacacc Itcccggctg tcct&cagte ctcaggactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacetacacc tgcaac^tag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcitcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggl cacgtgcgtg gtggtggacg tgagccaggd agaccccgag gtccagttca actggtacgt ggatggc^tg gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc ctgtctctgg gtaaagctag ctga <210> 51 <211> 705 <212> DNA <213>人造序列 <22〇> <223>人造序列之描述：合成聚核苷酸 <400> 51 atggtgtcca cttctcagct ccttggacti ttgcttttct ggacttcagc ctccagatgt gacattgtga tgactcagtc tccagccacc ctgtctgtga ctccaggaga tagagtctct ctttcctgca gggccagcca gafitattagc gactacttac actggtatca acaaaasttca 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1404 60 120 180 162948-序列表.doc •35- s 201247706 catgagtctc caaggcttct catcaaatat gctgcccaat ccatctcigg gatcccctcc aggttcagtg gcagtggatc agggtcagat ttcactctca gtatcaacgg tgtggaacct gaagatgttg gagtgtatta ctgtcaaaat ggtcacagct Ctccgcacac gttcggaggg gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca tctgatgagc agttgaaatc tggaactgcc tctgllgtgi gccigctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <21Q> 52 <211> 1395 <212> Wk <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 52 at^gaatgga ggatctttct cttcatcctg tcaggaactg caggtgtcca ctcccaggtt ca^ctgcggc agtctg£acc tgagctggtg aagccigggg cttcagt^aa gdtgtcctgc aaggcttctg gatacacatt tactgactat gttataagtt g££t£aagca ga£aaci£ga ca^ggccttg agtggatt££ agatatttflt cctggaagtg gttattcttt ctacaatgag aacttcaagg gcaag£ccac actgactgca gacaaatcct ccaccacagc ctacatgcag ctcagcagcc tgacatctga ggactctgcg gtctatttct gtgcaaccta ctataactac ccttttgctt actggggcca agggactctg gtcactgtct ct£〇agccaa aacaaceggc ccatccgtct tccccct££c gccctgctcc a^ga^cacct ccsaga£cac agccgccctg ggctgcctgg tcaaggacta crtccccgaa ccggtgacgs tgtcgt££aa ctcagscgcc ctgaccagcg gcgtgcacac atcccggct gtcctaca£i cctca找act ctactccctc agcagcgtgg t£accgtgcc ctccagcagc ttgg^cacga agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca tgcccaccct gcccagcaec tga^ttcgaa gsgggaccat cagtcttcct gttcccccca aaaccoaagg aeactctcat gatctcccgg acccctga^e tcacgtgcgt ggtgitggac gtgagcca^g aagaccccga ggtccagttc aacustacs taztggcgi ggag|tgcat a总tsecaaga caaagccgcg gga£ga$ca£ ttcaacagca cgUccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaac g£ca^££a£t aca^gtgcaa ggtctccaac aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagg^ca gccccsagag ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcct£ acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc tccgtgatgc atgaggctct gcacaaccao tacac&caga agflgcctctc cctgtctctg 1629幼-序列表.doc -36- 240 300 360 420 480 540 600 660 705 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1030 1140 1200 1260 1320 1380 201247706 ggtaaagcta gciga 1395 <210> 53 <211> 717 <212> »IA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 53 atgaagttgc ctgttaggct gttggt^cts atgttctgsa ttcctgcttc cagcagtgat 60 gttgtgatga cccaaactcc actctccctg cctgtccgtc ttggagalca agcctccatc 120 tcttgcagat ctagtcagag ccttgtacac agtaatggaa acacctaitt acattggtac 180 ctgcagaagc caggccagtc tccaaa^ctc ctgatctaca aagtticcaa ccgattttct 240 Sg££tcccag acaggttcas t£gcagtgga tcaggeacaa atttcacact caagatcagc 300 agagtggagg ctgageatct mactttat tcctgctctc aaagtacaca tgttccgtac 360 acgttcggag gggggaccaa gctcgagatc aaacgaactg t^gctgcacc atctgtcttc 420 auticccgc catcigatga gcagttgaaa tciggaacig cctctgttst gt£cctgctg 480 aataactict atcccagaga ggccaaagta cagtggaagg tfgataacgc cctccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcasc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 <210> 54 <211> 1410 <212> 廳 <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 54 atgacattga acatgctgtt ggggctgagg tgggttttct ttgttgtttt ttatcaaggt 60 gtgcattgtg aggtscagct tgttgagtct ggtggaggat tggtgcagcc taaagggtca 120 ttgaaactct catgtgcagc ctccg^atca accticaata tctacgccat gaactgggtc 180 cgccaisctc caggaaaggg tttggaatgg gttgctcgca taagaaataa aagtaataat 240 tatgcaacat attatgccga ttcagtgaaa gacaggttca ccatctccag agatgattca 300 caaagcttgc tctatctgca aatgaacaac ttgaaaactg aggacacagc catgtattac 360 tgtgtgggac gggactggtt tgattactgg ggccaaggga ctctggtcac tgtctctgca 420 gccaaa^cga agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tga^gtcacg 840 c 162948-序列表.doc -37- 201247706 tgcgtggtgg tgga〇£tgag ccaggaasac cccgaggtcc agttcaactg gtacgtggat 900 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960 cgtgtggtca £cgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tcc&tcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140 aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccstggag 1200 tgggagagca atgggcagcc ggagaacaac tacaaiacca c^cctcccgt gctggactcc 1260 gacggctcct tcttcctcta cagcaggcta ac〇£t£gaca a^caggtg scaggagggg 1320 aatgtcttct catgctccgt gatgcatgag gcictgcaca accactacac acagaagagc 1380 ctctccctgt ctctgggtaa agctagctga 1410 <210> 55 <211> 708 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 55 atggcctgsa tttcacttat actctctctc ctggctctca gatcaggsgc catttcccag 60 gct£ttgt£a ctcaggaatc tgcactcacc acatcacctg gtgaaacagt cacactcact 120 tgtcgctcaa gtactggggc t£ttacaact agtaactatg ccaactgggt ccaagaaaaa 180 ccagateatt tattc&ctgg tctaataggt ggtaccaaca accgagtttc aggtgttcct 240 Sccagattct caggctccct gattggagac aaggctgccc tcaccatcac agggicacag 300 actgaggatg aggcaatata tttctgtgct ctatggtaca gcaaccattg ggtgttcggt 360 ggaggaacca aactcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtscctgct gaataacttc 480 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacagagca ggacagcaag gacagcacct aca^cctcag cagc^ccctg 600 acgctgagca aagcagacta cgagaaacac aaagtciatg cctscgaagt cacccatcas 660 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agt£tta£ 708 <210> 56 <211> 13S6 <212> DNA <213：>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 56 atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60 gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcast gaagatatcc 120 tgcaaggcta ctggctacac attcggtagc tactggatag agt£ggtaaa gcagaggcct 180 ggacatggcc ttgagtggat cggagagatt ttacctggaa gtggtaatac taactacaat 240 162948-序列表.doc -38- 201247706 gagaacttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacaig 300 caactcacca stctgacatc tgaggactct gccgtccatt actgtgctag ggeggggact 360 uttggggcc aagggactct ggtcactgtc tctgcagcca aaacgaagg? cccatccgtc 420 ttccccctgg cgccctgctc caggagcacc tccgagagca cagccgccct gggctgcccg 480 gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 540 Egcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 600 ^tgaccgTgc cctccagcag cttgggcacg aagacctaca cctgcaacgt agatcacaag 660 cccagcaaca ccaaggtgga caagagagct gagtccaaat atggtccccc atgcccaccc 720 tgcccagcac ctgagttcsa agggggacca tcagtctccc tgttcccccc aaaacccaag 780 gacactctca tgatctcccg ^acccctgag gtcacgtgcg tggcggtgga cgtgagccag 840 gaagaccccg aggtccagtt caactgstac gtggatggcg tg^aggtgca taatgccaag 900 acaaagccgc gggaggagca gttcaacagc acgtaccgtg tggtcagcgt cctcaccgtc 960 ctgcaccagg actggctgaa cggcaa^gag taaaagtgca a££tctccaa caaaggcctc 1020 ccgccctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga gccacaggtg 1080 tacaccctgc ccccatccca g£agga^at£ accaagaacc a^gtcagcct gacctgcctg 1140 gtcaaa^gct tctaccccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1200 aacaactaca agaccacgcc tccc^tgctg gactccgacg gctccttctt cctctacagc 1260 aggctaaccg tgg&caagag caggtgscag gaggggaatg tcttctcatg ctccgtgatg 1320 catgaggctc tgcacaaccd ctaoacacag aagagcctct ccctgtctct gggtaaagct 1380 agctga 1386 <210> 57 <211> 717 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <40〇> 57 atggagaaag acacactcct gctatgsgtc ctgcttctct gggttccagg ttccacaggt 60 gacatt£tgc tgacccaatc tccagctttt ttggctgtgt ctcta.£sgca gassgccacc 120 atctcctgca gagccagcga aaitgttgat aattatggca ttagttttat gaactggttc 180 caacagaaac caggacagcc acccaaactc ctcatctatg ttgcatccaa gcaaggatcc 240 ggggtcccts ccaggtttag tggcaetg£g tctgggacag acttcagcct caacatccat 300 cctatggagg aggatgatac tgcaatgtat ttctgtca£〇 aaagtaagga ggttcctcgg 360 acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccgc catctgatga gcagttgaaa tctggaactg cctct£ttgt gtgcctgctg 480 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaattg 540 ggtaactccc aggagagtgt cacagagcag gacagcaaig acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagcctatgc ctgcgaagtc 660 acccatcags gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 162948-序列表.doc -39- c 201247706 <210> 58 <211> 1392 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <4〇0> 58 at£gaatgta actggatact tccttttatt ctgtc^giaa cttcaggggt ctactcagag gttcagctcc agcagtct£g gactgtgctg gcaag^cctg gggcttcagt gaagatgtcc t^caaggctt ctggctacac ctttaccagc tactg^atgc actsggtaaa acaeaggcct ggacagggtc tggaatggat tggcgctatt tatcctesaa atastgatac tacctacaac cagaagttca agegc^ggc caaactgact gcagtcacat ccaccagcac tgcctacatg gagctcagca gcctgacaaa tgaggactct gcggtctatt actgtacacc tacttactac tttgactact ggggccaagg cacctctctc acagtctcct cagccaaaac gaagggccca tccgtcttcc ccctggcgcc ctgctccagg agcacctccg agagcacagc cgccctgegc tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag agagttgagt ccaaatacgg tcccccatgc ccaccctsco cagcacccga gttcgaa^gg fgaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggac^tg agccassaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga g^agcagttc aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctsaac^gc aagga^taca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga ga&aaccatc tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag gagat^acca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggasag caatgggcag ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac acacagaaga gcctctccct gtctctgggt aaagctagct ga <210> 59 <211> 717 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 59 atgagtcctg cccaattcct gtttctgtta gtgctctgga ttcg^gaaac caacgstgat gttgtgatga cccagactcc actcactttg tcgettacca tt£gacaacc agcctccatc tcttgcaagt caagtcagag cctcttagat agtgatggaa agacatattt gaattggttc 162948-序列表.doc -40- 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1392 60 120 180 201247706 ttacaganc caggccagtc tccaaagcgc ctaatctacc tggtgtctaa actggactct ggagtccccg acaggttcac tggcagtgga tcagggacag aittcacact gaaaatcagc agagtggagg ctgaggattt ggsagtttat taltgctggc aaggtacaca ttnccgtgg acsttcggtg gaggcaccaa gctcgasatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catcteatga gcagtt£aaa tctg£aactg cctctgttgt gtgcctgctg aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacascaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagaciac gagaaacaca aagtctalgc ctgcgaagtc acccatcagg gcctgagctc goocglcaca aagagcttca nctggggaga gtgttag <210> 60 <21l> 1415 <212> DNA <213>人造序列 <220> <M3>人造序列之描述：合成聚核苷酸 <400> 60 atgggaggga tctggatctt tctcttcctc ct£tcaggaa ctgcaggtgc ccaclctgag atccasctgc agcagacigg acctgagccg gtgaagcctg gggcttcagi gaagatatcc t£caag£ctt ctggttatcc attcactgac lacatcatgg tctgggtgaa gcagagccat ggaaagagcc ttgagtggat tggaaatatt agtccttact atggtactac taactacaat ctgaagttca agggcaaggc cacattgact gtagacaaat cttccagcac agcctacatg cdgctc^aca gtctgacatc tg&ggactct gcagtctatt actgtgcaag atcccctaac tgggacgggg cctggtttgc tcactggggc caaggggctc tgglcactgt ctctgcagcc a^aacaaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac gaagacctac acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc ctgltccccc caaaacccaa g^acactctc atgatctccc ggacccctga ggtcacgtgc gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc StSS&ggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac S£ctccucc tcctctapag caggctaacc gtggacaaga gcaggtggca ggaggggaat fitcttctcac gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 240 300 360 420 480 540 600 660 717 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 162948-序列表.doc -41- c 201247706 tccctgtctc tgggtaaagc tagctgatta attaa 1415 <210> 61 <211> 717 <212> DNA <213>人造序列 <22〇> <223>人造序列之描述：合成聚核苷酸 <400> 61 μ atggagacag acacaatcct gctatgggtg ctgctsctct gggttccagg ctccaccggt 60 gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca sagggccacc 120 atctccigca asgccagcca aagtgctgat tatgatggtg atagttatat gaactggttc 180 caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tccagaatct 240 gggatcccag ccaggttcag tggcagtggg tctgggacag acttcaccct caacatccat 300 cctgtggagg tgcaacctat tactgtcagc aaagtaatga ggatccattc 360 acgttcggct 〇£gg£acaaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccec catct^atga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480 aataacttct atcccagaga ggccaaagta cagtggaags tggataacgc cctccaatcg 540 ggtaactccc aggagagcgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtccatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga glgttag 717 <210> 62 <211> 1403 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 62 atg^ctgtcc tggggctgct tctctgcctg £tgacgttcc caagctgtgt ccU(cccag 60 gtgcagctga a£gagtcagg acctggcctg gtggcaccct cacagagcct £tccatcaca 120 tgcactgtct ctgggttctc attatccaga tatagtgtat tttgggttcg ccagcctcca 180 ggaaagggtc tggagtggct gggattgata tggggtggt2 gaagcacaga ctataattca 240 gctctcaaat ccagactgag catcagcaag gaoaactcca agagccaagt tttcttaaaa 300 atgaacagtc tgcaaactga tgacacagcc atgtactact gtgccagaat ctactttgat 360 tacgacgggg ctatggacta ctggggtcaa ggaacctcas tcaccgtctc ctcagccaaa 420 acaacgggcc catccgtctt ccccctg^cg ccctgctcca g£3gcacctc cgagagcaca 480 gccgccctgg ^ctgcctggt caaggactac ttccccgaac c££tgacggt £tcgtggaac 540 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctca^gactc 600 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga stccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagt(cgaa£ £g£gaccatc agtcttcctg 780 -42· 162948·序列表.doc 201247706 ctccccccaa aacccaagga cactctcatg atctcccgga cccccgaggt cacgtgcgtg 840 ^tggtggacg tgagccag£a agaccccgag gtccagttca actggtacgt ggatggcgtg 900 ^aggtgcata atgccaagac aaagcc^cgg gaggagcagt tcaacagcac gtaccgtgtg 960 gtcagcgtcc tcaccgtcct ^caccaggac tggctgaacg gcaaggagta caagtgcaag 1020 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaa?c caaagggcag 1080 ccccgagagc cacaggtgta caccctgccc ccatcccasg aggagatgac caagaaccag 1140 gtcagcctga cctgcctgst caaasgcttc taccccagcg acatcgcc^t gga£tgggag 1200 ascaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260 tccctcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320 ttcteatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380 ctgtctctgg gtaaagctag ctg 1403 <210> 63 <21l> 732 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 63 atgcatcgca ccagcatggg catcaagatg gagtcacgga ttcaggcatt tgtattcgtg 60 tttctctggt igtctggtgX tggcsiagac attgtgat^a cccagtctca caaaltcatg 120 tccacatca£ taegagacag ggtcagcgtc acctgcaasg cca£tcag£a tgtgacttct 180 gctgtagcct ggtatcaaca aaaaccassg caatctccta aactactgat ttactgggca 240 tccacccggc acactggast cccc^atcsc ttcacaggca gtgsatctgg gacagattat 300 actctcacca tca£cagtgg gcaggcigaa gacctggcac mattactg tcaccaatat 360 tatagcgctc cccggacgtt cggt£gaggc accaagctcg agatcaaacg aactgtsgct 420 gcaccatctg tcttcatctt cccgccatct gatgagcast tgaaatctgg aactgcctct 480 gttgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggtggat 540 aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc 600 acctac&gcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc 660 tatgcctgcg aagtcaccca tcag£gcctg agctcgcccg tcacaaagag cttcaacagg 720 ggagagtgtt ag 732 <21〇> 64 <211> 1404 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 64 atggaatgga actgggtcgt ictcttcctc ctgtcattaa ctgcaggcgt ctatgcocag 60 ggtcagatgc agcagtctgg agctgagctg gtgaagcctg gggcttcagt gaagctgtcc 120 tgcaagactt ctggcttcac cttcagcagt aactatataa gttggttgaa gcaaaagcct 180 c 162948-序列表,doc -43 - 201247706 ggacagagtc ttgagtggat tgcatggatt tatgctggaa ctggtggtat tacctataat cagaagttca gaggcagggc ccaactgact gtagacacat cctccagcac agcctacatg cagttcagca gcctgacaac tgatgactct gccatctatt actgtscaag acac^tgagg ggttaccatc ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa acgaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccct^g gctgcctggt caaggactac ttccccgaac cggtgacggt stcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc ttccc£gctg tcctacagtc ctca^gactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga giccaaatat ggtcccccat £cccaccct£ cccagcacct gagttcgaag ggggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg gtggtg^acg tgagccagga agaccccgag gtccagttca actggtacgt £gatggcgtg gasstgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag agcaatsigc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcag gctaaccgtg gacaagagca g£tggcagga £gggaatgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc ctgtctctgg gtaaagccag ctga <2I0> 65 <211> 705 <212>DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 65 atggagtcac agactcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgatgga gacattgtga tgacccagtc tcaaaaattc atgtccgcat cagtagggga cag£gtca£c gtcacct£ca gggccagcca gaatgtggtt actaatgtag gctggtatca aca^aaacca gggcaatctc ctaaaatact gatttactcg gcatccttcc ggtacagtgg agtccctgat cgcttcacag gcagtggatc tggsaca^at ttcactctca ccatcaccaa tgticagtct gaagacttgg cagagtattt ctgtcagcaa tataacaact atccgtacac £ttcggag£g gggaccaagc tegagatcaa acgaac:tgig gctgcaccat ctgtcttcat cttcccgcca tctgatgagc agttgaaatc t£gaact£cc tctgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggig gataacgccc tccaatcsgg taactcccag gagagtgtca cagagcagge cagcaaggac agcacctaca gcctcagca^ caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 162948-序列表.doc -44 - 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 10SO 1140 1200 1260 1320 1380 1404 60 120 180 240 300 360 420 480 540 600 660 201247706 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <21Q> 66 <21I> 1407 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 66 _ atgggatgga gctatatcat octetttttg gtaecaacag ctacagatgt ccactcccag 60 ^tccaactgc agcagcctgg ggctgaactg gtgaagcctg gggcttcagt gaagctgtcc 120 tgcaaggctt ctggctacac cttcaccagc tact£gatsc actgggtgaa gcagaggcct 180 ggagaaggee ttgagtggat tggagagatt aatccugct acggtcgtac tgactacaat 240 gggaagitca agaacaaggc cacactgact gtagccaaat cctccagcac agcctacatg 300 caactcagca gcctgacatc tgaggactct geggtetatt actgtgcaas aggagattac 360 tacggtagta gctcgtttgc ttactggggc caagggactc tggtcactgt ctclgcagcc 420 aaaacaaagg geccatccgt cttccccctg gcgccctgct ccaggagcac ctcegagagc 480 acagccgccc tgggctgcct ggtcaaggac lacttccccg aaccggtgac ggtgtcgtgg 540 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gLcctcagga 600 ctccactccc teageagegt ggtgaccgtg ccctccagca gcttgggcac gaagacctac 660 acctgcaace tagatcacaa ecccagcaac accaag^tgg acaagagagt tgagtccaaa 720 tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780 ctgttccecc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtec 840 gtggxggtzs acgtga^cca ggaagacccc gasgtccagt tcaactggta cgtggatggc 900 gtggaggtgc ataatgccaa gacaaagccg cg£gag£agc aattcaacag cacgtaccgt 960 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaagsg 1080 cagccccgas agccacaggt gtacaccctg cccccatccc a^gaggagat gaccaagaac 1140 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260 ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat 1320 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc 1380 tccctgtctc tgggtaaagc tagctga 1407 <210> 67 <211> 705 <212> DNA <213>人造序列 <220> <223>人造序列之描述：合成聚核苷酸 <400> 67 atggagteae agactcaggt ctttgtatac atgttgctgt 2£ttgtc(gg tgtt£atgga 60 c 162948·序列表.doc -45. 201247706 gacattgtga tgacccagtc tcaaaaattc atgtccacat cattaggaga cagggtcagc gtcacctgca aggccagtca gaatgtgggt actaatgtag cctggtatca acagaaacca g£gcactc(c ctaaagcact gatttactcg gcatcctacc ggtacagtgg agtccctgat cgcctcacag gcagtggatc tgggacagat ticactctca ccatcagcaa tgtgcagtct gaagacttgg cagagtlttt ctgtcagcaa tataacaact atccgcacac gctcggaggg gggaccacgc tcgagatcaa acgaactgtg £ctgcaccat ctgtcttcat cttcccgcca cctgatgagc asttgaaatc tgsaactgcc tctgttgtgt gcctgctgaa taacticcat cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctc£c ccgtcacaaa gagcttcaac aggfgagagt gttag <2LO> 68 <211> 466 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 68

Met Gly Arg Leu Thr Scr Ser Phc Leu Leu Leu lie Val Pro Ala Tyr 15 10 15

Val Lea Ser Gin Val Thr Leu Lys Glu Scr Gly Pro Gly lie Leu Gin 20 25 30

Pro Ser Gla Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Hie Ser Leu 35 40 45

Ser Thr Ser Gly Met Ser VaJ Gly Trp He Arg Gin Pro Ser Gly Lys 50 55 60

Gly Leu Glu Trp Leu Ala His lie Trp Trp Asn Asp Asp Lys Tyr Tyr 65 70 75 80

Asn Pro Val Leu Lys Ser Arg Leu Thr lie Ser Lys Glu Thr Ser Asn «5 90 95

Asn Gin Val Phe Leu Lys lie Ala Ser Val Val Ser Ala Asp Thr Ala loo 105 no

Thr TVr Tyr Cys Ala Arg Phe Tyr Gly Asn Cys Leu Asp Tyr Trp Gly 115 120 125

Gin Cly Thr Thr Leu Thr Val Scr Ser Ala Lys Thr Lys Gly Pro Ser 130 135 140

Val Phe Pro Leu Ala Pro Cys Scr Arg Ser Tbr Ser Glu Ser Thr Ala 145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phc Pro Glu Pro Val Hir Val 165 170 175 •46· 162948-序列表.doc 201247706

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 180 1S5 190

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 195 200 205

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 210 215 220

Lys Pro Ser Asn Thr Lys Va] Asp Lys Arg Val Glu Ser Lys Tyr Gly 225 230 235 240

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phc Glu Gly Gly Pro Ser 245 250 255

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg 260 265 270

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro 275 280 285

Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asd Ala 290 295 300 、

Lys Thr Lys Pro Arg Gla Glu Gin Phe Asn Ser Thr Tyr Arg Val Val 305 310 315 320

Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr 325 330 335

Lys Cys Lys Val Set Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr 340 345 350 lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Va! Tyr Thr Leu 355 360 365

Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Scr Leu Thr Cys 370 375 380

Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser 3S5 390 395 400

Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 405 410 415

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 420 425 430

Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Sei Val Met His Glu Ala 435 440 445

Leu His Asn His Tyr Thr Gin Lys Ser Leu Sei Leu Ser Leu Gly Lys 450 455 460

Ala Ser 162948-序列表.doc -47- £ 201247706 465 <210> 69 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 69

Met Met Ser Ser Ala Gin Phe Leu Gly Leu Leu Leu Leu Cys Phe Gin 15 10 15

Gly Thr Arg Cys Asp lie Gin Met Thr Gin Thr Tht Ser Ser Leu Ser 20 25 30

Ala Ser Leu Gly Asp Arg Val Thr He Ser Cys Arg Ala Ser Gin Asp 35 40 45

Lie Ser Asn Tyr Lea Asn Txp Tyr Gin Gin Lys Pro Asp Gly Thr Val 50 55 60

Lys Leu Leu lie Tyr Tyr Thr Ser He Leu G)n Leu Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser GJy Ser Glu Thr Asp Tyr Ser Leu Thr lie Ser 85 90 95

Asn Leu Glu Gin Glu Asp lie Ala Thr Tyr Phe Cys Gin Gin Gly Asp 100 105 110

Ser Leu Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asj) Asrt Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Vai Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 70 <211> 464 • 48- 162948-序列表.doc 201247706 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 70

Met Arg Ala Leu lie Leu Leu Cys Leu Phe Thr Ala Phe Pro Gly lie 1 5 10 15

Leu Ser Asp Val Gin Leu Gin G】u Ser Gly Pro Asp Leu Val Lys Pro 20 25 30

Ser Gin Ser Leu Ser Leu Thr Cys Thr Va] Thr Gly Tyr Ser lie Thr 35 40 45

Ser Gly Tyr Ser Trp His Tip He Arg Gin Phe Pro Gly Asn Lys Leu 50 55 60

Glu Trp Met Gly Tyr lie Leu Phe Ser Gly Ser Thr Asn Tyr Asn Pro 65 70 75 80

Ser Leu Lys Ser Arg ]le Ser lie Thr Arg Asp Thr Ser Lys Asn Gin 85 90 95

Phe Phe Leu Gin Leu Asn Ser Val Thr Tht Glu Asp Thr AU Thr Tyr 100 105 110

Phe Cys Ala Arg Ser Asn Tyr Gly Ser Phe Ala Sei Trp Gly Gin Gly 115 120 125

Thr Leu Val TTir Val Ser Ala Ala Lys Thr Thr Gly Pro Ser Val Phe 130 135 140

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu SeT Thr Ala Ala Leu 145 150 155 160

Gly Cys Leu Va】 Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 165 170 175

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 180 185 190

Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Va] Val Thr Val Pro Ser 195 200 205

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro 210 215 220

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro 225 230 235 240

Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe 245 250 255

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Sei Arg Thr Pro 260 265 270 162948-序列表.doc -49- c 201247706

Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val 275 280 285 GLn Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 290 295 300

Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser Val 305 310 315 320

Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 325 330 335

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie Ser 340 345 350

Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro 355 360 365

Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val 370 375 380

Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn Gly 385 390 395 400

Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 405 410 415

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp 420 425 430

Gin Gla Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 435 440 445

Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Set Leu Gly Lys Ala Ser 450 455 460 <210> 71 <211> 235 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 71

Met Asp Phe Gin Val Gin He Phe Ser Phe Leu Leu lie Ser Ala Ser 15 10 15

Val lie lie Ser Arg Gly Gin He Val Leu Thr Gin Ser Pro Ala lie 20 25 30

Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Aia Ser 35 40 45

Ser Ser Val Ser His Met His Trp Tyr Gin Gin Lys Ser Gly Thr Ser 50 55 50 -50- 162948-序列表.doc 201247706

Pro Lys Arg Trp lie Tyr Asp Thr Ser Aig Leu AU Ser Gly Val Ρίΰ 65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr lie 85 90 95

Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gin Gin Trp 100 105 110

Ser Ser His Pro Trp Ser Phe Gly G]y Gly Thr Lys Leu ΰΐυ lie Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe He Phe Pro Pro Ser Asp Glu 130 135 140

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu A.sn Asn Phe 145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn A.la Leu Gin 165 170 175

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Sex Lys Asp Ser 130 185 190

Thr Tyr Ser Leu SeT Ser Thr Leu Thr Leu Scr Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 72 <211> 468 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 72

Met Ala Trp Val Trp Thr Leu Leu Phe Leu Met Ala Ala Ala Gin Ser 15 10 15

Ala Gin Ala Gin lie Gin Leu Val Gin Ser Gly Pro Glu Leu Lys Lys 20 25 30

Pro Gly Glu Thr Val Lys lie Ser Cys Lys Ala Scr Gly Tyr Thr Phe 35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Lys Gin Val Pro Gly Lys Gly Lea 50 55 60

Arg Trp Met Gly Trp Met Asp Thr Phe Thr Gly Glu Pro Thr Tyr Ala 65 70 75 80

Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser -51 - 162948-序列表.doc 201247706 85 90 95

Thr Ala Tyr Leu Gin lie Asn Sei Leu Lys Asn Glu Asp Thr Ala Thr 100 105 110

Tyr Phe Cys Ala Arg Gly Gly lie Leu Arg Leu Asn Tyr Phe Asp Tyr 115 120 125

Trp Gly Gin Gly Thr Thr Leu Thr Va] Ser Set Ala Lys Thr Lys Gly 130 135 140

Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 145 150 155 160

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190

Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205

Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 210 215 220

Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 225 230 235 240

Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly 245 250 255

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 260 265 270

Ser Arg Thr Pro Glu Val Thr Cys Val Va】 Val Asp Val Ser Gin Glu 275 280 2δ5

Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 290 ' 295 300

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg 305 310 315 320

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 325 330 335

Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu 340 345 350

Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 355 360 365

Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu 370 375 380 -52- 162948-序列表.doc 201247706

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp 385 390 395 400

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 405 410 415

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp 420 425 430

Lys Ser Arg Trp Gla Glu Gly Asn Val Phe Ser Cys Ser Val Met His 435 440 445

Glu Ala Leu His Asn His Tyr Thr Oln Lys Ser Leu Ser Leu Ser Leu 450 455 460

Gly Lys Ala Ser 465 <21〇> 73 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述··合成多肽 <400> 73

Met Lys Phe Pro Ser Gin Leu Leu Leu Leu Leu Leu Phe Gly lie Pro 15 10 15

Gly Met lie Cys Asp lie Gin Met Thr Gin Ser Ser Ser Ser Phe Ser 20 25 30

Val Ser Leu Gly Asp Arg Val Thr lie Thr Cys Lys Ala Ser Glu Asp 35 4C 45 lie Tyr Asn Arg Leu Gly Trp Tyr Gin Gin Lys Pro Gly Asn Ala Pro 50 55 60

Arg Leu Leu lie Ser Gly Ala TTir Ser Leu Glu Thi Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Lys Asp Tyr Ala Leu Ser lie Thr 85 90 95

Ser Leu Gin Thr Glu Asp Leu Ala Thr Tyr Tyr Cys Gin Gin Cys Trp 100 105 110

Thr Ser Pro TyrThr Phe Gly Gly Gly Thr Lys Uu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Stt Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asa Asn Phe Tyr 145 150 155 L60

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 162948·序列表.doc -53- £ 201247706 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 74 <211> 464 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 74

Met Gly Trp Ser Trp lie Phe Leu Phe Leu Leu Ser Gly Thr Gly Gly L 5 10 15

Val Leu Ser Glu Val Gin Leu Gin Gin Ser Gly Pro Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys Met Sci* Cys Lys AU Ser Gly Tyr Thr Phe 35 40 45

Thr Asp Tyr Tyr Met Lys Trp Val Lys Gin Ser His Gly Lys Ser Leu 50 55 60

Glu Trp lie Gly Asp lie Asn Pto Asti Tyr Gly Asp Thr Pile Tyr Asn 65 70 75 80

Gin Lys Phe Glu Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg 85 90 95 TTir Ala Tyr Met Gin Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Gly Arg Gly Asp Tyr Cty Tyr Phe Asp Val Trp Gly Ala 115 120 125

Gly Thr Thr Va] Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser Val 130 135 140

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 145 丨 50 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 165 170 175

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 180 185 390 -54- 162948-序列表.doc 201247706

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 195 200 205

Scr Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 210 215 220

Pro Ser Asn Thr Lys Va] Asd Lys Arg Va】Glu Ser Lys Tyr Gly Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 245 250 255

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 11c Ser Arg Thr 260 265 270

Pro Glu Val ITir Cys Val Val Val Asp Val Ser Gin Glii Asp Pro Glu 275 280 285

Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 290 295 300

Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser 305 310 315 320

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 325 330 335

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Lea Pro 355 360 365

Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu 370 375 380

Val Lys Gly Phe Tyr Pro Scr Asp lie Ala Val Glu Trp Glu Ser Asn 385 390 395 400

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 405 410 415

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Ihr Val Asp Lys Ser Arg 420 425 430

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met Hjs CIu Ala Leu 435 440 445

His Asn His Tyr Thr Gin Lys Ser Leu Leu Ser Leu Gly Lys Ala Scr 450 455 460 <210> 75 <211> 234 <212> PRT <213>人造序列 -55- 162948-序列表.doc 201247706 <220> <223>人造序列之描述：合成多肽 <400> 75

Met Glu Thr His Ser Gin Val Phe Val Tyr Met L«u Leu Trp Leu Ser 15 10 15

Gly Val Glu Gly Asp lie Val Met Thr Gin Ser His Lys Phe Met Ser 20 25 30

Thr Ser Val Gly Asp Arg Val Ser lie Thr Cys Lys Ma Ser Gin Asp 35 40 45

Val Gly Thr Ala Val Ala Ττρ Tyr Gin Gin Lys Pro Gly Gin Ser Pro 50 55 60

Lys Leu Leu lie Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp 65 70 75 80

Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Asn 85 90 95

Asn Val Gin Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gin Gin Tyr Ser 100 105 110

Ser Asn Pro Tyr ^let Phe Gly Gly Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Glu 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 145 150 155

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Scr Val Thr Giu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu S&r Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pio 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 76 <211> 469 <212> PRT <2L3>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 76 -56- 162948·序列表 _doc 201247706

Met Gly Trp Ser Trp lie Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly 15 10 15

Val Leu Ser Glu Val Gin Leu Gin Gin Ser Gly Pro Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Ser Cys Lys Thr Ser Gly Tyr Thr Phe 35 40 45

Thr Glu Tyr Thr Met His Trp Val Arg Scr His Gly Lys Ser Leu Giu 50 55 60

Trp lie Gly Gly He Asn Pro He Asn Gly Gly Pro Thr Tyr Asn Gin 65 70 75 80

Lys Phe Lys Gly Lys Ala Thr Leu Thr Va] Asp Lys Ser Ser Scr Thr 85 90 95

Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 100 105 110

Tyr Cys Ala Arg Trp Asp Tyr Gly Ser Arg Asp Val Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Val Set Ser Ala Lys Thr Lys Gly Pro 130 135 140

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Pro L65 170 175

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 180 185 190

Phe Pro Ala Val Leu Gin Scr Ser Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Scr 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 260 265 m lie Ser Arg Tlir Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin 275 2S0 285 GLu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val 290 295 300 c 162948·序列表.doc -57- 201247706

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Cln Phe Asn Ser Thr Tyr 305 310 315 320 kxg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie 340 345 350

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Glfl Val 355 360 365

Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 400

Trp Glu Ser Asn Gly Gin Pro Givi Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Lea Asp Set Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val 420 425 430

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys Ala Ser 465 <210> 77 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 77

Met Glu Thr His Ser Gin Val Phe Val Tyr Met Leu Leu Trp Leu Ser 15 10 15

Gly Val Glu Gly Asn lie Val Met Thr Gin Ser Pro Lys Ser Met Ser 20 25 30

Met Ser Val Gly Glu Arg Val Thr Leu Ser Cys Lys Ala Ser Glu Asn 35 40 45

Vaj Gly Thr Tyr Val Ser Trp Tyr Gin Gin Arg Pro Glu Gin Ser Pro 50 55 60

Lys Leu Leu lie Tyr Gly Ala Scr Asn Arg Tyr Thr Gly Val Pro Asp 65 70 75 80 •58· 162948-序列表.doc 201247706

Arg Phe Thr Gly Ser Gly Ser Ala Thr Asp Phe Thr Leu TTir lie Ser 85 90 95

Ser Val Gin Ala Glu Asp Leu Ala Asp Tyr His Cys Gly Gin Thr Tyr 100 105 110

Ser Tyr lie Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asti Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 78 <211> 467 <212> PRT <2I3>人造序列 <220> Θ23>人造序列之描述：合成多肽 <400> 78

Met G]y Trp Ser Arg lie Phe Leu Phe Leu Leu Ser He Thr Ala Gly 15 10 15

Val His Cys Gin Val Gin Val Gin Gin Ser Gly Pro Glu Leu Vat Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Ser Cys Lys Ala Ser Gly Asp Ala Phe 35 40 45

Ser Ser Ser Trp Met Asn Trp Val Lys Glu Arg Pro Gly GLn Gly Leu SO 55 60

Glu Trp lie Gly Arg He Tyr Leu Gly Asp Gly Asp lie Asn Tyr Asn 65 70 75 80

Gly Lys Phe Lys Gly Arg Ala Thr Leu ThT Ala Asp Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met Gin Leu Ser Ser Leu Thr Ser Val Asp Ser Ala Val 162948-序列表.doc -59- 201247706 100 105 110

Tyr Phe Cys Ala Arg Gin Leu Gly Leu Trp Tyr Val Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro 130 135 140

Sei Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Tin 145 150 155 160

Ah Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ί80 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Hu Lys Thr Tyr Thr Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 225 230 235 240

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pio 245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Lea Met He Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 280 285

Pto Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Ar^ Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val 305 310 315 320

Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu 325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400 -60- 162948-序列表.doc. 201247706

Set Asn Oly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 405 410 415

Asp Scr Asp Gly Ser Pbe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430

Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 79 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 79

Met Ser Val Pro Thr Gin Val Leu Gly Leu Leu Leu Leu Tip Leu Thr 15 10 15

Gly Ala Arg Cys Asp lie Gin Met Ala Cln Ser Pro Ala Ser Leu Ser 20 25 30

Ala Ser Val Gly Glu Thr Val Thr lie Thr Cys Arg Ala Ser Glu Asn 35 40 45 lie Tyr Ser Tyr Leu Ala Trp Tyr Gin Gin Lys Gin Gly Lys Scr Pro 50 55 60

Gin Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser 65 70 75 SO

Arg Phe Ser Gly Set Gly Ser Gly Thr Gin Phe Ser Leu Lys lie Asn 85 90 95

Ser Leu Gin Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gin His His Tyr 100 105 110

Gly Phe Pro Trp Thr Phe Gly Gly Gty Thr Lys Leu Glu lie Lys Arg 115 120 12S

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Scr Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr G]u G】n Asp Ser Lys Asp Ser Thr 162948-序列表.doc -61 - s 201247706 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Va】Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 80 <21L> 464 <212> P8T <213>人造序列 <220> <2M>人造序列之描述：合成多肽 <40〇> 80

Met Asn Phe Gly Leu Ser Leu lie Phe Leu Val Leu lie Leu Lys GJy 15 10 15

Val Gin Cys Glu Val Gin Leu Val Glu Ser Gly Gly Asp Leu Val Lys 20 25 30

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45

Ser Ser Tyr Gly Met Ser Trp Va] Arg Gin Thr Pro Asp Lys Arg Leu 50 55 60

Glu Trp Val Ala Val lie Ser Ser GJy Gly Ser Ser llir Phe Tyr Pro 65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr lie Ser Are Asp Asn Ala Lys Asn 85 90 95

Thr Leu Tyr Leu Gin Met Ser Ser Leu Lys Ser Glu Asp Thr Ala Val 100 105 110

Tyr Tyr Cys Ser Arg Gly Gly Tyr Tyr Phe Asp Tyr Trp Gly Gin Gly 115 120 125

Thr Thr Leu Thr Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val Phe 130 135 140

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Scr Thr Ala Ala Leu 145 150 155 160

Gly Cys Leu Val Lys Asp Tyr Phe Pro G】u Pm Val Thr Val Ser Trp 105 170 175

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu ISO 185 190

Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 195 200 205 • 62- 162948·序列表 _doc 201247706

Scr Ser Leu Gly Thr Lys Tfar Tyr Thr Cys Asn Val A$p His Lys Pro 210 215 220

Scr Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro 225 230 235 240

Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Giy Gly Pro Ser Val Phe 245 250 255

Leu Pbe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pro 260 265 270

Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val 275 280 285

Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 290 295 300

Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser Val 305 310 315 320

Leu Thr Val Leu His Gin. Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 325 330 335

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie Ser 340 345 350

Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro 355 360 365

Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val 370 375 380

Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu S&r Asn Gly 385 390 395 400

Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 405 410 415

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp 420 425 430

Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 435 440 445

Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser 450 455 460 <210> 81 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 -63- 162948-序列表,doc 201247706 <400> 81

Met Arg Phe Gin Val Gin Val Leu Gly Leu Leu Leu Leu Trp He Ser 15 10 15

Gly Ala Gin Cys Asp Val Gin lie Thr Gin Ser Pro Ser Tyr Leu Ala 20 25 30

Ala Ser Pro Gly Glu Thr lie Thr lie Asn Cys Arg Ala Ser Lys Thr 35 40 45 lie Ser Lys Tyr Leu Ala Trp Tyr Gin Glu Lys Pro Glu Lys Thr Asp 50 55 60

Lys Leu Leu lie Tyr Ser Gly Ser Thr leu Gin Ser Gly lie Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phc Thi Leu Thr lie Ser 85 90 95

Gly Leu Glu Pro Glu Asp Phe A]a Met Tyr Tyr Cys Gl*n Gin His Asn 100 105 110

Glu Tyr Pro Trp Thr Phe Gly Giy Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Va] Ala A】a Ρϊό Ser Val Phe He Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phc Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Scr 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Ihr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 82 <211> 462 <212> PRT <213>人造序列 <220> 人造序列之描述：合成多肽 <400> 82 Met Gly Trp Ser Trp 1 5 lie Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly 10 15 -64- 162948·序列表.doc 201247706

Val Leu Ser Glu Val Gin Leu Gin Gin Ser G】y Pro Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Ser Cys Lys Ala Ser Gly Tyr S^r Phe 35 40 45

Thr Gly Tyr Tyr Met His Trp Val Lys Gin Ser His Val Lys Ser Leu 50 55 60 G]u Trp lie Gly Arg I]e Asn Pro Tyr Asn Gly Ala TTir Ser Tyr Asn 65 70 75 80

Gin Asn Phe Lys Asp Lys Ala Ser Leu Thr Val Asp Lys Ser Set Ser 85 90 95

Thr Ala Tyr Met Clu Leu His Ser Leu T^r Ser GIu Asp Ser Ala Val 100 105 l]〇

Tyr Tyr Cys Ala Arg Glu Asp Tyr Val Tyr Trp Gly Gin Gly Thr Thr .115 120 125

Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu 130 135 140

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys 145 150 155 L60

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Trp Asn Ser 165 170 175

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser 180 185 190

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Scr Sei 195 200 205

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn 210 215 220

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro 225 230 235 240

Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe 245 250 255

Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val 260 265 270

Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Ola Val Gin Phe 275 280 2S5

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 290 295 300

Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 305. 310 315 320 -65- 162948-序列表.doc 201247706

Val Leu His Gin Asp Trp Leu Asji Gly Lys Glu Tyr Lys Cys Lys Val 325 330 335

Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie Ser Lys Ala 340 345 350

Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Tlir Leu Pro Pro Ser Gin 355 360 365

Glu G]u Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Giy 370 375 380

Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn Gly Gin Pro 385 390 395 400

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 405 410 415

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Set Arg Trp Gin Glu 420 425 430

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 435 440 445

Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser 450 455 460 <210> S3 <211> 238 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 83

Met Lys Leu Pro Va】Arg Leu Leu Val Leu Met Phe Trp I】e Pro Ala 15 10 15

Ser Ser Ser Asp Val Val Met Thr Gin Thr Pro Leu Ser Leu Pro Val 20 25 30

Ser Leu Gly Asp Gin Ala Ser He Ser Cys Arg Ser Ser Gin Ser Leu 35 4D 45

Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gin Lys Pro 50 55 60

Gly Gin Ser Pro Lys Leu Leu lie Tyr Lys Val Ser Asq Arg Phe Ser 65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ala 85 90 95

Leu Lys lie Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys 100 105 110 -66- 162948·序列表.doc 201247706

Ser Gin Ser Thr His Val Pro Irp Thr Phe Gly Gly Gly Tbr Lys Leu 115 120 125

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val Phe He Phe Pro Pto 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Gl« Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser 180 185 190

Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Uu Thr L^u Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 84 <^U> 469 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 84

Met Glu Trp Ser Trp He Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly 15 10 15

Val His Ser Glu Val Gin Leu Gin Gin Ser Gly Pro Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45

Thr Asp Tyr Val Leu His Trp Val Lys Gin Lys Pro Gly Gin Gly Leu 50 55 60

Glu Trp lie Gly Tyr lie Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn 65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser 85 90 9S

Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Gly Tyr Pro Ala Tyx Sex Gly Tyr Ala Met Asp 115 120 125

Tyr Trp Gly Gin Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys c 162948-序列表.doc -67- 201247706

130 135 HO

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser GIu 145 150 ]55 160

Ser Thr A】a Ala Leu G】y Cys Leu Val Lys As]> Tyr Phe Pro Glu Pro 165 170 175

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 180 185 190

Phe Pro Ala Val Leu Gin Ser Set Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val GIu Ser 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Gin Phe GIu Gly 245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 260 265 270 ILe Ser Arg Thr Pro GIu Val Tht Cys Vai Val Va] Asp Val Ser Gin 275 280 285 GIu Asp Pro GIu Val Gin Phe Asn Trp Tyr Val Asp Gly Val GIu Val 290 295 300

His Asn Ala Lys Thr Lys Fro Arg GIu GIu Gin Phe Asn Ser Thr Tyr 305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His G】n Asp Trp Leu Asn (Jly 325 330 335

Lys GIu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie 340 345 350

Clu Lys Thx He Ser Lys Ala Lys Giy Gin Pro Arg Glu Pro Gin Val 355 360 365

Tyr Thr Leu Pro Pro Ser GJn Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 400

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Scr Arg Leu Thr Val 420 425 430 •68- 162948*•序列表.doc 201247706

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phc Ser Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys Ala Ser 465 <210> 85 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 85

Met Met Ser Ser Ala Gin Phe Leu Gly Leu Leu Lev Leu Cys Phc Gin 1 5 10 15

Gly Thr Arg Cys Asp lie Gin Met Thr Gin Thr Thr Scr Ser Leu Ser 20 25 30

Ala Ser Leu Gly Asp Arg Val Thr ilc Ser Cys Arg Ala Ser Gin Asp 35 40 45 lie Ser Asn Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Asp Gly Thr Val 50 55 60

Lys Leu Leu lie Tyr Tyr Thr Ser Arg Leu His Scr Gly Val Pro Scr 65 70 75 SO

Arg Phe Ser Gly Ser Gly Scr Gly Thr Asp Tyr Ser Leu Thr lie Ser 85 90 95

Asn Leu Glu Gin Glu Asp lie Ala Thr Tyr Phc Cys His His Gly Asn 100 105 110

Thr Leu Pro Trp Thr Phe G】y Gly Gly llir Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu G]n 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asa Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Scr Thr 180 185 190

Tyr Ser Leo Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro c 162948-序列表.doc -69- 201247706 210 215 220

Val Thr Lys Scr Fhe Asn Arg Gly Glu Cys 225 230 <210> 86 <211> 467 <212> PRT <213>人造序列 <22Q> <223>人造序列之描述：合成多肽 <400> 86

Met Asn Leu Gly Leu Ser Leu lie Phe Leu Val Leu Val Leu Lys Gly 15 10 15

Val Gin Cys Glu Va】Lys Leu Va】Glu Ser Gly Gly Gly Leu Val Gin 20 25 30

Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe 35 40 45

Ser Asp Tyr Tyr Met Tyr Trp Val Arg Gin Thr Pro Glu Lys Arg Leu 50 55 60

Glu Tip Vai Ala Tyi He Asti SeT Gly Gly Gly Ser Thr Tyr Tyr Pro 65 70 75 80

Asp Ilir Val Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ala Lys Asn 85 90 95

Thr Leu Tyr Leu Gin Met Ser kig Leu Lys Ser Glu Asp .TTir Ala Met 100 105 110

Tyr Tyr Cys Ala Arg Arg Gly Leu Pro Phe His Ala Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro 130 135 HO

Ser Val Phe Pro Leu Al^ Pro Cys Ser Arg Scr Thr Ser Glu Sex Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 170 1 75

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 180 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 225 230 235 240 •70- 162948-序列表.doc 201247706

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 255

Ser Va】Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met IU Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 280 285

Pro Glu Val Gin Phe Asn Tip Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Are Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val 305 310 315 320

Val Ser Va! Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu 325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys G]y Leu Pro Ser Ser lie Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400

Scr Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thi Pro Pro Val Leu 405 410 415

Asp Ser Asp Gly SeT Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430

Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 87 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <4〇0> 87

Met Met Ser Ser Ala Gin Phe Leu Gly Leu Leu Leu Leu Cys Phe Gin 15 10 15 162948-序列表.doc -71 - s 201247706

Gly Thr Arg Cys Asp lie Gin Met Thr Gin Thr TTir Ser Ser Leu Ser 20 25 30

Ala Ser Leu Gly Asp Arg Va】Thr I]e Ser Cys Ser Ala Ser Gin Gly 35 40 45 lie Ser Asn Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Asp Gly Thr Val 50 55 60

Lys Lea Leu lie Tyr Tyr Thr Ser lie Leu His Ser Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Tbr Asp Tyr Ser Leu Thr lie Gly 85 90 95

Asn Lea Glu Pro Glu Asp lie Ala Thr Tyr Tyr Cys Gin Gin Phe Asn 100 105 110

Lys Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu He Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 2L0 215 220

Val Thr Lys Scr Phe Asn Arg Gly Glu Cys 225 230 <210> 88 <211> 467 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 88

Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gin Ser 15 10 15

Ala Gin Ala Gin lie Gin Leu Val Gin Ser Gly Pro Glu Leu Lys Lys 20 25 30 •72· 162948-序列表.doc 201247706

Pro Gly Glu Thr Val Lys lie Set Cys Lys Ala Ser Gly Tyr Ser Phe 35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Lys Gin Ala Pro Gly Lys Gly Leu 50 55 60

Lys Trp Met Gly Trp lie Asn Thr Tyr Thr Gly Glu Ser Thr Tyr Ala 65 70 75 80

Asp Asp Phe Lys Gly Arg Phc Ala Phe Ser Leu Glu Thr Ser Ala Ser 85 90 95

Thr Ala Tyr Leu Gin lie Ser Asn Leu Lys Asn Glu Asp Met Ala Thr 100 105 110

Tyr Phe Cys Ala Arg Gly Asp Phe Arg Tyr Tyr Tyr Phe Asp Tyr Trp 115 】20 125

Gly Gin Gly Thr Thr Leu Thr Gly Ser Ser Ala Lys Thr Lys Gly Pro 130 135 140

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gty Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 Π0 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 180 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Sex Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Va】Asp Lys Arg Va】Glu Ser Lys Tyr 225 230 235 240

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Va] Ser Gin 01¾ Asp 275 280 285

Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val 305 310 315 320

Val Ser Val Leu Thr Va! Leu His Gin Asp Trp Leu Asn Gly Lys Glu 325 330 335 c 162948-序列表.doc -73· 201247706

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Va】Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp GLu 3S5 390 395 400

Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430 S&r Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 89 <211> 233 <212> PKT <213>人造序列 <22Q> <223>人造序列之描述：合成多肽 <400> 89

Met Ser Val Leu Thr Gin Val Leu Ala Leu Leu Leu Leu Trp Leu Thr 15 10 15

Gly Ala Arg Cys Asp lie Gin Met Thr Gin Ser Pro Ala Ser Leu Ser 20 25 30

Ala Ser Val Gly Glu Thr Val Thr lie Thr Cys ktg Ala Ser Gly Asn 35 40 45 lie His Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Gin Gly Lys Ser Pro 50 55 60

Gin Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Scr Gly Thr Gin Tyr Ser Leu Lys lie Asn 85 90 95

Thr Leu Gin Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gin His Phe Trp 100 105 110 •74- 162948-序列表.doc 201247706

Asp Ser Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu lie Lys Arg Thr 115 120 125

Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin Leu 130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 145 150 1 55 160

Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly 165 170 175

Asn Sbt Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr 180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 195 200 205

Lys Val Tyr Ala Cys Gla Val Thr His Gin Gly Leu Ser Ser Pro Val 210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 90 <211> 465 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 90

Met Glu Trp ΊΤιγ Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly 15 10 15

Val His Ser Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Leu Met Lys 20 25 30

Pro Gly Ala Set Val Lys lie Ser Cys Lys Ala Thr Gly Tyr Thr Phe 35 40 45

Ser Ser Tyr Trp lie Glu Trp Val Lys Gin Arg Pro Gly His Gly Leu 50 55 60

Glu Trp lie Gly Glu lie Leu Pro Gly Ser Gly Arg Thr Asn Asp Asn 65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Tht Phe Thr Ala Asp Thr Ser Ser Lys 85 90 95

Lys Ala Tyr Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val LOO 105 110

Tyr Tyr Cys Ala Arg Arg Gly Gly Tyr Ser Phe Ala Tyr Trp Gly Gin 115 120 125

Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val c 162948-序列表 *doc -75- 201247706 130 135 140

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 145 150 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 165 170 175

Trp Asn Ser Gly Ala Leu Tlir Ser Gly Val His Thr Phe Pro Ala Val 180 185 190

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 195 200 205

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Va丨 Asp His Lys 210 215 220

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 245 250 255

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met He Ser Arg Thr 260 265 270

Pro Glu Val Thr Cys Val Va] Vxil Asp Val Set Gin Glu Asp Pro Glu 275 280 285

Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 290 295 300

Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser 305 310 315 320

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 325 330 335

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Scr lie Glu Lys Thr lie 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 355 360 365

Pra Ser Gin Glu Glu Met Thr Lys Asn Gin Val Scr Leu Thr Cys Leu 370 375 380

Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn 385 390 395 400

Gly GId Pro Glu Asa Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 405 410 415

Asp Gly Ser Phe Phe Leu Tyr Set Arg Leu Thr Val Asp Lys Ser Arg 420 425 430 -76· 162948-序列表.doc 201247706

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 435 440 445

His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala 450 455 460

Set 465 <210> 91 <231> 236 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 91

Met Thr Met Phe Ser Leu Ala Leu Leu Leu Ser Leu Leu Leu Leu Cys 15 10 15

Val Ser Asp Ser Arg Ala Glu Thr Thr Val Thr Gin Ser Pro Ala Ser 20 25 30

Leu Ser Met Ala lie Gly Glu Lys Val Thr lie Arg Cys Va】Thr Ser 35 40 45

Thr Asp lie Asp Asp Asp Val Asn Trp Tyr Gin Gin Lys Pro Gly Glu 50 55 60

Pro Pro Lys Leu Leu lie Ser Glu Gly Asn Thr Leu Arg Pro Gly Val 65 70 75 80

Pro Ser Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Val Phe Thr 85 90 95 lie Glu Asn Met Leu Ser Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gin 100 105 110

Ser Gly Asn Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu lie 115 120 125

Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp 130 135 140

Glu Gin Leu Lys Ser Gly Ήιγ Ala Ser Val Val Cys Leu Leu Asn Asn 145 150 155 160

Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu 165 170 175

Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp 180 185 190

Ser Thr Tyr Ser Leu Scr Scr Thr Leu Thr Leu Ser Lys Ala Asp Tyr 195 200 205

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser c 162948-序列表.doc -77- 201247706 210 215 220

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 92 <m> 467 <212> PRT <213>人造序列 <22ft> <223>人造序列之描述：合成多肽 <400> 92

Met Ala Trp Val Trp Thr Leu Leu Phe Leu Met Ala Ala Ala Gin Ser 15 10 15

Ala Gin Ala Gin He Gin Leu Val G1q Ser Gly Pro Glu Leu Lys Lys 20 25 30

Pro Gly Glu Thr Val Lys lie Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Lys Cln Ala Pro Gly Lys Gly Leu 50 55 60

Lys Trj> Val Gly Trp lie Asn Thr Phe Thr Gly Glu Pro Thr Tyr Val 65 70 75 80

Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser 85 90 95

Thr Ala Tyr Leu Gin lie Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr 100 105 110

Tyr Phe Cys Ala Arg Gly Asn Phe Arg Tyr Tyr Tyr Phe Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Thr Uu Thr Val Set Ser Ala Lys Thr Lys Qiy Pro 130 135 】40

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 180 185 190

Ala Va) Leu Gin Ser Scr Gly Leu Tyr Ser Leu Ser Scr Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Va] Asp Lys Arg Val Glu Ser Lys Tyr 225 230 235 240 -78- 162948·序列表 _doc 201247706

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser 260 265 270

Arg Thr Pro Gfu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 280 285

Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val 305 310 315 320

Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leai Asn Gly Lys Glu 325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400

Ser Asn Gly Gin Pro Gtu Asn Asn Tyr Lys Tbr Thr Pro Pro Val Leu 405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 «0

Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 93 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 93

Met Ser Val Leu Thr Gin Val Leu Ala Leu Leu Leu Leu Trp Leu Thr 15 10 15 162948-序列表.doc -79- c 201247706

Gly Ala Arg Cys Asp lie Gin Met TTir Cln Ser Pro Ala Ser Leu Set 20 25 30

Ala Ser Val Gly Glu Thr Val Thr lie Thr Cys Arg Thr Ser Gly Asn 35 40 45 lie Arg Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Gin Gly Lys Ser Pro 50 55 60

Gin Leu Leu Val Tyr Asn Ala Lys Ώιτ Leu Ala Asp Gly Val Pro Ser 65 70 75 80

Arg Phe Gly Gly Ser Gly Ser Gly Thf Gin Tyr Ser Leu Lys lie Asn 85 90 95

Ser Leu Gin Pro Glu Asp Phe Gly Asn Tyr Tyr Cys G】n His Phe Trp 100 105 110

Ser Ser Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu He Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Set Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 94 <211> 469 <212> PRT <2]3>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 94

Met Met G]y Trp Ser Tyr lie He Leu Phe Leu Val Ala Thr Ala Thr 15 10 15

Asp Val His Ser Gin Val Gin Leu Gin Gin Pro Gly Ala Glu Leu Val 20 25 30 •80- 162948-序列表.doc 201247706

Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr 35 40 45

Phe Thr Ser Tyr Trp Met His Trp Val Lys Gin Arg Pro Gly Glu Gly 50 55 60

Leu Glu Trp lie Gly Glu lie Asn Pro Ser Tyr Gly Arg Thr Asp Tyr 65 70 75 80

Asn Glu Lys Phe Lys Asn Lys Ala Thr Leu Thr Val Ala Lys Ser Ser 85 90 95

Ser Thr Ala Tyr Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala 100 105 110

Val Tyr Tyr Cys Ala Arg Gly Asp Tyr Tyr Gly Ser Ser Ser Phe Ala 115 120 125

Tyr Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys 130 135 140

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Atg Set Thr Ser Glu 145 ]50 155 160

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 165 170 175

Va】Thr Val Scr Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 180 185 190

Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 260 265 270 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin 275 280 285

Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val 290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr 305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gin A$p Trp Leu Asn Gly 325 330 335 162948-序列表.doc -81 - c 201247706

Lys Gla Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie 340 345 350

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 355 360 365

Tyr Tlu Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 3E0

Leu Tlu* Cys Leu Val Lys G]y Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 400

Trp Glu Set Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Leu Asp Ser Asp Cly Ser Phe Phe leu Tyr Ser Arg Leu Thr Val 420 425 430

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys Ala Ser 465

<210> 95 <211> 235 -<212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 95

Met Asp Phe Gin Val Gin He Phe Ser Phe Leu Leu Met Ser Ala Ser 15 10 15

Val lie Met Ser Arg Gly Gin lie Val Leu Thr Gin Ser Pro Ala Leu 20 25 30

Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser 35 40 45

Ser Asn lie Ser Tyr Met Tyr Trp Tyr Gin Glu Lys Pro Arg Ser Ser 50 55 60

Pro Lys Pro Trp lie Tyr Leu Thr Ser Asn Leu Ala Ser Gly Val Pro 65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Thr 85 90 95

Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Cys Cys Glo Gin Trp 100 105 110 • 82 - 162948-序列表.doc 201247706

Ser Ser Asn Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu lie Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu 130 135 140

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gift Τϊρ Lys Val Asp Asn Ala Leu Gin 165 170 175

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 180 185 190

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Lea Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 96 <211> 235 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 96

Met Asp Phe Arg Val Gin lie Phe Ser Phe Leu Leu Met Ser Ala Ser 15 10 15

Val lie Met Ser Arg Gly Gin lie Val Leu Thr Gin Ser Pro Ala Leu 20 25 30

Met Sct Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser 35 40 45

Ser Asn lie Ser Tyr Met Tyr Trp Tyr Gin Gin Lys Pro Arg Ser Ser 50 55 60

Pro Lys Pro Trp lie Tyr Leu Thr Ser Asn Leu Ala Ser Gly Val Pro 65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Uu Thr Ik 85 90 95

Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gin Gin Trp 100 105 110

Ser Sct Asn Pro Pro Thr Phe Gly Ala G3y Thr Lys Leu Glu lie Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe He Phe Pro Pro Ser Asp Glu 162948-序列表.doc -83- s 201247706

130 135 HO

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 165 170 175

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 180 185 190

Thr Tyr Ser Lea Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 97 <211> 238 <212> PRT <2I3>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 97

Met Glu Thr Asp Thr Leu Leu Leu Trp Vai Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Thr Gly Asp lie Val Leu lie Gin Ser Pro Ala Ser Leu Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Ser Cys Arg Ala Ser Glu Ser 35 40 45

Val Asp Ser Tyr Val Asn Ser Phe Met His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu lie Tyr Arg Val Ser Asn Leu Glu Ser 65 70 75 80

Gly lie Pro Ala Axg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr 85 90 95

Leu Thr lie Asn Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys 100 105 110

Gin Gin Ser Asn Glu Asp Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu 115 120 125

Glu lie Lys Arg TTir Val Ala Ala Pro Ser Val Phe He Phe Pro Pro 130 135 140

Ser Asp Glu Gla Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160 -84- 162948-序列表.doc 201247706

Asn Asn Phc Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser 180 185 190

Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 98 <21L> 465 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 98

Met Clu Cys Asn Trp lie Lea Pro Phe lie Leu Str Vat lie Ser Gly 15 10 15

Val Tyr Ser Glu Val Gin Leu Gin Gin Ser Gly Thr Val Leu Ala Arg 20 25 30

Pro Gly Ala Ser Val Asn Met Ser Cys Lys Ala Ala Gly Tyr Ser Phe 35 40 45

Thr Ser Tyr Trp Val Tyr Trp Val Lys Gin Arg Pro Gly Gin Gly Leu 50 55 60

Glu Trp lie Gly Ala lie Tyr Pro Lys Asn Ser Arg Thr Ser Tyr Asn 65 70 75 80

Gin Lys Phe Gin Asp Lys Ala Thr Leu Thr Ala Val Thr Ser Ala Ser 85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Thr Arg Pro His Tyr Asp Ser Phe Gly Tyr Trp Gly Gin 115 120 125

Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val 130 135 140

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 145 150 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 165 170 175 c 162948-序列表,doc -85- 201247706

Trp Asn Ser Gly Ala Leu Thr Ser Gly Va丨 His Thr Phe Pro Ala Val 180 185 190

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val TTir Val Pro 195 200 205

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 210 215 220

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Giy Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 24S 250 255

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr 260 265 270

Pro Glu Val Thr Cys Val Va] Val Asp Val Ser Gin Glu Asp Pro Glu 275 280 285

Va】 Gin Phe Asn Trp Tyr Va】 Asp Gly Va】 Glu Val His Asn Ala Lys 290 295 300

Thr Lys Pro krg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser 305 310 315 320

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 325 330 335

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 355 360 365

Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Lea Thr Cys Leu 370 375 3S0

Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn 385 390 395 400

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 405 410 415

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 420 425 430

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 435 440 445

His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala • 450 455 460

Ser 465 -86 - 162948-序列表.doc 201247706 <210> 99 <211> 238 <212> PRT <213>人造序列 <220> <M3>人造序列之描述：合成多肽 <400> 99

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Thr Gly Asp lie Val Leu Thr Gin Ser Pro Ala Ser Leu Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Ser Cys Arg Ala Ser Glu Ser 35 40 45

Val Asp Ser Tyr Gly lie Ser Phe Mel His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu lie Tyr Arg Ala Ser Asn Gin Glu Ser 65 70 75 80

Gly lie Fro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr 85 90 95

Leu Thr lie Asn Pro Val Glu A]a Asp Asp Val Ala Thr Tyr Tyr Cys 100 105 110

Gin Gin Ser Asn Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu 115 120 125

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glv Gin Asp Ser 180 185 190

Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205

Asp Tyi Glu Lys His Lys Val Tyr AU Cys Glu Val Thr His Gin Gly 210 215 220

Leu SeT Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235

<210> 100 <211> 473 <212> PRT •87· 162948·序列表,doc 201247706 <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 100

Asn Arg Leu Thr Ser Ser Leu Leu Leu Leu lie Val Pro Ala Tyr Val L 5 10 15

Leu Ser Gin Gin Val Thr Leu Lys Glu Ser Gly Pro Gly lie Leu Gin 20 25 30

Pro Ser Gin Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu 35 40 45

Ser Thr Ser Gly Met Gly Val Ser Trp He Arg Gin Pro Ser Gly Lys 50 55 60

Gly Leu Glu Trp Leu Ala His lie Tyr Trp Asp Asp Asp Lys Arg Tyr 65 70 75 80

Asn Pro Ser Leu Lys Ser Arg Leu Thr lie Phe Lys Asp Pro Ser Ser 85 90 95

Asn Gin Val Phe Leu Arg lie Thr Ser Val Asp Thr Ala Asp Thr Ala 100 105 110

Thr Tyr Tyr Cys Ala Arg Asn Ser His Tyr Tyr Gly Ser Thr Tyr GJy 115 120 125

Gly Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser 130 135 140

Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 145 150 155 160

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 165 】70 175

Phe Pro Cla Pro Val Thr Val Ser Trp Asn Set Gly Ala Leu Thr Ser 180 185 190

Gly Val His Tht* Phe Pro Ala Val Leu Gin Ser Ser Gly L&u Tyr Ser 195 200 205

Leu Ser Ser Val Val Thr Va] Pro Ser Ser Ser Leu Gly Thr Lys Thr 210 215 220

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 225 230 235 240

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 245 250 255

Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 260 265 270 -88- 162948-序列表.doc 201247706

Asu Thr Leu Met lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 275 2&0 285

Asp Va】Ser Gin Glu Asp Pro Glu Va】Gin Phe Asu Trp Tyr Val Asp 290 295 300

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Ar£ Glu Qlu Gin Phe 305 310 315 320

Asn Set Thr Tyr Arg Val Val Scr Val Leu Thr Val Leu His Gin Asp 325 330 335

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Set Asn Lys Gly Leu 340 345 350

Pro Ser Ser He Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg 355 360 365

Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys 370 375 380

Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 385 390 395 400 lie Ala Val Glu Trp GLu Scr Asn Gly Gin Pro Glu Asn Asn Tyr Lys 405 410 415

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 420 425 430

Arg Leu Thr Va丨 Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser 435 440 445

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser 450 455 460

Leu Ser Leu Ser Leu Gly Lys Ala Ser 465 470 <210> 101 <211> 238 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 101

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Gly Val Pro 15 10 15

Gly Ser Thr Gly Asn lie Val Leu Thr Gin Ser Pro Thr Sex Phe Thr 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Ser Cys Arg Ala Sex Glu Ser 35 40 45

Val His Ser Tyr Gly Asn Ser Phe Met His Trp Tyr Gin Gin Lys Pro -89- 162948·序列表.doc 201247706 50 55 60

Gly Gin Pro Pro Lys Leu Leu lie Tyr Leu Ala Scr Asn Val Glu Ser 65 70 75 80

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser kig Thr Asp Phe Thr 85 90 95

Leu Thr lie Asp Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys 100 105 110

Gin Gin Asn Ser Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu 115 120 125

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Lea Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser 180 185 m

Lys Asp Ser TTir Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 102 <211> 465 <212> PRT <2丨3>人造序列 <220> <223>人造序列之描述：合成多肽 <40Q> 102

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Va丨 Thr Ala Gly 1 5 10 15.

Val His Ser Gin Val Gin Leu Gin Gin Ser Gly Thr Glu Leu Met Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Set Cys Lys Ala Thr Gly Tyr Thr Phe 35 40 45

Ser Thr Tyr Trp lie Glu Trp Val Lys Gin Arg Pro Gly His Gly Leu 50 55 60

Glu Trp lie Gly Glu lie Leu Pro Gly Ser Gly Arg Thr Asn Asp Asn 65 70 75 80 -90- 162948-序列表.doc 201247706

Glu Lys Phe Lys Gly Lys Ala Thr lie Thr Ala Asp Thr Ser Ser Lys 85 90 95

Lys Ala Tyr Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Arg Gly Gly Tyr Ser Phe Ala Phe Trp Gly Gin 115' 120 125

Gly Thr Leu Val Ser Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val 130 135 140

Phe Pro Leu Ala Pro Cys Ser Aig Ser Thr Sei Glu Ser Thr Ala Ala 145 150 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 165 170 175

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 180 185 190

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 195 200 205

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 210 215 220

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu SeT Lys Tyr Gly Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 245 250 255

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr 260 265 270

Pro Glu Val Thr Cys Val Val Val Asp Val Set Gin Glu Asp Pro Glu 275 280 285

Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Va] His Asn Ala Lys 290 295 300

Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser 305 310 315 320

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 325 330 335

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 355 360 365

Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu -91 - 162948·序列表.doc 201247706 370 375 380

Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn 385 390 395 400

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 405 410 415

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 420 425 430

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met Hii Glu Ala Leu 435 440 445

His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala 450 455 460

Ser 465 <2l〇> L03 <211> 236 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400〉 103

Met Thr Met Phe Ser Leu Ala Leu Leu Leu Ser Leu Leu Leu Leu Cys 15 10 15

Val Ser Asp Ser Arg Ala Glu Thr Thr Val Thr Gin Ser Pro Ala Ser 20 25 30

Leu Ser Met Ala lie Gly Glu Lys Val Thr lie Arg Cys Val Thr Ser 35 40 45

Thr Asp lie Asp Asp Asp Val Asn Trp Tyr Gin Gin Lys Pro Gly Glu 50 55 60

Pro Pro Lys Leu Leu lie Set Glu Gly Asrt Thr Leu Afg Ala Gly Val 65 70 75 80

Pro Ser Arg Phe Ser Ser Ser Gly Tyr Gly Thr Asp Phe Val Phe Thf 85 90 95 lie Glu Asn Met Leu Ser Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gin 100 105 110

Ser Gly Asn Leu Pro Tyr Thr Phe Gly Gly Gly Thr LyS Leu Glu lie 115 120 125

Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp 130 135 140 GLu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asrt Asn 145 150 155 160 •92- 162948-序列表.doc 201247706

Phc Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu 165 170 175

Oln Ser Gly Asn Ser Gin Glu Sex Val Thr Glu Gin Asp Ser Lys Asp 180 185 190

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 195 200 205

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser 210 215 220

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 104 <211> 473 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 104

Met Asn Arg Leu Thr Ser Ser Leu Leu Leu Lev lie Val Pro Ala Tyr 15 10 15

Val Leu Ser Gin Val Thr Leu Lys Glu Ser G\y Pro Gly lie L&u Gin 20 25 30

Pro Ser Gin Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu 35 40 45

Ser Thr Ser Gly Met Gly Leu Ser Trp lie Arg Gin Pro Ser Gly Lys 50 55 60

Gly Leu Glu Trp Leu Ala His lie Tyr Trp Asp Asp Asp Lys Arg Tyr 65 70 75 80

Asn Pro Ser Leu Lys Ser Arg Leu Thr lie Ser Lys Asp Thr Ser Ser 85 90 95

Asn Gin Val Phe Leu Lys lie Thr lie Val Asp Thr Ala Asp Ala Ala LOO 105 110

Thr Tyr Tyr Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyt Gly Tyr Gly 115 120 125

Gly Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Val Thr Va丨 Ser Ser 130 135 140

Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 145 150 155 160

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Va] Lys Asp Tyr 165 170 175 c 162948-序列表.doc -93- 201247706

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 180 185 190

Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser 195 200 205

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 210 215 220

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 225 230 235 240

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 245 250 255

Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 260 265 270

Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 275 2θ0 285

Asp Val Ser Gin Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp 290 295 300

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe 305 310 315 320

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp 325 m 335

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 340 345 350

Pro Ser Ser lie Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg 355 360 365

Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Ly& 370 375 380

Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 385 390 395 400 lie Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys 405 410 415

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 420 425 430

Arg Leu Thr Val Asp Lys SeT Arg Trp Gin Glu Gly Asn Val Phe Ser 435 440 445

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser 450 455 460

Leu Ser Leu Ser Leu Gly Lys Ala Ser 465 470 -94- 162948-序列表.doc 201247706 c210> 105 <211> 238 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 105 fiet Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Ttir Gly Asn lie Val Leu Thr Gin Ser Pro Ala Ser Leu A]a 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Ser Cys Arg Ala Ser Glu Ser 35 40 45 lie His Ser Tyr Gly Asn Ser Phe Leu His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys lea Leu lie Tyr Leu Ala Ser Asn Leu Glu Ser 65 70 75 80

Qly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr 85 90 95 L&u Thr lie Asp Pro Val Glu Ala Asp Asp Ala Ala Thr Tyr Tyr Cys 100 105 110

Gin Gin Asn Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu 115 120 125

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser 180 185 190

Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235

<210> 106 <2tl> 467 <212> PRT -95· 162948·序列表.doc 201247706 <213>人造序列 <220> <223>人造序列之描述：合成多肽 <220> <221> MOD.RES <222> (309)..(309) <223>任意胺基酸 <400> 106

Met Lys Cys Ser Trp Val lie Phe Phe Leu Met Ala Val Val Thr Gly 15 10 15

Val Asn Ser Glu Val Gin Leu Gin Gin Ser G]y Ala Glu Leu Val Arg 20 25 30

Pro Gly Ala Leu Val Lys Leu Ser Cys Lys Ala Ser Gly Phe Asn lie 35 40 45

Asn Asp Tyr Tyr He His Trp Val Lys Gin Arg Pro Giu Gin Gly Leu 50 55 60

Glu Arg lie Gly Trp He Asp Pro Asp Asn Gly Asn Thr lie Tyr Asp 65 70 75 80

Pro Lys Phe Gin Gly Lys Ala Ser lie Thr Ala Asp TTir Ser Pro Asn 85 90 95

Thr Ala Tyr Leu Gin Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Thr Arg Ser Pro Met Val Thr Thr Gly Phe Val 115 120 125

Tyr Trp Gly Gin Gly Thr Val Val Thr Val Ser Ala Ala Lys Thr Lys 130 135 140

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu 145 150 155 160

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 165 170 175

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 180 185 190

Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Tlir Val Pro Ser Ser Ser Leu Gly Hr Lys TTir Tyr Thr Cys Asa 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 245 250 255 -96· 162948-序列表.doc 201247706

Gly Pro Scr Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 260 265 270 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Va】Asp Val Ser Gin 275 280 285

Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val 290 295 300

His Asn Ala Lys Xaa Lys Pro An Glu Glu Gin Phe Asn Ser Thr Tyr 305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie 340 345 350

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 355 360 365

Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 400

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Lew Thr Val 420 425 430

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Set Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys 465 <210> 107 <m> 474 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 107

Met Glu Arg His Trp He Phe Leu Phe Leu Phe Ser Val Thr Ala Gly 15 10 15

Val His Ser Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Leu Ala Lys 20 25 30 -97- 162948-序列表.doc 201247706

Pro Gly Ala Ser Val Lys Met Ser Cys Lys AU Ser Gly Tyr Thr Phe 35 40 45

Thr Thr Tyr Trp Met His Trp Val Lys Gin Arg Pro Gly Gin G]y Leu 50 55 60

Glu Trp lie Gly Tyr lie Asn Pro lie Thr Gly Tyr Thr Glu Tyr Asn 65 70 75 80

Gift Lys Ph& Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Wet Asp Tyr Trp Gly Gin 115 120 125

Gly Thr Ser Val Thr Val Thr Ser Ala Lys Thr Thr Ala Pro Ser Val 130 135 140

Tyr Pro Leu A]a Pro Val Cys Gly Asp Hir Thr Gly Ser Ser Val Thr 145 150 155 160

Leu Gly Cys Leu Val Lys Gly Tyr Phc Pro Glu Pro Val Thr Leu Thr 165 170 175

Trp Asn Ser Gly Ser Leu Ser Sei Gly Val His Thr Phe Pro Ala Val 180 185 190

Leu Gin Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser 195 200 205

Ser Thr Trp Pro Ser Gin Thr Val Thr Cys Ser Val Ala His Pro Ala. 210 215 220

Ser Ser Thr Thr Val Asp Lys Lys Leu Glu Pro Ser Cly Pro lie Ser 225 230 235 240

Thr lie Asn Pro Cys Pro Pto Cys Lys Glu Cys His Lys Cys Pro AU 245 250 255

Pro Asn Leu Glu Giy Gly Pro Ser Val Phe He Phe Pro Pro Asn lie 260 265 270

Lys Asp Val Leu Met lie Sex Leu Thr Pro Lys Val Thr Cys Val Val 275 280 285

Val Asp Val Ser Glu Asp Asp Pro Asp Val Gin lie Ser Trp Phe Val 290 295 300

Asn Asn Val Glu Val His Thr Ala Glu Thr Gin Thr His Arg Glu Asp 305 310 315 320

Tyr Asn Ser Ήϊγ lie Arg Val Val Ser Thr Leu Pro lie Gift His Gin 325 330 335 -98- 162948-序列表.doc 201247706

Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp 340 345 350

Leu Pro Ser Pro He Glu Arg Thr lie Ser Lys lie Lys Gly Leu Val 355 360 365

Arg Ala Pro Gin Val Tyr He Leu Pro Pro Pro Ala Glu Gin Leu Ser 370 375 380

Arg Lys Asp Val Ser Leu Thr Cys Leu Val Val Gly Phe Asn Pro Gly 385 390 395 400

Asp lie Ser Val Glu Trp Thr Ser Asn Gly His Thr Glu Glu Asn Tyr 405 410 415

Lys Asp Thr Ala Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe lie Tyr 420 425 430

Ser Lys Leu Asn Met Lys Thr Ser Lys Trp Glu Lys Thr Asp Ser Phe 435 440 445

Ser Cys Asn Val Arg His Glu Gly Leu Lys Asn Tyr Tyr Leu Lys Lys 450 455 460

Thr lie Ser Arg Ser Pro Gly Lys Ala Ser 465 470 <210> 108 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 108

Met Glu Ser Arg lie Gin Ala Phe Val Phe Va] Phe Leu Trp Leu Ser 15 10 15

Gly Val Gly Gly Asp lie Val Met Thr Gin Ser His Lys Phe Met Ser 20 25 30

Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gin Asp 35 40 45

Val Thr Ser Ala Val Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ser Pro 50 55 60

Lys Leu Lev Tie Tyt Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp 6 5 70 75 80

Arg Phe Thr Gly Ser Gly S&r Gly Thr Asp Tyr Thr Leu Thr lie Ser 85 90 95

Ser Gly Gin Ala Glu Asp Leu Ala Leu Tyr Tyr Cys His Gin Tyr Tyr 100 105 110 c 162948-序列表.doc -99- 201247706

Ser Ala Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Val Lys Arg 115 120 125

Ala Asp Ala Aia Pro Thr Va】Ser lie Phe Pro Pro Ser Ser Glu Gin 130 135 140

Leu Thr Ser Gly Gly Ala Ser Va】Va】Cys Phe Leu Asn Asn Phe Tyr 145 150 155 160

Pro Lys Asp He Asn Val Lys Trp Lys He Asp Gly Ser Glu Arg Gin 165 170 175

Asn Gly Val Leu Asn Ser Trp Thr Asp Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg 195 200 205 HLs Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro 210 215 220

He Val Lys Ser Phe Asn Arg Asn Olu Cys 225 230 <2I0> 109 <211> 465 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 109

Met Glu Arg His TrD lie Phe Leu Phe Leu Phe Ser Val Thr Ala Gly 15 10 15

Val His Ser Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Leu Ala Lys 20 25 30

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45

Thr Thr Tyr Trp Met His Trp Val Lys Gin Arg Pro Gly Gin Cly Leu 50 55 60

Glu Trp lie Gly Tyr lie Asn Pro lie Thr Gly Tyr Thr Glu Tyr Asn 65 70 75 80

Gla Lys Rie Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met Gin Leu Sex Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Met Asp Tyr Trp Gly Gin 115 120 125 • 100- 162948-序列表 *doc 201247706

Gly Thr Scr Val Thr Val Thr Ser Ala Lys Thr Thr Gly Pro Ser Val 130 135 140

Phe Pro Leu Ala Pro Cys Ser Arg Sei Thr Ser Glu Ser Thr Ala Ala 145 150 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 165 170 175

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 180 185 190

Leu Gin Ser Ser Giy Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 195 200 205

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 210 215 220

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 245 250 255

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr 260 265 270

Pro Glu Val Thr Cys Val Val Va】Asp Val Ser Gin Glu Asp Pro Glu 275 280 285

Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 290 295 300

Thr Lys Pto Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser 305 310 315 320

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 325 330 335

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Sei lie Glu Lys Thr lie 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 355 360 365

Pro Ser Gin Glu Glu Met ΊΤκ Lys Asn Gin Val Ser Leu Thr Cys Leu 370 375 380

Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn 385 390 395 400

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 405 410 415

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 420 425 430 -101 - 162948-序列表.doc 201247706

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 435 440 445

His Asn His Tyr Thr GJn Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala 450 455 460

Ser 465 <210> 110 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 110

Met Glu Ser Gin lie Gin Ala Phe Val Phe Val Phe Leu Trp Leu Ser 15 10 15

Gly Val Gly Gly Asp lie Val Met Thr Gin Ser His Lys Phe Met Ser 20 25 30

Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gin Asp 35 40 45

Val Thr Ser Ala Val Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ser Pro 50 55 60

Lys Leu Leu lie Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp 65 70 75 80

Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr He Ser 85 90 95

Ser Gly Gin Ala Glu Asp Leu Ala Leu Tyr Tyr Cys His Gin Tyr Tyr 100 105 110

Ser Ala Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 145 150 155 160

Pro Arg Glu Ala Lys Va] Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu ThT Leu Ser Lys AU Asp Tyr Glu Lys 195 200 205 -102- 162948-序列表.doc 201247706

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 111 <211> 466 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 111

Met Ala Val Leu Ala Lea Leu Leu Cys Leu Val Ala Phc Pro Thr Cys 1 5 10 15

Thr Leu Ser Gin Val Gin Leu Lys Glu Ser Gly Pro Gly Leu Val Ala 20 25 30

Pro Ser Gin Ser Leu Ser lie Thr Cys Ser Val Ser Gly Phe Ser Leu 35 40 45

Ser Asn Tyr Asp lie Ser Trp lie Arg Gin Pro Pro Gly Lys Gly Leu 50 55 60

Glu Trp Leu Gly Val Met Trp Thr Gly Gly Gly Ala Asn Tyr Asn Ser 65 70 75 80

Ala Phe Met Ser Arg Leu Ser lie Asn Lys Asp Asn Ser Lys Ser Gin 85 90 95

Val Phe Leu Lys Met Asn Asn Leu Gin Thr Asp Asp Thr Ala lie Tyr 100 105 110

Tyr Cys Val Arg Asp Ala Val Arg Tyr Tip Asn Phe Asp Val Trp Gly 115 120 125

Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser 130 135 140

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pio Glu Pro Val Thr Val 165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 180 185 190

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 195 200 205

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 210 215 220

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly c 162948-序列表 _doc - 103- 201247706 225 230 235 240

Pro Pro Cys Pro Pro Cys Pro Ala Pro GIu Phe Glu Gly Gly Pro Ser 245 250 255

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg 260 265 270

Thr Pro Glu Val Thr Cys Vai Val Val Asp Val Ser Gin Glu Asp Pro 275 280 285

Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 290 295 300

Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val 305 310 315 320

Ser Va] Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr 325 330 335

Lys Cys Lys Va】Ser Asn Lys Gly Leu Pro Ser Sei lie Glu Lys Thr 340 345 350 lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu 355 360 365

Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys 370 375 380

Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser 385 390 395 400

Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 405 410 415

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 420 425 430

Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 435 440 445

Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys 450 455 460

Ala Ser 465 <210> 112 <211> 235 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 112

Met Asp Phe Gin Ala Gin lie Phe Ser Phe Leu Leu lie Ser Ala Ser 15 10 15 •104· 162948-序列表.doc 201247706

Val lie Met Ser Arg Gly Gin lie Val Leu Ser Gin Ser Pro Ala lie 20 25 30

Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser 35 40 45

Ser Ser Val Ser Tyr lie His Trp Tyr Gin Gin Lys Pro Gly Ser Ser 50 55 60

Pro Lys Pro Trp lie Tyr Ala Thr Ser His Leu Ala Ser Gly Val Pro 65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr $er Tyr Ser Lev Thr lie 85 90 95

Ser Arg Val Glu Ala Glu Asp Thr Ala Thr Tyr Tyr Cys Gin Gin Trp 100 105 110

Ser Ser Asn Pro Phe Thr Phc Gly Ser Gly Thr Lys Leu Glu lie Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phc lie Phe Pro Pro Sct Asp Glu 130 135 140

Gin Leu Lys Ser (Jly Thr Ala Ser Val Val Cys Uu Leu Asn Asn Phe 145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 165 170 175

Ser Gly Asn Scr Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 180 185 190

Thr Tyr Ser Uw Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <no> ii3 <211> 469 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 113

Met Glu Arg His Trp lie Phe Leu Leu Leu Leu Ser Va! Thr Ala Gly 15 10 15

Va】His Ser Gin Val Gin Leu G】n Gin Ser Gly Ala Glu Leu Ala Arg 20 25 30 •105- 162948-序列表.doc 201247706

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 TTir Thr Tyr Thr Met His Trj) Val Lys Gin Ar^ Pro Gly Gin Gly Leu 50 55 60

Glu Trp He Gly Tyr lie Asn Pro Ser Ser Gly Tyr Thr Asn Tyr Asn 65 70 75 80

Gin Lys Phe Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser 85 90 95

Thr Ala Ser Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Glu Arg Ala Val Leu Val Pro Tyr Ala Met Asp 115 120 125

Tyr Trp G5y Gin Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Lys 130 135 140

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Set Arg Ser Thr Ser Glu 145 150 155 160

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 165 丨70 175

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thf 180 185 190

Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Are Val Glu Ser 225 230 235 240

Lys Tyr Gly Pio Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Giu Gly 245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 260 265 270 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin 275 280 285

Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val 290 295 300

His Asn Ala Lys Thr Lys Pro Arg GU Glu Gin Phe Asn Ser Thr Tyr 305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp L«u Asn G!y 325 330 335 •106- 162948-序列表.doc 201247706

Lys Cu^LysCysLysVa! Ser Asn Lys Gly U, Pro Ser Ser He

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 355 360 365

Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 3S0

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp He Ala Val Glu 385 390 395 400

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Leu Asp Scr Asp Gly Ser Phe Phe Leu Tyi Ser Arg Leu Thr Val 420 425 «0

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys Ala Ser 465 <2I0> 114 <211> 235 <2I2> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 114

Met His Phe Gin Val Gin lie Phe Ser Phe Leu Leu lie Ser Ala Ser 15 10 15

Val lie Met Ser Arg Gly Gin Tie Val Leu Thr Gin Ser Pro Ala Val 20 25 30

Met Ser Ala S&r Pro Gly Glu Lys Val Thr lie Thr Cys Thr Ala Ser 35 40 45

Ser Ser Leu Ser Tyi Met His Trp Phe Gin Gin Lys Pro Gly Thr Ser 50 55 60

Pro Lys Leu Trp Leu Tyr Ser Thr Ser lie Leu Ala Ser Gly Val Pro 65 70 75 80

Thr Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr lie 85 90 95

Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gin Gin Arg 100 105 110 c 162948-序列表.doc -107- 201247706

Ser Ser Ser Pro Phe Thr Phe Gly Ser Gly Thi Lys Leu Glu He Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu L30 135 140

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 145 150 155 160

Tyr Pro Arg Git Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 165 170 175

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 180 185 190

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 115 c211> 467 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> Π5

Met Gly Trp Thr Trp lie Phe He Leu lie Leu Ser Val Thr Thr Gly 1 5 10 15

Val His Ser Glu Val Gin Leu Gin Gin Scr Gly Pro Glu Leu Glu Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Scr Cys Lys Ala Ser Gly Tyr Ser Phe 35 40 45

Tlir Gly Tyr Asn Met Asn Trp Val Lys Gin Ser Asn Gly Lys Ser Leu 50 55 60

Glu Trp lie Gly Asn lie Asp Pro Tyr Tyr Gly Asp Thr Asn Tyr Asn 65 70 75 80

Gin Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met His L«u Lys Scr Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Pro Tyr Gly Ser Qh Ala Tyr Phe Ala Tyr Trp 115 120 125 -108- 162948-序列表.doc 201247706

Gly Gin Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys Gly Pro 130 135 140

Ser Val Phe Pro Leu Ala Pro Cys Ser A.rg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 180 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thi Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 225 230 235 240

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Aip Val Ser Gin Glu Asp 275 280 285

Pro G】u Va】Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyi Arg Val 305 310 315 320

Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu 325 330 335

Tyr Lys Cy$ Lys Val Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400

Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val L«u 405 410 415

Asp Ser Asp Gly Ser Phe Phe Lea Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430 162948-序列表.doc -109· c 201247706

Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Va】Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 m

Lys Ala Ser 465 <210> 116 <211> 214 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 116

Asp lie Val Met Thr Gin Ser Pro Ala Thr Leu Ser Va] Thr Pro Gly 15 10 15

Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gin Ser lie Ser Asp Tyr 20 25 30

Leu His Trp Tyr Gin Gin Lys Ser His Glu Ser Pro Arg Leu Leu lie 35 40 45

Lys Tyr Ala Ala Gin Ser lie Ser Gly He Pro Ser Arg Phe Ser Gly 50 55 60

Ser Gly Ser Gly Ser Asp Phe Thr Leu Ser lie Asn Gly Val Glu Pro 65 70 75 80

Glu Asp Val Gly Val Tyr Tyr Cys Gin Asn Gly His Ser Phe Pro Tyr 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu He Lys Arg Thr Val Ala Ala 100 105 110

Pro Ser Val Phe lie Phe Pro Pro Ser Asi> Glu Gin 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 Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Cln 145 150 155 160

Glu Ser Val Thr Glu Gin 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 Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 -110- 162948·序列表.doc 201247706

Phe Asn Arg Gly Glu Cys 210 <210> 117 <211> 446 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 117

Gin Val Gin Leu Arg Gin Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 15 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Hit Phe Ttr Asp Tyr 20 25 30

Val lie Ser Trp Val Lys Gin Arg Ήιγ Gly Gin Gly Leu Glu Trp lie 35 40 45

Gly Asp lie Tyr Pro Gly Ser Gly Tyr Scr Phe Tyr Asn Glu Asn Phe 50 55 60

Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Scr Scr Thr Thi Ala Tyr 65 70 75 80

Met Gin Leu Ser Ser Uu Thr Ser Glu Asp Ser Ala Val Τγτ Phe Cys 85 90 95

Ala Thr Tyr Tyr Asn Tyr Pro Phe Ala Tyr Ττρ Gly Gin Gly Thr Leu 100 105 110

Val Thr Val Ser Ala Ala Lys Thr Thr Gly Pro Ser Val Phe Pro Leu 115 120 125

Ala Pro Cys Scr Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys 130 135 140

Leu Va] Lys Asp Tyr Phe Pro Glu Pro Val Ήιγ Val Ser Trp Asn Scr 145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Scr 165 170 175

Ser Gly Leu Tyr Ser Uu Ser Ser Val Val Thr Val Pro Ser Ser Ser 180 185 190

Leu Gty Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn 195 200 205

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro 210 215 220

Pro Cys Pro Ala Pro Glu Phe Glu Gly Gty Pro Ser Val Phe Leu Phe 225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pio Glu Val c 162948·序列表.doc -Ill - 201247706 245 250 255

Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val Gin Phe 260 265 270

Asn Trp Tyr Val Asp Cly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285

Arg Glu Glu Gin Phe Asn Ser Thr Tyi Arg Val Val Ser Val Leu Thr 290 295 300

Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 305 310 315 320

Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr He Ser Lys Ala 325 330 335

Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Gin 340 345 350

Glu Glu Met Thr Lys Asn Gin Va] Ser Leu Thr Cys Leu Val Lys Gly 355 360 365

Phe Tyr Pro Ser Asp He Ala Val Glu Trj> Glu Ser Asn Gly Gin Pro 370 375 380

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 385 390 3^5 400

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gin Glu 405 410 415

Gly Asn Val Phe Ser Cys Ser Val Met His Glu AJa Leu His Asn His 420 425 430

Tyr Thr Gin Lys Ser Leu Scr Leu Ser Leu Cly Lys Ala Ser 435 440 445 <210> 118 <211> 219 <2!2> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 118

Asp Val Val Met Thr Gin Thr Pro Leu S&r Leu Pro Val Arg Leu Gly 1 5 10 15

Asp Gin Ala Ser lie Ser Cys Arg Ser Ser Gin Ser Leu Val His Ser 20 25 30

Asa Gly Asn Thr Tyr Leu His Trp Tyr Leu Gin Lys Pro GLy Gin Ser 35 40 45

Pro Lys Leu Leu lie Tyr Lys Val Scr Asn Arg Phe Ser Gly Va】 Pro 50 55 60 -112- 162948-序列表.doc 201247706 s 5 6 A 6 s Γ c s y G1 r 6 o s 7 y GI Γ e s c ph rg lo 18 sLy u Le Γ Th. c Γ Th e, s n 15 G9 Ti c s scy 6 ph Γ Ty u L9 y G, u Le p As u G1 na 15 A8 u GI val rg Γ Th Γ Ty oo prlo va s Hi Γ Th uo Ί* GI u Le s Ly Γ Th y G1 y5 Gllo G!

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As p As — 5 vals s Ly rp n 01 va so y5 LI a u G1 s Ti g p Γ 5 TV14 no 16 GI u u uo 17 GI Γ Th val Γ c s a G1 n5 n lo GI Fse n As c s P5 sc—* A1 s Ly Γ se p As G1 Γ Ty po s 〇s A1 ,a s Ly T 6 s u u rs "'8 u Le Γ Th Γ s Γ 6 s uo U1E Γ ov s Γ Ty Γ Th n GI s Hi Γ Th va lus G2 scy & TJ Ty val s 5 y9 L· 1* 5 Hi ys c s FI 6 s u Le u GI y G1 rg A n5 SI A2 e ph Γ c s s Ly Γ Th lo AO 11 V2 r0 列 1191¾ 0>1>2>3> IX lx <2<2<2<2 <220> <223>人造序列之描述：合成多肽 <400> 119

Met Thr Leu Asn Met Leu Leu Gly Leu Arg Trp Val Phe Phe Val Val 15 10 15

Phe Tyr Gin Gly Val His Cys Glu Val Gin Leu Val Glu Ser Gly Gly 20 25 30

Gly Leu Val Gin Pro Lys Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser 35 40 45

Gly Leu Thr Phe Asn lie Tyr Ala Met Asn Tip Val Arg Gin Ala Pro 50 55 60

Gly Lys Gly Leu Glu Trp Val Ala Arg lie Arg Asn Lys Ser Asn Asn 65 70 IS SO

Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr lie Ser 85 90 95 c 162948·序列表.doc -113- 201247706

Arg Asp Asp Ser GJn Ser Leu Leu Tyr Uu Gin Met Asn Asn Leu Lys 100 105 110

Tht Glu Asp Thr Ala Met Tyr Tyr Cys Val Gly Arg Asp Trp Phc Asp 115 120 125

Tyr Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys 130 135 140

Gly Pro Ser Val Rie Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu 145 150 155 160 S&r Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 165 170 175

Val Thr Val Ser Trp Asn Ser GJy Ala Leu Ώιγ Ser Gly Val His Thr 180 185 190

Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 195 200 205

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly 245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Ihr Leu Met 260 265 270 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin 275 2S0 285

Glu Asp Pro Glu Val Gin Phe Asn Trp Tyr Va) Asp Gly Val Glu Val 290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr 305 310 315 320

Arg Val Val Scr Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 325 330 335

Lys Glu Tyr Lys Cys Lys Val Scr Asn Lys Gly Leu Pro Ser Sei lie 340 345 350

Glu Lys Thr He Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 355 360 365

Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser 370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 400 -114- 162948-序列表.doc 201247706

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val 420 425 430

Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met 435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 450 455 460

Leu Gly Lys Ala Ser 465 <210> 120 <2U> 235 <212> PRT <2】3>人造序列 <22〇> <223>人造序列之描述：合成多肽 <400> 120

Met AU Trp He Ser Leu lie Leu Ser Leu Leu Ala Leu Ser Ser Gly 15 10 15

Ala lie Ser Gin Ala Val Val Thr Gin Glu Ser Ala Leu Thr Thr S^r 20 25 30

Pro Gly Glu Thr Val Leu Thr Cys Arg Ser Ser Thr Gly Ala Val 35 40 45

Thr Thr Ser Asn Tyr Ala Asn Trp Val Gin Glu Lys Prc Asp His Leu 50 55 60

Phe Thr Gly Leu lie Gly Gly Thr Asn Asn Arg Val Scr Gly Val Pro 65 70 75 80

Ala Arg Phe Ser Gly Ser Leu lie Gly Asp Lys Ala Ala Leu Thr lie 85 90 95

Thr Gly Ala Gin Thr Glu Asp Glu Ala lie Tyi Phe Cys Ala Leu Trp 100 105 110

Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Glu lie Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Va] Phe lie Phe Pro Pro Ser Asp Glu 130 135 140

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 145 150 155 160

Tyr Pro Arg Glu Ala Lys Val Gtn Trp Lys Val Asp Asn Ala Leu Gin 165 170 175 162948·序列表.doc •115· c 201247706

Ser Giy Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Set Lys Asp Ser 180 185 190

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Val Tyr Ala Cys Glu Val Thx His Gin Gly Leu Ser Ser 210 215 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 121 <211> 461 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 121

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala GLy 1 5 10 15

Val His Ser Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Leu Met Lys 20 25 30

Pro Gly Ala Ser Val Lys He Ser Cys Lys Ala Thr Gly Tyr Thr Phe 35 40 45

Gly Ser Tyr Trp lie Glu Trp Val Lys Gin Arg Pro Gly His Gly Leu 50 55 50

Glu Trp lie Gly Glu lie Leu Pro Gly Ser Gly Asn Thr Asn Tyr Asn 65 70 75 80

Glu Asn Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn 85 90 95

Thr Ala Tyr Met Gin Leu Thr Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Ala Gly lie Tyr Trp Gly Gin Gly Tbr Leu Val 115 120 125

Thr Val Ser Ala Ala Lys Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 130 135 140

Pro Cys Ser Arg Ser Thr Sex Glu Ser Thr Ala Ala Leu Gly Cys Leu 145 150 155 160

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 165 170 175 ALa Leu Thr Ser Gly Val His Thr Phe Pro Ala Val L&u Gin Ser Ser 180 185 190 -116- 162948-序列表.doc 201247706

Gly Leu Tyr Ser Lea Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 195 200 205

Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 210 215 220

Lys Val Asp Lys Arg Val Glu Set Lys Tyr Gly Pro Pro Cys Pro Pro 225 230 235 240

Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro 245 250 255

Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val Thr 260 265 270

Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val Gin Phe Asn 275 280 285

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 290 295 300

Glu G1o Gin Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 305 310 315 320

Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 325 330 335

Asn Lys Gly Leu Pro Ser Ser He Glu Lys Thr lie Ser lys Ala Lys 340 345 350

Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Gin Glu 355 360 365

Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe 370 375 380

Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu 385 390 395 400

Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Scr Phe 405 410 415

Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gin Glu Gly 420 425 430

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 435 440 445

Thr Gin Lys Scr Leu Ser Leu Scr L&u Gly Lys Ala Ser 450 455 460 <210> 122 <211> 23S <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 c 162948-序列表.doc •117· 201247706 <40Q> 122

Met Gin Lys Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15

Gly Ser Thr Gly Asp lie Val Leu Thr Gin Ser Pro Ala Phe Leu Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Ser Cys Arg Ala Ser Glu Ser 35 40 45

Val Asp Asn Tyr Gly lie Ser Phe Met Asn Trp Phe Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu lie Tyr Val Ala Ser Lys Gin Gly Ser 65 70 75 80

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly TTir Asp Phe Ser 85 90 95

Leu Asn lie His Pro Met Glu Glu Asp Asp Thr Ala Met Tyr Phe Cys 100 105 Π0

Gin Gin Ser Lys Glu Val Pro Arg Thr Phe Gly Gly Gly TKr Lys Uu

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Scr Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Aia Lys Val Gin Trp Lys Va】Asp Asn 165 170 175

Ala Leu Gin Ser Giy Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser 180 185 190

Lys Asp Scr Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu Ser Scr Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 123 <211> 463 <2L2> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 123 Met Glu Cys Asn Trp lie Leu Pro Phe lie Leu Ser Val Tht Ser Gly 10 15 -118· 162948-序列表，doc 201247706

Val Tyr Ser Glu Va丨 Gin Leu G】n Gin Se「G]y Thr Val Leu Ala Arg 20 25 30

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45

Thr Ser Tyr Trp Met His Trp Val Lys G!n Arg Pro Gly Gin Gly Leu 50 55 60

Glu Trp He Gly Ala lie Tyr Pro Gly Asn Ser Asp Thr Thr Tyr Asn 6S 70 7 5 80

Gin Lys Phe Lys Gly Lys Ala Lys Leu Thr Ala Val Thr SeT Thr Ser 85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Thr Pro Thr Tyr Tyr FQie Asp Tyr Trp Gly Gin Gly Thr 115 120 125

Ser Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser Val Phe Pro 130 135 140

Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly 145 150 155 160

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pto Val Thr Val Ser Trp Asn 165 170 175

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin 180 185 190

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 195 200 205

Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser 210 215 220

Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys 225 230 235 240

Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu 245 250 255

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pro Glu 260 265 270

Va】Thr Cys Va】Val Va】Asp Va】Ser G】n Gh Asp Pro Glu Va】Gin 275 280 285

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 290 295 300

Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Va] Ser Val Leu -119- 162948-序列表 _doc 201247706 305 310 315 320

Tht Val Leu His Gin Asp Trp Leu Asn G]y Lys GIu Tyr Lys Cys Lys 325 330 335

Va】Ser Asn Lys G】y Leu Pro Ser Ser lie Glu Lys Thr lie Ser Lys 340 345 350

Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Tlir Leu Pro Pro Ser 355 360 365

Gin Glu Giu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys 370 375 380

Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn Gly Gin 385 390 395 400

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 405 410 415

Ser Phe Phe Leu Tyr Ser Aig Leu Thr Va】Asp Lys Ser Arg Trp Gin 420 425 430

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 435 440 445

His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly Lys Ala Ser 450 455 460 <210> 124 <211> 238 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 124

Met Ser Pro Ala Gin Phe Leu Phe Leu Leu Val Leu Trp lie Arg Glu 15 10 】5

Thr Asn Gly Asp Val Va] Met Tlir Gin Thr Pro Leu Thr Leu Ser Val 20 25 30

Thr lie Gly Gin Pro Ala Scr lie Ser Cys Lys Ser Ser Gin Ser Leu 35 40 45

Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Phe Leu Gin Arg Pro 50 55 60

Gly Gin Ser Pro Lys Arg Leu lie Tyr Leu Val Ser Lys Leu Asp Ser 65 70 75 SO

Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr 85 90 95

Leu Lys lie Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys 100 105 110 -120- 162948-序列表.doc 201247706

Trp Gin Gly Thr His Phe Pro Trp Thr Phe Oly Gly Gly Thr Lys Leu 115 120 125

Glu lie Lys Arg Thr Val Ala Ala Pro Ser Vai Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Scr 180 185 190

Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Uu Ser Lys Ala 195 200 205

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val TTir His Gin Gly 210 215 220

Leu Ser Scr Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 125 <ill> 468 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 125

Met Gly Gly lie Trp lie Phe Leu Phe Leu Leu Scr Gly Thr Ala Gly 15 10 15

Ala His Ser Glu He Gin Leu Gin Gin Thr Gly Pro Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys lie Ser Cys Lys Ala Ser Gly Tyr Pro Phe 35 40 45

Thr Asp Tyr lie Met Val Trp Val Lys Gin Ser His Gly Lys Scr Leu 50 55 60

Glu Trp lie Gly Asn lie Ser Pro Tyr Tyr Gly Thr Thr Asn Tyr Asn 65 70 75 SO

Leu Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met Gin Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Ser Pro Asn Trp Asp Gly Ala Trp Phe Ala His 115 120 125 -121 - 162948-序列表.doc 201247706

Trp Gly Gin Gly Ala Leu Val Thr Val Ser Ala Ala Lys Thr Lys G]y 130 135 140

Pro Ser Val Phe Pro Leu Ala Pro Cys S^r Arg Ser Thr Ser Glu Ser 145 150 155 160

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175

Thr Va] Ser Ttp Asti Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190

Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205

Thr Va】 Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 210 215 220

Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu SeT Lys 225 230 235 240

Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ph« Glu Gly GJy 245 250 255

Pro Ser Va】 Phe Leu Phe Pro Pto Lys Pro Lys Asp Thr Leu Met lie 260 265 270 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu 275 280 285 Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val Wis 290 295 300

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr 305 310 315

Axg 320

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Giy Lys 325 330 335

Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Scr Ser He Glu 340 345 350

Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 355 360 365

Thr Len Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Va】 Ser Leu 370 375 380

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 385 390 395 is

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 405 430 415

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp 420 425 430 162948-序列表.doc -122, 201247706

Lys Ser Arg Trp Gin Gtu Gly Asn Val Phe Ser Cys Ser Val Met His 435 440 445

Glu Ala Leu His Asn His Tyr Tlir Gin Lys Ser Leu Ser Leu Scr Leu 450 455 460

Gly Lys Ala Ser 465 <210> 126 <211> 238 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 126

Met Glu Thr Asp Thr lie Leu Leu Tip Val Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Thr Gly Asp lie Val Leu Thr Gin Ser Pro Ala Scr L&u Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Scr Cys Lys Ala Ser Gin Ser 35 40 45

Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Phe Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu He Tyr Ala Ala Ser Asn Leu Glu Ser 65 70 75 80

Gly lie Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asd Phc Thr 85 90 95

Leu Asn lie His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys 100 105 110 G】n Gin Ser Asn Glu Asp Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu 115 120 125 G!a lie Lys Arg Thr Val Ma Ala Pro Ser Val Phe lie Phe Pro Pro 130 135 140

Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn 165 170 175

Ala Leu Gin Ser Gly Asn Scr Gin Gin Ser Val Thr Glu Gin Asp Ser 180 185 190

Lys Asp Scr Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala 195 200 205 £ 162948-序列表.doc - 123 - 201247706

Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly 210 215 220

Leu 225

Ser Scr Pro Val Thr Lys Ser Phe Asn Arg Gly Clu Qys 230 235 <210> 127 <211> 467 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <4QQ> 127

Met Ala Val Leu Gly Leu Leu Leu Cys Leu Val Thr Phe Pro Ser Cys 15 10 15

Val Leu Ser Gin Val Gin Leu Lys Glu Ser Gly Pro Gly Leu Val Ala 20 25 30

Pro Ser Gin Ser Leu Ser lie Thr Cys Thr Va】Ser Gly Phe Ser Leu 35 40 45

Ser Arg Tyr Ser Val Phe Trp Va] Arg Gin Pro Pro Gly Lys Gly Leu 50 55 60

Glu Trp Leu Gly Leu lie Trp Gly Gly Gly Ser TTir Asp Tyr Asn Ser 65 70 75 80

Ala Leu Lys Ser Arg Leu Ser lie Ser Lys Asp Asn Ser Lys Ser Gla 85 90 95

Val Phe Leu Lys Met Asn Ser Leu Gin Thr Asp Asp Thr Ala Met Tyr 100 】〇5 110

Tyr Cys Ala Arg lie Tyr Phe Asp Tyr Asp Gly Ala Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Gly Pro 130 135 140

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Scr Gly Val His Thr Phe Pro 180 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Scr Ser Val Val Τήτ 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyi Thr Cys Asn Val Asp 210 215 220 •124- 162948·序列表.doc 201247706

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Scr Lys Tyr 225 230 235 240

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 、 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met IU Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 280 285

Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300 AU Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val 305 310 315 320

Val Scr Val Leu Thr Val Lea His Gin Asp Trp Uu Asn Gly Lys Glu 325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Set Ser He Glu Lys 340 345 350

Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Fro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400

Ser Asn Gly Gin Pro Glu ^sn Asn Tyr Lys Thr Thr Pro Pro Val Leu 405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430,

Ser Arg Tip Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Uu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 128 « <211> 243 <212> PRT <213>人造序列 <220>

<223>人造序列之描述：合成多肽 <400> 12S

Met His Arg Ilir Ser Met Gly lie Lys Met Glu Ser Arg lie Gin Ala c 162948-序列表.doc -125- 201247706 15 10 15

Hie Val Phe Val Phe Leu Trp Leu Ser Gly Val Gly Gly Asp He Val 20 25 30

Met Tlir Gin Ser His Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val 35 40 45

Ser Val Thr Cys Lys Ala Scr Gin Asp Val Thr Ser Ala Val Ala Trp 50 55 60

Tyr Gin Gin Lys Pro Gly Gin Ser Pro Lys Leu Leu He Tyr Trp Ala 65 70 75 80

Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser 85 90 95

Gly Thr Asp Tyr Thr Leu Thr lie Ser Ser Gly Gin Ala Glu Asp Leu 100 】05 110

Ala Leu Tyr Tyr Cys His Gin Tyr Tyr Ser Ala Pro Arg Thr Phe Gly 115 120 125

Gly Gly Thr Lys Leu Glu lie Lys Arg Thr Val Ala Ala Pro Ser Val 130 135 140

Phe lie Phe Pro Pro Ser Asp Glu Gin Leu Lys S&r Gly Thr Ala Ser 145 150 155 160

Val Va】Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin 165 170 175

Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val ΙθΟ 185 190

Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Lea Ser Ser TTir Leu 195 200 205

Thr Leu Sei Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 210 215 220

Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 225 230 235 240

Gly Glu Cys <210> 129 <211> 467 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 129

Met Glu Trp Asn Trp Val Val Leu Phe Leu Leu Ser Leu Thr Ala Gly 15 10 15 -126- 162948-序列表.doc 201247706

Val Tyr Ala Gin Gly Gin Met Gin Gin Ser Gly Ala Glu Uu Val Lys 20 25 30

Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Thr Ser Gly Phe Thr Phe 35 40 45

Ser Scr Asn Tyr lie Ser Trp Leu Lys Gin Lys Pro Gly Gin Ser Leu 50 55 60

Glu Trp lie Ala Trp He Tyr Ala Gly Tlir Gly Gly lie Thr Tyr Asn 65 70 75 80

Gla Lys Phe Arg Gly Aig Ala Gin Leu Thr Val Asp Thr Scr Sct Scr 85 90 95

Thr Ala Tyr Met Gin Phe Ser Ser Leu Thr Thr Asp Asp Ser Ala lie 100 105 110

Tyr Tyr Cys Ala Arg Hij Val Aig Gly Tyr His Pro Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Va丨 Ser Ser Ala Lys Thr Lys Gly Pro 130 135 140

Scr Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pio Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro ISO J85 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 225 230 235 240

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro 245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met He Ser 260 265 270

Arg Thr Pro Glu Va】Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 280 285

Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val •127· 162948-序列表.doc 201247706 305 310 315 320

Val Ser V,1 Uu Val Leu His Gl„ A^p Trp I,u Asn G1y Lys G,u

Tyr Lys Cys Lys Val Scr Asn Lys Gly Leu Pro Ser Ser lie Glu Lys 340 345 350

Thx lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu 385 390 395 400

Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430

Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 435 440 445

Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 <210> 130 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 130

Met Glu Ser Gin Thr Gin Va】Pbe Val Tyr Met Leu Leu Trp Leu Ser 15 10 15 G.v Va. Asp Gly Asp lie Val Met Thr Gin Ser Gin Lys Phe Met Ser

Ala Scr Val Gly Asp Arg Val Ser Val Thr Cys Arg Ala Ser Gin Asn 35 40 45

Val Val Thr Asn Val Gly Trp Tyr Gin Gin Lys Pro Gly Gin Ser Pro 50 55 60

Lys Va] Leu lie Tyr Ser Ala Ser Phe Arg Tyi Ser Gly Val Pro Asp 65 70 75 80

Arg Rie Thr Gly Ser G】y Ser Gly Tlir Asp Phe Thr Leu Thr lie Tlu 85 90 95 -128· 162948·序列表.doc 201247706

Asn Val Gin Ser GIu Asp Leu Ala Glu Tyr Phe Cys Gin Gin Tyr Asn 100 105 110

Asn Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe He Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser G】y Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr H5 ISO 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu G】rt Asp Ser Lys Asp Ser Thr 180 185 190

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thi Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <no> m <2L1> 468 <212> PRT <213>人造序列 <220> 人造序列之描述：合成多肽 <400> L31

Met Gly Trp Ser Tyr lie He Leu Phe Leu Val Ala TTir Ala Thr Asp 15 10 15

Val His Ser Gin Val Gin Leu Gin Gin Pro Gly Ala Glu Leu Val Lys 20 25 30

Pro Gly Ala Ser Vai Lys Leu Sei Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45

Thr Ser Tyr Trp Met His Trp Val Lys Gin Arg Pro Gly Glu Gly Leu 50 55 60

Glu Trp lie Gly Glu lift Asn Pto Ser Tyr Gly Arg Ώπ Asp Tyr Asn 65 70 75 80

Gly Lys File Lys Asn Lys Ala Thr Leu Thr Val Ala Lys Ser Ser Ser 85 90 95

Thr Ala Tyr Met Gin Leu Scr Ser Leu Thr Ser Glu Asp Ser Ala Val 100 105 110 c 162948-序列表.doc -129- 201247706

Tyr Tyr Cys A】a Arg Gly Asp Tyr Tyr Gly Ser Ser Ser Phe Ala Tyr 115 120 125

Trp G]y Gin Gly Ήιγ Leu Val Thr Val Ser Ala Ala Lys Thr Lys Gly 130 135 140

Pro Ser Val Phc Pro Leu Ala Pro Cys Ser Arg Ser Thr Set Glu Ser 145 150 155 160

Tbr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190

Pro Ala Val Leu Oln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205

Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 210 215 220

Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 225 230 235 240

Tyr Gly Pro Pro Cys Fro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly 245 250 255

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 260 265 270

Ser Arg Thr Pro Glu Val Thr Cys Va】Val Va〗Asp Val Ser Gin Glu 275 280 285

Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 290 295 300

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg 305 310 315 320

Va】Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 325 330 335

Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Scr Ser He Glu 340 345 350

Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 355 360 365

Tbr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu 370 375 380

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Tip 385 390 395 400

Glu Ser Asn GJy Gin Pro G】u Asn Asn Tyr Lys Tbr Thr Pro Pro Va】 405 410 415 -130- 162948-序列表.doc 201247706

Leu Asp Ser Asp Gly Ser Phc Phe Leu Tyr Ser Arg Leu Thr Val Asp 420 425 430

Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Set Val Met His 435 440 445

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Leu 450 455 460

Gly Lys Ala Ser 46S <210> 132 <211> 234 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 132

Mel Glu Ser Gin Thr Gin Val Phe Val Tyr Met Leu Leu Trp Leu Ser 1 5 10 15

Gly Val Asp Gly Asp lie Val Met Thr Gin Ser Gin Lys Phe Met Ser 20 25 30

Thr Ser Leu Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gin Asn 35 40 45

Val Gly Thr Asn Val Ala Trp Tyr G]n Gin Lys Pro Gly His Ser Pro 50 55 60

Lys Ala Leu tie Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp 65 70 75 80

Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser 85 90 95

Asn Val Cfln Ser Glu Asp Leu Ala Glu Phe Phe Cys Gin Crln Tyr Asn 100 105 110

Asn Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Thr Leu Glu lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin 130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phc Tyr 145 150 155 160

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 165 170 175

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 180 185 190 £ 162948-序列表.doc -131 - 201247706

Tyr Ser Leu Sar Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Ti)r Lys Scr Phe Asd Arg Gly Glu Cys 225 230 <21Q> 133 <211> 60 <212> PST <213>人造序列 <220> <223>人造序列之描述：合成多肽 <4M)> 133

Met Trp Val Pro Val Val Phe Leu Thr Leu Ser Va丨 Thr Trp lie Gly 15 10 15

Ala Ala Pro Leu lie Leu Ser Arg lie Val Gly Gly Trp Glu Cys Glu 20 25 30

Lys His Ser Gin Pro Trp Gin Val Leu Val Ala Ser Arg Gly Arg Ala 35 40 45

Val Cys G】y Gly Va】Leu Val His Pro G]u Trj> Val 50 55 60 <210> 134 <21I> 60 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 134 t

Leu Thr Ala Ala His Cys He Arg Asn Lys Ser Va] He Leu Leu Gly 15 10 15

Arg His Ser Leu Phe His Pro Glu Asp Thr Gly Gin Val Phe Gin. Val 20 25 30

Ser His Ser Phe Pro His Pro Leu Tyr Asp Met Ser Leu Leu Lys Asn 35 40 45

Arg Phe Leu Arg Pro Gly Asp Asp Ser Ser His Asp 50 55 60 <210> 135 <21I> 60 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 135 -132- 162948-序列表.doc 201247706

Leu Met Leu Leu Arg Leu Ser Glu Pro Ala Glu Leu Thr Asp Ala Val 15 10 IS

Lys Val Met Asp Leu Pro Thr Gin Glu Pro Ala Leu Gly Thi Thr Cys 20 25 30

Tyr Ala Ser Gly Trp Gly Ser lie Glu Pro Glu Glu Phe Leu Thr Pro 35 40 45

Lys Lys Leu Gin Cys Val Asp Leu His Val He Ser 50 55 60 <210> 136 <211> 60 <212> PRT <2I3>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 136

Asn Asp Val Cys Ala Gin Val His Pro Gin Lys Val Thr Lys E^e Met 15 10 15

Leu Cys Ala Gly Arg Trp Thr Gly Gly Lys Ser Thr Cys Ser Gly Asp 20 25 30

Ser Gly Gly Pro Leu Val Cys Asn Gly Val Leu Gin Gly He Thr Ser 35 40 45

Tip Gly Ser Glu Pro Cys Ala Leu Pro Glu Arg Pro 50 55 60 <210> 137 <211> 21 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <40Q> 137

Ser Leu Tyr Thr Lys Val Val His Tyr Arg Lys Trp lie Lys Asp Thr 15 10 15 lie Val Ala Asn Pro 20 <210> 138 <211> 9 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <400> 138 lie Met Asp Gin Val Pro Phe Set Val <210> 139 -133- 162948·序列表.doc 201247706 <211> 9 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <400> 139 lie Thr Asp Gin Val Pro Phe Ser Val <21 (b 140 <211> 9 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <400> 140

Tyr Leu Glu Pro Gly Pro Val Thr Val <210> 141 <211> 9 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <400> 141

Tyr Leu Glu Pro Gly Pro Val Thr Ala <210> 142 <2U> 9 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成肽 <400> 142

Lys Thr Trp Gly Gin Tyr Trp Gin Va! 1 5 <210> 143 <211> 230 <212> PRT <213>人造序列 <220> 人造序列之描述：合成多肽 <400> 143

Asp Thr Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr Thr Pro Thr 15 10 IS

Thr Thr Lys Val Pro Arg Asn Gin Asp Trp Leu Gly Val Ser Arg Gin 20 25 30

Leu Arg Thr Lys Ala Trp Asn Arg Gin Leu Tyr Pro Glu Trp Thr Glu 35 40 45 -134- 162948-序列表.doc 201247706

Ala Gin Arg Leu Asp Cys Trp Arg Gly Gly Gin Val Ser Leu Lys Val 50 55 60

Ser Asn Asp Gly Pro Thr Leu lie Gly Ala Asn Ala Ser Phe Ser lie 65 70 75 80

Ala Leu Asn Phe Pro Gly Ser Gin Lys Val Leu Pro Asp Gly Gin Val 85 90 95 lie Trp Val Asn Asn Thr He lie Asji Gly Ser Gin Val Trp Gly GJy 100 105 110

Gin Pro Val Tyr Pio Gin Glu Thr Asp Asp Ala Cys He Phe Pro Asp 115 120 125

Gly Gly Pro Cys Pro Ser Gly Ser Trp Ser Gin Lys Arg Ser Phe Val 130 135 140

Tyr Val Trp Lys Thr Trp Gly G3n Tyr Trp Gin Val Leu Gly Gly Pro 145 150 155 160

Val Ser Gly Leu Ser lie Gly Thr Gly Arg Ala M«t Leu Gly Thr His 165 170 175

Thr Met Glu Val Thr Val Tyr His Arg Arg Gly Ser Gin Ser Tyr Val 180 185 190

Pto Leu Ala His Ser Ser Ser Ala Phe Thr lie Thr Asp Gin Val Pro 195 200 205

Phe Ser Val Ser Val Ser Gin Leu Arg Ala Leu Asp Gly Gly Asn Lys 210 215 220

His Phe Leu Arg Asn Gin 225 230 <210> 144 <211> 73 <212> PRT 人造序列 <220> <223>人造序列之描述：合成多肽 <220> <221> l«®_RES <222> (38)..(38) <223>任意胺基酸 <400> 144

Pro Leu Thr Phe Ala Leu Gin Leu His Asp Pro Ser Gly Tyr Leu Ala 15 10 15

Glu Ala Asp Leu Ser Tyr Thr Trp Asp Phe Gly Asp Sci Ser Gly Thr 20 25 30

Leu lie Ser Arg Ala Xaa Val Val Thr His Thr Tyr Leu Glu Pro Gly 162948-序列表.doc -135- c 201247706 35 40 45

Pro Lr Ala Gin Val gl Uu G.n Ala Ala He Pro Leu Ser

Cys GJy Ser Ser Pro Val Pro Ala Ser 65 70 <210> 145 <21i> 109 <212>PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 145

Gly Thr Thr Asp Gly His Arg Pro Thr Ala Glu Ala Pro Asn Thr Thr 15 10 15

Ala Gly Gin Val Pro Thr Thr Glu Val Val Gly Thr Thr Pro Gly Gin 20 25 30

Ala Pro Thr Ala Glu Pro Ser Gly Thr Thr Ser Val Gin Val Pro Thr 35 40 45 llu G】*i Val I】e Ser Thr A】a Pro Va] G]n Met Pro Thr Ala G]u Ser 50 55 60

Thr Gly Met Thr Pro Glu Lys Val Pro Val Ser Glu Val Met Gly Thr 65 70 75 80

Thr Leu Ala Glu Met Ser Thr Pro Glu Ala Thr Gly Met Thr Pro AJa 85 90 95

GluVa! Ser lie Val Val Leu Ser Gl? Thr Ala Ala <210> 146 <211> 75 <212> FRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 146

Gin Val Thr Tbr TTir Glu Trp Val Glu Thr Thr Ala Arg Glu Leu Pro 10 15 lie Pro Glu Pro Glu Gly Pro Asp Ala Ser Ser He Met Ser Thr Glu 20 25 30

Ser lie Hir GJy Ser Leu Gly Pro Leu Leu Asp Gly Thr Ala Thr Leu 35 40 45

Arg Leu Val Lys Arg Gin Val Pro Leu Asp Cys Val Leu Tyr Arg Tyr 50 55 60 -136- 162948-序列表.doc 201247706

Gly Ser Phe Ser Val Thr Leu Asp lie Val Gin 65 70 75 <210> 147 <211> 109 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 147

Gly He Glu Ser Ala Glu lie Leu Gin Ala Val Pro Ser Gly Glu Gly 15 10 15

Asp Ala Phe Glu Leu Thr Val Ser Cys Gin Gly Gly leu Pio Lys Glu 20 25 30

Ala Cys Met Glu lie Ser Sex Pro Gly Cys Gin Pro Pro Ala Gin Arg 35 40 45

Leu Cys Gin Pro Val Leu Pro Set Pro Ala Cys Gin Leu Val Leu His 50 55 60

Gin lie Leu Lys Gty Gly Ser Gly Thr Tyr Cys Leu Asn Val Ser Leu 65 70 75 80

Ala Asp Thr Asn Ser Lea Ala Va】Va】Ser T)ir Gin Leu lie Val Pro 85 90 95

Gly lie Leu Leu Thr Gly Gin Glu Ala Gly Leu Gly Gin 100 105 <2I0> 148 <211> 50 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 148

Met Glu Met Lys lie Leu A.rg Ala Leu Asn Phe Gly Leu Gly Arg Pro 15 10 15

Leu Pro Leu His Phe Leu Arg Arg AU Scr Lys lie Gly Glu Val Asp 20 25 30

Val Glu Gin His Thr Leu Ala Lys Tyr Leu Met Glu Leu Thr Met Leu 35 40 45

Asp Tyr 50 <2I0> 149 <211> 36 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 162948-序列表.doc -137- s 201247706 <400> 149

Asp Trp Leu Val Gin Val Gin Met Lys Phe Arg Leu Leu Gin GIu Thr 15 10 15

Met Tyr Met Thr Vai Ser lie lie Asp Arg Phe Met Gin Asn Asn Cyz 20 25 30

Val Pro Lys Lys 35 <210> 150 <211> 48 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 150

Met Glu His Gin Leu Leu Cys Cys Glu Val Glu Thr He Arg Arg Ala L 5 10 15

Tyr Pro Asp Ala Asn Leu Leu Asn Asp Arg Val Leu Arg Ala Met Leu 20 25 30

Lys Ala Glu Glu Thr Cys Ala Pro Ser Val Ser Tyr Phe Lys Cys Val 35 40 45 <210> 151 <211> 95 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 151

Gin Lys Glu Val Lea Pro Ser Met Arg Lys lie Val Ala Thr Trp Met 15 10 15

Leu Glu Val Cys Glu Glu Gin Lys Cys Glu Glu Glu Val Phe Pro Leu 20 2S 30

Ala Met Asn Tyr Leu Asp Arg Phe Leu Ser Leu Glu Pro Val Lys Lys 35 40 45

Ser Arg Leu Gin Leu Leu Gly Ala Tbr Cys Met Phe Val Ala Ser Lys 50 55 60

Met Lys Glu Thr lie Pro Leu Thr Ala Glu Lys Leu Cys He Tyr Thr 65 70 75 80

Asp Asn Ser lie Arg Pro Glu Glu Leu Leu Gin Met Glu Leu Leu 85 90 95 <210> 152 <211> 60 <212> PRT <213>人造序列 •138- 162948·序列表,doc 201247706 <22Q> <223>人造序列之描述：合成多肽 <400> 152

Leu Val Asn Lys Leu Lys Trp Asn Leu Ala Ala Met Thr Pro His Asp 1 5 10 15

Phe lie Glu His Phe Leu Ser Lys Met Pro Glu Ala Glu Clu Asn Lys 20 25 30

Gin lie lie Arg Lys His Ala Gin Thr Phe Val Ala Leu Cys Ala Thr 35 40 45

Asp Val Lys Phe lie Ser Asn Pro Pro SeT Met Val 50 55 60 <210> 153 <211> 91 <212> PRT <213>人造序列 <220> <223>人造序列之描述：合成多肽 <400> 153

Ala Gly Ser Val Val Ala Ala Val Gin Gly Leu Asn Leu Arg Ser Pro 15 10 15

Asn Asn Phe Leu Ser Tyr Tyr Arg Leu Thr Arg Phe Leu Ser Are Val 20 25 30 lie Lys Cys Asp Pro Asp Cys Leu Arg Ala Cys Gin Glu Gin lie Glu 35 40 45

Ala Leu Leu Glu Ser Ser Leu Arg Gin Ala <31n Gin Asn Met Asp Pro 50 55 60

Lys Ala Ala Glu Glu Glu Glu Glu Glu Glu Glu Glu Val Asp Leu Ala 65 70 75 80

Cys Thr Pro Thr Asp Val Arg Asp Val Asp lie 85 90

<210> L54 <211> 32 <212> PRT <21%人類免疫缺乏症病毒i <400> 154

Val Gly Phe Pro Val Thr Pro Gin Va] Pro Leu Arg Pro Met Thr Tyr 15 10 15

Lys Ala Ala Val Asp Leu Sef His Phe Leu Lys Glu Lys Gly G]y Leu 20 25 30

<210> 155 <211> 30 <212> PfiT <213>人類免疫缺乏症病毒1 162948·序列表.doc -139- c 201247706 <400> 155

His Thr Gin Gly Tyr Pbe Pro Asp Trp Gin Asn Tyr Thr Pro Gly Pro 15 10 15

Gly Val Arg Tyr Pro Leu Thr Phe Gly Trp Leu Tyr Lys Leu 20 25 30

<210> 156 <211> 19 <212> PRT d13〉人類免疫缺乏症病毒1 <400> 156

Glu Lys lie Arg Leu Arg Pro Gly Gly Lys Lys Lys Tyr Lys Leu Lys 15 10 15

His lie Val <210> 157 <211> 32 <212> PRT <213>人類免疫缺乏症病毒1 <400> 157

Asn Pro Pro lie Pro Val Gly Olu lie Tyr Lys Arg Trp He He Leu 15 10 15

Gly Leu Asa Lys lie Val Arg Met Tyr Ser Pro Thr Set lie Leu Asp 20 25 30

<210> 158 <211> 31 <212> PRT <213>人類免疫缺乏症病毒1 <400> 158

Ala He Phe Gin Ser Ser Met Thr Lys lie Leu Glu Pro Phe Arg Lys 1 5 10 15

Gin Asn Pio Asp He Val lie Tyr Gin Tyr Met Asp Asp Leu Tyr 20 25 30 <210> 159 <211> 9 <212> PRT <213>未知 <22Q> <223>未知物之描述：前列腺特異性抗原肽 <400> 159

Lys Leu Gin Cys Val Asp Leu His Val <21B> 160 <211> 9 <212> PRT <213>流感A型病毒 <400> 160

Gly lie Leu Gly Phe Val Phe Ttr Leu 140· 162948-序列表.doc

Claims (1)

1. 201247706 七、申請專利範圍： 1. 一種佐劑組合物，其包含： 結合至Toll樣受體（TLR)促效劑之抗樹突狀細胞（DC)特 異性抗體或其片段；及醫藥學上可接受之載劑，其中該 結合物及該促效劑之個別含量可以使得其組合可在需要 免疫刺激之人類或動物個體中有效產生免疫反應。 2. 如請求項1之組合物，其中該DC特異性抗體或片段係選 自抗 DCIR、MHC I 類、MHC II類、CD1、CD2、CD3、 CD4、CD8、CDllb、CD14、CD15、CD16、CD19、 CD20、CD29、CD31、CD40、CD43、CD44、CD45、 CD54、CD56、CD57、CD58、CD83、CD86、CMRF-44、 CMRF-56、DCIR、DC-ASPGR、CLEC-6、CD40、 BDCA-2、MARCO、DEC-205、甘露糖受體、蘭格素 (Langerin)、DECTIN-1 ' B7-1 ' B7-2、IFN-γ 受體及 IL-2 受體、ICAM-1、Fey受體、LOX-1 或 ASPGR。 3. 如請求項1之組合物，其中該DC特異性抗體之核苷酸序 列係選自 SEQ ID NO:3至 SEQ ID NO:67。 4. 如請求項1之組合物，其中該DC特異性抗體之胺基酸序 列係選自 SEQ ID NO:68至 SEQ ID NO:132。 5. 如請求項1之組合物，其中該組合物另外包含選自以下 之抗原狀：選自由gag、pol及env基因、Nef蛋白質、逆 轉錄酶、HIV 肽串（Hipo5)、PSA(KLQCVDLHV)四聚體 (SEQ ID NO:159)、源自 HIVgag 之 p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人類免疫缺乏症病毒 162948.doc 201247706 (HIV)抗原及基因產物；肝炎病毒抗原；選自由血球凝 集素、神經胺酸酶、來自H1N1流感病毒株之流感A血球 凝集素 HA-1、HLA-A201-FluMP(58-66)肽（GILGFVFTL) 四聚體（SEQ ID NO:160)及禽流感（HA5-1)組成之群的流 感病毒抗原及狀；來自熱纖梭菌（C. Aerwoce/Zww)之錫 定結構域（dockerin domain)、麻疹病毒抗原、風疹病毒 抗原、輪狀病毒抗原、細胞巨大病毒抗原、呼吸道融合 性病毒抗原、單純疱疹病毒抗原、水痘帶狀疱療病毒抗 原、日本腦炎病毒抗原、狂犬病毒抗原或其組合及其經 修飾物。 6.如請求項1之組合物，其中該組合物另外包含選自癌症 肽之抗原肽，該等癌症肽係選自包含來自以下各者之抗 原的Μ瘤相關抗原：白血病及淋巴瘤、諸如星形細胞瘤 或神經膠母細胞瘤之神經性腫瘤、黑色素瘤、乳癌、肺 癌、頭頸部癌症、胃腸腫瘤、胃癌、結腸癌、肝癌、胰 臟癌、諸如子宮頸癌、子宮癌、卵巢癌、陰道癌、睪丸 癌、前列腺癌或陰莖癌之泌尿生殖腫瘤、骨腫瘤、血管 瘤 '或唇 '鼻咽、咽及口腔、食道、直腸、膽囊、膽道 (biliary tree)'喉、肺及支氣管、膀胱、腎、腦部及神經 系統其他部分之癌症、甲狀腺癌、霍奇金氏病 (Hodgkin’s disease)、非霍奇金氏淋巴瘤（n〇n H〇dgkin|s lymPh〇ma)、多發性骨髓瘤及白血病。 7_如請求項1之組合物’其中該組合物另外包含選自腫瘤 相關抗原之抗原肽，該等腫瘤相關抗原係選自CM、前 162948.doc 201247706 列腺特異性抗原（PSA)、HER-2/neu、BAGE、GAGE、 MAGE 1-4、MAGE 6及 MAGE 12、MUC(黏蛋白）（例如 MUC-1、MUC-2 等）、GM2 及 GD2 神經節苷脂、ras、 myc、酪胺酸酶、MART(黑色素瘤抗原）、MARCO-• MART、細胞週期素B1、細胞週期素D、Pmel 17 . (gplOO)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移酶 V内含子V序列）、前列腺癌psm、前列腺血清抗原 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素（catenin)、 MUM-1-B(黑色素瘤遍佈突變基因產物（melanoma ubiquitous mutated gene product))、GAGE(黑色素瘤抗 原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、 EBNA(愛潑斯坦-巴爾病毒（Epstein-Barr Virus)核抗 原）1-6、gp75、人類乳頭狀瘤病毒（human papilloma virus)(HPV)E6及 E7、p53、肺耐藥蛋白質（LRP)、Bcl-2 及 Ki-67。 8 ·如請求項1之組合物，其中該DC特異性抗體經人類化。 9.如請求項1之組合物，其中該組合物係藉由經口途徑、 經鼻途徑、局部或以注射形式投與該人類或動物個體。 - 1 〇·如請求項9之組合物，其中該注射法係選自由以下組成 . 之群：皮下、靜脈内、腹膜内、肌肉内及靜脈内。 11. 一種疫苗纟且合物，其包含： 抗原；及 佐劑，其中該佐劑包含結合至Toll樣受體（TLR)促效劑 之抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學上 162948.doc 201247706 可接受之載劑，其中該結合物及該促效劑之個別含量可 以使得其組合可在需要免疫刺激之人類或動物個體中有 效產生免疫反應。 12.如請求項11之組合物，其中該DC特異性抗體或片段係選 自抗 DCIR、MHC I類、MHC II類、CD1、CD2、CD3、 CD4、CD8、CDllb、CD14、CD15、CD16、CD19、 CD20、CD29、CD31、CD40、CD43、CD44、CD45、 CD54、CD56、CD57、CD58、CD83、CD86、CMRF-44、 CMRF-56、DCIR、DC-ASPGR、CLEC-6、CD40、 BDCA-2、MARCO、DEC-205、甘露糖受體、蘭格素、 DECTIN-1、B7-1、B7-2、IFN-γ 受體及 IL-2 受體、 ICAM-1、Fey 受體、LOX-1 或 ASPGR。 13.如請求項11之組合物，其中該組合物另外包含選自以下 之抗原肽：選自由gag、ρ〇1及env基因、Nef蛋白質、逆 轉錄酶、HIV肽串（Hipo5)、PSA(KLQCVDLHV)四聚體 (SEQ ID N〇:159)、源自 HIVgag 之 p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人類免疫缺乏症病毒 (HI V)抗原及基因產物；肝炎病毒抗原；選自由血球凝 集素、神經胺酸酶、來自Η1N1流感病毒株之流感A血球 凝集素 HA-1、HLA-A201-FluMP(58-66)肽（GILGFVFTL) 四聚體（SEQ ID N〇:160)及禽流感（Avian Flu)(HA5-l)組 成之群的流感病毒抗原及肽；來自熱纖梭菌之錫定結構 域、麻疹病毒抗原、風疹病毒抗原、輪狀病毒抗原、細 胞巨大病毒抗原、呼吸道融合性病毒抗原、單純疮療病 162948.doc -4 - 201247706 毒抗原、水痘帶狀疮療病毒抗原、曰本腦炎病毒抗原、 狂犬病毒抗原或其組合及其經修飾物。 14. 如請求項11之組合物，其中該組合物另外包含選自癌症 肽之抗原肽，該等癌症肽係選自包含來自以下各者之抗 原的腫瘤相關抗原：白血病及淋巴瘤、諸如星形細胞瘤 或神經膠母細胞瘤之神經性腫瘤、黑色素瘤、乳癌、肺 癌、頭頸部癌症、胃腸腫瘤、胃癌、結腸癌、肝癌、胰 臟癌、諸如子宮頸癌、子宮癌、卵巢癌、陰道癌、睪丸 癌、前列腺癌或陰莖癌之泌尿生殖腫瘤、骨腫瘤、血管 瘤、或唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽 道、喉、肺及支氣管、膀胱、腎'腦部及神經系統其他 部分之癌症、曱狀腺癌、霍奇金氏病、非霍奇金氏淋巴 瘤、多發性骨髓瘤及白血病。 15. 如請求項14之組合物，其中該組合物另外包含選自腫瘤 相關抗原之抗原肽’該等腫瘤相關抗原係選自CEA、前 列腺特異性抗原（PSA)、HER-2/neu、BAGE、GAGE、 MAGE 1-4、MAGE 6及 MAGE 12、MUC(黏蛋白例如 MUC-1、MUC-2等）、GM2及GD2神經節苷月旨、ras、 myc、酪胺酸酶、MART(黑色素瘤抗原）、MARC〇_ MART、細胞週期素B1、細胞週期素D、Pmei 17 (gplOO)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移酶 V内含子V序列）、前列腺癌psm、前列腺血清抗原 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素、ΜυΜ_ΝΒ (黑色素瘤遍佈突變基因產物）、GAGE(黑色素瘤抗 162948.doc 201247706 原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、 EBNA(愛潑斯坦-巴爾病毒核抗原）1-6、gp75、人類乳頭 狀瘤病毒（HPV)E6及E7、p53、肺耐藥蛋白質（LRP)、 Bcl-2 及 Ki-67。 16. 如請求項11之組合物，其中該DC特異性抗體經人類化。 17. 如請求項11之組合物，其中該組合物係藉由經口途徑、 經鼻途徑、局部或以注射形式投與該人類或動物個體。 18. 如請求項17之組合物，其中該注射法係選自由以下組成 之群：皮下、靜脈内、腹膜内、肌肉内及靜脈内。 19. 一種提高由抗原呈現細胞所呈現抗原之有效性的活體外 方法，其包括： 使該抗原呈現細胞與組合物接觸，該組合物包含： 抗原；及 佐劑，其中該佐劑包含結合至Toll樣受體（TLR)促效劑 之抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學上 可接受之載劑，其中該結合物及該促效劑之個別含量可 以使得其組合可在需要免疫刺激之人類或動物個體中有 效產生免疫反應。 20_如請求項19之方法，其中該DC特異性抗體或片段係選自 抗 DCIR、MHC I 類、MHC II 類、CD1、CD2、CD3、 CD4、CD8、CDllb、CD14、CD15、CD16、CD19、 CD20、CD29、CD31、CD40、CD43、CD44、CD45、 CD54、CD56、CD57、CD58、CD83、CD86、CMRF-44、 CMRF-56 ' DCIR ' DC-ASPGR、CLEC-6 、CD40 、 162948.doc -6- 201247706 BDCA-2、MARCO、DEC-205、甘露糖受體、蘭格素、 DECTIN-1、B7-1、B7-2、IFN-γ 受體及 IL-2 受體、 ICAM-1、Fey 受體、LOX-1 或 ASPGR。 21. 如請求項19之方法，其中該組合物另外包含選自以下之 抗原肽：選自由gag、pol及env基因、Nef蛋白質 '逆轉 錄酶、HIV 肽串（Hipo5)、PSA(KLQCVDLHV)四聚體 (SEQ ID NO:159)、源自 HIVgag 之 p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人類免疫缺乏症病毒 (HI V)抗原及基因產物；肝炎病毒抗原；選自由血球凝 集素、神經胺酸酶、來自H1N1流感病毒株之流感A血球 凝集素HA-1、HLA-A20卜FluMP(58-66)肽（GILGFVFTL) 四聚體（SEQ田N〇:160)及禽流感（H A 5 -1)組成之群的流 感病毒抗原及肽；來自熱纖梭菌之錨定結構域、麻疹病 毒抗原、風珍病毒抗原、輪狀病毒抗原、細胞巨大病毒 抗原、呼吸道融合性病毒抗原、單純疱珍病毒抗原、水 殖帶狀范療病毒抗原、日本腦炎病毒抗原、狂犬病毒抗 原或其組合及其經修飾物。 22. 如請求項19之方法’其中該組合物另外包含選自癌症肽 之抗原肽，該等癌症肽係選自包含來自以下各者之抗原 的腫瘤相關拆原：白血病及淋巴瘤、諸如星形細胞瘤或 神經勝母細胞瘤之神經性腫瘤、黑色素瘤、乳癌 '肺 癌、頭頸部癌症、胃腸腫瘤、胃癌、結腸癌、肝癌、騰 臟癌、諸如孑宮頸癌、子宮癌、卵巢癌、陰道癌 '睪丸 癌、前列腺痛或陰莖癌之泌尿生殖腔瘤、骨腫瘤 '血管 £ 162948.doc 201247706 瘤、或唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽 道、喉、肺及支氣管、膀胱、腎、腦部及神經系統其他 部分之癌症、甲狀腺癌、霍奇金氏病、非霍奇金氏淋巴 瘤、多發性骨髓瘤及白血病。 23. 如請求項19之方法，其中該組合物另外包含選自腫瘤相 關抗原之抗原肽，該等腫瘤相關抗原係選自CEA、前列 腺特異性抗原（PSA)、HER-2/neu、BAGE、GAGE、 MAGE 1-4、MAGE 6及 MAGE 12、MUC(黏蛋白）（例如 MUC-1、MUC-2 等）、GM2 及 GD2 神經節苷脂、ras、 myc、酷·胺酸酶、MART(黑色素瘤抗原）、MARCO-MART、細胞週期素B1、細胞週期素D、Pmel 17 (gplOO)、GnT-V内含子V序列（N-乙醢基葡糖胺基轉移酶 V内含子V序列）、前列腺癌psm、前列腺血清抗原 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素、MUM-1-B (黑色素瘤遍佈突變基因產物）、GAGE(黑色素瘤抗 原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、 EBNA(愛潑斯坦-巴爾病毒核抗原）1-6、gp75、人類乳頭 狀瘤病毒（HPV)E6及E7、p53、肺耐藥蛋白質（LRP)、 Bcl-2及 Ki-67。 24. 如請求項19之方法，其中該DC特異性抗體經人類化。 25. —種包含抗原及佐劑之組合物的用途，其用於製造藥 物，經由使抗原呈現細胞與該組合物接觸而提高由該抗 原呈現細胞呈現抗原之有效性，其中該佐劑包含結合至 Toll樣受體（TLR)促效劑之抗樹突狀細胞（DC)特異性抗體 162948.doc 201247706 或其片段；及醫藥學上可接受之載劑，其中該結合物及 該促效劑之個別含量可以使得其組合可在需要免疫刺激 之人類或動物個體中有效產生免疫反應。 26. —種包含抗原及佐劑之疫苗組合物的用途，其用於製造 ' 藥物’供治療、預防或既治療又預防人類個體之一或多 . 種癌症’其中該佐劑包含結合至Toll樣受體（TLR)促效劑 之抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學上 可接受之載劑’其中該結合物及該促效劑之個別含量可 以使得其組合可在需要免疫刺激之人類或動物個體中有 效產生免疫反應。 27. —種包含抗原及佐劑之組合物的用途，其用於製造藥 物’藉由活化一或多個樹突狀細胞（DC)來向人類個體提 供免疫刺激，以預防、治療或既預防又治療一或多種病 毒、細菌、真菌、寄生蟲、原蟲及寄生蟲疾病及過敏性 病症，其中該佐劑包含結合至T〇u樣受體（TLR)促效劑之 抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學上可 接受之載劑，其中該結合物及該促效劑之個別含量可以 使得其組合可在需要免疫刺激之人類或動物個體中有效 . 產生免疫反應，且其中該提供免疫刺激之方法包括以下 . 步驟： 鑑別需要免疫刺激以預防 '治療或既預防又治療選自 自流感、HIV、癌症及免疫病症中選定之群的一或多種 疾病的該人類個體； 自該人類個體分離一或多個DC ; 162948.doc S 201247706 用可有效形成活化的DC之量的該組合物來活化該等經 分離之DC ;及 將該等活化的DC再引入該人類個體體内。 28.如請求項25至27中任一項之用途，其中該DC特異性抗體 或片段係選自抗DCIR、MHC I類、MHC II類、CD1、 CD2、CD3、CD4、CD8、CDllb、CD14、CD15、 CD16、CD19、CD20、CD29、CD31、CD40、CD43、 CD44、CD45、CD54、CD56、CD57、CD58、CD83、 CD86、CMRF-44、CMRF-56、DCIR、DC-ASPGR、 CLEC-6、CD40、BDCA-2 ' MARCO、DEC-205 ' 甘露糖 受體、蘭格素、DECTIN-1、B7-1、B7-2、IFN-γ受體及 IL-2 受體、ICAM-1、Fey 受體、LOX-1 或 ASPGR。 29.如請求項25至27中任一項之用途，其中該組合物另外包 含選自以下之抗原肽：選自由gag、pol及env基因、Nef蛋 白質、逆轉錄酶、HIV肽串（Hipo5)、PSA(KLQCVDLHV) 四聚體（SEQ ID N〇:159)、源自 HIVgag 之 p24-PLA HIV gag p24(gag)及其他HIV組分組成之群的人類免疫缺乏症 病毒（HIV)抗原及基因產物；肝炎病毒抗原；選自由血 球凝集素、神經胺酸酶、來自H1N1流感病毒株之流感A 血球凝集素 ha-1 、HLA-A201-FluMP(58-66)肽 (GILGFVFTL)四聚體（SEQ ID NO:160)及禽流感（HA5-1) 組成之群的流感病毒抗原及肽；來自熱纖梭菌之錨定結 構域、麻療病毒抗原、風奢病毒抗原、輪狀病毒抗原、 細胞巨大病毒抗原、呼吸道融合性病毒抗原、早純癌療· 162948.doc -10- 201247706 病毒抗原、水痘帶狀疱疹病毒抗原、日本腦炎病毒抗 原、狂犬病毒抗原或其組合及其經修飾物。 30. 如請求項25至27中任一項之用途，其中該組合物另外包 含選自癌症狀之抗原肤’該等癌症肽係選自包含來自以 下各者之抗原的腫瘤相關抗原.白金病及淋巴瘤、諸如 星形細胞瘤或神經膠母細胞瘤之神經性腫瘤、黑色素 瘤、乳癌、肺癌、頭頸部癌症、胃腸腫瘤、胃癌、結腸 癌、肝癌、胰臟癌、諸如子宮頸癌、子宮癌、印巢癌、 陰道癌、睪丸癌、前列腺癌或陰莖癌之泌尿生殖腫瘤、 骨腫瘤、血管瘤、或唇 '鼻咽、咽及口腔、食道、直 腸、膽囊、膽道、喉、肺及支氣管、膀胱、腎、腦部及 神經系統其他部分之癌症、甲狀腺癌、霍奇金氏病、非 霍奇金氏淋巴瘤、多發性骨餹瘤及白血病。 31. 如請求項25至27中任一項之用途，其中該組合物另外包 含選自腫瘤相關抗原之抗原肽，該等腫瘤相關抗原係選 自CEA、前列腺特異性抗原（PSA)、HER-2/neu、 BAGE、GAGE ' MAGE 1-4、MAGE 6 及 MAGE 12 ' MUC(黏蛋白）（例如MUC-1、MUC-2等）、GM2及GD2神經 節苷脂' ras、myc、酪胺酸酶、MART(黑色素瘤抗原）、 MARCO-MART、細胞週期素B1、細胞週期素D、Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯基葡糖胺基轉移 酶V内含子V序列）、前列腺癌psm、前列腺血清抗原 (PSA)、PRAME(黑色素瘤抗原）、β-索烴素、MUM-1-B (黑色素瘤遍佈突變基因產物）、GAGE(黑色素瘤抗 162948.doc •11· 201247706 原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、 EBNA(愛潑斯坦-巴爾病毒核抗原）1-6、gp75、人類乳頭 狀瘤病毒（HPV)E6及E7、p53、肺耐藥蛋白質（LRP)、 Bcl-2及 Ki-67。 32·如請求項25至27中任一項之用途，其中該DC特異性抗體 經人類化。 3 3.如請求項25至27中任一項之用途，其中該組合物係藉由 經口途徑、經鼻途徑、局部或以注射形式投與該人類或 動物個體。 34.如請求項33之用途，其中該注射法係選自由以下組成之 群：皮下、靜脈内、腹膜内、肌肉内及靜脈内。 162948.doc -12-