TW201208696A - Novel vaccine adjuvants based on targeting adjuvants to antibodies directly to antigen-presenting cells - Google Patents

Description

201208696 :、發明說明： 【發明所屬之技術領域】 本發明大體係關於樹突狀細胞（DC)標靶疫苗，且更特定 言之，係關於藉由直接連接直接針對DC標靶疫苗之佐劑 (例如TLR配位體）來增強疫苗功效。 【先前技術】 在不限制本發明之範疇的情況下，結合新穎佐劑、樹突 狀細胞（DC)疫苗及增強針對DC疫苗之免疫反應之策略描 述本發明之先前技術。 美國專利申請案20090004194(Kedl，2007)係關於促進抗 原特異性細胞免疫之新穎蛋白質及DNA結合物。亦關於此 等多肽結合物及DNA結合物作為免疫佐劑用於治療多種慢 性疾病（包括癌症、感染性疾病、自體免疫疾病、過敏及 發炎疾病）的用途。Kedl之發明揭示含有TLR/CD40/促效劑 及視情況選用之抗原組合的融合蛋白及DNA結合物。亦教 示此等蛋白質及DNA結合物作為免疫佐劑及作為疫苗用於 治療多種慢性疾病的用途。 美國專利申請案20080220011(Steven，2008)提供一種包 含鞭毛蛋白佐劑及腫瘤抗原之融合蛋白。亦提供包含鞭毛 蛋白佐劑及腫瘤抗原之組合物。該發明進一步提供誘發針 對腫瘤抗原之免疫反應的醫藥調配物及方法及治療個體之 腫瘤的方法。 美國專利申請案20080248068(Ljunggren等人，2008)係 關於鞭毛蛋白及其作為佐劑用於疫苗接種之用途。該發明 158138.doc 201208696 可用於疫苗調配物以改良針對任何在相同位置投與之其他 抗原的免疫性。抗原可與鞭毛蛋白在同一構築體中投與或 在相同位置給予的任何其他調配物中投與。作為替代，鞭 毛蛋白可用於激發針對在特定位置表現之抗原的免疫性。 為了形成發炎模型’鞭毛蛋白亦可用於誘發局部發炎。 頒予Sotomayor及Suarez(2008)之美國專利第7,404,963號 提供適用於引發免疫反應，尤其針對腫瘤抗原之免疫反應 的佐劑、疫省及相關方法。根據S〇t〇may〇r之發明，鞭毛 蛋白在與致耐受性抗原一起投與時能夠抑制耐受性。此效 應可能由鞭毛蛋白誘發IL-12同時保持比-1〇含量較低之能 力所介導。此外，可藉由使用鞭毛蛋白表現細胞以緩釋方 式提供鞭毛蛋白處理鞭毛蛋白表現細胞較佳使其不再能 夠複製，然而仍保留表現鞭毛蛋白之能力，諸如藉由致死 照射來處理。 【發明内容】 本發明描述用於製造以直接針對抗原呈現細胞之抗體的 軚靶佐劑為主之新穎疫苗佐劑的組合物及方法。本發明發 現藉由直接連接直接針對DC標靶疫苗之佐劑（例如^^^尺配 位體）可增強疫苗功效。如本文中所示，本發明之組合物 及方法廣泛適用於所有DC標靶疫苗且可推廣用於製造具 有意想不到之新賴特性之佐劑。 在一實施例中，本發明包括__種佐劑組合物，其包含： 與鞭毛蛋白之至少一部分結合之抗樹突狀細胞（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 I58138.doc 201208696 及促效劑各以與另一者組合可在需要免疫刺激之人類或動 物個體中有效引起免疫反應的量包含在内。在一態樣中， 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（Langerin)、DECTIN-1(樹突狀 細胞相關C型植物凝集素-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，該組合物進一步包含抗原性肽，其選自人類免疫 缺乏病毒（HIV)抗原及選自由gag、pol及env基因組成之群 的基因產物、Nef蛋白、逆轉錄酶、線性HIV肽（Hipo5)、 PSA(KLQCVDLHV)四聚物、來源於HIVgag之p24-PLAHIV gag p24(gag)及其他HIV組分、肝炎病毒抗原、流感病毒抗 原，及選自由以下組成之群的肽：血球凝集素、神經胺糖 酸苦酶（neuraminidase)、H1N1流感病毒株之A型流感血球 凝集素HA_1、HLA-A201-FluMP(58-66)肽（GILGFVFTL)四 聚物及禽流感（HA5-1)、嗜熱梭狀芽孢桿菌（C. thermocellum) 之錯定蛋白域（dockerin domain)、麻療病毒抗原、風療病 毒抗原、輪狀病毒抗原、巨細胞病毒抗原、呼吸道融合病 毒抗原、单純疮療病毒抗原、水症帶狀疮療病毒抗原、曰 本腦炎病毒抗原、狂犬病病毒抗原或其組合及修飾。在另 158138.doc 201208696 一態樣中，該組合物進一步包含選自癌肽之抗原性肽，該 等癌肽係選自腫瘤相關抗原，包含來自以下之抗原：白血 病及淋巴瘤、神經腫瘤（諸如星形細胞瘤或神經膠母細胞 瘤）、黑色素瘤、乳癌、肺癌、頭頸癌、胃腸腫瘤、胃 癌、結腸癌、肝癌、胰臟癌、泌尿生殖器腫瘤（諸如子宮 頸癌、子宮癌、卵巢癌、陰道癌、睾丸癌、前列腺癌或陰 莖癌）、骨腫瘤、血管瘤、或唇、鼻咽、咽及口腔、食 道、直腸、膽囊、膽管樹、喉、肺及支氣管、膀胱、腎 臟、腦及神經系統之其他部分、曱狀腺之癌症、霍奇金氏 病（Hodgkin's disease)、非霍奇金氏淋巴瘤（non-Hodgkin's lymphoma)、多發性骨髓瘤及白血病。在一特定態樣中， 該組合物進一步包含選自腫瘤相關抗原之抗原性肽，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、6及 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、週期素B1、週期素D、Pmel 17(gpl00)、GnT-V内 含子V序列（N-乙醯葡萄糖胺基轉移酶V内含子V序列）、前 列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗 原）、β-索烴素、MUM-1-B(黑色素瘤普遍性突變基因產 物）、GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗原μ-ΐΟ 、 c-ERB2(Her2/neu) 、 EBNA(EB病毒 核抗原（£卩31〇111-Barr Virus nuclear antigen))l-6、gp75、人類乳頭狀瘤病毒 (HPV)E6及 E7、p53、肺耐藥蛋白（LRP)、Bcl-2及 Ki-67。 158138.doc 201208696 在另一態樣中，DC特異性抗體經人類化。在另一態樣 中，該組合物經口途徑、鼻途徑、局部施用或以注射形式 投與人類或動物個體。在另一態樣中，注射係選自由皮 下、靜脈内、腹膜内、肌内及靜脈内組成之群。在一態樣 中，抗DC特異性抗體係選自成對之SEQ ID NO: 7與9、11 與13、15與17、19與21、23與25、27與29、31與33、35與 37 ' 39 與 41、43 與 45、47 與 49、51 與 53、55 與 57、59 與 61 ' 63 與 65、67 與 69、71 與 73、75 與 77、79 與 81 ' 83 與 85 、 87與89 、 91與93 、 95與97 、 99與101 、 103與105 、 107 與 109、111 與 113、115 與 117、119 與 121、123 與 125、127 與129 、 131與132 、 133與134 。 本發明之另一實施例包括一種疫苗組合物，其包含：抗 原及佐劑，其中該佐劑包含與鞭毛蛋白之至少一部分結合 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，其中該結合物及促效劑各以與另一者組合可 在需要免疫刺激之人類或動物個體中有效引起免疫反應的 量包含在内。在一態樣中，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 1 ' B7-1、B7-2、IFN-γ 受體及 il，2受體、ICAM-1、Fey 受 158138.doc 201208696 體 ' LOX-1 或 ASPGR。 在另一態樣中，該組合物進一步包含抗原性肽，其選自 人類免疫缺乏病毒（HIV)抗原及選自由gag、pol及env基因 組成之群之基因產物、Nef蛋白、逆轉錄酶、線性HIV肽 (Hip〇5)、PSA(KLQCVDLHV)四聚物、來源於HIVgag 之 p24-PLA HIV gag p24(gag)及其他HIV組分、肝炎病毒抗 原、流感病毒抗原、及選自由以下組成之群的肽：血球凝 集素、神經胺糖酸苷酶、H1N1流感病毒株之a型流感血球 凝集素 HA-1、HLA_A201-FluMP(58-66)肽（GILGFVFTL)四 聚物及禽流感（HA5-1)、嗜熱梭狀芽孢桿菌之錨定蛋白 域、麻疹病毒抗原、風疹病毒抗原、輪狀病毒抗原、巨細 胞病毒抗原、呼吸道融合病毒抗原、單純疱疹病毒抗原、 水疫帶狀疱疹病毒抗原、日本腦炎病毒抗原、狂犬病病毒 抗原或其組合及修御。在另一態樣中，該組合物進一步包 含選自癌肽之抗原性肽’該等癌肽係選自腫瘤相關抗原， 包含來自以下之抗原：白丘病及淋巴瘤、神經腫瘤（諸如 星形細胞瘤或神經膠母細胞瘤）、黑色素瘤、乳癌、肺 癌、頭頸癌、胃腸腫瘤、胃癌、結腸癌、肝癌、胰臟癌、 泌尿生殖器腫瘤（諸如子宮頸癌、子宮癌、印巢癌、陰道 癌、睾丸癌、前列腺癌或陰莖癌）、骨腫瘤、血管瘤、或 唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽管樹、喉、 肺及支氣管、膀胱、腎臟、腦及神經系統之其他部分、甲 狀腺之癌症、霍奇金氏病、非霍奇金氏淋巴瘤、多發性骨 髓瘤及白血病。在一特定態樣中，該組合物進一步包含選 158133.doc 201208696 自腫瘤相關抗原之抗原性肽，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、6及 12、MUC(黏蛋白）（例如 MUC-1、 MUC-2等）、GM2及GD2神經節普脂、ras、myc、絡胺酸 酶、MART(黑色素瘤抗原）、MARCO-MART、週期素B1、 週期素D、Pmel 17(gpl00)、GnT-V内含子V序列（N-乙醯葡 萄糖胺基轉移酶V内含子V序列）、前列腺Ca psm、前列腺 I清抗原（PSA)、PRAME(黑色素瘤抗原）、β_索烴素、 MUM-1-Β(黑色素瘤.普遍性突變基因產物）、GAGE(黑色素 瘤抗原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/ neu)、EBNA(EB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（LRP)、Bcl-2 及 Ki-67。 在另一態樣中’ DC特異性抗體經人類化β在另一態樣 中’該組合物經口途徑、鼻途徑、局部施用或以注射形式 投與人類或動物個體。在另一態樣中，注射係選自由皮 下、靜脈内、腹膜内、肌内及靜脈内組成之群。 本發明之另一實施例提供一種增強抗原呈現細胞之抗原 呈現有效性的方法’其包含：使該抗原呈現細胞與包含抗 原及佐劑之組合物接觸，其中該佐劑包含與鞭毛蛋白之至 少一部分結合之抗樹突狀細胞（DC)特異性抗體或其片段； 及醫藥學上可接受之載劑，其中該結合物及促效劑各以與 另一者組合可在需要免疫刺激之人類或動物個體中有效引 起免疫反應的量包含在内。在另一態樣中，DC特異性抗 158138.doc •9- 201208696 體或片段係選自抗DCIR、MHC I類、MHC II類、CDl、 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，該 組合物進一步包含抗原性肽，其選自人類免疫缺乏病毒 (HIV)抗原及選自由gag、pol及env基因組成之群之基因產 物、Nef蛋白、逆轉錄酶、線性HIV肽（Hipo5)、PSA (KLQCVDLHV)四聚物、來源於HIVgag之p24-PLAHIVgag p24(gag)及其他HIV組分、肝炎病毒抗原、流感病毒抗 原、及選自由以下組成之群的肽：血球凝集素、神經胺糖 酸苷酶、H1N1流感病毒株之A型流感血球凝集素HA-1、 HLA-A201-FluMP(58-66)肽（GILGFVFTL)四聚物及禽流感 (HA5-1 )、嗜熱梭狀芽孢桿菌之錨定蛋白域、麻疹病毒抗 原、風疹病毒抗原、輪狀病毒抗原、巨細胞病毒抗原、呼 吸道融合病毒抗原、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、狂犬病病毒抗原或其組合及 修飾。在另一態樣中，該組合物進一步包含選自癌肽之抗 原性肽，該等癌肽係選自腫瘤相關抗原，包含來自以下之 抗原：白血病及淋巴瘤、神經腫瘤（諸如星形細胞瘤或神 經膠母細胞瘤）、黑色素瘤、乳癌、肺癌、頭頸癌、胃腸

158138.doc • 10· S 201208696 腫瘤、胃癌、結腸癌、肝癌、胰臟癌、泌尿生殖器腫瘤 (諸如子宮頸癌、子宮癌、卵巢癌、陰道癌、睾丸癌、前 列腺癌或陰莖癌）、骨腫瘤、▲管瘤或唇、鼻咽'咽及口 腔、食道、直腸、膽囊、膽管樹、喉、肺及支氣管、膀 胱、腎臟、腦及神經系統之其他部分、甲狀腺之癌症、霍 奇金氏病、非霍奇金氏淋巴瘤、多發性骨髓瘤及白血病。 在特定態樣中，該組合物進一步包含選自腫瘤相關抗原之 抗原性肽，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、6及 12、MUC(黏蛋白）（例 wMUCM、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、週期素 B1、週期素 D、Pmel 17 (gplOO)、GnT-V内含子v序列（N-乙醯葡萄糖胺基轉移酶¥ 内含子v序列）、前列腺Ca psm、前列腺血清抗原（pSA)、 PRAME(黑色素瘤抗原）、β_索烴素、(黑色素瘤 普遍性突變基因產物）、GAGE(黑色素瘤抗原）丨、BaGE(黑 色素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(EB病毒核抗 原）1-6、gp75、人類乳頭狀瘤病毒（HPV)E6&E7、p53、肺 对藥蛋白（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，該組合物經口途徑、鼻 途徑、局部施用或以注射形式投與人類或動物個體。在另 一態樣中’注射係選自由皮下、靜脈内、腹膜内、肌内及 靜脈内組成之群。在一態樣中，抗DC特異性抗體係選自 成對之SEQ ID NO: 7與9、11與 13、15與 17、19與21、23 158138.doc 201208696 與25 、 27與29 、 31與33 、 35與37 、 39與41 、 43與45 、 47與 49、51 與 53、55 與 57、59 與 61、63 與 65、67與 69、71 與 73、75 與 77、79 與 81、83 與 85、87 與 89、91 與 93、95 與 97、99 與 101、103 與 105、107 與 109、111 與 113、115 與 117 、 119與121 、 123與125 、 127與129 、 131與132 、 133與 134。 在一實施例中，本發明包括一種針對人類個體之一或多 種癌症進行治療、預防或其組合之方法，其包含以下步 驟：鑑定需要治療、預防或其組合之人類個體；及投與包 含⑴抗原及（ii)佐劑之疫苗組合物，其中該佐劑包含與鞭 毛蛋白之至少一部分結合的抗樹突狀細胞（DC)特異性抗體 或其片段；及醫藥學上可接受之載體，其中該結合物及促 效劑各以與另一者組合可在需要免疫刺激之人類或動物個 體中有效引起免疫反應的量包含在内。在一態樣中，DC 特異性抗體或片段係選自抗DCIR、MHC I類、MHC II 類、CDl、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，該組合物進一步包含抗原性肽， 其選自人類免疫缺乏病毒（HIV)抗原及選自由gag、pol及 158I38.doc •12- 201208696 env基因組成之群之基因產物、Nef蛋白、逆轉錄酶、線性 HIV 肽（Hip〇5)、PSA(KLQCVDLHV)四聚物、來源於 HIVgag 之 p24-PLA HIV gag p24(gag)及其他 HIV組分、肝 炎病毒抗原' 流感病毒抗原、及選自由以下組成之群的 肽：血球凝集素、神經胺糖酸苦酶、H1N1流感病毒株之A 型流感血球凝集素HA-1、HLA-A201-FluMP(58-66)肽 (GILGFVFTL)四聚物及禽流感（HA5-1)、嗜熱梭狀芽孢桿 菌之錨定蛋白域、麻疹病毒抗原、風疹病毒抗原、輪狀病 毒抗原、巨細胞病毒抗原、呼吸道融合病毒抗原、單純范 疹病毒抗原、水痘帶狀疱疹病毒抗原、日本腦炎病毒抗 原、狂犬病病毒抗原或其組合及修飾。 在另一態樣中，該組合物進一步包含選自癌肽之抗原性 肽’該專癌肽係選自腫瘤相關抗原，包含來自以下之抗 原：白血病及淋巴瘤、神經腫瘤（諸如星形細胞瘤或神經 膠母細胞瘤）、黑色素瘤、乳癌、肺癌、頭頸癌' 胃腸腫 瘤、胃癌、結腸癌、肝癌、胰臟癌、泌尿生殖器腫瘤（諸 如子宮頸癌、子宮癌、卵巢癌、陰道癌、睾丸癌、前列腺 癌或陰莖癌）、骨腫瘤、血管瘤、或唇、鼻咽、咽及口 腔、食道、直腸、膽囊、膽管樹、喉、肺及支氣管、膀 胱、腎臟、腦及神經系統之其他部分、甲狀腺之癌症、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，該組合物進一步包含選自腫瘤相關抗原之 抗原性肽，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、6及 158138.doc -13- 201208696 12、MUC(黏蛋白）（例如 MUC-l、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、週期素 B1、週期素 D、Pmel 17 (gplOO)、GnT-V内含子V序列（N-乙醯葡萄糖胺基轉移酶V 内含子V序列）、前列腺Ca 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 普遍性突變基因產物）、GAGE(黑色素瘤抗原）1、BAGE(黑 色素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(EB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（LRP)、Bcl-2及Ki-67。在相關態樣中，DC特異 性抗體經人類化，該組合物經口途徑、鼻途徑、局部施用 或以注射形式投與人類或動物個體且注射係選自由皮下、 靜脈内、腹膜内、肌内及靜脈内組成之群。 本發明亦描述一種藉由活化一或多個樹突狀細胞（DC)而 向人類個體提供免疫刺激以便針對一或多種病毒疾病、細 菌疾病、真菌疾病、寄生蟲病、原蟲疾病及寄生蟲病及過 敏性病症進行預防、治療或其組合之方法，其包含以下步 驟.⑴鑑定需要免疫刺激以便針對一或多種選自流感、 HIV、癌症及免疫病症之群之疾病進行預防、治療或其組 合的人類個體’（ii)自人類個體分離出一或多個DC，及 (iii)用有效形成活化DC之量之組合物活化經分離之dc， 該組合物包含：抗原及佐劑，其中該佐劑包含與鞭毛蛋白 之至少一部分結合的抗樹突狀細胞（Dc)特異性抗體或其片 段，及醫藥學上可接受之載體，其中該結合物及促效劑各

158138.doc -14· S 201208696 以與另一者組合可在需要免疫刺激之人類或動物個體中有 效引起免疫反應的量包含在内；及將經活化之DC再引入 該人類個體中。 在一態樣中，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，該組合物進一步包含抗 原性肽，其選自人類免疫缺乏病毒（HIV)抗原及選自由 gag、pol及env基因組成之群之基因產物、Nef蛋白、逆轉 錄酶、線性HIV 肽（Hipo5)、PSA(KLQCVDLHV)四聚物、 來源於 HIVgag之 p24-PLA HIV gag p24(gag)及其他 HIV 組 分、肝炎病毒抗原、流感病毒抗原、及選自由以下組成之 群的肽：血球凝集素、神經胺糖酸苷酶、H1N1流感病毒 株之A型流感血球凝集素HA-1、HLA-A201-FluMP(58-66) 肽（GILGFVFTL)四聚物及禽流感（HA5-1)、嗜熱梭狀芽孢 桿菌之錨定蛋白域、麻殄病毒抗原、風疹病毒抗原、輪狀 病毒抗原、巨細胞病毒抗原、呼吸道融合病毒抗原、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、狂犬病病毒抗原或其組合及修飾。在另一態樣中’該 158138.doc •15· 201208696 組合物進一步包含選自癌肽之抗原性肽，該等癌肽係選自 腫瘤相關抗原’包含來自以下之抗原：白血病及淋巴瘤、 神經腫瘤（諸如星形細胞瘤或神經膠母細胞瘤）、黑色素 瘤、乳癌、肺癌、頭頸癌、胃腸腫瘤、胃癌、結腸癌、肝 癌、騰臟癌、泌尿生殖器腫瘤（諸如子宮頸癌、子宮癌、 印巢癌、陰道癌、睾丸癌、前列腺癌或陰莖癌）、骨腫 瘤、血管瘤、或唇、鼻咽、咽及口腔、食道、直腸、膽 囊、膽管樹、喉、肺及支氣管、膀胱、腎臟、腦及神經系 統之其他部分、甲狀腺之癌症、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，該組合 物進一步包含選自腫瘤相關抗原之抗原性肽，該等腫瘤相 關抗原係選自CEA、前列腺特異性抗原^从卜^丑尺- 2/neu、BAGE、GAGE ' MAGE 1-4、6及 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、週期素 B1、週期素D、Pmel 17(gpl00)、GnT_V 内 含子V序列（N-乙醯葡萄糖胺基轉移酶v内含子V序列）、前 列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗 原）、β-索烴素、黑色素瘤普遍性突變基因產 物）、GAGE(黑色素瘤抗原）i、BAGE(黑色素瘤抗原ρ- ΐΟ 、 c-ERB2(Her2/neu) 、 EBNA(EB 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（LRP)、Bcl-2及Ki-67。在一態樣中，DC特異性抗體經 人類化。在另一態樣中’該組合物經口途徑、鼻途徑、局 158138.doc •16- 201208696 部施用或以注射形式投與人類或動物個體。在另一態樣 中，注射係選自由皮下、靜腑& 睹 ^ Γ 靜脈内、腹膜内、肌内及靜脈内 組成之群。 【實施方式】 - 為更透徹地理解本發明之特徵及優點，現參考本發明之 - 實施方式以及隨附圖式。 雖然下文詳細討論本發明之各種實施例之製備及使用， 但應瞭解，本發明提供的許多可用性發明構想可在多種特 定情況下實施。本文討論之特定實施例僅說明製備及使用 本發明之特定方式且不限定本發明之範_。 為有助於理解本發明，下文定義許多術語。本文所定義 之術語具有本發明相關領域中之一般技術人員通常理解之 含義。諸如「一」及「該」之術語並不意欲僅指單數實 體’而疋包括其中特定實例可用於說明的一般種類。本文 之術語用於描述本發明之特定實施例，但其用法不限定本 發明’除非申請專利範圍中有概述。 如本文所用’術語「抗原呈現細胞」（APC)為能夠活化Τ 細胞之細胞且包括（但不限於）某些巨噬細胞、Β細胞及樹 突狀細胞。「樹突狀細胞」（DC)係指淋巴或非淋巴組織中 ， 所發現之形態上類似的細胞類型之多種群體之任何成員。 此等細胞之特徵在於其形態不同、表面MHC II類表現量高 (Steinman等人，Ann· Rev· Immunol. 9:271 (1991);關於該 等細胞之描述内容以引用的方式併入本文中）。如本文所 述’此等細胞可自許多組織來源分離且宜自外周血液分 158138.doc -17· 201208696 離。樹突狀細胞結合蛋白係指其受體表現於樹突狀細胞上 之任何蛋白質。實例包括GM-CSF、IL-l、TNF、IL-4、 CD40L、CTLA4、CD28及 FLT-3 配位體。 出於本發明之目的’術語「疫苗組合物」欲意謂可投與 人類或動物以便誘發免疫系統反應之組合物；此免疫系統 反應可引起抗體產生或僅引起某些細胞（詳言之抗原呈現 細胞、T淋巴細胞及B淋巴細胞）活化。疫苗組合物可為用 於預防目的或用於治療目的或兩者之組合物。如本文所 用’術語「抗原」係指任何可用於疫苗之抗原（無論其包 括完整微生物或次單位且無論其性質）：肽、蛋白質、醣 蛋白、多醣、糖脂、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，其序列經選 擇以便編碼需要由該等聚核苷酸所投與之個體表現的抗 原，在免疫技術情況下稱為DNA免疫。其亦可為一組抗 原，尤其在多價疫苗組合物情況下，其包含能夠預防若干 疾病之抗原，且其通常則稱為疫苗組合，或在組合物情況 下’其包含若干不同抗原以便預防單—疾病’例如針對_ 曰咳或流感之某些疫苗通常就是這樣。術語「抗體」係4 免疫球蛋白，無論天然或部分或完全人工產生⑼如』 組）。抗體可為單株或多株。在一些情況下，抗體可為^ 類免疫球蛋白之成員或免疫球蛋白種類組合，包括邮 IgM、IgA、IgD及 IgE。 術語「佐劑」或「免疫佐劑」可互換使用，且係# 強、加強或強化主體對抗原(例如疫苗之一部分的抗原 158138.doc

201208696 免疫反應的物質》 如本文所用，術語「鞭毛蛋白」係指任何來源（包括（但 不限於）任何細菌種類）之鞭毛蛋白。鞭毛蛋白可來自沙門 氏菌（Salmonella)種。亦特別涵蓋該鞭毛蛋白之片段變 異體、類似物、同源物或衍生物及其組合。本文所述之各 片段、變異體、類似物、同源物或衍生物可與特定細菌種 類（例如沙門氏菌）之野生型鞭毛蛋白5〇%、55%、6()%、 65〇/。、70%、75%、80%、85%、9〇%、95%、97%、州/❶或 99%—致。 術語「基因」用於係指功能蛋白、多肽或肽之編碼單 位。如熟習此項技術者應瞭解，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，包括已 由人工變異者。經純化之基因、核酸、蛋白質及其類似物 用於指該等在鑑定時已與至少一種一般相關的污染核酸或 蛋白質分離之實體。 如本文所用，術語「核酸」或「核酸分子」係指聚核苷 酸’諸如脫氧核糖核酸（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、煎 切、.核酸内切酶作用及核酸外切酶作用中之任一者產生之 片段。核酸分子可由單體構成，該等單體為天然存在之核 苷酸（.諸如DNA及RNA)或天然存在之核苷酸類似物（例如天 然存在之核苷酸的α-對映異構形式）或兩者之組合。經修 飾之核苷酸可在糖部分及/或嘧啶或嘌呤鹼基部分具有變 異。糖修飾包括例如用鹵素、烷基、胺及疊氮基置換一或 158138.doc -19- 201208696 多個羥基，或糖可經官能化成為醚或酯。此外，整個糖部 分可經空間上及電子上類似的結構（諸如氮雜糖及碳環糖 類似物）置換。鹼基部分中之修飾實例包括烷基化嘌呤及 嘧啶、醯化嘌呤或嘧啶，或其他熟知之雜環取代。核酸單 體可由磷酸二酯鍵或該等鍵聯之類似物連接。磷酸二酯鍵 聯之類似物包括硫代磷酸酯、二硫代磷酸酯、硒代磷酸 酯、二硒代磷酸酯、苯胺硫代磷酸酯、苯胺磷酸酯 (phosphoranilidate)、胺基磷酸酯及其類似物。術語「核酸 分子」亦包括所謂「肽核酸」，其包含天然存在或經修飾 之核酸鹼基連接於聚醯胺主鏈。核酸可為單股或雙股。 如本案中所用，術語「胺基酸」意謂蛋白質所包含之天 然存在之胺基羧酸之一。如本文所述，術語「多肽」係指 無論天然或合成產生之由肽鍵連接之胺基酸殘基之聚合 物。少於約10個胺基酸殘基之多肽通常稱為「肽」。「蛋白 質j為包含一或多個多肽鏈之巨分子。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 代基可由產生蛋白質之細胞添加至蛋白質中，減細胞類 型而改變。在本文中蛋白質係根據其胺基酸主鏈結構定 義；諸如碳水化合物基團之取代基一般不予說明，但仍可 存在。 如本文所用，術語「活體内」係指於身體内。本案令所 用之術語「活體外」應理解為指示在非生命系統中進行操 作0 如本文所用’術語「治療，音謂仅y 。縻」葸明任何投與本發明之化合 158138.doc -20- 201208696 物且包括（i)抑制正經歷或顯示疾病之病理或症狀之動物之 疾病（亦即阻止病理及/或症狀之進一步發展），或（2)改善 正經歷或顯示疾病之病理或症狀之動物之疾病（亦即逆轉 病理及/或症狀）。 本發明描述以直接針對抗原呈現細胞之抗體的標靶佐劑 為主之新穎疫苗佐劑。本發明發現藉由直接連接直接針對 DC標靶疫苗之佐劑（例如TLR配位體）可增強疫苗功效。如 本文所示，本發明之組合物及方法廣泛適用於所有Dc標 把疫田且可推廣用於製造具有意想不到之新穎特性之佐 劑。直接連接於佐劑之疫苗已熟知，例如開發連接於Cp<3 之Hep B疫苗（Dynavax)或連接於鞭毛蛋白之Flu抗原 (Vaxigen)。本發明為一種佐劑及製造與使用該佐劑之方 法’其中該佐劑與DC標靶疫苗結合（例如抗dc受體抗體與 抗原融合）。本發明之幾個態樣具有優於先前技術之優 點’包括節省劑量（藉由傳送直接針對於實際上接受抗原 之抗原呈現細胞之佐劑），出乎意料地，此發現提供一種 使佐劑之促效劑活性嚴格依賴所標靶DC受體類型的方 法。 連接DC標靶之佐劑連接體a(SEQ ID NO: 1):載體C959 編碼 rAB-pIRES2[mAnti-DCIR_9E8一H-LV-hIgG4H-C-Flex- vl-Flgn-l-Flgn-2]。 158138.doc -21- 201208696

SSGLRINS VRELAVC

QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDDKRY NPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVWGAGTTV TVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSWMHEALHmYTQKSLSLSLGKASQTPTNTISVTPTNNSTPmNSNPKPNPASIEKL 4SAKDDAAGQAIAP4RFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQR ^QSANSTNSQSDLDSIQAEITQRLNEroRVSGQTQFNGVKVLAQDNTLTIQVG ANDGETTO1DLK01NSOTLGLDSLNVO^.SOPELAEAAAKTTENPLOKIDAALAOVDALRS DLrTAVONRFNSAlTNLGNTVNNLSEARSRIEDSDYATEVSNMSRAOILOAS 粗體為階段2鞭毛蛋白[腸道沙門氏菌（Salmonella enterica)] gb|AAL30512.1|AF425736_l 殘基 14-161 之N端部 分。 下劃線為階段2鞭毛蛋白[腸道沙門氏菌]gb|AAL30512.1| AF425736_1 殘基 405-484 之 C 端部分。 斜體為gb|AAT79550.1|纖維素體錨定骨架蛋白B前驅體 [溶纖維素擬桿菌（Bacteroides cellulosolvens)]之柔性連接 子序列。 胺基端直至第一 AS序列為與-hIgG4H恆定區融合之小鼠 抗DCIR_9E8可變區之重鏈。呈粗斜體之AS序列為構築表 現載體之連接序列。 此載體在與合適L鏈表現載體共轉染於哺乳動物細胞（例 如CHO-S細胞）中時，引導連接於以鞭毛蛋白為主之佐劑 的DC標靶劑之典型實施例的有效分泌。 C1099編碼小鼠抗DCIR_9E8_H-LV-hIgG4H-C-錨定蛋白-v2-Flgn-l-Flgn-2](SEQ ID NO: 2)。 158138.doc -22- s 201208696

QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDDKRY

NPSLKSIILTISKDTSSNQVPLKITIVDTADAATYYCARSSHYYGYGYGGYFDVWGAGTTV

TVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL

QSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPS

VFLFPPKPKDTLM1SRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST

YRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEmSKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGIOlSSEDrgPJMm/GDW/lDG励

LRSATLTEEKILNADTDGNGTVNSTDLNYLXKYILRVISVFPAEGNKPPTPTPTKTPVATPSPTQP

IF7?SFJO)FT4SIERLSSGLRINSAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQT

TEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEroRVSGQTQFNGV

KVT.AODNTLTIOVfiANPGETroTDLKOlNSOTLGLDSLNVO^^OPELAEAAAKTTENPL

OKTDA ALAQVDALRSDiriA VONRFNS A ITNLGNTVNNT^EARSRTEDSDYATEVSNMSR A

OILOAS 斜體為|丫？_〇〇1〇36450.1|〇1-1>-阿拉伯呋喃糖苷酶8[嗜熱 梭狀芽抱桿菌（Clostridium thermocellum)ATCC 274〇5丨殘基 166-274-其為在其他域之間融合時完全起結合（例如黏結蛋 白（cohesin)-抗原融合）作用之錨定蛋白域（大多數其他錨定 蛋白域為C端，且其代表在最初黏結蛋白-錨定蛋白申請時 未主張之新發明）。 粗體為階段2鞭毛蛋白[腸道沙門氏菌]gb|AAL30512.1| AF425736_1殘基14-161之N端部分。 下劃線為階段2鞭毛蛋白[腸道沙門氏菌]gb|AAL30512.1| AF425736_1 殘基 405-484 之 C 端部分。 呈粗斜體之AS序列為構築表現載體之連接序列。 此載體在與合適L鏈表現載體共轉染於哺乳動物細胞（例 如CHO-S細胞）中時，引導連接於以鞭毛蛋白為主之佐劑 且連接於黏結蛋白-抗原（經由錨定蛋白域）的DC標靶劑之 典型實施例的有效分泌。在相關實施例中，任何所需抗原 亦可代替錨定蛋白域直接融合。 -23· 158138.doc 201208696 C566大腸桿菌·ρΕΤ28載體編碼所表現之[黏結蛋白-varl-FluMl-6xHis](SEQ ID NO: 3)

N©U)AVRIKVDTVNAKPGDTV^VRFSGIPSKGIANADFVYSYDPNVLEIIEIKPGELIVDP

NPIXSFDTAVYPDRKMIVFLFAEDSGTGAYAITKDGVFATIVAKVKEGAPNGLSVIKFVEV

GGFANNDLVEOKTOFFDGGVNVGDTTEPAlPITPVlTPTlTDDLDAASLLTEVETYVLSnP

SGPLKAEIAORLEDWAGKNTOl^VLMEWLKTRPILSPLTKGILGFVFrLTVPSERGLORRR

FVONALNGNGDPNNMDKAVKLYRKLKREITFHGAKEIALSYSAGALASCMGL1YNRMGA

VTTCVAFGLVCATCEOIADSOHRSHROMVTTTNPLIRHENRMVLASTTAKAMEOMAGSS

EOAAEAMDIASOAROMVOAMRTIGTHPSSSAGLKDDLLENLOAYOKRMGVOMORFKLE

粗體為黏結蛋白域，展示加下劃線之單個C變為A維持 錨定蛋白結合及3個C殘基（粗體-加下劃線）允許TLRL加合 物存在位點特異性順丁烯二醯亞胺鍵聯。流感Ml抗原序 列加有下劃線。呈粗斜體之AS序列為構築表現載體之連接 序列。 在相關形式中，任何具有游離cys殘基之黏結蛋白·抗原 可方便地用TLR7-L化合物修飾且與任何抗DC受體-錨定蛋 白-抗原疫苗連接。 C1450 編碼小鼠抗0(：111_9£8—1^1^-114〇411-(：416乂^1-vlC2(SEQ ID NO: 4)：

QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGLEWLAHIYWDDDKRYNPS

LKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGGYFDVWGAGTTVTVSSAK

TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS

SWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDT

LMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQD

WLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYT

QKSLSLSLGKASQTPTmiSVTPTmSTPTNNSNPKPNPASCQTPTNTISVTPimSTPTNNSNPKPCP

AS 粗體為攜帶兩個c殘基（加下劃線）之柔性連接子序列用 158138.doc -24·

S 201208696 於位點特異性連接TLRL加合物。此載體在與合適L鏈表現 載體共轉染於哺乳動物細胞（例如CHO-S細胞）中時，引導 連接於以化學試劑為主之佐劑的DC標靶劑之典型實施例 的有效分泌。在相關實施例中，其他載體可使用與C端密 碼子直接融合的任何所需抗原來製備。呈粗斜體之AS序列 為構築表現載體之連接序列。斜體為柔性連接子（前述）。 C1180引導表現6xHis-黏結蛋白-Flgn-卜Flgn-2融合蛋白 (SEQ ID NO: 5)之哺乳細胞之表現：

LOnSHHHHHHDDLDAVRIKVDTVNAKPGDTVRJPVRFSGlPSKGIANCDFVYSYDPNVLElIEIEPG D1IVDPNPDKSFDTA VYPDRK1IVFLFAEDSGTGA YA1TKDGVFA mAKVKEGAPNGLSVIKFVEVGG FANNDL VEQKTQFFDGGVNVGDTTEPA TPTTPm'PTJTDDLDAASiERLSSGLRiNSAKDOAAG QAIANKFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSD LDSIQAEITQRLNEroRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLG T.nST.NVOASOPET.AEAAAKTTENPLOKlDAALAOVDALRSDLGAVONRFNSAlTNLGNTVNN L 吓 ARSRIEDSDYATEVSNMSRAOELOAS 斜體為黏結蛋白域。粗體為階段2鞭毛蛋白[腸道沙門氏 菌]gb|AAL30512.1|AF425736_l 殘基 14-161 之 N端部分。階 段2鞭毛蛋白[腸道沙門氏菌]gb|AAL30512.1|AF425736_W^ 基405-484之C端部分加有下劃線。呈粗斜體之AS序列為構 築表現載體之連接序列。此形式允許功能Flgn連接於任何 抗DC受體-錨定蛋白-抗原疫苗。 具有不同DC特異性抗體或片段之構築體的一些其他非 限制性實例呈現於下文中： 抗CLEC_6_9B9.2G12_Hv-V-hIgG4H-C(SEQ ID NO: 6): 158138.doc -25- 201208696

ATGGGCAGGCTTACnCTTCATTCTTGCTACTGATTGTCCCTGCATATGTCCTGTCCCAGGT

TACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTCTGACCTGT

TCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGAGTGTAGGCTGGATTCGTCAGCCTTC

AGGGAAGGGTCTGGAGTGGCTGGCTCACATTTGGTGGAATGATGATAAGTACTATAATCC

AGTCCTGAAAAGCCGGCTCACAATCTCCAAGGAGACCTCCAACAACCAGGTATTCCTCAA

GATCGCCAGTGTGGTCTCTGCAGATACTGCCACATACTACTGTGCTCGATTCTATGGTAAC

TGTCTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCGGCCAAAACAaagggcccA

TCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCT

GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGA

CCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG

CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGITGAGTCCAAATATGGTCCCCCATGCCC

ACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC

AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC

GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC

CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAG

GTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGC

CTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCG

GAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACA

GCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGA

TGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGC

TAGCTGATTAATTAA 抗 CLEC_6一9B9.2G12_Hv-V-hIgG4H-C(SEQ ID NO: 7):

MGRLTSSFLLLIVPAYVLSQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMSVGWIRQP

SGKGLEWLAHIWWNDDKYYNPVLKSRLTISKETSNNQVFLKIASWSADTATYYCARFYGNC

LDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTXVDKRVESKYGPPCPPCPAPE feggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqf

NSTYRVVSVLIYLHQDWLNGKEYKOCVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

FSCSVMHEALHNHYTQKSLSLSLGKAS 抗 CLEC_6_9B9.2G12_Kv-V-hIgGK-C(SEQ ID NO: 8): 158138.doc -26- s 201208696

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGTTTTCAAGGTACCAGATGTGA

TATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATC

AGTTGCAGGGCAAGTCAGGACATTAGCAATTATTTAAACTGGTATCAGCAGAAACCAGAT

GGAACTGTTAAACTCCTGATCTACTACACATCAATATTACAATTAGGAGTCCCATCAAGAT

TCAGTGGCAGTGGGTCTGAAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAG

ATATTGCCACTrACrnTGCCAACAGGGTGATTCGCTTCCATTCACGTTCGGCTCGGGGAC

AAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGrTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 CLEC_6_9B9.2G12_Kv-V-hIgGK-C(SEQ ID NO: 9):

MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGT

VKLLIYYTSILQLGVPSRFSGSGSETDYSLTISNLEQEDIATYFCQQGDSLPFTFGSGTKLEIKRT

VAAPSWIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST

YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 ASGPR_49Cll_7H-LV-hIgG4H-C(SEQ ID NO: 10):

ATGAGAGCGCTGATTCTTTTGTGCCTGTTCACAGCCTITCCTGGTATCCTGTCTGATGTGCA

GCTTCAGGAGTCAGGACCTGACCTGGTGAAACCTTCTCAGTCACTTTCACTCACCTGCACT

GTCACTGGCTACTCCATCACCAGTGGTTATAGCTGGCACTGGATCCGGCAGTTTCCAGGAA

ACAAACTGGAATGGATGGGCTACATACTCTTCAGTGGTAGCACTAACTACAACCCATCTCT

GAAAAGTCGAATCTCTATCACTCGAGACACATCCAAGAACCAGTTCTTCCTGCAGTTGAAT

TCTGTGACTACTGAGGACACAGCCACATATTTCTGTGCAAGATCTAACTATGGTTCCTTTG

CTTCCTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACAACGGGCCCATCCGT

CTTCCCCCTGGCGCCCTCiCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTG

GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC

GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGG

TGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGC

CCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCT

GCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTrCCTGTTCCCCCCAAAACCCAAGG

ACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGG

AAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGA

CAAAGCCGCGGGAGGAGCAGTrCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC

TGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC

CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGT

ACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGG

TCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA -27- 158138.doc 201208696

ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAG

GCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTrCTCATGCTCCGTGATGCA

TGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGC

TGATTAATTAA 抗 ASGPR_49Cll_7H-LV-hIgG4H-C(SEQ ID NO: 11):

MRALILLCLFTAFPGILSDVQLQESGPDLVKPSQSLSLTCTVTGYSITSGYSWHWIRQFPGNKLE

WMGmFSGSTNVWSLKSRISITRDTSKNQFFLQLNSVTTEDTATYFCARSNYGSFASWGQGT

LVTVSAAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ

SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLF

PPKPKDTLMISRrPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSV

LTVLHQDWLNGKEYKCKVSNKGLPSSBE^SKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYK1TPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKAS 抗 ASGPR_49Cll_7K-LV-hIgGK-C(SEQ ID NO: 12):

ATGGATTTTCAAGTGCAGATTTTCAGCTTCCTGCTAATCAGTGCCTCAGTCATAATATCCA

GAGGACAAATTGTTCTCACCCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGT

CACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTCACATGCACTGGTACCAGCAGAAGTC

AGGCACTTCCCCCAAAAGATGGATTTATGACACATCCAGACTGGCTTCTGGAGTCCCTGCT

CGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAATCAGCAGCATGGAGGCTG

AAGATGCTGCCACTTATTACTGCCAGCAGTGGAGTAGTCACCCATGGTCGTTCGGTGGAGG

CACCAAACTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCA

GAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG

AGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCITCAACAGGGGAGAGTGTTAG 抗 ASGPR_49Cll_7K-LV-hIgGK-C(SEQ ID NO: 13):

MDFQVQIFSFLLISASVIISRGQIVLTQSPAIMSASPGEKVTMTCSASSSVSHMHWYQQKSGTSP

KRWIYDTSRLASGVPARFSGSGSGTSYS^SSMEAEDAATYYCQQWSSHPWSFGGGTKLEIK

RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 ASGPR_4G2.2_Hv-V-hIgG4H-C(SEQ ID NO: 14): 158138.doc -28- s 201208696

ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCACAGA tccagttggtgcagtctggacctgagctgaagaAgcctggagagacagtcaagatctcct

jCCTATTTGCA 3GGGGGATTTT

GCAAGGCTTCTGGGTATACCTTCACAAACrATGGAATGAACTGGGTGAAGCAGGTTCCAG GAAAAGGTTTAAGGTGGATGGGCTGGATGGACACCTTCACTGGAGAGCCAACATATGCTG ATGACTTCAAGGGACGGTrTGCCTTCTCnTGGAAACCTCTGCCAGCACTGCCl GATCAACAGCCTCAAAAATGAGGACACGGCTACTTATTTCTGTGCAAGAGi ACGACTCAACTACITTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCAGCCAAA ACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACT CAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTA CTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGC AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT CCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCC CCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT CTGGGTAAAGCTAGCTGATTAATTAA 抗 ASGPR_4G2.2_Hv-V-hIgG4H-C(SEQ ID NO: 15)

MAWVWTLLFLMAAAQSAQAQIQLVQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQVP

GKGLRWMGWMDTFTGEPTYADDFKGRFAFSLETSASTAYLQINSLKNEDTATYFCARGGILR

LNYFDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL

TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP

APEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPRE

EQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗 ASGPR—4G2.2_Kv-V-hIgGK-C(SEQ ID NO: 16):

ATGAAGTTTCCTTCTCAACTTCTGCTCTTACTGCTGTTTGGAATCCCAGGCATGATATGTGA

CATCCAGATGACACAATCTTCATCCTCCTTTTCTGTATCTCTAGGAGACAGAGTCACCATT

ACTTGCAAGGCAAGTGAGGACATATATAATCGGTTAGGCTGGTATCAGCAGAAACCAGGA

AATGCTCCTAGGCTCTTAATATCTGGTGCAACCAGTTTGGAAACTGGGGTTCCTTCAAGAT •29- 158138.doc 201208696

TCAGTGGCAGTGGATCTGGAAAGGATTACGCTCTCAGCATTACCAGTCTTCAGACTGAAG

ATCTTGCTACTTATTACTGTCAACAGTGTTGGACTTCTCCGTACACGTTCGGAGGGGGGAC

CAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 ASGPR_4G2.2_Kv-V-hIgGK-C(SEQ ID NO: 17):

MKFPSQLLLLLLFGIPGMICDIQMTQSSSSFSVSLGDRVTrrCKASEDIYNRLGWYQQKPGNAPR

LLISGATSLETGVPSRFSGSGSGKDYALSITSLQTEDLATYYCQQCWTSPYTFGGGTKLEIKRTV

AAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTY

SLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 ASGPR_5F10H-LV-hIgG4H-C(SEQ ID NO: 18):

ATGGGATGGAGCTGGATCTTTCTCTTTCTCTTGTCAGGAACTGGAGGTGTCCTCTCTGAGG

TCCAGCTGCAACAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTrCAGTGAAGATGTCCT

GCAAGGCTTCTGGATACACCTTCACTGACTACTACATGAAGTGGGTGAAGCAGAGCCATG

GAAAGAGCCTTGAGTGGATTGGAGATATTAATCCTAACTATGGTGATACTTTCTACAACCA

GAAGTTCGAGGGCAAGGCCACATTGACTGTAGACAAATCCTCCAGGACAGCCTACATGCA

GCTCAACAGCCTGACATCTGAGGACTCTGCAGTCTATTATTGTGGAAGAGGGGACTATGG

ATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACAAAGGG

CCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGACjCACCTCCGAGAGCACAGCCGCCCTG

GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCC

CTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCA

GCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAG

ATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCAT

GCCCACCCTGCCCAGCACCTGAGITCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAA

ACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGT

GAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAA

TGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCT

CACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA

AGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCC

ACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGAC

CTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCA

GCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC

TACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCC

GTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTA

AAGCTAGCTGA •30· 158138.doc 201208696 抗 ASGPR__5F10H-LV-hIgG4H-C(SEQ ID NO: 19):

MGWSWIFLFLLSGTGGVLSEVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMKWVKQSHG

KSLEWIGDINPNYGDTFYNQKFEGKATLTVDKSSRTAYMQLNSLTSEDSAVYYCGRGDYGYF

DVWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV

HTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEF

EGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN

STYRWSVLTVLHQDWLNGKEYKCKVSlSIKGLPSSIEmSKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTFPVLDSDGSFFLYSRLTVDKSRWQEGNVF

SCSVMHEALHNHYTQKSLLSLGKAS 抗 ASGPR—5F10K-LV-hIgGK-C(SEQ ID NO: 20):

ATGGAGACACATTCTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGTTGAAGGAG

ACATTGTGATGACCCAGTCTCACAAATTCATGTCCACATCAGTAGGAGACAGGGTCAGCA

TCACCTGCAAGGCCAGTCAGGATGTGGGTACTGCTGTAGCCTGGTATCAACAGAAACCAG

GGCAATCTCCTAAACTACTGATTTACTGGGCATCCACCCGGCACACTGGAGTCCCTGATCG

CTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATTAACAATGTGCAGTCTGAA

GACTTGGCAGATTATTTCTGTCAGCAATATAGCAGCAATCCGTACATGTTCGGAGGGGGG

ACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG

ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAG

AGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGA

GTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGA

GCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGA

GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 ASGPR_5F10K-LV-hIgGK-C(SEQ ID NO: 21): methsqvfvymllwlsgvegdivmtqshkfmstsvgdrvshckasqdvgtavawyqqkpg

QSPKLLIYWASTRHTGVPDRFTGSGSGTDFTLTINNVQSEDLADYFCQQYSSNPYMFGGGTKL

EIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDMALQSGNSQESVTEQD

SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗ASGPRlHll_H-V-hIgG4H-C(SEQ ID NO: 22):

ATGGGATGGAGCTGGATCTTTCTCTTTCTCCTGTCAGGAACTGCAGGTGTCCTCTCTGAGG

TCCAGCTGCAACAGTCTGGACCTGAGTTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCTG

CAAGACTTCTGGATACACATTCACTGAATACACCATGCACTGGGTGAGGCAGAGCCATGG

AAAGAGCCTTGAGTGGATTGGAGGTATTAATCCTATCAATGGTGGTCCTACCTACAACCAG

AAGTTCAAGGGCAAGGCCACATTGACTGTTGACAAGTCCTCCAGCACAGCCTACATGGAG

CTCCGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGATGGGACTATGGTA

GTCGAGATGTTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAAAA -31- 158138.doc 201208696

CGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAG

CCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTACCGGTGACGGTGTCGTG

GAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA

CTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACA

CCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAAT

ATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCT

GTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTG

GTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGITCAACTGGTACGTGGATGGCGTG

GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGT

GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAACiGAGTACAAGTGCAA

GGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCA

GCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCA

GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGA

GAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG

CTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGT

CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCC

CTGTCTCTGGGTAAAGCTAGCTGA 抗ASGPRlHll_H-V-hIgG4H-C(SEQ ID NO: 23):

MGWSWIFLFLLSGTAGVLSEVQLQQSGPELVKPGASVKISCKTSGYTFTEYIMHWVRS

HGKSLEWIGGINPINGGPTYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARWDYGS

RDVMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCP

PCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTK

PREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSPPLYSRLTVDKSRW

QEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗ASGPRlHllK-LV-var2-hIgGK-C(SEQ ID NO: 24):

ATGGAATCACAGACTCTGGTCTTCATATCCATACTGCTCTGGTTATATGGTGCTGATGGGA

ACATTGTAATGACTCAATCTCCCAAATCCATGTCCATGTCAGTAGGGGAGAGGGTCACCTT

GAGCTGCAAGGCCAGTGAGAATGTGGGAACTTATGTATCCTGGTATCAACAGAGACCAGA

ACAGTCTCCAAAACTGCTGATATACGGGGCATCCAACCGGTACACTGGGGTCCCCGATCG

CTTCACAGGCAGTCKjATCTGCAACAGATTTCACTCTGACCATCAGCAGTGTGCAGGCTGAG

GACCTTGCAGATTATCACTGTGGACAGACTTACAGCTATATATTCACGTTCGGCTCGGGGA

CAAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGA

TGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGA

GAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGT

GTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGC

AAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGC

TCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTrAG 158138.doc -32- s 201208696 抗ASGPRlHllK-LV-var2-hIgGK-C(SEQ ID NO: 25):

METHSQVFVYMLLWLSGVECMVMTQSPKSMSMSVGERVTLSCKASENVGTYVSWYQQRPE

QSPKLLIYGASNRYTGVPDRFTGSGSATDFTLTISSVQAEDLADYHCGQTYSYIFTFGSGTKLEI

KRTVAAPSWDFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK

DSTYSLSSTLTLSKADYEKHKVYACEV1HOGLSSPVTXSFNRGEC 抗CDld_2B5.3G10_H-V-hIgG4H-C(SEQ ID NO: 26):

. ATGGGATGGAGCCGGATCTTTCTCTTCCTCCTGTCAATAACTGCAGGTGTCCATTGCCAGG

' TCCAGGTGCAGCAGTCGGGACCTGAGTTGGTGAAGCCTGGGGCCTCAGTGAAGATTTCCT

GCAAAGCCTCTGGCGACGCATTCAGTAGTTCTTGGATGAACTGCMjTGAAGCAGAGGCCTG GACAGGGTCTTGAGTGGATTGGACGGATTTATCTTGGAGATGGAGATATTAATTACAATG GGAAGTTCAAGGGCAGGGCCACACTGACTGCAGACAAATCCTCCAGCACAGCCTACATGC AGCTCAGCAGCCTGACCTCTGTGGACTCTGCGGTCTATTTCTGCGCGAGGCAGCTCGGGCT ATGGTATGTTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAAAACA AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCC GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCA GGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACT CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCA ACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTC CCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT CTGGGTAAAGCTAGCTGA 抗 CDld_2B5.3G10_H-V-hIgG4H-C(SEQ ID NO: 27): mgwsriflfIlsitagvhcqvqvqqsgpelvkpgasvkisckasgdafssswmnwvkqrpgq

GLEWIGRIYLGDGDINYNGKFKGRATLTADKSSSTAYMQLSSLTSVDSAVYFCARQLGLWYV

MDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE

FEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE^SKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

FSCSVMHEALHNHYTQKSLSLSLGKAS 33· 158138.doc 201208696 抗 CDld_2B5.3G10_K-V-hIgGK-C(SEQ ID NO: 28):

ATGAGTGTGCCCACTCAGGTCCTGGGGTTGCTGCTGCTGTGGCTTACAGGTGCCAGATGTG

ACATCCAGATGGCTCAGTCTCCAGCCTCCCTATCTGCATCTGTGGGAGAAACTGTCACCAT

CACATGTCGAGCAAGTGAGAATATTTACAGTTATTTAGCATGGTATCAGCAGAAACAGGG

AAAATCTCCTCAGCTCCTGGTCTATAATGCAAAAACCTTAGCAGAAGGTGTGCCATCAAG

GTTCAGTGGCAGTGGATCAGGCACACAGTTTTCTCTGAAGATCAACAGCCTGCAGCCTGA

AGATTrTGGGAGTTATTACTGTCAACATCATTATGGTTTTCCGTGGACGTTCGGTGGAGGC

ACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG

ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAG

AGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGA

GTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGA

GCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGA

GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗CDld_2B5.3G10_K-V-hIgGK-C(SEQ ID NO: 29):

MSVPTQVLGLLLLWLTGARCDIQMAQSPASLSASVGEIVnTCRASENIYSYLAWYQQKQGKS

PQLLVYNAKTLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYYCQHHYGFPWTFGGGTKLEIK

RTVAAPSVFEFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 CDld_2H11.2G5_H-V-hIgG4H-C(SEQ ID NO: 30):

ATGAACTTCGGGCTCAGCTTGATTTTCCTTGTCCTCATTTTAAAAGGTGTCCAGTGTGAGGT

GCAGCTGGTGGAGTCTGGGGGAGACTTAGTGAAGCCTGGAGGGTCCCTGAAACTCTCCTG

TGCAGCCTCTGGATTCACTrTCAGTAGCTATGGCATGTCITGGGTTCGCCAGACTCCAGAC

AAGAGGCTGGAGTGGGTCGCAGTCATTAGTAGTGGTGGAAGTrCCACCTTCTATCCAGAC

AGTGTGAAGGGGCGAnCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAA

ATGAGCAGTCTGAAGTCTGAGGACACAGCCGTGTATTACTGTTCAAGAGGAGGTTACTAC

TTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCGCAGCCAAAACAAAGGGCCCA

TCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCT

GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGA

CCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG

CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC

ACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC

AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC

GTCCTGCACCAGGACIXjGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC

CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAG

GTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGC

158138.doc ·34· S 201208696

CTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCG

GAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACA

GCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGA

TGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGC

TAGCTGA 抗 CDld_2H11.2G5_H-V-hIgG4H-C(SEQ ID NO: 31):

MNFGLSLIFLVLILKGVQCEVQLVESGGDLVKPGGSLKLSCAASGFTFSSYGMSWVRQTPDKR LEAWAVISSGGSSTFYPDSVKGRFnSRDNAKNTLYLQMSSLKSEDTAVYYCSRGGYYFDYW ' GQGTTLTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AX^QSSGLYSLSSWTWSSSLGTKIYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR WSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV MHEALHNHYTQKSLSLSLGKAS 抗 CDld_2H11.2G5_K-V-hIgGK-C(SEQ ID NO: 32):

ATGAGGTTCCAGGTTCAGGTTCTGGGGCTCCTTCTGCTCTGGATATCAGGTGCCCAGTGTG

ATGTCCAGATAACCCAGTCTCCATCrrATCTTGCTGCATCTCCTGGAGAAACCATTACTATT

AATTGCAGGGCAAGCAAGACCATTAGCAAATATTTAGCCTGGTATCAAGAGAAACCTGAG

AAAACTGATAAGCTTCITATCTACTCTGGATCCACTTTGCAATCTGGAATTCCATCAAGGT

TCAGTGGCAGTGGATCTGGTACAGATTTCACTCTCACCATCAGTGGCCTGGAGCCTGAAGA

TTTTGCAATGTATTACTGTCAACAGCATAATGAATACCCGTGGACGTTCGGTGGAGGCACC

AAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATG

AGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGA

GGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGT

CACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 CDld_2H11.2G5_K-V-hIgGK-C(SEQ ID NO: 33):

MRFQVQVLGLLLLWISGAQCDVQITQSPSYLAASPGETITINCRASKTISKYLAWQEKPEKTD

KLLIYSGSTLQSGIPSRFSGSGSGIDFTLnSGLEPEDFAMYYCQQHNEYPWTFGGGTKLEIKRT

VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST

YSLSSILTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 CD40_llB6.1C3_H-LV-hIgG4H-C(SEQ ID NO: 34): •35- 158138.doc 201208696

ATGGGATGGAGCTGGATCTTTCTCTTTCTCCTGTCAGGAACTGCAGGTGTCCTCTCTGAGG

TCCAGCTGCAACAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCT

GCAAGGCTTCTGGTTACTCATTCACTGGCTACTACATGCACTGGGTGAAGCAAAGCCATGT

AAAGAGCCTTGAGTGGATTGGACGTATTAATCCTTACAATGGTGCTACTAGCTACAACCAG

AATTTCAAGGACAAGGCCAGCTTGACTGTAGATAAGTCCTCCAGCACAGCCTACATGGAG

CTCCACAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGAGGACTACGTCT

ACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCAGCCAAAACGAAGGGCCCATCCGTCT

TCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGT

CAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGG

CGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTG

ACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCC

AGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGC

CCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGAC

ACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAA

GACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACA

AAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG

CACCAGGACTGGfCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCG

TCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTAC

ACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC

AAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAA

CAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGG

CTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCAT

GAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCT

GA 抗 CD40_llB6」C3_H-LV-hIgG4H-C(SEQ ID NO: 35):

MGWSWIFLFLLSGTAGVLSEVQLQQSGPELVKPGASVKISCKASGYSFTGYYMHWVKQSHVK

SLEWIGRINPYNGATSYNQNFKDKASLTVDKSSSTAYMELHSLTSEDSAVYYCAREDYVYWG

QGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYQPPCPPCPAPEFEGGPS

VFLFPPKPKDTIAIISRTPEWCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVyTLPPSQEEMTICNQVS

LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV

MHEALHNHYTQKSLSLSLGKAS 抗 CD40一 11B6.1C3一K-LV-hIgGK-C(SEQ ID NO: 36):

ATGAAGTTGCCTGTTAGGCTGTTGGTGCTGATGTTCTGGATTCCTGCTTCCAGCAGTGATGT

TGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTT

GCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTACATTGGTACCTGCA

GAAGCCAGGCCAGTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACCGAITTTCTGGGGTC

CCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCGCACTCAAGATCAGTAGAGTG •36- 158138.doc 201208696

GAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAAGTACACATGTrCCGTGGACGTTCG

GTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCrGCACCATCTGTCTTCATCTTCCC

GCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTC

TATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCC

CAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCA

GGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 CD40_llB6_lC3_K-LV-hIgGK-C(SEQ ID NO: 37):

LVLMFWIPA IYKVSNRFS EIKRTVAAP： ISKDSTYSLS

PASSSDWMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQK PGQSPKLLIYKVSNRFSGWDRFSGSGSGTDFALKISR\^EAEDLGVYFCSQSTHWWTFGGGTK

SVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ I^SILTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 CD40—12B4.2C10_H-LV-hIgG4H-C(SEQ ID NO: 38)

ATGGAATGGAGTTGGATATTTCTCTTTCTTCTGTCAGGAACTGCAGGTGTCCACTCTGAGG

TCCAGCTGCAGCAGTCTGGACCTGAGCTGGTAAAGCCTGGGGCTTCAGTGAAGATGTCCT

GCAAGGCTTCTGGATACACATTCACTGACTATGTTTTGCACTGGGTGAAACAGAAGCCTGG

GCAGGGCCTTGAGTGGATTGGATATATTAATCCTTACAATGATGGTACTAAGTACAATGAG

AAGTTCAAAGGCAAGGCCACACTGACTTCAGACAAATCCTCCAGCACAGCCTACATGGAG

CTCAGCAGCCTGACCTCTGAGGACTCTGCGGTCTATTACTGTGCAAGGGGCTATCCGGCCT

ACTCTGGGTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAA

AACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCAC

AGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA

CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTC

TACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCT

GCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATAT

GGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGT

TCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGT

CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT

CAGCCTGACCTGCCTGGTCAAAGGCITCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG

CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTGCGACGGCTC

CTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTT

CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTG

TCTCTGGGTAAAGCTAGCTGA -37- 158138.doc 201208696 抗 CD40_12B4.2C10_H-LV-hIgG4H-C(SEQ ID NO: 39):

MEWSWIFLFLLSGTAGVHSEVQLQQSGPELVKPGASVKMSCKASGYTFTDYVLHWVKQKPG

QGLEWIGYINPYNDGTKYNEKFKGKATLTSDKSSSTAYMELSSLTSEDSAVYYCARGYPAYSG

YAMDYWGQGTSVTVSSAKTKGPSWPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL

TSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCP

APEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPRE

EQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIE^SKAKGQPREPQVYTLPPSQE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗 CD40_12B4.2C10_K-LV-v2-hIgGK-C(SEQ ID NO: 40)：

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGTTTTCAAGGTACCAGATGTGA

TATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATC

AGTTGCAGGGCAAGTCAGGACATTAGCAATTATTTAAACTGGTATCAGCAGAAACCAGAT

GGAACTGTTAAACTCCTGATCTACTACACATCAAGATTACACTCAGGAGTCCCATCAAGGT

TCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAG

ATATTGCCACTTACTTTTGCCATCATGGTAATACGCTTCCGTGGACGTTCGGTGGAGGCAC

CAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 CD40_12B4.2C10_K-LV-v2-hIgGK-C(SEQ ID NO: 41)：

MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGT

VKLLIYYTSRLHSGVPSRFSGSGSGTDYSLnSNLEQEDIATYFCHHGNTLPWTFGGGTKLEIKR

TVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS

TYSI^STLILSKADYEKHKWACEVTHQGLSSPVTKSFNRGEC 抗CD40_12E12.3F3_H-V-hIgG4H-C(SEQ ID NO: 42): 158138.doc -38-

S 201208696

ATGAACTTGGGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTGTCCAGTGTGAAGT

GAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTCTCCTG

TGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAG

AAGAGGCTGGAGTGGGTCGCATACATTAATTCTGGTGGTGGTAGCACCTATTATCCAGAC

ACTGTAAAGGGCCGATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAA

ATGAGCCGGCTGAAGTCTGAGGACACAGCCATGTATTACTGTGCAAGACGGGGGTTACCG

TTCCATGCTATGGACTATTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAAAACGA

AGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGC

CCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGG

CGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC

CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAAC

GTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC

CCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGG

ACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC

ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCA

ACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG

AGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC

TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATG

GGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT

TCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCAT

GCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCT

GGGTAAAGCTAGCTGA 抗 CD40—12E12.3F3_H-V-hIgG4H-C(SEQ ID NO: 43):

MNLGLSLIFLVLVLKGVQCEVKLVESGGGLVQPGGSLKLSCATSGFTFSDYYMYWVRQTPEK

RLEWVAYINSGGGSTYYPDTVKGRFTISRDNAKNTLYLQMSRLKSEDTAMYYCARRGLPFHA

MDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE

FEGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

FSCSVMHEALHNHYTQKSLSLSLGKAS 抗 CD40_12E12.3F3_K-LV-hIgGK-C(SEQ ID NO: 44):

ATGATGTCCTCTGCTCAGTTCCTTGGTCTCCTGTTGCTCTGTTTTCAAGGTACCAGATGTGA

TATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTAGGAGACAGAGTCACCATC

AGTTGCAGTGCAAGTCAGGGCATTAGCAATTATTTAAACTGGTATCAGCAGAAACCAGAT

GGAACTGTTAAACTCCTGATCTATTACACATCAATTTTACACTCAGGAGTCCCATCAAGGT

TCAGTGGCAGTGGGTCTGGGACAGATTATTCTCTCACCATCGGCAACCTGGAACCTGAAG -39- 158138.doc 201208696

ATATTGCCACTTACTATTGTCAGCAGTTTAATAAGCTTCCTCCGACGTTCGGTGGAGGCAC

CAAACTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 CD40_12E12.3F3—K-LV-hIgGK-C(SEQ ID NO: 45):

MMSSAQFLGLLLLCFQGTRCDIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGT νΚϋΙΥΥΤ5ΐυΚ〇νΡ5ΚΡ565050ΤΟΥ3υΠΟΝυΕΡΕΟΙΑΤΥΥΟ(3(3ΡΝΚίΡΡΉΌ60ΤΚυΕΙΚΚΤ

VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST

YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR_24A5.4A5_H-V-hIgG4H-C(SEQ ID NO: 46):

ATGGATTGGCTGTGGAACTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCACAG

ATCCAGTTGGTGCAGTCTGGACCTGAGCTGAAGAAGCCTGGAGAGACAGTCAAGATCTCC

TGCAAGGCTTCTGGGTATTCCTTCACAAACTATGGAATGAACTGGGTGAAACAGGCTCCA

GGAAAGGGTTTAAAGTGGATGGGCTGGATAAACACCTACACTGGAGAGTCAACATATGCT

GATGACITCAAGGGACGGTTTGCCTTCTCTTTGGAAACCTCTGCCAGCACTGCCTATTTGC

AGATCAGTAACCTCAAAAATGAGGACATGGCTACATATTTCTGTGCTAGAGGGGACTTTA

GGTACTACTAmTGACTACTGGGGCCAAGGCACCACTCTCACAGGCTCCTCAGCCAAAAC

GAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGC

CGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCA

GGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACT

CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCA

ACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTC

CCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT

GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG

CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG

AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG

CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA

TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT

CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC

ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT

CTGGGTAAAGCTAGCTGAT 抗DCIR_24A5.4A5_H-V-hIgG4H-C(SEQ ID NO: 47): 158138.doc -40·

S 201208696

MDWLWNLLFLMAAAQSAQAQIQLVQSGPELKKPGETVKISCKASGYSFTNYGMNWVKQAPG

KGLKWMGWINTYTGESTYADDFKGRPAFSLETSASTAYLQISNLKNEDMATYFCARGDFRYY

YFDYWGQGTTLTGSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS

GVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP

EFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ

FNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYIOTPPVLDSDGSFFLYSRLTVDKSRWQEGN

VFSCSVMHEALHNHYTQKSLSLSLGKAS 抗 DCIR—24A5.4A5_K-V-hIgGK-C(SEQ ID NO: 48):

ATGAGTGTGCTCACTCAGGTCCTGGCGTTGCTGCTGCTGTGGCTTACAGGTGCCAGATGTG

ACATCCAGATGACTCAGTCTCCAGCCTCCCTATCTGCATCTGTGGGAGAAACTGTCACCAT

CACGTGTCGAGCAAGTGGGAATATTCACAATTATTTAGCATGGTATCAGCAGAAACAGGG

AAAATCTCCTCAGCTCCTGGTCTATAATGCAAAAACCTTGGCAGATGGTGTGCCATCAAGG

TTCAGTGGCAGTGGATCAGGAACACAATATTCTCTCAAGATCAACACCCTGCAGCCTGAA

GATITTGGGAGTTATTACTGTCAACATTTTTGGGATTCTTGGACGTTCGGTGGAGGCACCA

AGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGA

GCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAG

GCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTC

ACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAA

AGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTC

GCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_24A5.4A5_K-V-hIgGK-C(SEQ ID NO: 49): MSVLTQVLALLLLWLTGARCDIQMTQSPASLSASVGETVnTCRASGNIHNYLAWYQQKQGK：

SPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINTLQPEDFGSYYCQHFWDSWTFGGGIXLEI

KRTVAAPSWIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK

DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR—24E7.3H9_H-V-hIgG4H-C(SEQ ID NO: 50):

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCACTCCCAGG

TTCAGCTGCAGCAGTCTGGAGCTGAGCTGATGAAGCCTGGGGCCTCAGTGAAGATATCCT

GCAAGGCTACTGGCTACACATTCAGTAGCTACTGGATAGAGTGGGTAAAGCAGAGGCCTG

GACATGGCCTTGAGTGGATTGGAGAGAmTACCTGGAAGTGGTAGGACTAACGACAATG

AGAAGTTCAAGGGCAAGGCCACATTCACTGCAGATACATCCTCCAAGAAAGCCTACATGC

AACTCAGCAGCCTGACATCTGAGGACTCTGCCGTCTATTATTGTGCAAGAAGGGGTGGTTA

CTCCTTrGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACAAAGGGC

CCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGG

GCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT • 41 · 158138.doc 201208696

GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC

AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGC

CCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAAC

CCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGA

GCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATG

CCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCA

CCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG

GCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC

AGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT

GCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC

CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTA

CAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGT

GATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAA

AGCTAGCTGA 抗DCIR_24E7.3H9_H-V-hIgG4H-C(SEQ ID NO: 51):

MEWTWVFLFLLSVTAGVHSQVQLQQSGAELMKPGASVKISCKATGYTFSSYWIEWVKQRPG

HGLEWIGEILPGSGRTNDNEKFKGKATFTADTSSKKAYMQLSSLTSEDSAVYYCARRGGYSFA

YWGQGTLVTVSAAKTKGPSVFPLAPCSIRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE

GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS

CSVMHEALHNHYTQKSLSLSLGKAS 抗DCIR_24E7.3H9_K-V-hIgGK-C(SEQ ID NO: 52):

ATGACCATGTTCTCACTAGCTCTTCTCCTCAGTCTTCTTCTCCTCTGTGTCTCTGATTCTAGG gcagaaacaactgtGacccagtctatgaccatgttctcactagctcttctcctcagtcttct

TCTCCTCTGTGTCTCTGATTCTAGGGCAGAAACAACTGTGACCCAGTCTCCAGCATCCCTG

TCCATGGCTATAGGGGAAAAAGTCACCATCAGATGCGTAACCAGCACTGATATTGATGAT

GATGTGAACTGGTACCAGCAGAAGCCAGGGGAACCTCCTAAACTCCTTATTTCAGAAGGC

AATACTCTTCGTCCTGGAGTCCCATCCCGAITCTCCAGCAGTGGCTATGGTACAGATTTTGT

TTTTACAAITGAGAACATGCTCTCAGAAGATGTTGCAGATTACTACTGTTTGCAAAGTGGT

AACTTGCCGTACACGTrCGGAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCA

CCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTrGAAATCTGGAACTGCCTCTGTTGT

GTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGC

CCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTA

CAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGC

CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGA

GTGTTAGCCAGCATCCCTGTCCATGGCTATAGGGGAAAAAGTCACCATCAGATGCGTAAC 158138.doc • 42· s 201208696

CAGCACTGATATTGATGATGATGTGAACTGGTACCAGCAGAAGCCAGGGGAACCTCCTAA

ACTCCTTATTTCAGAAGGCAATACTCTTCGTCCTGGAGTCCCATCCCGATTCTCCAGCAGT

GGCTATGGTACAGAmTGTTTTTACAATTGAGAACATGCTCTCAGAAGATGTTGCAGATT

ACTACTGTTTGCAAAGTGGTAACTTGCCGTACACGTTCGGAGGGGGGACCAAGCTCGAGA

TCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAA

ATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA

CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAG

GACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTAC

GAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACA

AAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_24E7.3H9_K-V-hIgGK-C(SEQ ID NO: 53):

MTMFSLALLLSLLLLCVSDSRAETTVTQSPASLSMAIGEKVTIRCVTSTDIDDDVNWYQQKPGE

PPKLLISEGNTLRPGVPSRFSSSGYGTDFVFTmNMLSEDVADYYCLQSGNLPYTFGGGTKLEIK

RTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 DCIRJ29E9.2E2_H-VhIgG4H-C(SEQ ID NO: 54):

ATGGCTTGGGTGTGGACCTTGCTATTCCTGATGGCAGCTGCCCAAAGTGCCCAAGCACAGA

TCCAGTTGGTGCAGTCTGGACCTGAGCTGAAGAAGCCTGGAGAGACAGTCAAGATCTCCT

GCAAGGCTTCTGGGTATACCTTCACAAACTATGGAATGAACTGGGTGAAGCAGGCTCCAG

GAAAGGGTTTAAAGTGGGTGGGCTGGATAAACACCTTCACTGGAGAGCCAACATATGTTG

ATGACTTCAAGGGACGGTTTGCCTTCTCTTTGGAAACCTCTGCCAGCACTGCCTATTTGCA

GATCAACAACCTCAAAAATGAGGACACGGCTACATATTTCTGTGCAAGAGGGAATTTTAG

GTACTACTACTTrGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCAGCCAAAACA

AAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCC

GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCA

GGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACT

CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCA

ACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTC

CCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT

GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG

CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG

AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG

CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA

TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT

CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC

ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT

CTGGGTAAAGCTAGCTGA •43- 158138.doc 201208696 抗 DCIR_29E9.2E2_H-VhIgG4H-C(SEQ ID NO: 55):

MAWVWTLLFLMAAAQSAQAQIQLVQSGPELKKPGETVKISCKASGYTFTNYGMNWVKQAP

GKGLKWVGWINTFTGEPTYVDDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARGNFRY

YYFDYWGQGTTLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALT

SGVHTFPAVLQSSGLYSLSSWTVPSSSLGIXTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA

PEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREE

QFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSffimSKAKGQPREPQVYTLPPSQEE

MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗 DCIR_29E9.2E2_K-V-hIgGK-C(SEQ ID NO: 56):

ATGAGTGTGCTCACTCAGGTCCTGGCGTTGCTGCTGCTGTGGCTTACAGGTGCCAGATGTG

ACATCCAGATGACTCAGTCCCCAGCCTCCCTATCTGCATCTGTGGGAGAAACTGTCACCAT

CACATGTCGAACAAGTGGGAATATTCGCAATTATTTAGCATGGTATCAGCAGAAACAGGG

AAAATCTCCTCAACTCCTGGTCTATAATGCAAAAACCTTAGCAGATGGTGTGCCATCAAGG

TTCGGTGGCAGTGGATCAGGAACACAATATTCTCTCAAGATCAACAGCCTGCAGCCTGAA

GATITTGGGAATTATTACTGTCAACATTTTTGGAGTAGTCCGTACACGTTCGGAGGGGGGA

CCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGA

TGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGA

GAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGT

GTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGC

AAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGC

TCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_29E9.2E2_K-V-hIgGK-C(SEQ ID NO: 57):

MSVLTQVLALLLLWLTGARCDIQMTQSPASLSASVGETVTITCRTSGNIRNYLAWYQQKQGKS

PQLLVYNAKTLADGVPSRFGGSGSGTQYSLKINSLQPEDFGNYYCQHFWSSPYTFGGGTKLEI

KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVrEQDSK

DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 DCIR_29G10.3D9_H-V-hIgG4H_C(SEQ ID NO: 58):

ATGATGGGATGGAGCTATATCATCCTCTTnTGGTAGCAACAGCTACAGATGTCCACTCCC

AGGTCCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGCTTCAGTGAAGCTGT

CCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGGTGAAGCAGAGGC

CTGGAGAAGGCCTTGAGTGGATTGGAGAGATTAATCCTAGCTACGGTCGTACTGACTACA

ATGAGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAAATCCTCCAGCACAGCCTACA

TGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTGTGCAAGAGGAGATTA

CTACGGTAGTAGCTCGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCC 158138.doc -44- s 201208696

AAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGC

ACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGG

AACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGAC

TCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACAC

CTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATA

TGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTG

TTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGG

TGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGG

AGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTrCAACAGCACGTACCGTGTG

GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAG

GTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAG

CCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAG

GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG

AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC

TCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTC

TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCC

TGTCTCTGGGTAAAGCTAGCGGATGGAGCTATATCATCCTCTmTGGTAGCAACAGCTAC

AGATGTCCACTCCCAGGTCCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGC

TTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATGCACTGG

GTGAAGCAGAGGCCTGGAGAAGGCCTTGAGTGGArTGGAGAGATTAATCCTAGCTACGGT

CGTACTGACTACAATGGGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAAATCCTCC

AGCACAGCCTACATGCAACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTGTG

CAAGAGGAGATTACTACGGTAGTAGCTCGTTTGCTTACTGGGGCCAAGGGACTCTGGTCA

CTGTCTCTGCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAG

CACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT

GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA

CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCA

CGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGA

GTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGA

CCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTG

AGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGT

ACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAAC

AGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAG

GAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCC

AAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGA

GATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACAT

CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCG

TGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTG

GCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC

ACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗DCIR_29G10.3D9_H-V-hIgG4H-C(SEQ ID NO: 59): •45- 158138.doc 201208696

MMGWSYIILFLVATATDVHSQVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRP

GEGLEWIGEINPSYGRTDYNEKFKNKATLTVAKSSSTAYMQLSSLTSEDSAVYYCARGDYYGS

SSFAYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALT

SGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPA

PEFEGGPSVFLFPPKPKDTLMSRTTEWCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREE

QFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE

MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗DCIR_29G10.3D9_K-Varl-V-hIgGK-C(SEQ ID NO: 60):

ATGGATTTTCAAGTGCAGATTTTCAGCTTCCTGCTAATGAGTGCCTCAGTCATAATGTCCA

GGGGACAAATTGTTCTCACCCAGTCTCCAGCACTCATGTCTGCATCTCCAGGGGAGAAGGT

CACCATGACCTGCAGTGCCAGCTCAAATATAAGTTACATGTACTGGTACCAGCAGAAGCC

AAGATCCTCCCCCAAACCCTGGAITTATCTCACATCCAACCTGGCTTCTGGAGTCCCTGCT

CGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAACCAGCAGCATGGAGGCTG

AAGATGCTGCCACTTATTGCTGCCAGCAGTGGAGTAGTAACCCACCCACGTTCGGTGCTGG

GACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCA

GAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG

AGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_29G10.3D9_K-Varl-V-hIgGK-C(SEQ ID NO: 61):

MDFQVQIFSFLLMSASVMSRGQIVLTQSPALMSASPGEKVTMTCSASSNISYMYWYQQKPRS

SPKPWIYLTSNLASGVPARFSGSGSGTSYSLTTSSMEAEDAATYCCQQWSSNPPTFGAGTKLEI

KRIYAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK

DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR—29G10.3D9_K-Vaf2-V-hIgGK-C(SEQ IDNO: 62):

ATGGATTTTCGAGTGCAGAmTCAGCTTCCTGCTAATGAGTGCCTCAGTCATAATGTCCA

GGGGACAAATTGTTCTCACCCAGTCTCCAGCACTCATGTCTGCATCTCCAGGGGAGAAGGT

CACCATGACCTGCAGTGCCAGCTCAAATATAAGTTACATGTACTGGTACCAGCAGAAGCC

AAGATCCTCCCCCAAACCCTGGATTTATCTCACATCCAACCTGGCTTCTGGAGTCCCTGCT

CGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAATCAGCAGCATGGAGGCTG

AAGATGCTGCCACTTATTACTGCCAGCAGTGGAGTAGTAACCCACCCACGTTCGGTGCTGG

GACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCA

GAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG 158138.doc • 46· s 201208696

AGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_29G10.3D9_K-Var2-V-hIgGK-C(SEQ ID NO: 63):

MDFRVQIFSFLLMSASVIMSRGQIVLTQSPALMSASPGEKVTMTCSASSNISYMYWYQQKPRSS

PKPWIYLTSNLASGWARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPPTFGAGTKLEIK

RTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSIXTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR_2C9K-V-hIgGK-C(SEQ ID NO: 64):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTCCACAGGTG

ACATTGTGCTGATCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCAT

ATCCTGCAGAGCCAGTGAAAGTGTTGATAGTTATGTCAATAGTTTTATGCACTGGTACCAG

CAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCGTGTATCCAACCTAGAATCTGGG

ATCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTTCACCCTCACCATTAATCCTG

TGGAGGCTGATGATGTTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCATTCACGTT

CGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTC

CCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACT

TCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT

CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACC

CTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_2C9K-V-hIgGK-C(SEQ ID NO: 65):

METDTLLLWVLLLWVPGSTGDIVLIQSPASLAVSLGQRAnSCRASESVDSYVNSFMHWYQQK

PGQPPKLLIYRVSNLESGffARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPFTFGSGTKL

EIKRTVAAPSWIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC. 抗 DCIR—31A6.1F5—H-var2-V-hIgG4H-C(SEQ ID NO: 66):

ATGGAATGTAACTGGATACTTCCTTTTATTCTGTCGGTAATTTCAGGGGTCTACTCAGAGG

TTCAGCTCCAGCAGTCTGGGACTGTGCTGGCAAGGCCTGGGGCTTCCGTGAATATGTCCTG

TAAGGCTGCTGGCTACAGCTTTACCAGTTACTGGGTGTACTGGGTCAAACAGAGGCCTGG

ACAGGGTCTGGAATGGATTGGTGCTATTTACCCTAAAAATAGTAGAACTAGCTACAACCA

GAAGTTCCAGGACAAGGCCACACTGACTGCAGTCACATCCGCCAGCACTGCCTACATGGA

GCTCAGCAGCCTGACAAATGAGGACTCTGCGGTCTATTACTGTACAAGACCTCACTATGAT

TCGTTTGGTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACAaagggcccA

TCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCT

GCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGA

CCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG -47· 158138.doc 201208696

CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCC

ACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCC

AAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGC

CAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACC

GTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGC

CTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAG

GTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGC

CTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCG

GAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACA

GCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGA

TGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGC

TAGCTGA 抗 DCIR一31A6.1F5一H-var2-V-hIgG4H-C(SEQ ID NO: 67):

MECNWILPFILSVISGVYSEVQLQQSGTVLARPGASVNMSCKAAGYSFTSYWVYWVKQRPGQ

GLEWIGAIYPKNSRTSYNQKFQDKATLTAVTSASTAYMELSSLTNEDSAVYYCTRPHYDSFGY

WGQGTLVTVSAAKTKGPSWPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT

FPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEG

GPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEA^HNAKTKPREEQFNST

YRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQEEMTKNQ

VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSC

SVMHEALHNHYTQKSLSLSLGKAS 抗 DCIR_31A6.1F5一K-var2-V-hIgGK-C(SEQ ID NO: 68):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGTTCCACAGGTG

ACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCAT

ATCCTGCAGAGCCAGTGAAAGTGTAGATAGTTATGGCATTAGTTTTATGCACTGGTACCAG

CAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCGTGCATCCAACCAAGAATCTGGG

ATCCCTGCCAGGTTCAGTGGCAGTGGGTCTAGGACAGACTTCACCCTCACCATTAATCCTG

TGGAGGCTGATGATGTTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCGCTCACGTT

CGGTGCTGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTC

CCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACT

TCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT

CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACC

CTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCAT

CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR_31A6.1F5_K-var2-V-hIgGK-C(SEQ ID NO: 69): 158138.doc •48- s 201208696

METDTLLLWVLLLWVPGSTGDIVLTQSPASLAVSLGQRATISCRASESVDSYGISFMHWYQQK PGQPPKLLIYRASNQESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPLTFGAGm

EIKRTVAAPSVnFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD

SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR_3C2.2D9_H-LV-hIgG4H-C(SEQ ID NO: 70):

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTCCCAGGT

TACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTCTGACTTGT

TCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTGTGAGCTGGATTCGTCAGCCTTC aggaaagggtctggagtggctggcacacatttactgggatgatgacaagcgctataatcc

ATCCCTGAAGAGCCGGCTCACAATCTTTAAGGATCCCTCCAGCAACCAGGTATTCCTCAGG

ATCACCAGTGTGGACACTGCAGATACTGCCACATACTACTGTGCTCGAAACTCCCATTACT

ACGGTAGTACTTACGGGGGATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCT

CCTCAGCCAAAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTC

CGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGT

GTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCC

TCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAG

ACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAG

TCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCA

GTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCA

CGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGG

ATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACG

TACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC

AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCC

AAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC

AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTG

GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA

CTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGA

GGGGAATGTCTTCTCATGCTCCXjTGATGCATGAGGCTCTGCACAACCACTACACACAGAA

GAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗DCIR一3C2-2D9_H-LV-hIgG4H-C(SEQ ID NO: 71):

NRLTSSLLLLIVPAYVLSQQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGL

EWLAHIYWDDDKRYNPSLKSRLTIFKDPSSNQVFLRITSVDTADTATYYCARNSHYYGSTYGG

YFDVWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS

GVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP

EFEGGPSWLFPPKPKDTI,MISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ

FNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEOTSKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSC^VMHEALHNHYTQKSLSLSLGKAS. •49· 158138.doc 201208696 抗DCIR_3C2.2D9_K-LV_hIgGK-C(SEQ ID NO: 72):

ATGGAGACAGACACACTCCTGCTATGGGTGCTGCTGCTCGGGGTTCCAGGTTCCACAGGTA

ACATTGTGCTGACCCAGTCTCCAACTTCTTTCACTGTGTCTCTTGGGCAGAGGGCCACCAT

ATCCTGCAGAGCCAGTGAAAGTGTTCATAGTTATGGCAATAGTTTTATGCACTGGTACCAG

CAGAAACCAGGGCAGCCACCCAAACTCCTCATCTATCTTGCATCCAACGTAGAATCTGGG

GTCCCTGCCAGGTTCAGTGGTAGTGGGTCCAGGACAGACTTCACCCTCACCATTGATCCTG

TGGAGGCTGATGATGCTGCAACCTATTACTGTCAGCAAAATAGTGAGGATCCGTGGACGT

TCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC

TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC

TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC

CCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCA

TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 DCIR_3C2.2D9_K-LV-hIgGK-C(SEQ ID NO: 73):

METDTLLLWVLLLGVPGSTGNIVLTQSPTSFTVSLGQRATISCRASESVHSYGNSFMHWYQQK

PGQPPKLLIYLASNVESGVPARFSGSGSRTDFTLnDPVEADDAATYYCQQNSEDPWTFGGGTK

LEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ

DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 DCIR_6C8.1G9_H-V-hIgG4H-C(SEQ ID NO: 74):

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCACTCCCAGG

TTCAGCTGCAGCAGTCTGGAACTGAGCTGATGAAGCCTGGGGCCTCAGTGAAGATATCCT

GCAAGGCTACTGGCTACACATTCAGTACCTACTGGATAGAGTGGGTAAAGCAGAGGCCTG

GACATGGCCTTGAGTGGATTGGAGAGATTTTACCTGGAAGTGGTAGGACTAACGACAATG

AGAAGTTCAAGGGCAAGGCCACAATCACTGCAGATACATCCTCCAAGAAAGCCTACATGC

AACTCAGCAGCCTGACATCTGAGGACTCTGCCGTCTATTACTGTGCAAGAAGGGGTGGTTA

CTCCTTTGCTTTCTGGGGCCAAGGGACTCTGGTCTCTGTCTCTGCAGCCAAAACAAAGGGC

CCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGG

GCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT

_GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC

AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGAT

CACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGC

CCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAAC

CCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGA

GCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATG

CCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCA

CCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG

GCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCAC 158138.doc -50- s 201208696

AGGTGTACACGCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCT

GCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC

CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTA

CAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGT

GATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAA

AGCTAGCTGA 抗DCIR_6C8.1G9JH-V-hIgG4H-C(SEQ ID NO: 75) ··

MEWTWVFLFLLSVTAGVHSQVQLQQSGTELMKPGASVKISC3CATGYTFSTYWIEWVKQRPG

HGLEWIGEILPGSGRTNDNEKFKGKAITrADTSSKKAYMQLSSLTSEDSAVYYCARRGGYSFA

FWGQGTLVSVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHkPSNTKVDKRVESKYGPPCPPCPAPEFE

GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSl^KGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS

CSVMHEALHNHYTQKSLSLSLGKAS 抗DCIR_6C8.1G9—K-V-hIgGK-C(SEQ ID NO: 76):

ATGACCATGTTCTCACTAGCrOTCTCCTCAGTCrTCTTCTCCTCTGTGTCTCTGATTCTAGG

GCAGAAAGAACTGTGACCCAGTCTCCAGCATCCCTGTCCATGGCTATAGGAGAAAAAGTC

ACCATCAGATGCGTAACCAGCACTGATATTGATGATGATGTGAACTGGTACCAGCAGAAG

CCAGGGGAACCTCCTAAGCTCCTTATTrCAGAAGGCAATACTCTTCGTGCTGGAGTCCCAT

CCCGATTCTCCAGCAGTGGCTATGGTACAGATTTTGTTTTTACAATTGAGAACATGCTCTC

AGAAGATGTTGCAGATTACTACTGTTTGCAAAGTGGTAACTTGCCGTACACGTTCGGAGGG

GGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCAT

CTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCC

CAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA

GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCT

GAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCT

GAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DCIR—6C8.1G9—K-V-hIgGK-C(SEQ ID NO: 77):

MTMFSLALLLSLLLLCVSDSRAETTVTQSPASLSMAIGEK\TnRCVTSTDIDDDVNWYQQKPGE

PPKLLISEGNTLRAGWSI^SSSGYGTDFVFTIENMLSEDVADYYCLQSGNLPYTFCXXiTKLEIK

RTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSTLILSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR_9E8.1E3_H-V-hIgG4H-C(SEQ ID NO: 78): -51 · 158138.doc 201208696

ATGAACAGGCTTACTTCCTCATTGCTGCTGCTGATTGTCCCTGCATATGTCCTGTCCCAGGT

TACTCTGAAAGAGTCTGGCCCTGGGATATTGCAGCCCTCCCAGACCCTCAGTCTGACTTGT

TCTTTCTCTGGGTTTTCACTGAGCACTTCTGGTATGGGTCTGAGCTGGATTCGTCAGCCTTC

AGGAAAGGGTCTGGAGTGGCTGGCACACATTTACTGGGATGATGACAAGCGCTATAACCC

ATCCCTGAAGAGCCGGCTCACAATCTCCAAGGATACCTCCAGCAACCAGGTTTTCCTCAAG

ATCACCATTGTGGACACTGCAGATGCTGCCACATACTACTGTGCTCGAAGCTCCCATTACT

ACGGTTATGGCTACGGGGGATACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCT

CCTCAGCCAAAACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTC

CGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGT

GTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCC

TCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAG

ACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAG

TCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCA

GTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCA

CGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGG

ATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACG

TACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTAC

AAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCC

AAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACC

AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTG

GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA

CTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGA

GGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAA

GAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTGA 抗DCIR_9E8.1E3_H-V-hIgG4H-C(SEQ ID NO: 79):

MNRLTSSLLLLIVPAYVLSQVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGLSWIRQPSGKGL

EWLAHIYWDDDKRYNPSLKSRLTISKDTSSNQVFLKITIVDTADAATYYCARSSHYYGYGYGG

YFDWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS

GVmPPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP

EFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ

FNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKrTPPVLDSDGSFFLYSRLTVDKSRWQEGN

VFSCSVMHEALHNHYTQKSLSLSLGKAS 抗DCIR_9E8.1E3_K-LV-hIgGK-C(SEQ ID NO: 80) ··

ATGGAGACAGACACACTCCTGCTATGGGTCiCTGCTGCTCTGGGTTCCAGGTTCCACAGGTA

ACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCAT

ATCCTGCAGAGCCAGTGAAAGTATTCATAGTTATGGCAATAGTTTTCTGCACTGGTACCAG

CAGAAACCAGGACAGCCACCCAAACTCCTCATCTATCTTGCATCCAACCTAGAATCTGGG

GTCCCTGCCAGGTTCAGCGGCAGTGGGTCTAGGACAGACTTCACCCTCACCATTGATCCTG 158138.doc •52- s 201208696

TGGAGGCTGATGATGCTGCAACCTATTACTGTCAGCAAAATAATGAGGATCCGTGGACGT

TCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC

TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC

TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC

CCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCA

TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAGGCGGCCGC

ACTAGCGCGGGCCGCATTCGAAGAGCTCGGTACCCGGGGATCCTCTAGAGTCGACCTGCA

GGCATGCAAGCTGGCCGCGACTCTAGATCATAATCAGC 抗DCIR_9E8.1E3_K-LV-hIgGK-C(SEQ ID NO: 81):

METDTLLLWVLLLWVPGSTGNIVLTQSPASLAVSLGQRATISCRASESIHSYGNSFLHWYQQK

PGQPPKLLIYLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPWTFGGGTK

LEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ

DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗DCIR2C9H-LV-hIgG4H-V-hIgG4H-C(SEQ ID NO: 82):

ATGAAATGCAGCTGGGTCATCTTCTTCCTGATGGCAGTGGTTACAGGGGTCAATTCAGAGG

TTCAGCTGCAGCAGTCTGGGGCTGAGCTTGTGAGGCCAGGGGCCTTAGTCAAGTTGTCCTG

CAAAGCTTCTGGCTTCAACATTAATGACTACTATATCCACTGGGTGAAGCAGCGGCCTGAA

CAGGGCCTGGAGCGGArrGGATGGATTGATCCTGACAATGGTAATACTATATATGACCCG

AAGTTCCAGGGCAAGGCCAGTATAACAGCAGACACATCCCCCAACACAGCCTACCTGCAG

CTCAGCAGCCTGACATCTGAGGACACTGCCGTCTATTACTGTGCTAGAACCCGATCTCCTA

TGGTTACGACGGGGTTTGTTTACTGGGGCCAAGGGACTGTGGTCACTGTCTCTGCAGCCAA

AACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCAC

AGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA ctcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcAggactc

TACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCT

GCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGrTGAGTCCAAATAT

GGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGT

TCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACRAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGT

CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT

CAGCCTGACCTGCCTGGTCAAAGGCTrCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG

CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC

CTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTT

CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTG

TCTCTGGGTAAATGA -53- 158138.doc 201208696 抗 DCIR2C9H-LV-hIgG4H-V-hIgG4H-C(SEQ ID NO: 83):

MKCSWVIFFLMAWTGVNSEVQLQQSGAELVRPGALVKLSCKASGFNINDYYIHWVKQRPEQ

GLERIGWE)PDNGNHYDPKFQGKASITADTSPNTAYLQLSSLTSEDTAVYYCARTRSPMVTTG

FVYWGQGTWTVSAAKIXGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE

FEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKXKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

FSCSVMHEALHNHYTQKSLSLSLGK 抗DC-SIGNL16E3H(SEQ ID NO: 84):

ATGGAAAGGCACTGGATCTTTCTCTTCCTGinnTCAGTAACTGCAGGTGTCCACTCCCAGG

TCCAGCTTCAGCAGTCTGGGGCTGAGCTGGCAAAACCTGGGGCCTCAGTGAAGATGTCCT

GCAAGGCTTCTGGCTACACCTTTACTACCTACTGGATGCACTGGGTAAAACAGAGGCCTGG

ACAGGGTCTGGAATGGATTGGATACATTAATCCTATCACTGGTTATACTGAGTACAATCAG

AAGTTCAAGGACAAGGCCACCTTGACTGCAGACAAATCCTCCAGCACAGCCTACATGCAA

CTGAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGAGGGTTTAAGTG

CTATGGACTATTGGGGTCAGGGAACCTCAGTCACCGTCACCTCAGCCAAAACAACAGCCC

CATCGGTCTATCCACTGGCCCCTGTGTGTGGAGATACAACTGGCTCCTCGGTAACTCTAGG

ATGCCTGGTCAAGGGTTATTTCCCTGAGCCAGTGACCTTGACCTGGAACTCTGGATCCCTG

TCCAGTGGTGTGCACACCTTCCCAGCTGTCCTGCAGTCTGACCTCTACACCCTCAGCAGCT

CAGTGACTGTAACCTCGAGCACCTGGCCCAGCCAGACCGTCACCTGCAGCGTTGCTCACCC

AGCCAGCAGCACCACGGTGGACAAAAAACTTGAGCCCAGCGGGCCCATTTCAACAATCAA

CCCCTGTCCTCCATGCAAGGAGTGTCACAAATGCCCAGCTCCTAACCTCGAGGGTGGACCA

TCCGTCTTCATCTTCCCTCCAAATATCAAGGATGTACTCATGATCTCCCTGACACCCAAGGT

CACGTGTGTGGTGGTGGATGTGAGCGAGGATGACCCAGACGTCCAGATCAGCTGGTTTGT

GAACAACGTGGAAGTACACACAGCTCAGACACAAACCCATAGAGAGGATTACAACAGTA

CTATCCGGGTGGTCAGCACCCTCCCCATCCAGCACCAGGACTGGATGAGTGGCAAGGAGT

TCAAATGCAAGGTCAACAACAAAGACCTCCCATCACCCATCGAGAGAACCATCTCAAAAA

TTAAAGGGCTAGTCAGAGCTCCACAAGTATACATCTTGCCGCCACCAGCAGAGCAGTTGT

CCAGGAAAGATGTCAGTCTCACTTGCCTGGTCGTGGGCTTCAACCCTGGAGACATCAGTGT

GGAGTGGACCAGCAATGGGCATACAGAGGAGAACTACAAGGACACCGCACCAGTCCTGG

ACTCTGACGGTTCTTACTTCATATATAGCAAGCTCAATATGAAAACAAGCAAGTGGGAGA

AAACAGATTCC1TCTCATGCAACGTGAGACACGAGGGTCTGAAAAATTACTACCTGAAGA

AGACCATCTCCCGGTCTCCGGGTAAAGCTAGCTGA 抗DC-SIGNL16E3H(SEQ ID NO: 85):

MERHW1FLFLFSVTAGVHSQVQLQQSGAELAKPGASVKMSCKASGYTFTTYWMHWVKQRPG

QGLEWIGYINPITGYTEYNQKFKDKATLTADKSSSTAYMQLSSLTSEDSAVYYCAREGLSAMD 158138.doc -54-

S 201208696

YWGQGTSVTVTSAKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVH

TFPAVLQSDLYTLSSSVTVTSSTWPSQTVrCSVAHPASSTTVDKKLEPSGPISTINPCPPCKECHK

CPAPNLEGGPSWIFPPNIKDVLMISLTPKVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTH

MD 憾 TmWSTLPIQHQDWMSGKEFKCKVNNKDLPSPIERTISKIKGLVRAPQVYILPPPAEQ

LSRKDVSLTCLWGFNPGDISVEWTSNGHTEENYKDTAPVLDSDGSYFIYSKLNMKTSKWEKT DSFSCNVRHEGLKNYYLKKTISRSPGKAS. 抗 DC-SIGNL16E3K(SEQ ID NO: 86):

ATGGGCATCAAGATGGAGTCACGGATTCAGGCATTTGTATTCGTGTTTCTCTGGITGTCIG

GTGTTGGCGGAGACATTGTGATGACCCAGTCTCACAAATTCATGTCCACATCAGTAGGAG

ACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGGATGTGACTTCTGCTGTAGCCTGGTATCA

ACAAAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGGCATCCACCCGGCACACTGG

AGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTATACTCTCACCATCAGCAGT

GGGCAGGCTGAAGACCTGGCACTTTATTACTGTCACCAATATTATAGCGCTCCTCGGACGT

TCGGTGGAGGCACCAAGCTGGAAGTCAAACGGGCTGATGCTGCACCAACTGTATCCATCT

TCCCACCATCCAGTGAGCAGTTAACATCTGGAGGTGCCTCAGTCGTGTGCTTCTTGAACAA

CTTCTACCCCAAAGACATCAATGTCAAGTGGAAGATTGATGGCAGTGAACGACAAAATGG

CGTCCTGAACAGTTGGACTGATCAGGACAGCAAAGACAGCACCTACAGCATGAGCAGCAC

CCTCACGTTGACCAAGGACGAGTATGAACGACATAACAGCTATACCTGTGAGGCCACTCA

CAAGACATCAACTTCACCCATCGTCAAGAGCTTCAATAGGAATGAGTGTTAG 抗 DC-SIGNL16E3K(SEQ ID NO: 87):

MESRIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCKASQDVTSAVAWYQQKPG

QSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLTISSGQAEDLALYYCHQYYSAPRTFGGGTKL

EVKRADAAPTVSDFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTOQD

SKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC 抗 DC_SIGNL16E7H-LV-hIgG4H-C(SEQ ID NO: 88):

ATGGAAAGGCACTGGATCTTTCTCTTCCTGTnTCAGTAACTGCAGGTGTCCACTCCCAGG

TCCAGCTTCAGCAGTCTGGGGCTGAGCTGGCAAAACCTGGGGCCTCAGTGAAGATGTCCT

GCAAGGCTTCTGGCTACACCTTTACTACCTACTGGATGCACTGGGTAAAACAGAGGCCTGG

ACAGGGTCTGGAATGGATTGGATACATTAATCCTATCACTGGTTATACTGAGTACAATCAG

AAGTTCAAGGACAAGGCCACCTTGACTGCAGACAAATCCTCCAGCACAGCCTACATGCAA

CTGAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGAGGGTTTAAGTG

CTATGGACTATTGGGGTCAGGGAACCTCAGTCACCGTCACCTCAGCCAAAACAACGGGCC

CATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG

CTGCCTGGTCAAGGACTACTrCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG

ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA

GCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATC

ACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCC •55· 158138.doc 201208696

CACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACC

CAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAG

CCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGC

CAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCAC

CGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGG

CCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACA

GGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTG

CCTGGTCAAAGGCITCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC

GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC

AGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTG

ATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAA

GCTAGCTGA 抗DC-SIGNL16E7H-LV-hIgG4H-C(SEQ ID NO: 89):

MERHWIFLFLFSVTAGVHSQVQLQQSGAELAKPGASVKMSCKASGYTFnYWMHWVKQRPG

QGLEWIGYINPITGYTEYNQKFKDKATLTADKSSSTAYMQLSSLTSEDSAVYYCAREGLSAMD

YWGQGTSVTVTSAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE

GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGKAS. 抗DC-SIGNL16E7K-LV-hIgGK-C(SEQ ID NO: 90):

ATGGGCATCAAGATGGAGTCACAGATTCAGGCATTTGTATTCGTGTTTCTCTGGTTGTCTG

GTGTTGGCGGAGACATTGTGATGACCCAGTCTCACAAATTCATGTCCACATCAGTAGGAG

ACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGGATGTGACTTCTGCTGTAGCCTGGTATCA

ACAAAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGGCATCCACCCGGCACACTGG

AGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTATACTCTCACCATCAGCAGT

GGGCAGGCTGAAGACCTGGCACTTrATTACTGTCACCAATATTATAGCGCTCCTCGGACGT

TCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC

TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC

TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC

CCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCA

TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗DC-SIGNL16E7K-LV-hIgGK-C(SEQ ID NO: 91): 158138.doc •56·

S 201208696

MESQIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCKASQDVTSAVAWYQQKPG

QSPKLLIYWASTRHTGWDRFTGSGSGTDYTLUSSGQAEDLALYYCHQYYSAPRTFGGGTKL

EKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD

SKDSTYSLSST1,TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗Dectin—l_llB6.4_H-V-hIgG4H-C(SEQ ID NO: 92):

ATGGCTGTCCTGGCACTACTCCTCTGCCTGGTGGCTTTCCCAACTTGTACCCTGTCCCAGGT

GCAACTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCACAGAGCCTGTCCATTACCTG

CTCTGTCTCTGGGTTCTCATTAAGCAACTATGATATAAGCTGGATTCGCCAGCCACCAGGA

AAGGGTCTGGAGTGGCTTGGAGTAATGTGGACTGGTGGAGGCGCAAATTATAATTCAGCT

TTCATGTCCAGACTGAGCATCAACAAGGACAACTCCAAGAGCCAAGTTnTTTAAAAATG

AACAATCTGCAAACTGATGACACAGCCATTTAITACTGTGTCAGAGATGCGGTGAGGTACT

GGAACTTCGATGTCTGGGGCGCAGGGACCACGGTCACCGTCTCCTCAGCCAAAACGAAGG

GCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCT

GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACCXjTGTCGTGGAACTCAGGCGC

CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC

AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTA

GATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCA

TGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAA

AACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACG

TGAGCCAGGAAGACCCCGAGGTCCAGHCAACTGGTACGTGGATGGCGTGGAGGTGCATA

ATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCC

TCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACA

AAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGC

CACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGA

CCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC

AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCT

CTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTC

CGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGT

AAAGCTAGCTGA 抗Dectin一l_llB6.4_H-V-hIgG4H-C(SEQ ID NO: 93):

MAVLALLLCLVAFPTCTLSQVQLKESGPGLVAPSQSLSITCSVSGFSLSNYDISWIRQPPGKGLE

WLGVMWTGGGANYNSAFMSRLSINKDNSKSQWLKMNNLQTDDTAIYYCVRDAVRYWNFD

VWGAGTTVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE

GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTXPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNWS

CSVMHEALHNHYTQKSLSLSLGKAS •57· 158138.doc 201208696 抗Dectin_l_llB6.4_K-LV-hIgGK-C(SEQ ID NO: 94):

ATGGATTTTCAAGCGCAGATTTTCAGCTTCCTGCTAATCAGTGCTTCAGTCATAATGTCCA

GAGGACAAATTGTTCTCTCCCAGTCACCAGCAATCCTGTCTGCATCTCCAGGGGAGAAGGT

CACAATGACTTGCAGGGCCAGCTCAAGTGTAAGTTACATACACTGGTACCAGCAGAAGCC

AGGATCCTCCCCCAAACCCTGGATTTATGCCACATCCCACCTGGCTTCTGGAGTCCCTGCT

CGCTTCAGTGGCAGTGGGTCTGGGACCTCTTACTCTCTCACAATCAGCAGAGTGGAGGCTG

AAGATACTGCCACTTATTACTGCCAGCAGTGGAGTAGTAACCCATTCACGTTCGGCTCGGG

GACAAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCA

GAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG

AGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Dectin_l_llB6.4_K-LV-hIgGK-C(SEQ ID NO: 95):

MDFQAQIFSFLLISASVIMSRGQIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWYQQKPGSSPK

PWIYATSHLASGVPARFSGSGSGTSYSLTISRVEAEDTATYYCQQWSSNPFTFGSGTKLEIKRTV

AAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTY

SLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗Dectin丄15E2.5_H-V-hIgG4H-C(SEQ ID NO: 96):

ATGGAAAGGCACTGGATCTTTCTACTCCTGTTGTCAGTAACTGCAGGTGTCCACTCCCAGG

TCCAGCTGCAGCAGTCTGGGGCTGAACTGGCAAGACCTGGGGCCTCAGTGAAGATGTCCT

GCAAGGCTTCTGGCTACACCmACTACCTACACTATGCACTGGGTAAAACAGAGGCCTGG

ACAGGGTCTGGAATGGATTGGATACATTAATCCTAGCAGTGGTTATACTAATTACAATCAG

AAGTTCAAGGACAAGGCCACATTGACTGCAGACAAATCCTCCAGCACAGCCTCCATGCAA

CTGAGCAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGAGAGAGGGCGGTA

TTAGTCCCCTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCA

AAACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA

CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA

ACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACT

CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACC

TGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATAT

GGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGT

TCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGT

CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC 158138.doc -58- Λ s 201208696

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT

CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG

CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC

CTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTT

CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTG

TCTCTGGGTAAAGCTAGCTGA 抗 Dectin一l_15E2.5_H-V-hIgG4H-C(SEQ ID NO: 97):

MERHWDFLLLLSVTAGVHSQVQLQQSGAELARPGASVKMSCKASGYTFTTYTMHWVKQRPG qglewigyinpssgytnynqkfkdkatltadkssstasmqlssltsedsavyycareravlvp

YAMDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL

TSGVHTFi APEFEGGF

FFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN1KVDKRVESKYGPPCPPCP EGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPRE EQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSDEmSKAKGQPREPQVYTLPPSQE EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWOE GNVFSCSVMHEALHNHYTQKSLSLSLGKAS 抗Dectin一l_15E2.5_K-V-hIgGK-C(SEQ ID NO: 98):

ATGCATTTTCAAGTGCAGATTTTCAGCTTCCTGCTAATCAGTGCCTCAGTCATAATGTCCAG

AGGACAAATTGTTCTCACCCAGTCTCCAGCAGTCATGTCTGCATCTCCAGGGGAGAAGGTC

ACCATAACCTGCACTGCCAGCTCAAGTTTAAGTTACATGCACTGGTTCCAGCAGAAGCCAG

GCACTTCTCCCAAACTCTGGCTTTATAGCACATCCATCCTGGCTTCTGGAGTCCCTACTCGC

TTCAGTGGCAGTGGATCTGGGACCTCTTACTCTCTCACAATCAGCCGAATGGAGGCTGAAG

ATGCTGCCACTTATTACTGCCAGCAAAGGAGTAGTTCCCCATTCACGTTCGGCTCGGGGAC

AAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Dectin_l_15E2.5JC-V-hIgGK-C(SEQ ID NO: 99):

MHFQVQIFSFLLISASVIMSRGQIVLTQSPAVMSASPGEKVnTCTASSSLSYMHWFQQKPGTSP

KLWLYSTSILASGVPTRFSGSGSGTSYSLTISRMEAEDAATYYCQQRSSSPFTFGSGTKLEIKRT

VAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDST

YSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗Dectin_l_2D8.2D4H-V-hIgG4H-C (SEQ ID N0:100): -59- 158138.doc 201208696

ATGGGATGGACCTGGATCTTTATTTTAATCCTGTCAGTTACTACAGGTGTCCACTCTGAGG

TCCAGCTGCAGCAGTCTGGACCTGAGCTGGAGAAGCCTGGCGCTTCAGTGAAGATATCCT

GCAAGGCTTCTGGTTACTCCTTCACTGGCTACAACATGAACTGGGTGAAACAGAGCAATG

GAAAGAGCCTTGAGTGGATTGGAAATATTGATCCTTACTATGGTGATACTAACTACAACCA

GAAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCA

CCTCAAGAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGACCCTACGGTAGT

GAGGCCTACTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACGA

AGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGC

CCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGG

CGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC

CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAAC

GTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC

CCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGG

ACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC

ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCA

ACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG

AGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC

TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATG

GGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT

TCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCAT

GCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCT

GGGTAAAGCTAGCTGA 抗Dectin一l_2D8.2D4H-V-hIgG4H-C (SEQ ID NO:101):

MGWTWIFILILSVTTGVHSEVQLQQSGPELEKPGASVKISCKASGYSFTGYNMNWVKQSNGKS

LEWIGNIDPYYGDTNYNQKFKGKATLTVDKSSSTAYMHLKSLTSEDSAVYYCARPYGSEAYF

AYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV

HTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEF

EGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTXPREEQFN

STYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF

SCSVMHEALHNHYTQKSLSLSLGKAS 抗 Dectin一 1 一2D8.2D4K-V-hIgGK-C (SEQ ID NO: 102):

ATGGTGTCCACTTCTCAGCTCCTTGGACTTTrGCnTTCTGGACTTCAGCCTCCAGATGTGA

CATTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGACTCCAGGAGATAGAGTCTCTCTT

TCCTGCAGGGCCAGCCAGAGTATTAGCGACTACTTACACTGGTATCAACAAAAATCACAT

GAGTCTCCAAGGCTTCTCATCAAATATGCTGCCCAATCCATCTCTGGGATCCCCTCCAGGT

TCAGTGGCAGTGGATCAGGGTCAGATTTCACTCTCAGTATCAACGGTGTGGAACCTGAAG 158138.doc -60- s 201208696

ATGTTGGAGTGTATTACTGTCAAAATGGTCACAGCTTTCCGTACACGTTCGGAGGGGGGAC

CAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Dectin—1 一2D8.2D4K-V-hIgGK-C (SEQ ID NO: 103): ΌΐνΜΤζ^ΡΑΤΧ5νΠΌΟΙΐν5Ι^α^Α5(^ΚΟΥυΓίνΥ(5(5Κ8ίΙΕ5ΡΚΙΧΙΚΥΑΑ(^Ι8αΡ3ΚΡ$ΰ3

GSGSDFTLSINGVEPEDVGVYYCQNGHSFPYTFGGGTKLEKRTVAAPSVFIFPPSDEQLKSGTA

SWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY

ACEVTHQGLSSPVTKSFNRGEC 抗蘭格素 15B10H-LV-hIgG4H-C(SEQ ID NO: 104):

ATGGAATGGAGGATCTTTCTCTTCATCCTGTCAGGAACTGCAGGTGTCCACTCCCAGGTTC

AGCTGCGGCAGTCTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATGTCCTGCA

AGGCTTCTGGATACACATTTACTGACTATGTTATAAGTTGGGTGAAGCAGAGAACTGGAC

AGGGCCTTGAGTGGATTGGAGATATTTATCCTGGAAGTGGTTATTCTTTCTACAATGAGAA

CTTCAAGGGCAAGGCCACACTGACTGCAGACAAATCCTCCACCACAGCCTACATGCAGCT

CAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTTCTGTGCAACCTACTATAACTACCCT

TTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACAACGGGCCCAT

CCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTG

CCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC

CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC

GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCrGCAACGTAGATCAC

AAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCA

CCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCA

AGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCC

AGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCA

AGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG

TCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCC

TCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGG

TGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCC

TGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG

AGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAG

CAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGAT

GCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCT

AGCTGA 抗蘭格素 15B10H-LV-hIgG4H-C(SEQ ID NO: 105): •61 · 158138.doc 201208696

QVQLRQSGPELVKPGASVKMSCKASGYTFTDYVISWVKQRTGQGLEWIGDIYPGSGYSFYNE

NFKGKATLTADKSSTTAYMQLSSLTSEDSAVYFCATYYNYPFAYWGQGTLVTVSAAKTTGPS

VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTV

PSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLM1SRT

PEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRWSVLTVLHQDWLNGK

EYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLS LGKAS. 抗蘭格素 15B10K-LV-hIgGK-C(SEQ ID NO: 106):

ATGAAGTTGCCTGTTAGGCTGTTGGTGCTGATGTTCTGGATTCCTGCTTCCAGCAGTGATGT

TGTGATGACCCAAACTCCACTCTCCCTGCCTGTCCGTCTTGGAGATCAAGCCTCCATCTCTT

GCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTACATTGGTACCTGCA

GAAGCCAGGCCAGTCTCCAAAGCTCCIGATCTACAAAGTTTCCAACCGATTTTCTGGGGTC

CCAGACAGGTTCAGTGGCAGTGGATCAGGGACAAATTTCACACTCAAGATCAGCAGAGTG

GAGGCTGAGGATCTGGGACTTTATTTCTGCTCTCAAAGTACACATGTTCCGTACACGTTCG

GAGGGGGGACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCC

GCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTC

TATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCC

CAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCA

GCXjCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗蘭格素 15B10K-LV-hIgGK-C(SEQ ID NO: 107):

DWMTQTPLSLPVRLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGV

PDRFSGSGSGTWTLKISRVEAEDLGLYFCSQSTHVPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQ

LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY

EKHKVYACEVTHQGLSSPVTKSFNRGEC 抗蘭格素2G3H-LV-hIgG4H-C(SEQ ID NO: 108):

ATGACATTGAACATGCTGTTGGGGCTGAGGTGGGITTTCTTTGTTGTTTTTTATCAAGGTGT

GCATTGTGAGGTGCAGCTTGTTGAGTCTGGTGGAGGATTGGTGCAGCCTAAAGGGTCATTG

AAACTCTCATGTGCAGCCTCTGGATTAACCTTCAATATCTACGCCATGAACTGGGTCCGCC

AGGCTCCAGGAAAGGGTTTGGAATGGGTTGCTCGCATAAGAAATAAAAGTAATAATTATG

CAACATATTATGCCGATTCAGTGAAAGACAGGTTCACCATCTCCAGAGATGATTCACAAA

GCTTGCTCTATCTGCAAATGAACAACTTGAAAACTGAGGACACAGCCATGTATTACTGTGT

GGGACGGGACTGGTTTGATTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAA

AACGAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCAC

AGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA

CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTC

TACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCT 158138.doc •62· s 201208696

GCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATAT

GGTCCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGT

TCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGT

GGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGA

GGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGT

CAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGT

CAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAG

CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTC

CTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTT

CTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTG

TCTCTGGGTAAAGCTAGCTGA 抗蘭格素2G3H-LV-hIgG4H-C(SEQ ID NO: 109):

MTLNMLLGLRWVFFWFYQGVHCEVQLVESGGGLVQPKGSLKLSCAASGLTFNIYAMNWVR

QAPGKGLEWVARIRNKSNNYATYYADSVKDRFTISRDDSQSLLYLQMNNLKTEDTAMYYCV

GRDWFDYWGQGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPP

CPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKP

REEQFNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLGKAS. 抗蘭格素2G3L-LV-hIgGK-C(SEQ ID NO: 110):

ATGGCCTGGATTTCACTTATACTCTCTCTCCTGGCTCTCAGCTCAGGGGCCATTTCCCAGGC

TGTTGTGACTCAGGAATCTGCACTCACCACATCACCTGGTGAAACAGTCACACTCACTTGT

CGCTCAAGTACTGGGGCTGTTACAACTAGTAACTATGCCAACTGGGTCCAAGAAAAACCA

GATCATTTATTCACTGGTCTAATAGGTGGTACCAACAACCGAGTTTCAGGTGTTCCTGCCA

GATTCTCAGGCTCCCTGATTGGAGACAAGGCTGCCCTCACCATCACAGGGGCACAGACTG

AGGATGAGGCAATATATTTCTGTGCTCTATGGTACAGCAACCATTGGGTGTTCGGTGGAGG

AACCAAACTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCT

GATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCA

GAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTG

AGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗蘭格素2G3L-LV-hIgGK-C(SEQ ID NO: 111):

MAWISLILSLLALSSGAISQAWTQESALTTSPGETVTLTCRSSTGAVTTSNYANWVQEKPDHL

FTGLIGGTNNRVSGVPARFSGSLIGDKAALTITGAQTEDEAIYFCALWYSNHWVFGGGTKLEIK

RTVAAPSWIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD

STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC -63- 158138.doc 201208696 抗Lox_l_10F9H-LV-hIgG4H-C(SEQ ID NO: 112):

ATGGAATGGACCTGGGTCTTTCTCTTCCTCCTGTCAGTAACTGCAGGTGTCCACTCCCAGG

TTCAGCTGCAGCAGTCTGGAGCTGAGCTGATGAAGCCTGGGGCCTCAGTGAAGATATCCT

GCAAGCX：TACTGGCTACACATTCGGTAGCTACTGGATAGAGTGGGTAAAGCAGAGGCCTG

GACATGGCCTTGAGTGGATTGGAGAGATTTTACCTGGAAGTGGTAATACTAACTACAATG

AGAACTTCAAGGGCAAGGCCACATTCACTGCAGATACATCCTCCAACACAGCCTACATGC

AACTCACCAGTCTGACATCTGAGGACTCTGCCGTCTATTACTGTGCTAGGGCGGGGATTTA

TTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAAACGAAGGGCCCATCCGTCTTC

CCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGC

GTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGA

CCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCA

GCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCC

CAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACA

CTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAG

ACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAA

AGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGC

ACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGT

CCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACA

CCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCA

AAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAAC

AACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGC

TAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATG

AGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGCTG

A 抗Lox_l_10F9H-LV-hIgG4H-C(SEQ ID NO: 113):

MEWTWVFLFLLSVTAGVHSQVQLQQSGAELMKPGASVKISCKATGYTFGSYWffiWVKQRPG

HGLEWIGEDLPGSGNTNYNENFKGKATFTADTSSNTAYMQLTSLTSEDSAVYYCARAGIYWG

QGTLVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPS vflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeq™styr

WSVLTVLHQDWLNGKEYKCKVSNKGLPSSffimSKAKGQPREPQVYTLPPSQEEMTKNQVS

LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV

MHEALHNHYTQKSLSLSLGKAS 抗Lox_l_10F9K-LV-hIgGK-C(SEQ ID NO: 114) lS8138.doc -64- s 201208696

ATGGAGAAAGACACACTCCTGCTATGGGTCCTGCTTCTCTGGGTTCCAGGTTCCACAGGTG

ACATTGTGCTGACCCAATCTCCAGCTnTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCAT

CTCCTGCAGAGCCAGCGAAAGTGTTGATAATTATGGCATTAGinTATGAACTGGTTCCAA

CAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGTTGCATCCAAGCAAGGATCCGGG

GTCCCTGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCAGCCTCAACATCCATCCTA

TGGAGGAGGATGATACTGCAATGTATTTCTGTCAGCAAAGTAAGGAGGTTCCTCGGACGT

TCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC

TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAAC

TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC

CCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCA

TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Lox丄 10F9K-LV-hIgGK-C(SEQ ID NO: 115):

MEKDTLLLWVLLLWVPGSTGDIVLTQSPAFLAVSLGQRATISCRASESVDNYGISFMNWFQQK

PGQPPKLLIYVASKQGSGVPARFSGSGSGTDFSLNIHPMEEDDTAMYFCQQSKEVPRTFGGGT

KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTE

QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗 LOX-lllC8H-LV-hIgG4H-C(SEQ ID NO: 116):

ATGGAATGTAACTGGATACTTCCTTTTATTCTGTCGGTAACTTCAGGGGTCTACTCAGAGG

TTCAGCTCCAGCAGTCTGGGACTGTGCTGGCAAGGCCTGGGGCTTCAGTGAAGATGTCCTG

CAAGGCTTCTGGCTACACCTTTACCAGCTACTGGATGCACTGGGTAAAACAGAGGCCTGG

ACAGGGTCTGGAATGGATTGGCGCTATTTATCCTGGAAATAGTGATACTACCTACAACCAG

AAGTTCAAGGGCAAGGCCAAACTGACTGCAGTCACATCCACCAGCACTGCCTACATGGAG

CTCAGCAGCCTGACAAATGAGGACTCTGCGGTCTATTACTGTACACCTACTTACTACTTTG

ACTACTGGGGCCAAGGCACCTCTCTCACAGTCTCCTCAGCCAAAACGAAGGGCCCATCCG

TCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCT

GGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG

CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTG

GTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAG

CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCC

TGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGG

ACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGG

AAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGA

CAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC

TGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC

CGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGT

ACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGG

TCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGA

ACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAG -65- 158138.doc 201208696

GCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCA

TGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGTAAAGCTAGC

TGA 抗LOX-lllC8H-LV-hIgG4H-C(SEQ ID NO: 117) ··

MECNWILPFILSVTSGVySEVQLQQSGTVLARPGASVKMSCKASGYTFTSYWMHWVKQRPG

QGLEWIGAIYPGNSDTTYNQKFKGKAKLTAVTSTSTAYMELSSLTNEDSAVYYCTPTYYFDY

WGQGTSLTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT

FPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEG

GPSVFLFPPKPKDTLMISRTPEVTCWVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST

YRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQEEMTKNQ

VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSC

SVMHEAUINHYTQKSLSLSLGKAS 抗LOX-lllC8K-LV-hIgGK-C(SEQ ID NO: 118):

ATGAGTCCTGCCCAAITCCTGTTTCTGTTAGTGCTCTGGATTCGGGAAACCAACGGTGATG

TTGTGATGACCCAGACTCCACTCACTTTGTCGGTTACCATTGGACAACCAGCCTCCATCTCT

TGCAAGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAGACATATTTGAATTGGTTCTTAC

AGAGGCCAGGCCAGTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAACTGGACTCTGGAGT

CCCTGACAGGTTCACTGGCAGTGGATCAGGGACAGATTTCACACTGAAAATCAGCAGAGT

GGAGGCTGAGGATTTGGGAGTTTATTATTGCTGGCAAGGTACACATTTTCCGTGGACGTTC

GGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCC

CGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTT

CTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTC

CCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCC

TGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATC

AGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗LOX-lllC8K-LV-hIgGK-C(SEQ ID NO: 119): mspaqflfllvlwiretngdwmtQtpltlsvtigqpasisckssqslldsdgktylnwflqrp

GQSPKRLryLVSKLDSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPWTFGGGTK

LEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ

DSKDSTYSLSSTLILSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗LOX-115C4H-LV-hIgG4H-C(SEQ ID NO: 120):

ATGGGAGGGATCTGGATCTTTCTCTTCCTCCTGTCAGGAACTGCAGGTGCCCACTCTGAGA

TCCAGCTGCAGCAGACTGGACCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCT

GCAAGGCTTCTGGTTATCCATTCACTGACTACATCATGGTCTGGGTGAAGCAGAGCCATGG aaagagccttgagtggattggaaatattagtccttactatggtactactAactacaatctg • 66· 158138.doc 201208696

AAGTTCAAGGGCAAGGCCACATTGACTGTAGACAAATCTTCCAGCACAGCCTACATGCAG

CTCAACAGTCTGACATCTGAGGACTCTGCAGTCTATTACTGTGCAAGATCCCCTAACTGGG

ACGGGGCCTGGTTTGCTCACTGGGGCCAAGGGGCTCTGGTCACTGTCTCTGCAGCCAAAAC

AAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGC

CGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCA

GGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACT

CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCA

ACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTC

CCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCC

CCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT

GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG

CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG

AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG

CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA tgggcagccggagaacaactacaagaccacgcctcccgtgctggactccgacggctcctt

CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC

ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT

CTGGGTAAAGCTAGCTGATTAATTAA 抗 LOX-115C4H-LV-hIgG4H-C(SEQ ID NO: 121):

MGGIWIFLFLLSGTAGAHSEIQLQQTGPELVKPGASVKISCKASGYPFTDYIMVWVKQSHGKSL

EWIGNISPYYGTTNYNLKFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYYCARSPNWDGAWF

AHWGQGALVTVSAAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE

FEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

FSCSVMHEALHNHYTQKSLSLSLGKAS 抗LOX-115C4K-LV-hIgGK-C(SEQ ID NO: 122):

ATGGAGACAGACACAATCCTGCTATGGGTGCTGCTGCTCTGGGTTCCAGGCTCCACTGGTG

ACATTGTGCTGACCCAATCTCCAGCrrCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCAT

CTCCTGCAAGGCCAGCCAAAGTGTTGATTATGATGGTGATAGTTATATGAACTGGTTCCAA

CAGAAACCAGGACAGCCACCCAAACTCCTCATCTATGCTGCATCCAATCTAGAATCTGGG

ATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCACCCTCAACATCCATCCTG

TGGAGGAGGAGGATGCTGCAACCTAnACTGTCAGCAAAGTAATGAGGATCCATTCACGT

TCGGCTCGGGGACAAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC •67- 158138.doc 201208696 ttctatcccagagaggccaaagtacagtggaaggtggataacgccctccaatcgggtaac

TCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC

CCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCA

TCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗 LOX-115C4K-LV-hIgGK-C(SEQ ID NO: 123):

METDTILLWVLLLWVPGSTGDIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWFQQ

KPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPFTFGSGTK

LEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ ϋ$ΚΟ3ΊΎ$Ι^3ΤυΓΙ^ΚΑΌΥΕΚΗΚνΥΑ0ΕνΤΗ(^Ι^3ΡνΤΚ8ΡΝΙ«3Ε€ 抗Marco—10B7.3G4H-LV-hIgG4H-C(SEQ ID NO: 124):

ATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACGTTCCCAAGCTGTGTCCTGTCCCAGGT

GCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCACCCTCACAGAGCCTGTCCATCACATG

CACTGTCTCTGGGTTCTCATTATCCAGATATAGTGTATTTTGGGTTCGCCAGCCTCCAGGAA

AGGGTCTGGAGTGGCTGGGATTGATATGGGGTGGTGGAAGCACAGACTATAATTCAGCTC

TCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGA

ACAGTCTGCAAACTGATGACACAGCCATGTACTACTGTGCCAGAATCTACTTTGATTACGA

CGGGGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAAAACAAC

GGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCC

CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC

GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCC

TCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACG

TAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCC

CATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCCC

AAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGA

CGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCA

TAATGCCAAGACAAAGCCGCGGGACKjACiCAGTTCAACAGCACGTACCGTGTGGTCAGCGT

CCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAA

CAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA

GCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCT

GACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGG

GCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC

CTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGC

TCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGG

GTAAAGCTAGCTG 抗Marco_10B7.3G4H-LV-hIgG4H-C(SEQ ID NO: 125):

MAVLGLLLCLVTFPSCVLSQVQLKESGPGLVAPSQSLSITCTVSGFSLSRYSVFWVRQPPGKGL

EWLGLIWGGGSTDYNSALKSRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARIYFDYDGAMD 158138.doc -68 · s 201208696

YWGQGTSVTVSSAKTTGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE

GGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRWSVLTVLHQDWLNGKEYKCKVSl^KGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS

CSVMHEALHNHYTQKSLSLSLGKAS 抗 Marco—10B7.3G4K_H-V-hIgGK-C(SEQ ID NO: 126):

ATGCATCGCACCAGCATGGGCATCAAGATGGAGTCACGGATTCAGGCATTTGTATTCGTGT

TTCTCTGGTTGTCTGGTGTTGGCGGAGACATTGTGATGACCCAGTCTCACAAATTCATGTC

CACATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGGATGTGACTTCTGC

TGTAGCCTGGTATCAACAAAAACCAGGGCAATCTCCTAAACTACTGATTTACTGGGCATCC

ACCCGGCACACTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTATACTC

TCACCATCAGCAGTGGGCAGGCTGAAGACCTGGCACTTTATTACTGTCACCAATATTATAG

CGCTCCTCGGACGTTCGGTGGAGGCACCAAGCTCGAGATCAAACGAACTGTGGCTGCACC

ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGT

GCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCC

TCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACA

GCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTATGCCT

GCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGT

GTTAG 抗Marco_10B7.3G4K_H-V-hIgGK-C(SEQ ID NO: 127):

MHRTSMGKMESRIQAFVFVFLWLSGVGGDIVMTQSHKFMSTSVGDRVSVTCKASQDVTSAV

AWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLnSSGQAEDLALYYCHQYYSAPR

TFGGGIXLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNS

QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗Marco—llA8.3C9_H-V-hIgG4H-C(SEQ ID NO: 128):

ATGGAATGGAACTGGGTCGTTCTCTTCCTCCTGTCATTAACTGCAGGTGTCTATGCCCAGG

GTCAGATGCAGCAGTCTGGAGCTGAGCTGGTGAAGCCTGGGGCTTCAGTGAAGCTGTCCT

GCAAGACTTCTGGCTTCACCTTCAGCAGTAACTATATAAGTTGGTTGAAGCAAAAGCCTGG

ACAGAGTCTTGAGTGGATTGCATGGATTrATGCTGGAACTGGTGGTATTACCTATAATCAG

AAGTTCAGAGGCAGGGCCCAACTGACTGTAGACACATCCTCCAGCACAGCCTACATGCAG

TTGAGCAGCCTGACAACTGATGACTCTGCCATCTATTACTGTGCAAGACACGTGAGGGGTT

ACCATCCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCCAAAACGA

AGGGCCCATCCGTCrrCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGC

CCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGG

CGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC

CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAAC •69· 158138.doc 201208696

GTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCC

CCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCCCCC

CAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGG

ACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGC

ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCA

ACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG

AGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCC TGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATG GGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT TCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCAT GCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCT GGGTAAAGCTAGCTGA ...... 抗 Marco_llA8.3C9_H-V-hIgG4H-C(SEQ ID NO: 129):

MEWNWWLFLLSLTAGVYAQGQMQQSGAELVKPGASVKLSCKTSGFTFSSNYISWLKQKPG

QSLEWIAWIYAGTGGITYNQKFRGRAQLTVDTSSSTAYMQFSSLTTDDSAIYYCARHVRGYHP

MDYWGQGTSVTVSSAKTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPE

FEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKnSKAKGQPREPQVYTLPPSQEEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV

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

ATGGAGTCACAGACTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGTTGATGGAG

ACATTGTGATGACCCAGTCTCAAAAATTCATGTCCGCATCAGTAGGGGACAGGGTCAGCG

TCACCTGCAGGGCCAGTCAGAATGTGGTTACTAATGTAGGCTGGTATCAACAGAAACCAG

GGCAATCTCCTAAAGTACTGATTTACTCGGCATCCTTCCGGTACAGTGGAGTCCCTGATCG

CTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCACCAATGTGCAGTCTGAA

GACTTGGCAGAGTATTTCTGTCAGCAATATAACAACTATCCGTACACGTTCGGAGGGGGG

ACCAAGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTG

ATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAG

AGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGA

GTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGA

GCAAAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGA

GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Marco_llA8.3C9_H-V-hIgGK-C(SEQ ID NO: 131): 158138.doc 70- s 201208696

MESQTQVFVYMLLWLSGVDGDIVMTQSQKFMSASVGDRVSVTCRASQNWTNVGWYQQKP

GQSPKVLIYSASFRYSGVPDRFTGSGSGTDFTLTITNVQSEDLAEYFCQQYNNYPYTFGGGTKL

EIKRTVAAPSVFIEPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD

SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 抗Marco_3H10.1F3_H-V-hIgG4H-C(SEQ ID NO: 132):

ATGGGATGGAGCTATATCATCCTCTTTTTGGTAGCAACAGCTACAGATGTCCACTCCCAGG

TCCAACTGCAGCAGCCTGGGGCTGAACTGGTGAAGCCTGGGGCTTCAGTGAAGCTGTCCT

GCAAGGCrTCTGGCTACACCTTCACCAGCTACTGGATGCACTGGGTGAAGCAGAGGCCTG

GAGAAGGCCTTGAGTGGATTGGAGAGATTAATCCTAGCTACGGTCGTACTGACTACAATG

GGAAGTTCAAGAACAAGGCCACACTGACTGTAGCCAAATCCTCCAGCACAGCCTACATGC

AACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCTATTACTGTGCAAGAGGAGATTACTA

CGGTAGTAGCTCGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCAGCCAAA

ACAAAGGGCCCATCCGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA

GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACT

CAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTA

CTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGC

AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGT

CCCCCATGCCCACCCTGCCCAGCACCTGAGTTCGAAGGGGGACCATCAGTCTTCCTGTTCC

CCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGT

GGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGT

GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAG

CGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG

AGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAG

CCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA

TGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT

CTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTC

ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCT

CTGGGTAAAGCTAGCTGA 抗Marco一3H10.1F3_H-V-hIgG4H-C(SEQ ID NO: 133):

MGWSYIILFLVATATDVHSQVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWVKQRPG

EGLEWIGEINPSYGRTDYNGKFKNKATLTVAKSSSTAYMQLSSLTSEDSAVYYCARGDYYGSS

SFAYWGQGTLVTVSAAKTKGPSWPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS

GVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP

EFEGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ

FNSTYRWSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN

VFSCSVMHEALHNHYTQKSLSLSLGKAS -71- 158138.doc 201208696 抗 Marco_3H10.1F3_K-V-hIgGK-C(SEQ ID NO: 134):

ATGGAGTCACAGACTCAGGTCTTTGTATACATGTTGCTGTGGTTGTCTGGTGTTGATGGAG

ACATTGTGATGACCCAGTCTCAAAAATTCATGTCCACATCATTAGGAGACAGGGTCAGCGT

CACCTGCAAGGCCAGTCAGAATGTGGGTACTAATGTAGCCTGGTATCAACAGAAACCAGG

GCACTCTCCTAAAGCACTGATTTACTCGGCATCCTACCGGTACAGTGGAGTCCCTGATCGC

TTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAATGTGCAGTCTGAAG

ACTrGGCAGAGTTmCTGTCAGCAATATAACAACTATCCGTACACGTTCGGAGGGGGGAC

CACGCTCGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT

GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAG

AGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCA

AAGCAGACTACGAGAAACACAAAGTCTATGCCTGCGAAGTCACCCATCAGGGCCTGAGCT

CGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG 抗Marco—3H10.1F3_K-V-hIgGK-C(SEQ ID NO: 135):

MESQTQVFVYMLLWLSGVDGDIVMTQSQKFMSTSLGDRVSVTCKASQNVGTNVAWYQQKP

GHSPKAUYSASYRYSGVPDRFTGSGSGTDFTLnSNVQSEDLAEFFCQQYNNYPYTFGGGTTL

EIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD

SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 本發明之抗原包含一或多個選自以下之病毒抗原或肽： 腺病毒、反轉錄病毒、小核糖核酸病毒、疮療病毒、輪狀 病毒、漢坦病毒（hantavirus)、冠狀病毒、彼衣病毒、黃病 毒、棒狀病毒、副黏液病毒、正黏液病毒、布尼亞病毒 (bunyavirus)、沙狀病毒、里奥病毒（reovirus)、乳頭瘤病 毒、細小病毒、痘病毒、嗜肝DNA病毒或海錦狀病毒、 HIV、CMV、A型、B型及C型肝炎、流感；麻疹、脊髓灰 質炎、天花、風疹；呼吸道融合病毒、單純疱疹病毒、水 痘帶狀疮療病毒、EB病毒、日本腦炎病毒、狂犬病病毒、 流感病毒或感冒病毒。抗原係選自：Nef(66-97): VGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGL(SEQ ID NO:

136) ； Nef(116-145) ： HTQGYFPDWQNYTPGPGVRYPLTFGWL 72· 158138.doc 201208696 YKL(SEQ ID NO: 137) ； Gag pl7(17-35) ： EKIRLRPGGKKK YKLKHIV(SEQ ID NO: 138) ； Gag pl7-p24(253-284) ： NPPIP VGEIYKRWIILGLNKIVRMYSPTSILD(SEQ ID NO: 139);及/或 Pol 325-355(RT 158-188)為：AIFQSSMTKILEPFRKQNPDIVI YQYMDDLY(SEQ ID NO: 140)。在一態樣中，該抗原為 19 至32個殘基且選自在MHC I型分子情形中呈現之HIV-1 Nef、Gag及Env蛋白中所鑑定之細胞毒性T淋巴細胞（CTL) 抗原決定基。在另一態樣中，抗原係選自HIV gpl20、 gp41、Gag、pl7、p24、p2、p7、pi、p6、Tat、Rev、 PR、RT、IN、Vif、Vpr、Vpx、Vpu及 Nef。 在另一態樣中，抗原係選自腫瘤相關抗原，該等腫瘤相 關抗原選自CEA、前列腺特異性抗原（PSA)、HER-2/neu、 BAGE、GAGE、MAGE 1-4、6及 12、MUC相關蛋白（黏蛋 白）(MUC-1、MUC-2 等）、GM2 及 GD2神經節苷脂、ras、 myc、酿·胺酸酶、MART(黑色素瘤抗原）、MARCO-MART、週期素 B 1、週期素 D、.Pmel 17(gp 100)、GnT-V 内 含子V序列（N-乙醯葡萄糖胺基轉移酶V内含子V序列）、前 列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗 原）、β-索烴素、MUM-1-B(黑色素瘤普遍性突變基因產 物）、GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗原ρ-ΐΟ 、 c-ERB2(Her2/neu) 、 EBNA(EB 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（LRP)、Bcl-2及Ki-67。在另一態樣中’抗原係選自腫瘤 相關抗原，包含來自以下之抗原：白血病及淋巴瘤、神經 158138.doc -73- 201208696 腫瘤（諸如星形細胞瘤或神經膠母細胞瘤）、黑色素瘤、乳 癌、肺癌、頭頸癌、胃腸腫瘤、胃癌、結腸癌、肝癌、胰 臟癌、泌尿生殖器腫瘤（諸如子宮頸癌、子宮癌、卵巢 癌、陰道癌、睾丸癌、前列腺癌或陰莖癌）、骨腫瘤、血 管瘤、或唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽管 樹、喉、肺及支氣管、膀胱、腎臟、腦及神經系統之其他 部分、甲狀腺之癌症、霍奇金氏病、非霍奇金氏淋巴瘤、 多發性骨聽瘤及白血病。 抗原係選自以下中之至少一者： MWVPWFLTLSVTWIGAAPLILSRIVGGWECEKHSQPW QVLVASRGRAVCGGVLVHPQWV(SEQ ID NO: 141)； LTAAHCIRNKSVILLGRHSLFHPEDTGQVFQVSHSFPHPL YDMSLLKNRFLRPGDDSSHD(SEQ ID NO: 142)； LMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWG SIEPEEFLTPKKLQCVDLHVIS(SEQ ID NO: 143)； NDVCAQVHPQKVTKFMLCAGRWTGGKSTCSGDSGGPL VCNGVLQGITSWGSEPCALPERP(SEQ ID NO: 144);或 SLYTKVVHYRKWIKDTIVANP(SEQ ID NO:145)。 在另一態樣中，抗原係選自以下中之至少一者： IMDQVPFSV(SEQ ID NO: 146)； ITDQVPFSV(SEQ ID NO: 147)； YLEPGPVTV(SEQ ID NO: 148)； YLEPGPVTA(SEQ ID NO: 149)； KTWGQYWQV(SEQ ID NO: 150)； 158138.doc -74- s 201208696 DTTEPATPTTPVTTPTTTKVPRNQDWLGVSRQLRTKAW NRQLYPEWTEAQRLDCWRGGQVSLKVSNDGPTLIGANAS FSIALNFPGSQKVLPDGQVIWVNNTIINGSQVWGGQPVYP QETDDACIFPDGGPCPSGSWSQKRSFVYVWKTWGQYWQ VLGGPVSGLSIGTGRAMLGTHTMEVTVYHRRGSQSYVPL AHSSSAFTITDQVPFSVSVSQLRALDGGNKHFLRNQ(SEQ ID NO: 151)； PLTFALQLHDPSGYLAEADLSYTWDFGDSSGTLISRAXV VTHTYLEPGPVTAQVVLQAAIPLTSCGSSPVPAS(SEQ ID NO: 152)； GTTDGHRPTAEAPNTTAGQVPTTEVVGTTPGQAPTAEPS GTTSVQVPTTEVISTAPVQMPTAESTGMTPEKVPVSEVMG TTLAEMSTPEATGMTPAEVSIVVLSGTTAA(SEQ ID NO: 153)； QVTTTEWVETTARELPIPEPEGPDASSIMSTESITGSLGP LLDGTATLRLVKRQVPLDCVLYRYGSFSVTLDIVQ(SEQ ID NO: 154);及 GIESAEILQAVPSGEGDAFELTVSCQGGLPKEACMEISSP GCQPPAQRLCQPVLPSPACQLVLHQILKGGSGTYCLNVSL ADTNSLAVVSTQLIVPGILLTGQEAGLGQ(SEQ ID NO: 155)及其片段。 在另一態樣中，抗原係選自以下中之至少一者：

MEMKILRALNFGLGRPLPLHFLRRASKIGEVDVEQHTL AKYLMELTMLDY(SEQ ID NO: 156);及 DWLVQVQMKF 158138.doc -75- 201208696 RLLQETMYMTVSIIDRFMQNNCVPKK(SEQ ID NO: 157)。 在另一態樣中，抗原係選自以下中之至少一者： MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETC APSVSYFKCV(SEQ ID NO: 158)； QKEVLPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLD RFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIY TDNSIRPEELLQMELL(SEQ ID NO: 159)； LVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRKH AQTFVALCATDVKFISNPPSMV(SEQ ID NO: 160);及 AGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCDPDC LRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDL ACTPTDVRDVDI(SEQ ID NO: 161)及其片段。 在另一態樣中，抗原為19至32個胺基酸長。在另一態樣 中，抗原為17至60個胺基酸長且選自在PSA或週期素1中 所鑑定之細胞毒性T淋巴細胞（CTL)抗原決定基。 在另一態樣中，癌肽係選自腫瘤相關抗原，該等腫瘤相 關抗原選自CEA、前列腺特異性抗原（PS A)、HER-2/neu、 BAGE、GAGE、MAGE 1-4、6及 12、MUC相關蛋白（黏蛋 白）(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、週期素B1、週期素D、Pmel 17(gpl00)、GnT-V内 含子V序列（N-乙醯葡萄糖胺基轉移酶V内含子V序列）、前 列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗 原）、β-索烴素、MUM-1-B(黑色素瘤普遍性突變基因產

158138.doc -76- S 201208696 物）、GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗原ρ-ΐΟ 、 c-ERB2(Her2/neu) 、 EBNA(EB 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（LRP)、Bcl-2及 Ki-67。 製備細胞：在收集知情同意書後，對健康個體進行單採 血液成分程序。此方案由貝勒研究院機構審查委員會 (Baylor Research Institute Institutional Review Board)審查 及批准。自單採血液樣品純化PBMC且在極冷保藏後使 用。在 Cellgenix，用與 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（淘析溶離份5 ’ Lemarie等人，J. Immunological Methods，2007)製備來源於單核細胞之IFNa-DC。 胞外細胞因子分泌檢定。PBMC或來源於單核細胞之 IFNa-DC(2xl06細胞/毫升，200 微升/孔）在 37°C 及 5% C02 下，在含有10%人類AB血清、2 mM L-麩胺醯胺、50 U青 黴素（penicillin)、50 pg/nil鏈徽素（streptomycin)、IX必需 胺基酸、25 mM hepes、55 μΜ 2-巯基-乙醇與DC標靶疫苗 及所關注之TLR配位體的cRPMI中培養24小時或保持不受 刺激（陰性對照）24小時。接著收集培養液上清液且隨後使 用BioPlex200 Luminex(BioRad)量測培養液上清液中之所 分泌細胞因子。 j 圖1A-1D展示鞭毛蛋白及若干本發明之抗體-鞭毛蛋白構 築體。 圖2展示用於測試本發明之抗體-鞭毛蛋白構築體活性之 158138.doc -77- 201208696 研究設計。 圖3A至3C展示用本發明之構築體活化多種類型細胞時 IL-6之分泌情況。在2個鞭毛蛋白域⑺糾丨及flgn2)之間添 加柔性連接子（flex)消除活性。多種細胞為IFNa活化之DC 及外周血液單核細胞（PBMC)。 圖4A至4B展示如依據IL-6及IL-Ιβ之分泌情況所量測之 多種構築體的劑量滴定情況。鞭毛蛋白活性與標靶抗體相 關且甚至在最低〇. 1 nM劑量下有效，而同型對照物僅在25 nM劑量下得到反應。圖4C至4D展示如依據IL-6及IL-Ιβ之 分泌情況所量測之多種構築體的劑量滴定情況。鞭毛蛋白 活性與標靶抗體相關且甚至在最低〇 . 1 nM劑量下有效，而 同型對照物僅在25 nM劑量下得到反應。此外，添加游離 抗體至同型對照物中並未恢復鞭毛蛋白活性。 圖5展示所列基因之基因表現熱圖（使用連有或不連有鞭 毛蛋白之抗LOX-1抗體）。在自與flgn一起培養之 IFNa-DC獲得的熱圖中發現，作為對‘οχ」flgn刺激的反 應’ Π種轉錄物受到過度表現。 預期本說明書中討論之任何實施例可結合本發明之任何 方法、套組、試劑或組合物加以實施，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係為了說明，而非為了 限制本發明而展示。本發明之主要特徵可用於各種實施例 中而不悖離本發明之範疇。熟習此項技術者將意識到或僅 僅使用常規實驗便能夠確定本文中所述之特定程序的眾多 158138.doc •78·

S 201208696 等效物。該等等效物被視為屬於本發明之範嘴内且由申請 專利範圍所涵蓋。 本說月書中提及之所有公開案及專利申請案代表熟習本 發明所屬技術者之技術水準。所有公開案及專利申請案係 以引用之方式併入本文中，其引用程度如同特定地及個別 : 地指明將各個別公開案或專利申請t以引用之方式併入一 般。 申請專利範圍及/或本說明書中使用詞「一」當結合術 00包合」使用’可意謂「一個」’但亦符合「一或多 個」、「至少一個」及「一個或一個以上」之含義。申請專 利範圍中使用術語「或」係用以意謂「及/或」，除非明確 說明係指唯一選擇項或選擇項互相排斥，但本發明支持唯 一選擇項及「及/或」之定義。在整篇本申請案中，術語 「約」對於用以測定值的裝置、方法而言用以指示包括固 有誤差變化或研究個體中存在之變化之值。 如本說明書及申請專利範圍中所用，詞語「包含」（及 包含之任何形式）、「具有」（及具有之任何形式）、「包括」 (及包括之任何形式）或「含有」（及含有之任何形式）具包 涵性或開放性且不排除其他未經陳述之要素或方法步驟。 : 如本文所用，術語「或其組合」係指該術語前面所列項 舀之所有排列及組合。舉例而言，「A、B、C或其組人 思欲包括以下至少一者：A、B、C、AB、AC、bc咬 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。才艮據此 158138.doc -79- 201208696 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、CAB ABB等。熟習此項技術者應理解，除非自 上下文顯而易見，否則對任何組合中之項目或術語之數目 通常不存在限制。 不經過度實驗便可根據本發明形成並實施本文中所揭示 並主張之所有組合物及/或方法。雖然本發明之組合物及 方法已根據較佳實施例描述，但熟習此項技術者顯而易 見，在不悖離本發明之概念、精神及範疇之情況下，可對 本文所述之組合物及/或方法及方法之步驟或步驟次序進 行變更。熟習此項技術者顯而易見之所有該等類似替代及 修改視為在如隨附申請專利範圍所限定之本發明精神、範 疇及概念内。 參考文獻 美國專利申請案 20090004194 : TLR agonist (flagellin)/ CD40 agonist/antigen protein and DNA conjugates and use thereof for inducing synergistic enhancement in immunity o 美國專利申請案20080220011 : Use of flagellin in tumor immunotherapy ° 美國專利申請案 20080248068 : 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】 158138.doc -80 - 201208696 々圖1A ID展不鞭毛蛋白及本發明之若干抗體·鞭毛蛋白構 築體：圖1A :保守性N端及c端區殘基合起來足以活化 TLR5-對於此功能而言’，心殘基為不必要的；請：鞭 毛蛋白與DC標靶抗體直接融合之活性組態之實例，以使 鞭毛蛋白片段之活化特性特定針對表現特定DC受體之細 胞，從而將鞭毛蛋白之免疫刺激特性與抗DC受體抗體之 免疫刺激特性組合；_lc: 1B之變異體，其+兩個保守 性鞭毛蛋白域之片段由連接子或抗原序列分隔-在圖3A明 示之實例中，具有特定連接子序列之此組態無活性；圖 1D:圖1A之變異體，纟中抗原或蛋白質蛋白質相互作用 域（在此情況下為錨定蛋白）直接連接在鞭毛蛋白與抗體域 之間。圖3及4展示藉由該變異體免疫刺激之實例； 圖2展示用於測試本發明之抗體_鞭毛蛋白構築體活性之 研究設計； 圖3A至3C展示用本發明之構築體活化多種類型細胞 時，IL-6之分泌情況； 圖4A至4D展示如依據IL-6及IL-1 β分泌情況所量測之多 種構築體的劑量滴定情況。資料證明鞭毛蛋白片段之免疫 刺激作用與構築體之DC標靶抗體部分所介導之DC受體相 互作用（在此情況下為LOX-1)相關-對照hIgG4-鞭毛蛋白構 築體僅在高得多的濃度下具有活性^其他對照物展示鞭毛 蛋白片段與DC標粗抗體之直接融合為免疫刺激效能增強 的原因；及 圖5展示所列基因之基因表現熱圖（使用連接或不連接鞭 158138.doc -81· 201208696 毛蛋白之抗LOX-1抗體）。上調之免疫刺激分子之確切組合 將隨連接於鞭毛蛋白片段之不同抗DC受體抗體構築體而 變化，因為將涉及標靶細胞之不同組合且經由鞭毛蛋白及 DC標靶抗體之信號傳導將存在不同組合形式。 158138.doc -82-

S 201208696 序列表 <11〇>美商貝勒研究協會 <120>以直接針對抗原呈現細胞之抗體的標乾佐劑為主之新穎疫苗佐劑

<130> BHCS ： 2468TW <140> 100128970 <141> 2011-08-12 <150> 61/373,763 <151> 2010-08-13 <160> 161 <170> Patentln version 3.5 <210> 1 <211> 715 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 1

Gin Val Thr Leu Lys Glu Ser Gly Pro Gly lie Leu Gin Pro Ser Gin 15 10 15

Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser 20 25 30

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

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

Leu Lys Ser Arg Leu Thr He Ser Lys Asp Thr Ser Ser Asn Gin Val 65 70 75 80

Phe Leu Lys He Thr He Val Asp Thr Ala Asp Ala Ala Hir Tyr Tyr S5 90 95 .

Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr 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 Ser Thr Ser 130 135 140

Glu Ser Thr Ala Ala Leu Gly Cys Leu Va! Lys Asp Tyr Phe Pro Glu 145 150 155 160

Pro Val ITir Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 158138·序列表.doc 201208696

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

Val Val Thr Val Pro Ser Scr Ser Leu Gly 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 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu 225 230 235 240

Gly Gly 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

Val 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

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

He Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin 340 345 350

Val Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val 355 360 365

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

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

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

Val Asp Lys Ser Arg Trp Gin Giu Gly Asn Val Phe Ser Cys Scr Val 420 425 430

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

Ser Leu Gly Lys Ala Ser Gin Thr Pro Thr Asn Thr He Ser Va] Thr 450 455 460

Pro Thr Asn Asn Ser Thr Pro Thr Asn Asn Ser Asn Pro Lys Pro Asn 465 470 475 480 158138-序列表.doc _2- s 201208696

Pro Ala Ser lie Glu Arg Leu Ser Ser Gly Leu Arg lie Asn Ser Ala 485 490 495

Lys Asp Asp Ala Ala Gly Gin Ala He Ala Asn Arg Phe Thr Ala Asn 500 505 510 lie Lys Gly Leu Thr Gin Ala Ser Arg Asn Ala Asn Asp Gly He Ser 515 520 525 lie Ala Gin Thr Thr Glu Gly Ala Leu Asn Glu lie Asn Asn Asn Leu 530 535 540

Gin Arg Val Arg Glu Leu Ala Val Gin Ser Ala Asn Ser Thr Asn Ser 545 550 555 560

Gin Ser Asp Leu Asp Ser lie Gin Ala Glu lie Thr Gin Arg Leu Asn 565 570 575

Glu He Asp Arg Val Ser Gly Gin Thr Gin Phe Asn Gly Val Lys Val 580 585 590

Leu Ala Gin Asp Asn Thr Leu Thr lie Gin Val Gly Ala Asn Asp Gly 595 600 605

Glu Thr lie Asp lie Asp Leu Lys Gin lie Asn Ser Gin Thr Leu Gly 610 615 620

Leu Asp Ser Leu Asn Val Gin Ala Ser Gin Pro Glu Leu Ala Glu Ala 625 630 635 640

Ala Ala Lys Thr Thr Glu Asn Pro Leu Gin Lys He Asp Ala Ala Leu 645 650 655

Ala Gin Val Asp Ala Leu Arg Ser Asp Leu Gly Ala Val Gin Asn Arg 660 665 670

Phe Asn Ser Ala lie Thr Asn Leu G!y Asn Thr Val Asn Asn Leu Ser 675 680 685

Glu Ala Arg Ser Arg lie Glu Asp Ser Asp Tyr Ala Thr Glu Val Ser 690 695 700

Asn Met Ser Arg Ala Gin lie Leu Gin Ala Scr 705 710 715 <210> 2 <21.1> 797 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 2

Gin Val Thr Leu Lys Glu Ser Gly Pro Gly lie Leu Gin Pro Ser Gin 15 10 15 158138-序列表.doc 201208696

Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phc Ser Leu Ser Thr Ser 20 25 30

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

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

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

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

Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr 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 Ser Thr Ser 130 135 140

Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160

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

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

Val Val Thr Val Pro Ser Ser Ser Leu Gly 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 Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu 225 230 235 240

Gly Gly 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 Va! Ser 260 265 270

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

Val 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 -4- 158138·序列表.doc s 201208696

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335 lie Glu Lys llir lie Ser Lys Ala Lys Giy Gin Pro Arg Glu Pro Gin 340 345 350

Val Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val 355 360 365

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

Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro 3SS 390 395 400

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

Val Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val 420 425 430

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

Scr Leu Gly Lys Ala Ser Ser Glu Asp Thr Gin Pro Pro Ala Pro Thr 450 455 460

Leu lie Gly Asp Val Asa Ala Asp Gly Lys lie Asp Ser Thr Asp Leu 465 470 475 480

Thr Leu Leu Lys Arg Tyr Leu Leu Arg Ser Ala Thr Leu Thr Glu Glu 485 490 495

Lys lie Leu Asn Ala Asp Thr Asp Gly Asn Gly Thr Val Asn Ser Thr 500 505 510

Asp Leu Asn Tyr Leu Lys Lys Tyr lie Leu Arg Val He Ser Val Phe 515 520 525

Pro Ala Glu Gly Asn Lys Pro Pro Thr Pro Thr Pro Thr Lys Thr Pro 530 535 540

Val Ala Thr Pro Ser Pro Thr Gin Pro Leu Phe Thr Pro Ser Phe Lys 545 550 555 560

Asp Val Thr Ala Ser lie Glu Arg Leu Ser Ser Gly Leu Arg lie Asn 565 570 575

Ser Ala Lys Asp Asp Ala Ala Gly Gin Ala lie Ala Asn Arg Phc Thr 580 585 590

Ala Asn lie Lys Gly Leu Thr Gin Ala Ser Arg Asn Ala Asn Asp Gly 595 600 605 lie Ser He Ala Gin Thr Thr Glu Gly Ala Leu Asn Glu lie Asn Asn 158138-序列表.doc 201208696 610 615 620

Asn Leu Gin Arg Val Arg Glu Leu Ala Val Gin Ser Ala Asn Ser Thr 625 630 635 640

Asn Ser Gin Set Asp Leu Asp Ser lie Gin Ala Glu lie Thr Gin Arg 645 650 655

Leu Asn Glu lie Asp Arg Val Ser Gly Gin Thr Gin Phe Asn Gly Val 660 665 670

Lys Val Leu Ala Gin Asp Asn Thr Leu Thr He Gin Val Gly Ala Asn 675 680 685

Asp Gly Glu Thr lie Asp lie Asp Leu Lys Gin He Asn Ser Gin Thr 690 695 700

Leu Gly Leu Asp Ser Leu Asn Val Gin Ala Ser Gin Pro Glu Leu Ala 705 710 715 720

Glu Ala Ala Ala Lys Tlu Thr Glu Asn Pro Leu Gin Lys lie Asp Ala 725 730 735

Ala Leu Ala Gin Val Asp Ala Leu Arg Ser Asp Leu Gly Ala Val Gin 740 745 750

Asn Arg Phe Asn Ser Ala lie Thr Asn Leu Gly Asn Thr Val Asn Asn 755 760 765

Leu Sei* Glu A]a Arg Ser Arg lie G]u Asp Ser Asp Tyr Ala Thr Glu 770 775 780

Val Ser Asn Met Ser Arg Ala Gin lie Leu Gin Ala Ser 785 790 795 <210> 3 <211> 430 <212> PRT <213>人工序列 <220> <223>合成肽《 <400> 3

Met Asp Leu Asp Ala Val Arg lie Lys Val Asp Thr Val Asn Ala Lys 1 5 10 15

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

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

Leu Glu He lie Glu lie Lys Pro Gly Glu Leu lie Val Asp Pro Asn 50 55 60

Pro Thr Lys Ser Phe Asp Thr Ala Val Tyr Pro Asp Arg Lys Met lie 65 70 75 80 158138-序列表.doc s 201208696

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 lie Val Ala Lys Val Lys Glu Gly Ala 100 105 110

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

Asn Asn Asp Leu Val Glu Gin Lys Thr Gin 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 】45 150 155 160

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 lie Pro Ser Gly Pro Leu Lys Ala 180 185 190

Glu lie Ala Gin Arg Leu Glu Asp Val Phe Ala Gly Lys Asn Thr Asp 195 200 205

Leu Glu Val Leu Met Glu Trp Leu Lys Thr Arg Pro He Leu Ser Pro 210 215 220

Leu Thr Lys Gly lie 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 Tyr 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 lie 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 lie 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 158138-序列表.doc 201208696 370 375 380

Ala Met Arg rFhr lie 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 Gin Arg Phe Lys Leu Glu His His His His His His 420 425 430 <210> 4 <211> 513 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 4 lie Leu Gin Pro Ser Gin 15

Gin Val Tlir Leu Lys Glu Ser Gly Pro Gly 1 5 10

Thr Leu Ser Leu Thr Cys Scr Phc Scr Gly Phe Ser Leu Ser Thr Ser 20 25 30

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

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

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

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

Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr 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 Ser Thr Ser 130 135 140

Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160

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

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

Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys 195 200 205 158138-序列表.doc 201208696

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

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

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

Met lie Ser Arg Thr Pro Glu Vai 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

Val 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

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335 lie Glu Lys Thr He Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin 340 345 350

Val Tyr Thr Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val 355 360 365

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

Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Ty了 Lys Thr Thr Pto 385 390 395 400

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

Val Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val 420 425 430

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

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

Pro Thr Asn Asn Ser Thr Pro Thr Asn Asn Scr 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 ΤΪΓ Pro Thr Asn Asn Ser Asn Pro Lys Pro Cys Pi〇 Ala 158138-序列表.doc 201208696 500 505 510

Ser <210> 5 <2I1> 415 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 5

Leu Asp lie Thr Ser His His His His His His Asp Asp Leu Asp Ala 15 10 15

Val Arg lie Lys Val Asp Thr Val Asn Ala Lys Pro Gly Asp Thr Val 20 25 30

Arg lie Pro Val Arg Phe Ser Gly lie Pro Ser Lys Gly lie Ala Asn 35 40 45

Cys Asp Phe Val Tyr Ser Tyr Asp Pro Asn Val Leu Glu lie lie Giu 50 55 60

Tie Glu Pro Gly Asp lie lie Val Asp Pro Asn Pro Asp Lys Ser Phe 65 70 75 80

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

Glu Asp Ser Gly Thr Gly Ala Tyr Ala lie Thr Lys Asp Gly Vat Phe 100 105 110

Ala Thr He Val Ala Lys Val Lys Glu Gly Ala Pro Asn Gly Leu Ser 115 120 125

Val lie Lys Phe Val Glu Val Gly Gly Phe Ala Asn Asn Asp Leu Val 130 135 140

Glu Gin Lys Thr Gin Phe Phe Asp Gly Gly Val Asn Val Gly Asp Thr L45 150 155 160

Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Thr Thr Pro Thr Thr Thr 365 Π0 175

Asp Asp Leu Asp Ala Ala Ser He Glu Arg Leu Ser Ser Gly Leu Arg 180 185 190 [lc Asn Ser Ala Lys Asp Asp Ala Ala Gly Gin Ala lie Ala Asn Arg 195 200 205

Phe Thr Ala Asn lie Lys Gly Leu Thr Gin Ala Ser Arg Asn Ala Asn 210 215 220

Asp Gly lie Ser lie Ala Gin Thr Thr Glu Gly Ala Leu Asn Glu lie 225 230 235 240 158138-序列表.doc -10-

S 201208696

Asn Asn Asn Leu Gin Arg Val Arg Glu Leu Ala Val Gin Ser Ala Asn 245 250 255

Ser Thr Asn Ser Gin Ser Asp Leu Asp Ser lie Gin Ala Glu lie Thr 260 265 270

Gin Arg Leu Asn Glu lie Asp Arg Val Scr Gly Gin Thr Gin Phe Asn 275 280 285

Gly Val Lys Val Leu Ala Gin Asp Asn Thr Leu Thr lie Gin Val Gly 290 295 300

Ala Asn Asp Gly Glu Thr lie Asp lie Asp Leu Lys Gin He Asn Scr 305 310 315 320

Gin Thr Leu Gly Leu Asp Ser Leu Asn Val Gin Ala Scr Gin Pro Glu 325 330 335

Leu Ala Glu Ala Ala Ala Lys Thr Thr Glu Asn Pro Leu Gin Lys He 340 345 350

Asp Ala Ala Leu Ala Gin Val Asp Ala Leu Arg Ser Asp Leu Gly Ala 355 360 365

Val Gin Asn Arg Phe Asn Scr Ala lie rihr Asn Leu Gly Asn Thr Val 370 375 380

Asn Asn Leu Ser Glu Ala Arg Ser Arg lie Glu Asp Ser Asp Tyr Ala 385 390 395 400

Thr Glu Val Ser Asn Met Ser Arg Ala Gin He Leu Gin Ala Ser 405 410 415 <210> 6 <211> 1409 <212> m <213>人工序列 <220> <223>合成寡核苷酸。 <400> 6 atgggcaggc ttaettette attettgeta ctgattgtcc ctgcatatgt cctgtcccag gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgacc tgctctttct ctgggttttc actgagcact tctggtatga gtgtaggctg gattegteag ccttcaggga agggtctgga gtggctggct cacatttggt ggaatgatga taagtactat aatccagtcc tgaaaagccg gctcacaatc tccaaggaga cctccaacaa ccaggtattc ctcaagatcg ccagtgtggt ctctgcagat actgccacat actactglgc tegattetat £gtaactgtc ttgactactg gggccaaggc accactctca cagtctcctc ggccaaaaca aagggcccat ccgtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac -11- 158138·序列表.doc 201208696 tccctcagca gcgtgfitgac cstgccctcc ascagcttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcg£gag gagcagttca acagcacgta ccgtgtggtc agcgtcclca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctgglcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgct^gactc cgacggctcc ttcttcctct acagcaggct aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc tcaigctccg tgatgcatga ggctctgcac aaccactaca cacagaagas cctctccctg tctctgggta aagctagctg attaattaa <210> 7 <211> 466 <212> PRT <213>人工序列 <220> <223>合成肽。 <400〉7

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

Val Leu Ser Gin Val Thr Leu Lys Glu Scr 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 Scr Gly Met Ser Val 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 He Ser Lys Glu TTir Ser Asn 85 90 95

Asn Gin Val Phe Leu Lys lie Ala Ser Val Val Ser Ala Asp Thr Ala 100 105 110

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

Gin Gly Thr Thr Leu Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Ser 130 135 140 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1409 158138-序列表doc •12- s 201208696

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 Pro Glu Pro Val Thr Val 165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 380 185 190

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

Pro Scr 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 225 230 235 240

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

Lys Cys Lys Val Ser Asn Lys G!y Leu Pro Scr Ser Jlc 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 m

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

Scr 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 •13· 158138·序列表.doc 201208696

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

Ala Ser 465 <210> 8 <211> 705 <212> DNA <213>人工序列 <220> <223>合成募核苷酸· <400> δ atgatgtcct ctgctcagtt ccttggtctc ct^ttgctct gttttcaagg taccagatgt 60 gatatccaga tgacacagac tacatcctcc ctgictgcct ctctgggaga cagagtcacc 120 atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcasaaacca 180 gatggaactg ttaaactcct gatctactac acatcaatat tacaattagg agtcccatca 240 agattcagtg gcagtgggtc tgaaacagat tattctctca ccattagcaa cctggagcaa 300 gaagatattg ccacttactt ttgccaacag ggtgattcgc ttccattcac gttcggctcg 360 gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc t£gaactgcc tctgttgtgt 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 aggggagagl gttag 705 <210> 9 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 9

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 Thr Ser Ser Leu Ser 20 25 30

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

He 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 lie Leu Gin Leu Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Glu Thr Asp Tyr Ser Leu Thr lie Ser 85 90 95 158138·序列表 doc • 14·

S 201208696

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

Ser Leu Pro Phe Thr Phe Gly Scr 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 Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Scr Lys Asp Scr 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 Scr Ser Pro 210 215 220

Val Thr Lys Ser Phe Asn Arg G!y G1u Cys <210> 10 <211> 1403 <212> DNA <213>人工序列 <220> 合成寡核苷酸。 <400> 10 atgagagege tgattctttt gtgcctgttc acagcctttc ctggtatcct gtclgatgtg cagcttcagg agtcaggacc tgacctggtg aaaccttctc agtcactttc actcacctgc actgtcactg gctactccat caccagtggt tatagctggc actggatccg gcagtttcca ggaaacaaac tggaatggat gggctacata ctcttcagtg gtagcactaa ctacaaccca tctctgaaaa gtcgaatctc tatcactcga gacacatcca agaaccagtt cttcctgcag ttgaattctg tgactactga ggacacagcc acatatttct gtgcaagatc taactatggt teetttgett cctggggcca agggactctg gtcactgtct ctgcagccaa aacaacgggc ccatccgtct tccccctggc gcccigctcc aggagcacct ccgagagcac agccgccctg ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcttcct gttcccccca aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 158138·序列表.doc -15- 201208696 900 960 1020 1080 1140 1200 1260 1320 1380 1403 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcal aatsccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctagctgaac ggcaaggagt acaagtgcaa ggtctccaac aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg cagccggaga acaaclacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg ggtaaagcta gctgattaat taa <210> 11 <211> 464 <212〉 PRT <213>人工序列 <220> <223>合成肽。 <400> 11

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

Leu Ser Asp Va】G]n Leu Gin Glu Ser Gly Pro Asp Leu Val Lys Pro 20 25 30

Ser Gin Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser lie Thr 35 40 45

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

Glu Trp Met Gly Tyr lie Uu Phe Ser Gly Ser Lr Asn Tyr Asn Pro

Ser Leu Lys Ser Arg lie Ser He T.r Arg Asp Thr Ser Lys Asn Gin

Phe Phe Leu Gin Uu Asn Ser Val Thr Glu Asp TT,r Ala Thr Tyr

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

Ttir Leu Val Thr 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 Ser Thr Ala Ala Leu 145 150 155 160

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Sei Trp 165 170 175 158138-序列表.d〇c • 16 - s 201208696

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

Gin Scr Ser Gly Leu Tyr Ser Leu Ser Ser Val 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 Fro Pro 225 230 235 240

Cys Pro- Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Scr Val Phe 245 250 255

Leu Phe 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 Scr 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 Scr Asp 405 410 415

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg T;p 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> 12 <211> 708 <212> DNA 17- 158138-序列表.doc 201208696 <213>人工序列 <220> <223>合成寡核苷酸。 <400> 12 atggattttc aagtgcagat tttcagcttc ctgciaatca gtgcctcagt cataatatcc agaggacaaa ttgltctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag gtcaccatga cctgcagtgc cagctcaagt gtaagtcaca tgcactggta ccagcagaag tcaggcactv cccccaaaag atggatttat gacacatcca gactggcttc tggagtccct gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagcatggag gctgaagatg ctgccactta ttaclgccag cagtggagta gtcacccatg gtcgttcggt ggaggcacca aactcgagat caaacgaact stggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact scctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc caggagaglg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag <210> 13 <211> 235 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 13

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

Val lie 1,= Ser ArgG,y Geneva, Leu Gin Scr Pro A!a I,e

Met SerAlaSerProClyGluLvsVal^Met^gsSerAlaSer

Ser Ser Va] Ser His Met His Trp Tyr Gin Gin Lys Ser Gly Thr Ser 50 55 60

ProLysAreTrpI.eTyrAspT.rScrArgLeuA.aSe.GlyVa.Pjo

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

Ser Ser Met Glu A,a G.u Asp Ala Ala Tyr TyrCs Gin Gin Trp

SerSerHisPr〇TrpSerPheG.vGlyGlyThrLysLeuG,UIleLyS

Ar^rVal A,a Ala P:o Ser Va! Phe 1 le Phe Pro Pro Ser Asp Glu 158138-序列表.doc • 18 · s 201208696

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 ISO 185 190

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

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Uu Ser Ser 210 2L5 220

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 14 <211> 1415 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 14 atggcttggg tgtggacctt gctattcctg atggcagctg cccaaagtgc ccaagcacag 60 atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagi caagatctcc 120 tgcaaggctt ctgggtaiac cttcacaaac latggaatga actgggtgaa gcaggltcca 180 ggaaaaggtt taaggtggat gggctggatg gacaccttca ctggagagcc aacatatgct 240 gatgacltca agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg 300 cagatcaaca gcctcaaaaa tga£gacacg gctacttatt tct£tgcaag aggggggatt 360 ttacgactca actactttga ctactggggc caaggcacca ctctcacagt ctcctcagcc 420 aaaacgaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480 acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gctigggcac gaagacctac 660 acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagc tgagtccaaa 720 tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 960 gtfigtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080 cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac 1140 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200 -19· 158138·序列表.doc 201208696 gagagcaatg ggcagccsga gaacaactac aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc tccctgtctc tgggtaaagc tagctgatta attaa <2I0> 15 <211> 468 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 15

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 Ser Gly Tyr Thr Phe 35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Lys Gin Val Pro Gly Lys Gly Uu

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 85 90 95

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

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

Trp C.y G.n G,y Τ.Γ Uu Val Ser Ser A,a LyS Ι,γ LyS GIy

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 Vat 165 170

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

Pro Ala Val Leu Gla Ser Ser Gly Leu Τγτ 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 • 20· 158138-序列表·doc 201208696

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 Val Val Asp Vai 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

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 Scr Asn Lys Gly Leu Pro Ser Ser He Glu 340 345 350

Lys Thr He 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

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 Gin Glu Gly Asn Val Phe Scr Cys Ser 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 465 <210> 16 <211> 705 <212> DNA <213>人工序列 <22Q> <223>合成寡核苷酸。 <400> 16 atgaagtttc cttctcaact tetgetetta ctgctgtttg gaatcccagg catgatatgt 60 -21 · 158138-序列表.doc 201208696 gacatccaga attacttgca ggaaatgctc agattcagtg gaa£atcttg gggaccaagc tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc tgacacaatc aggcaagtga ctaggctctt gcagtggatc ctacttatta tcgagatcaa agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa ttcatccicc ggacatatat aatatctggt tggaaaggat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaacacaaa gagcttcaac ttttctgtat aatcggttag gcaaccagtt tacgctctca tgttggactt gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctatgcct aggggagagt ctctaggaga gctggtatca tggaaactgg gcattaccag ctccgtacac ctgtcttcat gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag cagagtcacc gcagaaacca ggttccttca tcttcagact gttcggaggg cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc 120 180 240 300 360 420 480 540 600 660 705 <210> 17 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 17

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 Uu Gly Asp Arg Val Thr He Thr Cys Lys Ala Ser Gl« Asp lie Tyr Asn Arg Leu Gly Trp Tyr Gin Gin Lys Pro Gly Asn Ala Pro 50 55 60

Arg Uu Leu lie Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser 65 70 75 80

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

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

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

Leu Lys Ser Gly Thr Ala Scr 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 Uu Gin Ser 165 170 175 .22- 158138-序列表.doc 201208696

Gly Asn Ser Gin GIu 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> 18 <211> 1398 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 18 atgggatgga gctggatctt tctctttctc ttgtcaggaa ctggaggtgt cctctctgag 60 gtccagctgc aacagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatgtcc 120 tgcaaggctt ctggatacac cttcactgac tactacatga agtgggtgaa gcagagccat 180 ggaaagagcc ttgagtggat tggagatatt aatectaact atggtgatac tttctacaac 240 cagaagttcg agggcaaggc cacattgact gtagacaaat cclccaggac agcctacatg 300 cagctcaaca gcctgacat.c tgaggactct gcagtctatt attgtggaag aggggactac 360 ggataetteg atgtctgggg cgcagggacc acggtcaccg tctcctcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca geggegtgea 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 840 gaegtgagee aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc gegggaggag 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 gggeageegg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtettetea 1320 tgctxcgiga tgeatgagge tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 23- 158138-序列表.doc 201208696 <210> 19 <211> 464 <212> ?RT <213>人工序列 <220> <223>合成肽。 <400> 19

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

Val Leu Ser Glu Val Gin Lea Gin Gin Ser Gly Pro Glu Leu VaJ 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 Tyr Met Lys Trp Val Lys Gin Ser His Gly Lys Ser Leu 50 55 60

Glu Trp He Gly Asp lie Asn Pro Asn Tyr Gly Asp Thr Phe Tyr Asn

65 70 75 SO

Gin Lys Phe Glu Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Arg 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 Gly Arg Gly Asp Tyr Gly Tyr Phe Asp Val Trp Gly Ala 115 120 125

Gly Thr Thr Val 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 145 150 155 160

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Scr 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 Ser Lys Tyr Gty Pro 225 230 235 240

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 245 250 255 158138-序列表.doc • 24· s 201208696

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 Ser Gin GIu 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 Va! Ser Asn Lys Gly Leu Pro Ser Ser lie Glu Lys Thr lie 340 345 350

Scr 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 370 375 380

Vat 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 丁yr 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 Leu Ser Leu Gly Lys Ala Ser 450 455 460 <210> 20 <211> 705 <2)2> DNA <213>人工序列 <22Q> <223>合成寡核苷酸》 <400> 20 atggagacac attctcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgaagga gacattgtga tgacccagtc tcacaaattc algtccacat cagtaggaga cagggtcagc atcacctgca aggccagtca ggatgtgggt actgctgtag cctggtatca acagaaacca gggcaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat cgcttcacag gcagtggatc tgggacagat ttcactctca ccattaacaa tgtgcagtct £aagacttgg cagattattt clgtcagcaa tatageagea atccgtacat gttcgaaggg ggg&ccaagc tcgagatcaa acgaactgt2 gctgcaccat ctgtcttcat cttcccgcca 25- 158138·序列表.doc 201208696 tctfiatgagc agttgaaatc tggaact£cc tctgttgtgt gccigctgaa taacttctat cccagagagg ccaaagtaca gtggaag^tg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa fiagcttcaac aggggagagt gttag <210> 21 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 21

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

Gly Val Glu Gly Asp lie Val Met Thr Gin Scr His Lys Phe Met Ser

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

Va, Glv Τ.Γ Ala Val Ala Trp Tyr Gin Gin Lys Pro G.y G.n Ser Pro

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

Val A,a Ala Pro Ser Val Phe lie Phe Pro P, Ser Asp Glu Oln I^u 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 Set 165 170 175

Gly Asn Ser Gin Glu Scr 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 -26- 158138-序列表.doc 201208696

Vai Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 22 <211> 1413 <212> <213>人工序列 <220> <223>合成募核苷酸。 <A〇〇> 22 atgggatgga gctggatctt tctcttlctc ctgtcaggaa ctgcaggtgt cctctctgag 60 gtccagctgc aacagtctgg acctgagttg gtgaagcctg gggcttcagt gaagatatcc 120

tgcaagactt ctggatacac attcactgaa tacaccatgc actgggtgag gcagagccat ISO ggaaagagcc ttgagtggat tggaggtatt aatcctatca atggtggtcc tacctacaac 240 cagaagttca agggcaaggc cacattgact gttgacaagt cctccagcac agcctacatg 300 gagctccgca gcctgacatc tgaggactct gcagtctatt actgtgcaag atgggactat 360 ggtagtcgag atgttatgga ctactggggt caaggaacct cagtcaccgt ctcctcagcc 420 aaaacgaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480 acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtacc ggtgacggtg 540 tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 600 tcaggactct actccctcag cagcgtggtg accstgccct ccagca£ctt gggcacgaag 660 acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gagagttgag 720 tccaaatatg gtcccccatg cccaccctgc ccagcacctg agttcgaagg gggaccatca 780 gtcttcctgt tccccccaaa acccaaggac actctcatga tctcccggac ccctgaggtc 840 acgtgcgtgg tggtggacgt gagccaggaa gaccccgagg tccagttcaa ctggtacgtg 900 gatggcgtgg aggtgcataa tgccaagaca aagccgc£gg aggagcagtt caacagcacg 960 taccgtglgg tcagcgtcct caccgtcctg caccaggact ggctgaacgg caaggagtac 1020 aagtgcaagg tctccaacaa aggcctcccg tcctccatcg agaaaaccat ctccaaagcc 1080 aaagggcagc cccgagagcc acaggtgtac accctgcccc catcccagga ggagaigacc 1140 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1200 gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc ogtgctggac 1260 tccgacggct ccttcttcot ctacagcagg ctaaccgtgg acaagagcag gtggcaggag 1320 gggaatgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacacagaag 1380 agcctctccc tgtctctggg taaagctagc tga 1413 <210> 23. <213> 469 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 23

Met Gly Tip Ser Trp He Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly -27· 158138-序列表.doc 201208696 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 Ser His Gly Lys Ser Leu Glu 50 55 60

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

Lys Phe Lys Oly Lys Ala Thr Leu ΤΗτ Val Asp Lys Ser Ser Ser Thr 85 90 95

Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 100 105 Π0

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

Val ThT Val vSer 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 Tlir 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 Scr 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 158138-序列表.doc -28 · s 201208696

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Phe Asn Ser ThT 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 Uu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Scr 370 375 380

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

Trp Glu Scr Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Fro 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 G.ln 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 <21Q> 24 <21]> 705 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 24 atggaatcac agactctggt cttcatatcc atactgctct ggttatalgg tgctgatggg 60 aacattgtaa tgactcaatc tcccaaatcc atgtccatgt cagtagggga gagggtcacc 120 ttgagctgca aggccagtga gaatgtggga aettatgtat cctggtatca acagagacca 180 gaacagtctc caaaactgct gatataeggg gcatccaacc ggtacactgg ggtccccgat 240 cgcttcacag gcagtggatc tgcaacagat ttcactctga ccatcagcag tgtgcaggct 300 gaggaccttg cagattatca ctgtggacag acttacagct atatattcac gtteggeteg 360 gggacaaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tetgatgage agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taaettetat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gegaagteae ccatcagggc 660 • 29- 158138·序列表.doc 201208696 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <210> 25 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 25

Met Glu Thr His Ser Gin Val Phe Val Tyr Met Leu Leu Trp Leu Ser 1 5 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

Val 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 Ser Asn Arg Tyr Thr Gly Val Pro Asp 65 70 75 80

Arg Phe Thr Gly Ser Gly Ser Ala Thr Asp Phe Thr Leu Thr 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 A1a 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 Uu 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> 26 <211> 1404 -30- 158138·序列表.doc 201208696 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 26 atgggatgga gccggatctt tctcitcctc ctgtcaataa ctgcaggtgt ccattgccag gtccaggtgc agcagtcggg acctgagttg gtgaagcctg gggcctcagt gaagatttcc tgcaaagcct ctggcgacgc attcagtagt tcttggatga actgggtgaa gcagaggcct ggacagggtc ttgagtggat tggacggatt tatcttggag atggagatat taattacaat gggaagttca agggcagggc cacactgact gcagacaaat cctccagcac agcctacatg cagctcagca gccigacctc tgtggactct gcggtctatt tctgcgcgag gcagctcggg ctatggtatg ttatggacta ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa acaaagggcc catccgtcit ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc ttcccggcte tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttcgaag ggggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg gaggtgcaia atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag gtcagccrga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcag gctaaccglg gacaagagca sgtggcagga ggggaatgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc ctgtctctgg gtaaagctag clga <210> 27 <211> 467 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 27

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

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

Pro Gly Ala Ser Val Lys He Ser Cys Lys Ala Ser Gly Asp Ala Phe 158138-序列表.doc -31· 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1404 201208696 35 40 45

Ser Ser Ser Trp Met Asn Trp Val Lys Gin Are Pro Gly Gin Gly Leu 50 55, 60

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

Gly Lys Phe Lys Gly Arg Ala Thr Leu Thr 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 100 105 Π0

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

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 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 Vai 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 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 Leu Asn Gly Lys Glu 325 330 335 158138·序列表.doc -32- s 201208696

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

Thr lie Scr 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 Phc 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 TTu Va丨 Asp Lys 420 425 430

Scr Arg Tip Gin Glu Gly Asn Val Phe Ser Cys Sci 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> 28 <21i> 705 <212> DNA <213>人工序列 <220〉 <«3>合成寡核苷酸。 <400> 28 atgagtgtgc ccactcaggt cctggggttg ctgctgctgt ggcttacagg tgccagatgt 60 gacatccaga tggctcagtc tccagcctcc etatetgeat ctgtgggaga aactgtcacc 120 atcacatgtc gagcaagtga gaatatttac agttatttag catggtatca gcagaaacag 180 ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tageagaagg tgtgccatca 240 ag^ttcagtg gcagtggatc aggcacacag ttttctctga agatcaacag cctgcagcct 300 gaagattttg ggagttatta ctgtcaacat cattatggtt ttccgtggac gttcggtgga 360 ggcaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tetgatgage agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taaettetat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacciaca gcctcagcag caccclgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gegaagteae ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <210> 29 <211> 234 <212> Pi?T <213>人工序列 33 · 158138-序列表.doc 201208696 <220> <223〉合成肽。 <400> 29

Met Ser Val Pro Thr Gin Val Leu Oly Leu Leu Leu Leu Trp Leu Thr 15 10 15

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

Ala Ser Val Gly Glu Thr Val Tlir lie Thr Cys Arg Ala Ser Glu Asti 35 40 45 lie Tyr Ser 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 Glu Gly Val Pro Ser 65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Thr Gin Phe Scr 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 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 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 2⑻ 205

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

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 30 <211> 1395 <212> m <213>人工序列 <220> <223>合成募核苷酸》 <400> 30 atgaacttcg egctcagctt gattttcctt gtcctcattt taaaaggtgt ccagtgtgag • 34· 158138·序列表.doc 201208696 gtgcagctgg tggagtctgg gggagaetta gtgaagcctg gagggtccct gaaactctcc 120 tgtgcagcct ctggattcac tttcagtagc tatggcatgt cttgggttcg ccagacicca 180 gacaagaggc tggagtgggt egeagteatt agtagtggtg gaagttccac cttctatcca 240 gacagtgtga aggggcgatt caccatctcc agagacaatg ccaagaacac cctgiacctg 300 caaatgagca gtctgaagtc tgaggacaca gccgtgtatt acrgttcaag aggaggttac 360 tactttgact actggggcca aggcaccact ctcacagtct ccgcagccaa aacaaagggc 420 ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480 ·. ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 600 . agcagcgtgg tgaccgtgcc ctccagcagc ttgggcacga agacctacac ctgcaacgta 660 gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720 tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcucct gttcccccca 780 aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtgeac 840 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 900 aatgccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 960 ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020 aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1080 ccacaggtgt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140 acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaalggg 1200 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260 ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc 1320 tccgtgatgc atgaggetet gcacaaccac tacacacaga agagcctctc cctgtctctg 1380 ggtaaagcta gctga 1395 ^ > > > Q 1 z 3 n n 1 <2<2<2<2 31 464

PRT 人工序列 <220> <223> <400> Met Asn 合成肽。 31 Phe Gly Leu

Val Gin Cys Glu Val 20

Pro Gly Cly Ser Leu 35

Ser Ser Tyr Gly Met 50

Glu Trp Val Ala Val

Ser Leu Gin Leu Lys Leu Scr Trp 55 lie Ser lie Val Ser 40 Val Scr

Phe Glu 25 Cys Arg Gly

Leu 10 Scr Ala Gin Gly

Val Leu Gly Gly Ala Ser Thr Pro 60 Scr Ser lie Leu Lys Gly 15

Asp Leu Val Lys 30

Gly Phe Thf Phe 45

Asp Lys Arg Leu

Thr Phe Tyr Pro -35- 158138-序列表.doc 201208696 65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr lie Ser Arg 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 丁yr Cys Ser Arg Gly Gly Tyr Tyr Phe Asp Tyr Trp Gly Gin Gly 115 120 125

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

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

Gly Cys Leu Val 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 Val 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 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 TTir 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 He Ser 340 345 350

Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr T*hr Leu Pro Pro 355 360 365 158138-序列表.doc -36- s 201208696

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 He Ala Val Glu Trp Glu Ser Asn Gly 385 390 395 400

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

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Va. Asp Lys Ser Arg Trp

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> 32 <211> 705 <212> DNA <ί!3>人工序列 <220> <223>合成寡核苷酸。 <400> 32 atgaggucc aggucaggt tctggggctc cttctgctct ggatatcagg tgcccagtgt 60 gatgtccaga taacccagtc tccatcttat ettgetgeat ctcctggaga aaccattact 120 attaattgea gggcaagcaa gaccattagc aaatatttag cctggtatca agagaaacct 180 gagaaaactg ataagettet tatctactct ggatccactt tgcaatctgs aattccatca 240 aggttcagtg gcagtggatc tggtacagat ttcactctca ccatcagtgg cctggagcct 300 gaagattttg caatgtatta ctgtcaacag cataatgaat acccgtggac gttcggtgga 360 ggcaccaagc tegagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tefgatgage agttgaaat,c tggaactgcc tctgttgtgt gcctgctgaa taaettetat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg laactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gegaagteae ccatcagggc 660 ctgagctcgc ccgtcacaaa gagettcaac aggggagagt gttag 705 <210> 33 <211> 234 <212> PRT d13》人工序列 <220> <223>合成肽《 <400> 33

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

Gly Ala Gin Cys Asp Val Gin lie Thr Gin Ser Pro Ser Tyr Leu Ala 20 25 30 -37- 158138·序列表.doc 201208696

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 Tip Tyr Gin Glu Lys Pro Glu Lys Thr Asp 50 55 60

Lys Leu Leu lie Tyr Ser Gly Ser^r Leu Gin Ser Gly He Pro Ser

Are Phe Scr Gly Ser Gly Ser Gly T.r Asp Phe T.r Leu lie Ser

Gly Leu Glu Pro Glu Asp Phe Ala Met Tyr Tyr Cys Gin Gin His Asn 100 105 110

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

Thr Val Ala Ala Pro Ser Val Phe 丨le 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 Set 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> 34 <211> 1389 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <4〇〇> 34 atgggatgga gctggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag 60 gtccagctgc aacagtctgg acctgagctg gtgaagcctg ggscttcagt gaagatatcc 120 tgcaaggctt ctggttactc attcactggc tactacatgc actgggtgaa gcaaagccat 180 gtaaagagcc ttgagtggat tggacgtatt aatccttaca atggtgctac tagctacaac 240 cagaatttca aggacaaggc cagcttgact gtagataagt cctccagcac agcctacatg 300 gagctccaca gcctgacatc tgaggactct gcagtctatt actgtgcaag agaggaclac 360 gtctactggs sccaaggcac cactctcaca gtcicctcag ccaaaacgaa gggcccatcc 420 158138·序列表.doc -38 - s 201208696 gtcttccccc tggcgccctg ciccaggagc acctccgaga gcacagccgc cctgggctgc 480 ctggtcaagg actacttccc cgaaccggtg acggtgtcgt ggaactcagg cgccctgacc 540 agcggcgigc acaccttccc ggctgtccta cagtcctcag gactctactc cctcagcagc 600 gtggtgaccg tgccctccag cagcttgggc acgaagacct acacctgcaa cgtagatcac 660 aagcccagca acaccaaggt ggacaagaga gttgagtcca aatatggtcc cccatgccca 720 ccctgcccag cacctgagtt cgaaggggga ccatcagtct tcctgttccc cccaaaaccc 780 aaggacactc tcatgatctc ccggacccct gaggtcacgt gcgtggtggt ggacgtgagc 840 caggaagacc ccgaggtcca gitcaactgg tacgtggatg gcgtggaggt gcataatgcc 900 aagacaaagc cgcgggagga gcagttcaac agcacgtacc gtgtggtcag cgtcctcacc 960 gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc caacaadggc 1020 ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agagccacag 1080 gtgtacaccc tgcccccatc ccaggaggag atgaccaaga accaggtcag cctgacctgc 1140 ctggtcaaag gcttctaccc cagcgacatc sccgtggagt gggagagcaa tgggcagccg 1200 gagaacaact acaagaccac gcctcccgt^ ctggactccg acggctcctt cttcctctac 1260 agcaggctaa ccgtggacaa gagcaggtgg caggagggga atgtcttctc atgctccgtg 1320 atgcatgagg ctctgcacaa ccactacaca cagaagagcc tctccctgtc tctgggtaaa 1380 gctagctga 1389 <210> 35 <211> 462 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 35

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

Val Leu Scr 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 Ala Sei Gly Tyr Ser Phe 35 40 45

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

Glu Trp He Gly Arg lie Asn Pro Tyr Asn Gly Ala Thr Ser Tyr Asn 65 70 75 80

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

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

Tyr Tyr Cys Ala Arg Glu Asp Tyr Val Tyr Trp Gly Gin Gly Thr Thr -39- 158138·序列表.doc 201208696 115 !20 125

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

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

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 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 Ser Ser 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 Va) 260 265 270

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

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

Val Leu His Gin Asp Trp Leu Asn 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 Thr Leu Pro Pro Ser Gin 355 360 365

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

Phe Tyr Pro Ser Asp lie Ala Va] 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 •40· 158138-序列表.doc 201208696

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 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 Scr Leu Ser Leu Gly Lys Ala Ser 450 455 460 <2L0> 36 <211> 717 <2L2> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 36 atgaagttgc ctgttaggct gttgglgctg atgttctgga ttcctgcttc cagcagtgat 60 gttgtgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120 tcttgcagat ctagtcagag ccttgtacac agtaalggaa acacctattt acattggtac 180 ctgcagaagc caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240 ggggtcccag acaggttcag tggcagtgga tcagggacag atttcgcact caagatcagt 300 agastggagg ctgaggatct gggagtttat ttctgctctc aaagtacaca tgttccgtgg 360 acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480 aataacttct atcccagaga ggccaaagta cagtggaagg tggaiaacgc cctccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 <210> 37 <211> 238 <212> PRT <213>人工序列 <220> <M3>合成肽。 <400> 37

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp lie Pro Ala 1 5 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 Uu 35 40 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 Asn Arg Phe Ser 65 70 75 80 -41 - 158138-序列表.doc 201208696

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 GJu Ala Glu Asp Leu Gly Val Tyr Phe Cys LOO 105 110

SeT Gin Ser Thr His Val 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 He 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 Scr 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 GJy 210 215 220

Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 3S <211> 1410 <212> Wk <213>人工序列 <22Q> 合成募核苷酸。 <400> 38 atggaatgga gttggatatt tetetttett ctgtcaggaa ctgcaggtgt ccactctgag 60 gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120 tgcaaggett ctggatacac attcactgac tatgttttgc aclgggtgaa acagaagcct 180 mcagg^cc ttgagtggai tggataran aatccttaca atgatggtac taagtacaai 240 gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300 gagctcagca gcctgacctc tgaggactct geggtetatt actgtgcaag gggctatccg 360 gcctactctg ggtatgetat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420 gccaaaacga agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 480 agcacagccs ccctgggctg cctg£lcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660 tacacctgca aegtagatea caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 158138-序列表.doc •42· s 201208696 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa gggcagcccc sagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc gacggctcct tcltcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc ctctccctgt ctctgggtaa agctagctga <210> 39 <211> 469 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 39

Wet Glu Trp Ser Ττρ lie Phe Leu Phc Leu Leu Ser Gly Thr Ala Gly 1 5 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 ΤΙίγ 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 7〇 75. 80

Glu Lys Phe Lys G,y LyS Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser

Thr Ala Tyr Met Glu Leu Ser Scr Leu Thr Ser Glu Asp Ser Ala Val 100 105 110 TVr Tyr Cys Ala Arg Gly Tyr Pro Ala Tyr Ser Gly Tyr Ala Met Asp 115 120 125

Tyr Ττρ Gly Gin Gly Thr Ser Va] Thr Val Ser Ser Ala Lys Thr Lys 130 135 140

Glv Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu 145 l5〇 155 160

Scr Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro -43 - 158138-序列表doc 201208696 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 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 Va丨 Ser Val Leu Thr VaJ Leu His G]n Asp Trp Leu Asn Gly 325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser He 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 Fro 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 158138·序列表.doc -44. s 201208696

Leu Gly Lys Ala Ser 465 <210> 40 <211> 705 <212> DNA <213>人工序列 <220> <223>合成募核苷酸。 <400> 40 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 cctggagcaa 300 gaagatattg ccacitactt ttgccatcat ggtaatacgc ttccgtggac gttcggtgga 360 ggcaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcg£g taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa glctatgcct gcgaagtcac ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <2iO> 41 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 41

Met Met Scr 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 Thr Scr Ser Leu Ser 20 25 30

Ala Ser Leu Gly Asp Arg Vat Thr lie Ser Cys Arg Ala Ser Gin Asp 35 40 45 I.eSerAsnTyrUuAsnTrpIyrGlnGlnLysProAspGlyTT.rVal

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

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

Asn Leu Glu Gin Glu Asp lie Ala Thr Tyr Phe Cys His His Gly Asn 100 105 110 -45- 158138·序列表.doc 201208696

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

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

Leu Lys Ser Gly Thr Ala Ser Val Vat 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 SeT Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser TTir 180 185 190

Tyr Ser Leu Scr 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> 42 <211> 1404 <212> I>NA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 42 atgaaettgg ggctcagctt gattttcctt gtccttgttt taaaaggtgt ccastgtgaa gtgaagctgg tggagtctgg gggaggetta gtgcagcctg gagggtccct gaaactctcc tgtgcaacct ctggattcac tttcagtgac tattacatgt attgggttcg ccagactcca gagaagagge tggagtgggt cgcatacatt aattctggtg gtgstagcac ctattatcca gacactgtaa agggeegatt caccatctcc agagacaatg ccaagaacac cctgtacctg caaargagcc ggctgaagtc tgaggacaca gccatgtatt actgtgcaag acgggggtta ccgttccatg cUtggacta【tgggglcaa ggaacctcag tcaccgtctc ctcagccaaa aegaagggee catcc^tctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt £tcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atclcccgga cccctgaggi cacgtscgtg gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg gaggtgcata atgccaagac aaageegegg gaggageagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 158138-序列表.doc • 46· 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 201208696 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080 ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200 agcaatgggc ageeggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260 tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 13&0 ctgtctctgg gtaaagctag ctga 1404 0>1>2>3> <21<21<21<21 43 467

FRT 人工序列 <220> <223>合成肽。 <400> 43

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

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

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

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

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

Glv Gin Gly Thr Ser Val Thr Val 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 Gly Cys Leu Val LyS Asp Tyr Phe Pro Glu Pro Val T.r

Vai 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 •47- 158138-序列表.doc 201208696 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 Scr Lys Tyr 225 230 235 240

Gly Pro Pro Cys Fro 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 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 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 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 Thx 355 360 365

Leu Pro Pro Ser Gin Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr 370 375 3S0

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> 44 <2U> 705 <212> DNA <213>人工序列 -48- 15813 8-序列表.doc 201208696 <220> <223>合成寡核苷酸。 <400> 44 atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt 60 gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctaggaga cagagtcacc 120 atcagttgca glgcaagtca gggcatugc aauatttaa actggtatca gcagaaacca 180 gatggaactg ttaaactcct gatctattac acatcaattt tacactcagg agtcccatca 240 aggttcagtg gcagtgggtc tgggacagat tattctctca ccatcggcaa cct£gaacct 300 gaagatattg ccacttacta ttgtcagcag tttaataagc ttcctccgac gttcggtgga 360 ggcaccaaac tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagaciacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <210> 45 <21i> 234 <?,12> PRT <2i3>人工序列 <220> <223>合成肽。 <400> 45

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 Thr Ser Ser Leu Ser 20 25 30

Ala Ser Leu Gly Asp Arg Val Thr lie Ser Cys Scr 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 Leu Leu lie Tyr Tyr Thr Ser lie Lea His Ser Gly Val Pro Ser 65 70 75 80

Arg Phe Ser GLy Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr He Gly 85 90 95

Asn Leu 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 lie Lys Arg 115 120 125

Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Fro Ser Asp Glu Gin 130 135 140 -49- 158138-序列表.doc 201208696

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

Pro Arg Olu 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丨n 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> 46 <211> 1405 <212> DNA <213>人工序列 <220> <223>合成肽。 <400> 46 atggattggc tgtggaactt gctattcctg atggcagctg cccaaagtgc ccaagcacag 60 atccagttgg tgcagtctgg acctgagcts aagaagcctg gagagacagt caagatctcc 120

tgcaaggctt ctgggtattc cttcacaaac tatggaatga actgggtgaa acaggctcca ISO ggaaagggtt taaagtggat gggctsgata aacacctaca ctggagagtc aacatatgct 240 gatgaettea agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg 300 cagatcagta acctcaaaaa tgaggacatg gctacatatt tctgtgctag aggggacttt 360 aggtactact attttgacta ctggggccaa ggcaccactc tcacaggctc ctcagccaaa 420 aegaagggee catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgiggaac 540 tcaggcgccc tgaccagcgg cgtgcacacc ticccggctg tcctacagtc ctcaggactc 600 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg 780 ttccccccaa aacccaagga cactctcatg atctcccgsa cccctgaggt cacgtgcgtg 840 gtggtggacg tgagccag£a agaccccgag gtccagttca actggtacgt ggatggcgtg 900 gaggtgcata atgccaagac aaageegegg gaggageagt tcaacagcac gtaccgtgts 960 gtcagcgtcc tcaccg(cct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020 gtctccaaca aaggcctccc gtcctccatc sagaaaacca tctccaaagc caaagggcag 1080 ccccgagagc cacaggtgta caccctgccc ccatoccagg aggagatgac caagaaccag 1140 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200 agcaatgggc ageeggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1260

158138·序列表.doc -50- S 201208696 tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380 ctgtctctgg gtaaagctag ctgat 1405 <210> 47 <2H> 467 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 47

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

Ala Gin Ala G】n 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 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 Phe Ala Phe Scr 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 115 120 125

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

Ser Val Phe Pro Leu Ala Fro 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 ISO 185 190

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

Val Pro Ser Scr 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 Scr Lys Tyr -51 · 158138-序列表.doc 201208696 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 Fro Giu 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 Leu Asn Gly Lys Glu 325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 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 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> 48 <211> 702 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 48 atgaglgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tgccagatgt gacatccaga tgactcagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc •52· 158138·序列表.doc 201208696 atcacgtgtc gagcaagtgg gaatattcac aattatttag catggtatca gcagaaacag ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tggcagatgg tgtgccatca aggttcagtg gcagtggatc aggaacacaa tattctctca agatcaacac cctgcagcct gaagattttg ggagttatta ctgtcaacat ttttgggatt cttggacgtt cggtggaggc accaagctcg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggcggat aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc iatgcctgcg aagtcaccca tcagggcctg agctcgcccg tcacaaagag cttcaacagg ggagagtgtt ag <230> 49 <211> 233 <212> PRT <213>人工序列 <220> <223>合成肽《 <400> 49

Met Ser Val Leu Tlir Gin Val Leu Ala Leu Leu Leu Leu Trp Leu Thr 1 5 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 Arg 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 Ser Gly Thr Gin Tyr Ser Leu Lys He Asn 85 90 95

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

Asp Ser Trp Phe Gly G,y Gly Thr Lys Leu Glu lie Lys Arg T,r

Val Ala Ala Pro Ser Val Fhe He 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 145 150 155 160

Arg Glu Ma Lys Val Gin Trp Lys Val Asp ^sn Ala Leu Gin Scr Gly 165 170 175 -53- 158138·序列表.doc 201208696

Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Scr Lys Asp Scr 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 Glu Val Thr His Gin Gly Leu Ser Ser Pro Val 210 215 220

Ttir Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 50 <211> 1398 <212> DNA <2】3>人工序列 <220> <223>合成募核苷酸。 <400> 50 atggaatgfia cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60 gticagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120 tgcaaggcia ctggctacac attcagtagc tactggatag agtgggtaaa gcagaggcct 180 ggacatggcc ttgagtggat tggagagatt ctacccggaa gtggtaggac taacgacaat 240 gagaagttca agggcaaggc cacattcact gcagatacat cctccaagaa agcctacatg 300 caactcagca gcctgacatc tgaggactct gccgtctatt attgtgcaag aaggggtggt 360 tactcclttg cttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca gcsgcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 600 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac 660 gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgastccaa atatggtccc 720 ccacgcccac cctgcccagc acctgagttc gaagggggac catcagtclt cctgttcccc 780 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg g40 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 960 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agiacaagtg caaggtctcc 1020 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080 gagccacagg tgiacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc 1140 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1200 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320 tgctccstga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 -54- 158138-序列表.doc s 201208696 <210> 51 <211> 465 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 51

Met Glu Trp Thr 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 Ser 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 He Leu Pro Gly Ser Gly Arg ΤΚτ Asn Asp Asn 65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Lys S5 90 95

Lys Ala Tyr Met G3n Leu Ser Scr Leu Thr Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Arg Giy Gly Tyr Ser Phe Ala Tyr Trp Gly Gin 115 320 125

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 Tlir 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 Giy Ala i.eu 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 19S 200 205

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

Pro Sei 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 -55- 158138-序列表.doc 201208696 260 265 270

Pro Glu Val Thr Cys Val Val Val 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 Pro Arg Glu Glu G】n 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 He Glu Lys ΤΊ,γ He

Ser Lys Ala Lys Gly Gin Pro Arj Glu Pro Gin Val Tyr Leu Pro

Pro Ser Gin Glu Glu Met TTir 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 Oln 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 ΊΪΓ 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 <210> 52 <211> 1422 <212> 1M <213>人工序列 <220> <223>合成募核苷酸。 <400> 52 atgaccatgt tctcactagc tcitctcctc agtettette tcctctgtgt ctctgattct agggcagaaa caactgtgac ccagtctatg accalgttct cactagctct tctcctcagt cttcttctcc tctgtgtctc tgattetagg gcagaaacaa ctgtgaccca gtctccagca tccctgtcca tggetatagg ggaaaaagtc accatcagat gcgtaaccag cactsatatt gatgatgatg tgaactggta ccagcagaag ccaggg£aac ctcctaaact ccttatttca gaaggcaata ctcttcgtcc tggagtccca tcccgattct ccagcagtgg ctatggtaca 56- 158138·序列表.doc 201208696 gattttgttt ttacaattga gaacatgctc tcagaagatg ttgcagatta ctactgtttg 420 caaagtggta acttgccgta cacgttcgga ggggggacca agctcgagat caaacgaact 480 gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact 540 gcctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtggaag 600 gtggataacg ccctccaatc gggtaactcc caggagagtg 丨cacagagca ggacaficaag 660 gacagcaccl acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac 720 aaagtctatg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagcttc 780 aacaggggag agtgttagcc agcatccctg tccatggcta taggggaaaa agtcaccatc S40 agatgcgtaa ccagcactga tattgatgat gatgtgaact ggtaccagca gaagccaggg 900 gaacctccta aaetccttat ttcagaaggc aatactcttc gtcctggagt cccatcccga 960 ttctccagca gtggctatgg tacagatttt gtttttacaa ttgagaacat gctctcagaa 1020 i；atgttgcag atlactactg tttgcaaagt ggtaacttgc cgtacacgtt cggagggggg 1080 accaagctcg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 1140 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaaiaa cttctatccc 1200 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 1260 agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 1320 agcaaagcag actacgagaa acacaaagtc tatgcctgcg aagtcaccca tcagggcctg 1380 agctcgcccg tcacaaagag cttcaacagg ggagagtgtt ag 1422 <210> 53 <211> 236 <212> PRT <213>人工序列 <220> <223>合成肽。 <40〇> 53

Met Hu Met Phe Ser Leu Ala Leu Leu Leu Ser Leu Leu Leu Leu Cys 1 5 10 15

Val Ser Asp Ser Arg Ala GIu Thr Thr Val Thr Gin Ser Pro Ala Scr 20 25 30

Leu Ser Met Ala lie Gly GIu Lys Val Thr lie Arg Cys Val Thr Ser 35 40 45

Thr Asp He Asp Asp Asp Val Asn Trp Tyr Gin Gin Lys Pro Gly GIu 50 55 60

Pro Pro Lys Leu Leu lie Ser GIu 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 Phc Thr 85 90 95 lie GIu Asn Met Leu Ser GIu Asp Val Ala Asp Tyr Tyr Cys Leu Gin 100 105 110 -57- 158138-序列表.doc 201208696

Scr Gly Asn Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu GIu 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 Asn Asn 145 150 155 160

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

Gin Ser Gly Asn Scr Gin Glu Ser 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> 54 <211> 1404 <212> DNA <213>人工序列 <220> <223>合成募核苷酸。 <400> 54 atggcttggg tgtggacctt gctattcclg atggcagctg cccaaagtgc cceagcacag atccagttgg tgcagtctgg acctgagctg aagaagcctg gagagacagt caagatctcc tgcaaggctt ctgggtatac cttcacaaac tatggaatga actgggtgaa gcaggctcca ggaaagggtt taaagtgggt gggctggata aacaccttca ctggagagcc aacatatgtt gatgaettea agggacggtt tgccttctct ttggaaacct ctgccagcac tgcctatttg cagatcaaca acctcaaaaa igaggacacg gctacatatt tctgtgcaag agggaatttt aggtactact aetttgacta ctggggccaa ggcaccactc tcacagtctc ctcagccaaa acaaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca gccgccctgg gctgcctggi caaggactac ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg icctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg gaggtgcata atgccaagac aaageegegg £ag£agcagt tcaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac t£gctgaacg gcaaggagta caagtgcaag 60 120 L80 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 158丨38-序列表.doc •58· s 201208696 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> 55 <211> 467 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 55

Met Ala Trp Val Trp Thr Leu Leu Phe Leu Kfet Ala Ala Ala Gin Scr 1 5 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 Ser Gly Tyr Phe

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

Lys Trp 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 Scr Leu Glu Thr Scr Ala Ser 85 90 95

Th, Ala Tyr Lgu Gin lie Asn Asn Leu Lys AS„ Glu Asp Thr Ala Br

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

Gly Gin G.y ΤΤ,γ Lea Br Va, Ser Ser Ala Lys Thr Lys Gly Pro

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 Pro Val Thr 165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser G.y Val His Thr Phe Pro

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 59- 1080 1140 1200 1260 1320 1380 1404 158138·序列表.doc 201208696 195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Lys Thx 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 lie 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

Ala Lys Thr Lys Pro Arg G]u Glu Gin Phe Asn Scr Thr Tyr Arg Val 305 310 315 320

Val Scr 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

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 Scr Leu Ser Leu Gly 450 455 460

Lys Ala Ser 465 0717^^7 56 705

DNA 人工序列 •60- 158138-序列表.doc 201208696 <220> <223>合成寡核苷酸。 <400> 56 atgagtgtgc tcactcaggt cctggcgttg ctgctgctgt ggcttacagg tgccagatgt 60 gacatccaga tgactcagtc cccagcctcc ctatctgcat ctgtgggaga aactgtcacc 120 atcacatgtc gaacaagtgg gaatattcgc aattatttag catggtatca gcagaaacag 180 j^gaaaatctc ctcaactcct ggtctataat gcaaaaaccl tagcagatgg tgtgccatca 240 aggttcggtg gcagtggatc aggaacacaa tattctctca agatcaacag cctgcagcct 300 gaagattttg ggaattatta ctgtcaacat ttttggagta gtccgtacac gttcggaggg 360 gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 420 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 480 cccagagagg ccaaagtaca gtggaaggtg galaacgccc tccaatcggg taactcccag 540 gasagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 <210> 57 <211> 234 <212> PRT <213>人工序列 <22〇> <2i3>合成肽。 <400> 57

Met Ser Val Leu Thr Gin Val Lext Ala Leu Leu Leu Leu Trp Leu Thr 15 10 35

Gly Ala Arg Cys Asp lie Gin Met Thr Gin Ser Pro Ala Set Leu Ser 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 Thr Leu Ala Asp Gly Val Pro Ser 65 70 75 80

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

Ser Leu Gin Pro GIu Asp Phe Gly Asn Tyr Tyr Cys Gin His Phe Trp 100 105 110

Scr Ser 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 lie Phe Pro Pro Scr Asp Glu Gin 130 135 140 -61 - 158138-序列表.doc 201208696

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 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 Thr His Gin Gly Leu Ser Ser Pro 210 215 220

Val Thr Lys Ser Phc Asn Arg Gly Glu Cys 225 230 <210> 58 <21l> 2811 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 58 atgatgggat gsagetatat catcctcttt ttggtagcaa ca^ctacaga tgtccactcc 60 caggtccaac tgcagcagcc tggggctgaa ctggtgaagc ctggggcttc agtgaagctg 120 tcctgcaagg cttctggcta caccttcacc agctactgga tgcactgggt gaageagagg 180 cctggagaag geettgagtg gattggagag attaatccta getaeggteg tactgactac 240 aatgagaagt tcaagaacaa ggccacactg actgtagcca aatcctccag cacagcctac 300 atgcaactca gcagcctgac atet^aggae tctgcggtct attactgtgc aagaggagat 360 tactacggta gtagdcgtt tgcttactgg ggccaaggga ctctggtcac tgtctctgca 420

gccaaaacaa aggscccatc cgicttcccc ctggcgccct gctccaggag cacc'tccgag 4SO agcacagcce ccctgggctg cctggtcaag gactacttcc ccgaaccggt gaegstgteg S40 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660 tacacctgca aegtagatea caagcccagc aacaccaagg tggacaagas agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840 tgcgtggtee tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900 ggcgtggagg tgcataatgc caagacaaag ccgcgggaes agcagttcaa cagcacgtac 960 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccag^agga gatgaccaag 1140 aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcfiacat cgccgtggag 1200 tgggagagca atg£gcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 158138·序列表.doc • 62·

S 201208696 gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320 aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380 ctctccctgt ctctgggtaa agctagcgga tggagctata tcatcctctt tttggtagca 1440 acagctacag atgtccactc ccaggtccaa ctgcagcagc ctggggctga actggtgaag 1500 cctggggctt cagtgaagct gtcctgcaag gcttctggct acaccttcac cagctactgg 1560 atgcactggg tgaagcagag gcctggagaa ggccttgagt ggattggaga gattaatcct 1620 agctacggtc gtactgacta caatgggaag ttcaagaaca aggccacact gactgtagcc 1680 aaatcctcca gcacagccta catgcaactc agcagcctga catctgagga ctctgcggtc 1740 tattactgtg caagaggaga ttactacggt agtagctcgt ttgcttactg gggccaaggg 1800 actctggtca ctgtctctgc agccaaaaca aagggcccat ccgtcttccc cclggcgccc 1860 igctccagga gcacctccga gagcacagcc gccctgggct gcctggtcaa ggactacttc 1920 cccgaaccgg tgacggtgtc gtggaactca ggcgccct£a ccagcggcgt gcacaccttc 1980 ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 2040 agcagcttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaag 2100 gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag 2160 ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc 2220 tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc 2280 cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcgggag 2340 gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 2400 ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag 2460 aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac cctgccccca 2520 tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctac 2580 cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 2640 acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct aaccgtggac 2700 aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga ggctctgcac 2760

aaccactaca cacagaagag cctctccctg tctctgggta aagctagctg a 2&1I

<210> 59 <211> 469 <212> PRT 人工序列 <220> <223>合成肽。 <400> 59

Met Met Gly Trp Ser Tyr lie lie Leu Phe Leu Val Ala Thr Ala Thr 1 5 10 15

Asp Val His Ser Gin Val Gin Leu Gin Gin Pro Gly Ala Glu Leu Val 20 25 30

Lys Pro Gly Ala Ser Val Lys Leu Scr Cys Lys Ala Ser Gly Tyr Thr -63- 158138-序列表.doc 201208696

Phe Thr Set 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 Fhe 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 Tip Gly Gin Gly Thr Leu Val Thr Val Ser Ala Ala Lys Thr Lys 130 135 140

Gly Pro Set 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 Fro 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 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 Va] Asp Lys Arg Val Glu Ser 225 230 235 240

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Fro 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 Tlir 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 Tlir 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 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 158138·序列表.doc - 64 · s 201208696

Glu Lys Thr lie Set 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 Set 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 Phc Phe Leu Tyr Ser Arg Leu Thr Val 420 425 430

As;p Lys Ser Arg 丁rp 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> 60 <2ll> 708 <212> DNA <2l3>人工序列 <220> <2ί3>合成寡核苷酸。 <400> 60 atggattttc aagtgcagat tttcagcttc ctgctaatga gtgcctcagt cataatgtcc 60 aggggacaaa ttgitctcac ccagtctcca gcactcatgt ctgcatctcc aggggagaag 120 gtcaccatga cctgcagt£c cagctcaaat ataagttaca tgtactggta ccagcagaag 180 ccaagatcct cccccaaacc ctggatttat ctcacatcca acctggcttc tggagtccct 240 gctcgcttca gtggcagtgg gtcigggacc Vcttactctc tcacaaccag cagcatggag 300 gctgaagatg ctgccactta ttgctgccag cagtggagta gtaacccacc cacgttcggt 360 gctgggacca agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacasagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag 660 ggcctgagct cgcccgtcac asagagcttc aacagggsag agtgttag 708 <210> 61 <211> 235 <212> PRT <213>人工序列 <220> <223>合成肽。 65· 158138-序列表.doc 201208696 <400> 61

Met Asp Phe Gin 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 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 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 Leu Thr Thr 85 90 95

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

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 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> 62 <211> 708 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 60 <400> 62 atgfiattttc eagtgeagat tttcagcttc ctgctaatga gtgcctcagt cataatgtcc aggggacaaa ttgttctcac ccagtctcca gcactcatgt ctgcatctcc aggggagaag 158138-序列表.doc •66· s 120 201208696 gtcaccatga ccaagatcct gctcgcttca gctgaagatg gctgggacca ccatctgatg tatcccagag caggagagtg acgctgagca ggcctgagct cctgcagtgc cccccaaacc gtggcagtgg ctgccactta agctcgagat agcagttgaa aggccaaagt tcacagagca aagcagacta cgcccgtcac cagctcaaat ctggatttat gtctgggacc ttactgccag caaacgaact atctggaact acagtggaag ^gacagcaag cgagaaacac aaagagcttc ataagttaca ctcacatcca tcttactctc cagtggagta gtggctgcac gcctctgttg gtggataacg gacagcacct aaagtctatg aacaggggag tgtactggta acctggcttc tcacaatcag gtaacccacc catctgtctt tgtgcctgct ccctccaatc acagcctcag cctgcgaagt agtgttag ccagcagaag tggagtccct cagcatggag cacgttcggt catcttcccg gaaiaacttc gggtaactcc cagcaccctg cacccatcag 180 240 300 360 420 480 540 600 660 708 <210> 63 <231> 235 <212> PRT <213>人工序列 <220> <223>合成肽。 <400〉 63

Met Asp Phe Arg Val Gin lie Phe Ser Phe Leu Leu Met Ser Ala Scr 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

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

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

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Scr 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 Asn Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu He Lys 115 120 125

Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Scr 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 Gin Trp Lys Val Asp Asn Ala Leu Gin 165 170 175 •67- 158138·.序列表.doc 201208696

Ser Gly Asn Ser Gin Glu Ser Val Thr GIu 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> 64 <211> 717 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 60 120 180 240 300 360 420 480 540 600 660 717 <400> 64 atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt gacattgtgc tgatccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc atatcctgca gagccagtga aagtgttgat agttatgtca atagltttat gcactggtac cagcagaaac caggacagcc acccaaactc ctcatctatc gtgtatccaa cctagaatct gggatccctg ccaggttcag tggcagtggg tctaggacag acttcaccct caccattaat cctgtggagg ctgatgatgt tgcaacctat tactgtcagc aaagtaatga ggatccattc acgttcggct cggggacaaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga gcagtigaaa tctggaactg cctctgttgt gtficctgctg aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaags acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg gcctgagctc gcccgicaca aagagcttca acaggggaga gtgttag <210> 65 <211> 238 <2!2> PRT <213>人工序列 <220> <223>合成肽。 <400> 65

Met Glu Thr 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 lie Gin Ser Pro Ala Ser Leu Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr He 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 158138·序列表.doc -68- s 201208696

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

Gly He Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phc Thr 85 90 95

Leu Thr lie Asn Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys loo 105 no

Gin Gin Ser Asn Glu Asp Pro Phe Thr Phe Gly Ser 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 llir Ala Ser Val Val Cys Leu Uu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Vai 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> 66 <2U> 1398 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <40O> 66 atggaatgta actggatact tccttttatt ctgtcggtaa tttcaggggt ctactcagag 60 gttcagctcc agcagtctgg gactgtgctg gcaaggcctg gggcttccgt gaatatgtcc 120 tgtaaggctg ctggctacag ctttaccagt lactgggtgt actgggtcaa acagaggcct 180 ggacagggtc tggaatggat tggtgciatt taccctaaaa atagtagaac tagctacaac 240 cagaagttcc aggacaaggc cacactgact gcagtcacat ccgccagcac tgcctacatg 300 gagctcagca gcctgacaaa tgaggactct geggtetatt actgtacaag acctcactat 360 gattcgtttg gttactgggg ccaagggact ctggtcactg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca geggegtgea caccttcccg gctgtcctac agtcctcagg actctactcc 600 69- 158138-序列表.doc 201208696 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctscaac 660 gtagatc&ca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc 720 ccatgcccac cctgcccagc acctgagttc gaagggggac catcagtctt cctgttcccc 780 ccaaaaccca aggacactct catgatctcc cg^acccctg aggtcacgtg cgtggtggtg 840 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtg£at£g cgtggaggtg 900 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgt£gtcagc 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 a^cgacatcg ccgtggagtg ggagagcaat 1200 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 <210> 67 <211> 465 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 67

Met Glu Cys Asn Trp lie Leu Pro Phe lie Leu Ser Val He Ser Gly 15 10 15

Val Tyr Ser Glu Va】Gin Leu Gin Gin Ser GJy 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 Vai Lys Gin Arg Pro Gly Gin Giy 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 •70· 158138·序列表.doc 201208696

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Scr 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 Scr 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 SeT Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 210 215 220

Pro Scr 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 Val Val 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 Pro Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Scr 30.5 310 315 320

Vai 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 370 375 380

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

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

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

Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 435 440 445 -71 · 158138·.序列表.doc 201208696

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

Ser 465 <2J0> 6S <211> 717 <212> DMA <213>人工序列 <220> <223>合成募核苷酸。 60 120 180 240 300 360 420 480 540 600 660 717 <400> 68 atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc atalcctgca gagccagtga aagtgtagat agttatggca ttagltttat gcactggtac cagcagaaac caggacagcc acccaaactc ctcatctalc gtgcatccaa ccaagaatct gggatccctg ccaggltcag tggcagtggg ictaggacag acttcaccct caccattaat cctgtggagg ctgatgatgt tgcaacctat tactgtcagc aaagtaatga ggatccgctc acgttcggtg ctgggaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctaigc ctgcgaagtc acccatcagg gcctgagctc scccgtcaca aagagcttca acaggggaga gtgttag <210> 69 <211> 238 <212> PRT <213>人工序列 <220> <έ223>合成狀。 <400> 69

Met Glu Thr 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 Scr Pro Ala Ser Leu Ala 20 25 30

Val Ser Leu Gly Gin Arg Ala Thr lie Scr Cys Arg Ala Ser Glu Ser 35 40 45

Val Asp Scr Tyr Gly He Ser Phc Met His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Uu He Tyr Arg Ala Ser Asn Gin Glu Ser

Gly lie Pro Ala Arg Phc Ser Gly Scr Gly Ser Arg Thr Asp Phe Tbr 85 90 95 15 813 8·序列表.doc •72· s 201208696

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 Leu Thr Phe Gly Ala Gly Thr Lys Leu 115 120 125

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

Ser Asp Glu Gin Leu Lys Scr 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 1S5 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 Scr Phe Asn Arg Gly Glu Cys 225 230 235 <210> 70 <211> 1422 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 70 atgaacaggc ttacttcctc attgctgctg clgattgtcc ctgcatatgt cctgtcccag 60 gttactctga aagagtctgg ccctgggata ttgcagccct cccagaccct cagtctgact 120 tgttctttct ctgggttttc actgagcact tctggtatgg gtgtgagctg gaitcgtcag 180 ccticaggaa agggtctgga gtggctggca cacatttact gggatgatga caagcgctat 240 aatccatccc tgaagagccg gctcacaatc tttaaggatc cctccagcaa ccaggtattc 300 ctcaggatca ccagtgtgga cactgcagat actgccacat actact£tgc tcgaaactcc 360 cattactacg gtagtaetta cgggggatac Ucgatgtct ggggcgcagg gaccacggtc 420 accgtctcct cagccaaaac aaagggccca tccgtcttcc ccctggcgcc ctgctccagg 4S0 agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 540 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660

Sgcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720 agagttgagt ccaaataigg tcccccatgc ccaccctgcc cagcacctga gtccgaaggg 780 ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc S40 -73- 158138-序列表.doc 201208696 cctgaggtca cstgcgtgst ggtggacgtg agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc accgtcctsc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccga^agcca caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agtgggagag caatgggcae ccggagaaca aciacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac acacagaaga gcctctccct gtctctgggt aaagctagct ga <210> 71 <211> 473 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 71 A$n Arg Leu Thr Ser Scr Leu Leu Leu Leu lie Val Pro Ala Tyr Val 1 5 10 15

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

Pro Ser Gin Thr Lau Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu 35 40 45

Ser ?〇r Ser Gly Met Gly Va! Ser Trp He Arg G,n Pro Ser G,y Lys

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 Gly Π5 120 125 serser

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

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 165 170 175 74 900 960 1020 1080 1140 1200 1260 1320 1380 1422 158丨38·序列表,doc s 201208696

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

Gly Va! 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 Fro Ala Pro 245 250 255

Glu Phe Glu Gly Gly Pro Scr 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 275 280 285

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 325 330 335

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 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 Val 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 Scr 450 455 460

Leu Ser Leu Ser Leu Gly Lys Ala Ser 465 470 -75- 158138-序列表.doc 201208696 <210> 72 <211> 717 <212> DNA <213>人工序列 <220> <223>合成募核苷酸。 <400> 72 60 120 180 240 300 360 420 480 540 600 660 717 atggagacag acacactcct gctatgggtg ctgctgctcg gggttccagg ttccacaggt aacattgtgc tgacccastc tccaacttct ttcactgtgt ctcttgggca gagggccacc atatcctgca gagccagtga aaglgttcat agttatggca atagttttat gcactggtac cagcagaaac cagggcagcc acccaaactc ctcatctatc ttgcatccaa cgtagaatct ggggtccctg ccaggttcag tggtagtggg tccaggacag acttcaccct caccattgat cctgtggaeg ctgatgatgc tgcaacctat tactgtcagc aaaatagtga ggatccgtgg acgUcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga gcagttgaaa tciggaactg cctctgttgt gtgcctgctg aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag <210> 73 <211> 238 <212> PRT <213>人工序列 <220> <2公> 合成肽。 <400> 73

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 Scr Pro The Ser Phe Thr 20 25 30

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

Val His Ser Tyr Gly Asn Ser Phe Met His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Fro Pro Lys Leu Leu lie Tyr Leu Ala Ser Asn Val Glu Ser 65 70 75 80

Gly Val Pro Ala Arg Phe Ser G,y Ser Gly Ser Arg l,r Asp Phe TT,r

Leu^IieAspProVa, Glu Ala Asp Asp Λ,a Ala Tyr Tyr Cys

Gin Gin Asn Ser Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu 115 120 125 158丨38-序列表.doc -76- s 201208696

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 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Va】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 Scr 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

Li；u Scr Scr Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 74 <211> 1398 <212> DNA <之13>人工序列 <220> <223>合成寡核苷酸。 <400> 74 atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60 gttcagctgc agcagtctgg aactgagctg atgaagcctg gggcctcagt gaagatatcc 120 tgcaaggcta ctggctacac attcagtacc tactggatag agtgggtaaa gcagaggcct 180 ggacatggcc ttgagtggat tggagagatt tiacctggaa gtggtaggac taacgacaat 240 gagaagttca agggcaaggc cacaatcact gcagatacat cctccaagaa agcctacatg 300 caactcagca gcctgacatc rgaggactct gccgtctalt actgtgcaag aaggggtggt 360 taciccttig ctttctgggg ccaagggact ctggtctctg tctctgcagc caaaacaaag 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc . 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca geggegtgea 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 840 gaegtgagee aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc gegggaggag cagttcaaca gcacgtaccg tgtggtcagc 960 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 1020 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1080 • 77· 158138-序列表,doc 201208696 gagccacagg tgtacaccct gcccccatcc casgaggaga tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtg^agtg ggagagcaat gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct ctgggtaaag ctagctga <210> 75 <211> 465 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 75

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly I 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 I.e Ser Cys LyS Ala T,r G.y Tyr PHe

Ser?〇rTyr TrP I,e Glu Trp Val Lys Gin Arg Pro Gly His Gly Leu

Glu Trp lie Gly Glu lie Leu Pro Gly Ser Gly Arg Thr Asn Asp Asn 65 70 75 g〇

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

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

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

Gly T^r Leu Val Ser Va. Ser Ala Ala Lys Π,γ Lg Gly Pro Ser Val

Phe Pro Leu Ala Pro Cys Scr 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 Scr 165 170 175

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

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Va) Thr Val Pro 195 200 205 78- 1140 1200 1260 1320 1380 1398 158138·序列表.doc 201208696

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 Val 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

Tlir 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 He Glu Lys Thr He 340 345 350

Ser Lys Ala Lys Gly Gin Pro Arg GJu 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 370 375 380

Val Lys Gly Phe Tyr Pro SeT Asp He 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 Asa 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 <210> 76 <211> 711 <212> mh <213>人工序列 <220> <223>合成寡核苷酸。 -79- 158138-序列表.doc 201208696 <400> 76 Λ atgaccatgt tctcactagc tcttctcctc agtcttcttc tcctctgtgt ctctgatrct 60 agggcagaaa caactgtgac ccagtctcca gcatccctgt ccatggctat aggagaaaaa 120 gtcaccatca gatgcgtaac cagcactgat attgatgatg atgtgaactg gtaccagcag 180 aagccagggg aacctcctaa gctccttatt tcagaaggca atactcttcg tgctggagtc 240 ccatcccgat tctccagcag tggctatggt acagattttg tttttacaat tgagaacatg 300 ctctcagaag atgttgcaga ttactactgt ttgcaaagtg gtaacttgcc gtacacgttc 360 ggagggggga ccaagctcga gatcaaacga actgtggctg caccatctgt cttcatcttc 420 ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 480 ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 540 tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 600 ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct atgcctgcga agtcacccat 660 cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgtta g 711 <210> 77 <211> 236 <212> PRT <213>人工序列 <220> <223>合成肽》 <400> 77

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 Ser Glu Gly Asn Thr Leu Arg Ala Gly Val 65 70 75 80

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

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

Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 145 150 155 160 158138-序列表.doc 201208696 pn Γ Ty e£ U5 G116 r8 5 a5 17 A1 Π As p As va s Ly po ΤΓ17 n G1 1* va s Ly

Th — 5 38 V 1 Γ c s u 5 n Γ c s no s 8 A — y cl Γ c s n G1

As s Ly r o e 9 s u p s p s 3 s 5 yo L2 Γ c s u Lc F Th u u r o Th20 Γ e s Γ c s u Le r- c s Γ 53 Γ Th f c s c s u Le y 5 n G, s • 12 H2 Γ Th va u G, s cy ΛΛ 5 n T1 A2 Γ Ty va s Ly s Hi so y 1 L2 r8 A n s c ph Γ o c 3 S2 s Ly Γ Th va r0 pr Γ 5 ¢2 列 22A 工 7814DN人 0>1>2>3> 1i 1 n n <2<2<2<2 <220> <223>合成寡核苷酸。 <400> 78 atgaacaggc ttacttcctc attgctgctg ctgattgtcc ctgcatatgt cctgtcccag 60 gttactctga aagagtctgg cccigggata ttgcagccct cccagaccct cagtctgact 120 tgttctttct ctgggttttc actgagcact tctggtatgg gtctgagctg gattcgtcag 180 ccttcaggaa agggtctgga gtggctggca cacaittact gggatgatga caagcgctat 240 aacccatccc tgaagagccg gctcacaacc tccaaggata cctccagcaa ccaggttttc 300 ctcaagatca ccatxgtgga cactgcagat gctgccacat actactgtgc tcgaagctcc 360 cai:tactacg gttatggcta cgggggatac ttcgatgtct ggggcgcagg gaccacggtc 420 accgtctcct cagccaaaac gaagggccca tccgtcttcc ccctggcgcc ctgctccagg 480 agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg 540 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 600 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 660 ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag 720 agagttgagt ccaaatatgg tcccccacgc ccaccctgcc cagcacctga gttcgaaggg 780 ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 840 cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 900 tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtlc 960 aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 1020 aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1080 tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag 1140 gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac 1200 atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1260 gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg 1320 -81 · 158138-序列表.doc ]380 201208696 1422 tggcaggagg ggaatgtcti ctcatgctcc gtgatgcatg aggctctgca caaccactac acacagaaga gcctctccct gtctctgggt aaagctagct ga <210> 79 <211> 473 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 79

Met Asn Arg Leu Thr Ser Ser Leu Leu Leu Leu lie Val Pro Ala Tyr 15 10 15

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

Pro Ser Gin Tlir 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 He 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 100 105 110

Thr Tyr Tyr Cys Ala Arg Ser Ser His Tyr Tyr Gly Tyr Gly Tyr Gly 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 165 170 175

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 Va丨 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 158138·序列表.doc -82 - s 201208696

Arg Val Glu Ser Lys Tyr Giy Pro Pro Cys Pro Pro Cys Pro Ala Pro 245 250 255

Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pto Pro Lys Pro Lys 260 265 270

Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 275 280 285

Asp Val Ser Gin Glu Asp Pro Glu Val Gin Phe Asg Trp Tyr Val Asp

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 325 330 335

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 Scr Gin Glu Glu Met Thr Lys 370 375 380

Asn Gin Val Scr Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Scr 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 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〉 80 <211> 823 <212> Wk <213>人工序列 <220> <223>合成寡核苷酸。 <400> 80 atggagacag acacactcct gctaigggtg ctgctgctct gggttccagg ttccacaggt g〇 aacattglgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120 atatcctgca gagccagtga aagtattcat agttatggca atagttttct gcactggtac 180 -83- 158138-序列表.doc 201208696 cagcagaaac caggacagcc acccaaactc ctcatctatc ttgcatccaa cctagaatct ggggtccctg ccaggttcag cggcagtgeg tctaggacag acttcaccct caccattgat cctgtggagg ctgatgatgc tgcaacctat tactgtcagc aaaataatga ggatccgtgg acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgaiga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg aataacitct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aaglctatgc ctgcgaagtc acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttaggcg gccgcactag cgcgggccgc attcgaagag ctcggtaccc ggggatcctc tagagtcgac ctgcaggcat gcaagctggc cgcgactcta gatcataatc age <210> 81 <211> 238 <212> PRT <213>人工序列 <220> <223〉合成肽。 <400> 81

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Thr Gly Asn He Val Leu Thr Gin Set 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 lie His Ser Tyr Gly Asn Scr Phe Leu His Trp Tyr Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu lie Tyr Leu Ala Ser Asn Leu Glu Ser 65 70 75 80.

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

Leu Thr He Asp Pro Val Glu A.la As§ Asp Ala Ala T^r Tyr Tyr Cys

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 Oly Thr Ala Ser Val Val Cys Leu Leu 145 150 155 160

Asn Asn Phe Tyr Pro Arg Glu Ala Lys Va] Gin Trp Lys Val Asp Asn 165 170 175 158138·序列表 doc -84· s 201208696

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

Lys Asp Ser Thr Tyr Ser Leu Sex Scr Thr Leu Thr Leu Scr 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> 82 <211> 1404 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 82 atgaaatgea gclgggtcat cttcttcctg atggcagtgg ttacaggggl caattcagag 60 gttcagctgc agcagtctgg ggctgagcit gtgaggccag gggccttagt caagttgtcc 120

tgcaaagctt ctggcttcaa cattaatgac tactatatcc actgggtgaa gcagcggcct ISO gaacagggcc tggageggat tggatggatt gatcctgaca atggtaatac tatata'tgac 240 ccgaagttcc agggcaaggc cagtataaca gcagacacat cccccaacac agcctacctg 300 cagclcagca gccteacatc tgaggacact geegtetatt actgtgctag aacccgatct 360 cctatggtta cgacggggtt tgtttactgg ggccaaggga ctgtggtcac tgtctctgca 420 gccaaaacga agggcccatc cgtcttcccc ctgscgccct gctccaggag cacctccgag 480 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagicctca 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcrtggg cacgaagacc 660 tacacctgca aegtagatea caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840 tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900 gacgtggagg tgcataatgc caagacraag ccgcgggagg agcagttcaa cagcacgtac 960 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc egaaeggeaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgiacacc ctgcccccat cccaggagga gatgaccaag 1140 aaccagglca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200 tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320 aatgtcttct catgctccgt gatgeatgag gctctgcaca accactacac acagaagagc 1380 ctctccctgt ctctgggtaa atga 1404 -85- 158138-序列表.doc 201208696 <210> 83 <211> 467 <212> PRT <213>人工序列 <220> <223>合成肽。 <220> <221> misc_feature <222> (309)..(309) <223> Xaa可為任何天然存在之胺基酸 <400> 83

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 Gly 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 Glu 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 Thr 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 llir 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 H5 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 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asti 210 215 220

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser 225 230 235 240 -86 - 158138·序列表.doc 201208696

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

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

Asp Lys SeT Arg 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> 84 <211> 1425 <212>. DMA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 84 atggaaaggc actggatctt tctcttcctg ttttcagtaa ctgcaggtgt ccactcccag gtccagcttc agcagtctgg ggctgagctg gcaaaacctg gggcctcagt gaagatgtcc -87- 158138-序列表.doc 201208696 tgcaaggctt ctggctacac ctttactacc tactggatgc actgggtaaa acagaggcct 180 ggacagggtc tggaatggat tgsatacatt aatcctatca ctggttatac tgagtacaat 240 cagaagttca agsacaaggc caccttgact gcagacaaat cctccagcac agcctacat£ 300 caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagggttta 360 agtgctatgg actattgggg tcagggaacc tcagtcacc^ tcacctcagc caaaacaaca 420 gccccatcgg tctatccact ggcccctgtg tgtggagata caactggctc ctcggtaact 480 ctaggatgcc tggtcaaggg ttatttccct gagccagtga ccttgacctg gaactcigga 540 iccctgtcca gtggtgtgca caccttccca gctgtcctgc agtctgacct ctacaccctc 600 agcagctcag tgactgtaac ctcgagcacc tggcccagcc agaccgtcac ctgcagcgtt 660 gctcacccag ccagcagcac cacggtggac aaaaaacttg agcccagcgg gcccatttca 720 acaatcaacc cctgtcctcc atgcaaggag tgtcacaaat gcccagctcc taacctcgag 780 ggtggaccat ccgtcttcat cttccctcca aatatcaagg atgtactcat gatciccctg 840 acacccaagg tcacgtgtgt ggtgstggat gtgagcgagg atgacccaga cgtccagatc 900 agctggtttg tgaacaacgt ggaastacac acagctcaga cacaaaccca tagagaggat 960 tacaacagta ctatccgggt ggtcagcacc ctccccatcc agcaccagga ctggatgagt 1020 ggcaaggagt tcaaatgcaa ggtcaacaac aaagacctcc catcacccat ceagagaacc 1080 atctcaaaaa ttaaagggct agtcagagct ccacaagtat acatcttgcc gccaccagca 1140 gagcagttgt ccaggaaaga tgtcagtctc acttgcctgg tcgtgggctt caaccctgga 1200 gacatcagtg tggagtggac cagcaatggg catacagagg agaactacaa ggacaccgca 1260 ccagtcccgg actctgacgg ttcttacttc atatatagca agctcaatat gaaaacaagc 1320 aagtgggaga aaacagattc cttctcatgc aacgtgagac acgagggtct gaaaaattac 1380 lacctgaaga agaccatctc ccggtctccg ggtaaagcta gctga 1425 <210> 85 <211> 474 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 85

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

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 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 -88 - 158138-序列表.doc s 201208696

Gin Lys Phe 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 Tlir Ser Glu Asp Ser Ala Val 100 105 110

Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Met Asp Tyr Trp Oly Gin 115 120 125

Gly Thr Ser Val Thr Val Thr Ser Ala Lys Thr Thr Ala Pro Ser Val 130 135 140 'ryr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr 145 150 155 160

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

Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro A1a 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 Gly Pro lie Ser 225 230 235 240

Thr He Asn Pro Cys Pro Pro Cys Lys Glu Cys His Lys Cys Pro Ala 245 250 255

Pro Asn Leu Glu Gly Gly Fro Ser Val Phe lie Phe Pro Pro Asn lie 260 265 270

Lys Asp Val Leu Met He Ser 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 Gin Tlir Gin Thr His Arg Glu Asp 305 310 315 320

Tyr Asn Ser Thr He Arg Val Val Ser Thr Leu Pro lie Gin His Gin 325 330 335

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 l*hr lie Ser Lys lie Lys Gly Leu Val 355 360 365

Arg Ala Pro Gin Val Tyr lie Leu Pro Pro Pro Ala Glu Gin Leu Ser 370 375 380 -89- 158138-序列表.doc 201208696

Arg Lys Asj) Va】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 Asd 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 ITir 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> 86 <211> 717 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸》 <400> 86 atgggcatca agatggagtc acggattcag gcatttgtat tcgtgtttct ctggttgtct £gtgttggcg gagacattgt gatgacccag tctcacaaat tcatgtccac atcagtagga gacagggtca gcgtcacctg caaggccagt caggatgtga cttctgctgt agcctggtat caacaaaaac cagggcaatc tcctaaacta ctgatttact gggcatccac ccggcacact ggagtccctg atcgcttcac aggcagtgga tctgggacag altatactct caccatcagc agtgggcagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg acgttcggtg gaggcaccaa gctggaagtc aaacgggctg atgctgcacc aactgtatcc atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc agcaccctca cgttgaccaa ggaegagtat gaacgacata acagctatac ctgtgaggcc actcacaaga catcaacttc acccatcgtc aagagettea ataggaatga gtgttag <210> 87 <211> 234 <212> PRT <213>人工序列 <220> <223>合成肽。 <•87

Met Glu Ser Arg 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 •90- 60 120 180 240 300 360 420 480 540 600 660 717 158138-序列表.doc s 201208696

Thr Sei 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 5〇 55 60

LysLeuLeuIlcTyrTrpAlaSerl,rArgHis^G.yVal Pro Asp

Arg Phe Thr Gly Ser Gly Ser 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

Ser Ala Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Val Lys Arg Π5 120 125

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

Leu Thr Ser Gly Gly Ala Scr Val Val Cys Phe Leu Asn Asn Phe Tyr ]45 150 155 160

Pro Lys Asp Lie Asn Val Lys Trp Lys lie 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 Scr Ser Thr Leu ^ Leu T.r Lys Asp Glu Tyr Glu Arg

His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro 210 215 220 lie Val Lys Ser Phe Asn Arg Asn Glu Cys 225 230 <210> 88 <21.1> 1398 <212> DNrA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 88 atggaaaggc actggatctt tctcttcctg ttttcagtaa ctgcaggtgt ccactcccag gtccagcttc agcagtctgg ggctgagctg gcaaaacctg gggcctcagt gaagatgtcc tgcaaggctt ctggctacac ctttactacc tactggatgc actgggtaaa acagaggcct ggacagggtc tggaatggat tggatacatt aatcctatca ctggttatac tgagtacaat cagaagttca aggacaaggc caccttgact gcagacaaat cctccagcac agcctacaig caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagggttta 91- 158138·序列表.doc 201208696 agtgctatgg actattgggg tcagggaacc tcagtcaccg tcacctcagc caaaacaacg 420 ggcccatccg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 480 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 540 gccctgacca gcggcgtgca caccttcccg sctgtcctac 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 840 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 900 cataatgcca agacaaagcc 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 ggag^caat 1200 gggcagccgg agaacaacia caagaccacg cctcccgtgc tggactccga cggctccttc 1260 ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1320 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct 1380 ctgggtaaag ctagctga 1398 <210> 89 <211> 465 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 89

Met Glu Arg His Trp lie Phe I^u Phe Leu Phe Ser Val Thr Ala Gly ] 5 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 Gly Leu 50 55 60

Glu Trp lie Gly Tyr He Asn Pro He Thr Gly Tyr Thr Glu 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 Tyr Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val l〇〇 105 110 158138·序列表.doc -92- s 201208696

Tyr Tyr Cys Ala Arg Glu Gly Leu Ser Ala Met Asp Tyr Trp Gly Gin 115 120 125

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

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 Thr Ser Gly Val His Thr Phe Pro Ala Val ISO 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 Fhe 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 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 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 Tlir Leu 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 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 -93- 158138-序列表.doc 201208696

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

Trp Gin Olu 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 <210> 90 <211〉717 <212> WA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 90 atgggcatca agatggagtc acagattcag gcatttgtat tcgtgtttct ctggttglct ggtgttggcg gagacattgt gatgacccag tctcacaaat tcatgtccac atcagtagsa gacagggtca gcgicacctg caaggccagt caggatgtga cttctgctgt agcctggtat caacaaaaac cagggcaatc tcctaaacta ctgatttact gggcatccac ccggcacact ggagtccctg atcgcttcac aggcaetgga tctgggacag attatactct caccatcagc agtgggcagg ctgaagacct ggcactttat tactgtcacc aatattatag cgctcctcgg acgttcggtg gaggcaccaa gctcgagatc aaacgaactg tsgctgcaoc atctgtcttc atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag <210> 91 <211> 234 <212> PRT <2]3>人工序列 <220> <223>合成肽。 <400> 91

Met Glu Ser Gin lie Gin Ala Phe Val Phe Val Phe Leu Trp Leu Ser 1 5 10 15

Gly Val Gly Gly Asp lie Val Met Gin Ser His Lys Phe Met Ser

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

Val Thr Ser Ala Va] Ala Trp Tyr G】n Gin Lys Pro Gly Gin Ser Pro 50 55 60 • 94· 60 120 180 240 300 360 420 480 540 600 660 717 15813 8·序列表.doc s 201208696

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 lie Ser 85 90 95

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

Ser AV, Pro ATg Τ,χ Phe Glv Glv Gly Thr Lvs Leu Glu He Lys Arg

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 I^u 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> 92 <211> 1401 <212> DNA <213>人工序列 <220> <223>合成募核苷酸e <400> 92 atggctgtcc tggcactact cctctgcctg gtggctttcc caacttgtac cctgtcccag gtgcaactga aggagtcagg acctggcctg gtggcgccct cacagagcct gtccattacc tgctctgtct ctgggttctc attaagcaac tatgatataa gctggattcg ccagccacca ggaaagggtc tggagtggct tggagtaatg tggactggtg gaggcgcaaa ttataattca gctttcatgt ccagactgag catcaacaag gacaactcca agagccaast ttttttaaaa atgaacaatc tgcaaactga tgacacagcc atttaitact gtgtcagaga tgcggtgagg Cactggaact tcgatgtctg gggcgcaggg accacggtca ccgtctcctc agccaaaacg aagggcccat ccgtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc gccctgggcc gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccaficggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 95· 158138·序列表.doc 201208696 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc aacgtagatc acaascccag caacaccaag gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag ttcgaagggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccecggsag gagcasttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccassactgg ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtstacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtg£gagagc aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagag cclctccctg tctctgggta aagctagctg a <210> 93 <21l> 466 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 93

Met Ala Val Leu Ala Leu Leu Leu Cys Leu Val Ala Phe 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 Trp Asn Phe Asp Val Trp Gly 115 120 125

Ala Gly Thr Thr Val Thr Val Ser Ser Ala Lys Thr Lys Gly Pro Scr 130 135 140 * -96- 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1401 158138·序列表.doc s 201208696

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

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phc Pro 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 Va] Asp His 210 215 220

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

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

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

Lys Thi Lys Pro Arg Glu 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 Ser Asn Lys G!y Leu Pro Ser SeT lie Glu Lys Ήιγ 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 He 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 -97· 158138-序列表.doc 201208696

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

Ala Ser 465 <210> 94 <2】1> 70S <212> DNA <2]3>人工序列 <220> <223>合成寡核苷酸。 <400> 94 atggatttlc aagcgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60 agaggacaaa ttgttctctc ccagtcacca gcaatcctgt ctgcatctcc aggggagaag 120 gtcacaatga cttgcagggc cagctcaagt gtaagttaca tacactggta ccagcagaag 180 ccaggatcct cccccaaacc ctggatttat gccacatccc acctggcttc tggagtccct 240 gctcgcttca stggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300 gctgaagata ctgccactta ttactgccag cagtggagta gtaacccatt cacgttcggc 360 tcggggacaa agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag 660 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agt£ttag 708 ^Λ > > ¢123 1 1 1 1 <2<2<2<2

列 <22〇> <223>合成肽》 <4〇〇> 95

Met Asp Phe Gin Ala Gin lie Phc Ser Phe Leu Leu lie Ser Ala Ser 15 10 15

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

Leu Ser Ala Ser Pro Gly Glti 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 Scr Ser 50 55 60

Pro Lys Pro Trp He 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 Ser Tyr Ser Leu Thr lie 85 90 95 -98- 158138·序列表.doc 201208696

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

Ser Ser Asn Pro Phc Thr Phe Gly Ser Gly Tlir Lys Leu Glu lie Lys Π5 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 Gin Trp Lys Val Asp Aso 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 Scr Leu Scr Scr Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 195 200 205

Lys His Lys Va] Tyr Ala Cys Glu Va丨 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> 1410 <212> m <2】3>人工序列 <220> <223>合成寡核苷酸。 <400> 96 atggaaaggc actggatctt tctactcctg ttfitcagtaa ctgcaggtgt ccactcccag 60 gtccagct£c agcagtctgg ggctgaactg gcaagacctg gggcctcagt gaagatgtcc 120 tgcaaggctt ctggctacac ctttactacc tacactatgc actgggtaaa acagaggcct 180 ggacagggtc tggaatggat tggatacatt aatcctagca gtggttatac taattacaat 240 cagaagttca aggacaaggc cacattgact gcagacaaat cctccagcac agcctccatg 300 caactgagca gcctgacatc tgaggactct gcagtctatt actgtgcaag agagagggcg 360 gtattagtcc cctatgctat ggactactgg ggtcaaggaa cctcagtcac cgtctcctca 420 gccaaaacaa 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 aegtagatea caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcgaaggggg accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840 -99- 158138·序列表.doc 201208696 900 960 1020 1080 1140 1200 1260 1320 1380 1410 tgcfit£gtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat ggcgtggagg tgcacaatgc caagacaaag ccgcgggags agcagttcaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccglcc tccatcgaga aaaccatctc caaagccaaa gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag tgggagagca atgsgcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg aatgtcttct catgctccet gatgcatgag gctctgcaca aocactacac acagaagagc ctctccctgt ctctgggtaa agctagctga <210> 97 <211> 469 <212> ?RT <213>人工序列 <220> <223>合成肽。 <400> 97

Met GIu Arg His Trp He Phe Leu Leu Leu Leu Ser VaJ Thr Ala Gly 15 10 15

Va. His Ser Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Leu Ala Ar2

Pro Gly Ala Ser Va. Lys Met Ser Cys Lys Ala Ser Gly I^r-Thr Phe

Thr Tyr Met His Trp Val Lys Gin Ar8 Pro Gly Gin Gly Leu

GluTrpIIeGlyTyrlleAsnProSer Ser Gly Tyr ^ Asn Tyr Asn

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 HO

Tyr Tyr Cys Ala Arg Glu Arg Ala Val Leu Val Pro Tyr Ala Met Asp 115 120 125

Tyr Trp Gly Gin Servant Val Ser Ser A,a Lys Lys 01, Pr〇 Ser Val Phe Pro Leu Ala Pro Cys Ser Are Ser^r Ser Glu

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 165 170 175 158138-序列表 *d〇c -100-

S 201208696

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

Phe Pro Ala Va] 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 Asa 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 Va丨 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 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

Tyv 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 Scr 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 Tyr Ser Arg Leu 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 Ala Ser 465 -101 - 158138·序列表.doc 201208696 <210> 98 <211> 708 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 98 atgcattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt cataatgtcc 60 agaggacaaa ttgttctcac ccagtctcca gcagtcatgt ctgcatctcc aggggagaag 120 gtcaccataa cctgcactgc cagctcaagt ttaagttaca tgcactggtt ccagcagaag 180 ccaggcactt ctcccaaact ctggctttat agcacatcca tcctggcttc tggagtccct 240 actcgcttca gtggcagtgg atctgggacc tcttactctc tcacaatcag ccgaatggag 300 gctgaagatg ctgccactta ttaclgccag caaaggagta gttccccatt cacgttcggc 360 tcggggacaa agctcgagat caaacgaact gtggctgcac catctgtctt catcttcccg 420 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 480 tatcccagag aggccaaast acagtggaag gtggataacg ccctccaatc gggtaactcc 540 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 600 acgctgagca aagcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag 660 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 708 <210> 99 <21]> 235 <212> PRT <213>人工序列 <220> <223>合成肽》 <400> 99

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 He Val Leu Thr Gin Ser Pro Ala Val 20 25 30

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

Ser Ser Leu Ser Tyr 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

Ser Ser Ser Pro Phe Thr Phe Gly Ser GJy Thr Lys Leu Glu lie Lys 115 120 125 158138·序列表.doc -102- s 201208696

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 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 1S5 190

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

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

Pro Val Thr Lys Scr Phe Asn Arg Gly Glu Cys 225 230 235 <210> 100 <211> 1404 <212> DNA <2!3>人工序列 <220> <223>合成寡核苷酸。 <400> 100 atgggatgga cctggatctt tattttaatc ctgtcagtta ctacaggtgt ccactctgag 60 gtccagctgc agcagtctgg acctgagctg gagaagcctg gcgcttcagt gaagatatcc 120 tgcaaggctt ctggttactc cttcactggc tacaacatga actgggtgaa acagagcaat 180 ggaaagagcc ttgagtggat tggaaatatt gaicctlact atggtgatac taactacaac 240 cagaagttca agggcaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300 cacctcaaga gcctgacatc tgaggactct gcagtctatt actgtgcaag accctacggt 360 agtgaggcct aclttgctta ctggggccaa gggactctgg tcactgtctc tgcagccaaa 420 aegaagggee catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600 taciccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg 780 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 900 gaggtgcata atgccaagac aaageegegg gaggageagt tcaacagcac gtaccstgtg 960 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 1020 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080 -103- 158138-序列表.doc 201208696 ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag 1140 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag 1200 agcaatgggc ageeggagaa caactacaas accacgcctc ccgtgctgga ctccgacggc 1260 tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc 1320 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc 1380 ctgtctctgg gtaaagctag ctga 1404 0>1>2>3> <21<21<21<21 101 467

PRT 人工序列 <220> <223>合成肽。 <400> 101

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

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

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

Thr Gly Tyr Asn Met Asn Trp Val Lys GJn 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 Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val loo 105 no

Tyr Tyr Cys Ala Arg Pro Tyr Gly Ser Glu Ala Tyr Phe Ala Tyr Trp 115 120 125

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 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 Val Leu Gin Ser Ser Gly Ley Tyr Ser Leu Ser Ser Val Val Thr 195 200 205 104· 158138·序列表.doc 201208696

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 lie Ser 260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp 275 2S0 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 Tlir 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 He 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 Scr Leu Ser Leu Ser Leu Gly 450 455 . 460

Lys Ala Ser 465 <210> 102 <211> 705 <212> DNA <213>人工序列 <220> <223>合成寡校苷酸《 158138·序列表.doc -105- 201208696 60 120 180 240 300 360 420 480 540 600 660 705 <400> 102 atggtgtcca cttctcagct ccttggactt ttgcttttct ggacttcagc ctccagatgt gacattgtga tgactcagtc tccagccacc ctgtctgtga ctccaggaga tagagtctct ctttcctgca gggccagcca gagtattagc sactacttac actgstatca acaaaaatca catgagtctc caaggcttct catcaaatat gctgcccaat ccatctctgg ^atcccctcc aggttcagtg gcagtggatc agggtcagat ttcactctca gtatcaacgg tgtggaacct gaagatgttg gagtgtatta ctgtcaaaat ggtcacagct ttccgtacac gttcggaggg gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaasgac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgccl gcgaagtcac ccatcagggc ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag <210> 103 <21i> 214 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 103

Asp He Val Met Thr Gin Ser Pro Ala Thr Leu Ser Val 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 Cly 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 I】e Lys Arg Thr Val Ala Ala 100 105 110

Pro Ser Val Phe lie Phe Pro Pro Ser Asp 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 ϊνς Val Gin Trp Lys Va】Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160 158138·序列表doc 106.

S 201208696

U5 V ]c Gl L Γ s s 6 ·1 y s H c u Γ uh 1 T G Γ Γ o . 1 y h h8 a 1 V Ήι V G 1 u U5 svaLeGl19Ar Γ Γ s no seThcyAS21 u r Aa c 1 c l uu G s A p

Ly Γ c s p As n Gl ys u Le yo n· G 2 n G1

Av ,y c STS u 5 1 s 6 7 a y LI V L Γ s ο Γ c y9 nn s LIΏ Γ s 15 ·1 2 Au τ Η V 2 Γ s o ThLVPI rut c 1 e SOS po Γ T S7 _y e A1 T s P5 s 8 104sr. 0>1>2>3> 1 *1 1« <2<2<2<2 列 序 <220> <223>合成寡核苷酸。 <400> 104 atggaatgga ggatctttct cttcatcctg tcaggaactg caggtgtcca ctcccaggtt 60 cagctgcggc agtctggacc tgagctggtg aagcctgggg cttcagtgaa gatgtcctgc 120

aaggcttctg gatacacatt tactgactat gttataagtt gggtgaagca gagaactgga ISO cagggccttg agtggattgg agatatttat cctggaagtg gttattcm ctacaatgag 240 aacttcaagg gcaaggccac adgactgca gacaaatcct ccaccacagc ctacatgcag 300 ctcagcagcc tgacatctga g£actctgcg gtctatttct gtgcaaccta ctataactac 360 ccttttgctt actggggcca agggactctg gtcactgtct ctgcagccaa aacaacgggc 420 ccatccgtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 480 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 540 ctgaccagcg gcgigcacac cttcccggct gtcctacagt cctcaggact ctactccctc 600 agcagcgtgg tgaccgtgcc ctccagcagc itgggcacga agacctacac clficaacgta 660 gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 720 tgcccaccct gcccagcacc tgagttcgaa gggggaccat cagtcttcct gttcccccca 780 aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 840 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 900 aatgccaaga caaagccgcg ggaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 960 ctcaccgtcc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtctccaac 1020 aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca iccccgagag 1080 ccacaggigt acaccctgcc cccatcccag gaggagatga ccaagaacca ggtcagcctg 1140 acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1200 cagccggaga acaactacaa gaccacgcct cccgigctgg actccgacgg clccttcttc 1260 ctctacagca ggctaaccgt ggacaagagc aggtggcagg aggggaatgi cttcicatgc 1320 tccgtgatgc atgaggctct gcacaaccac tacacacaga agagcctctc cctgtctctg 1380 ggtaaagcta gctga 1395 -107- 158138-序列表.doc 201208696 <210> ]〇5 <211> 446 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 105

Gin Val Gin Leu Arg Gin Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 15 10 15

Ser Va丨 Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 20 25 30

Val lie Ser Trp Val Lys Gin Arg Thr Gly Gin Gly Leu Glu Trp lie 35 40 45

Gly Asp lie Tyr Pro Gly Ser Gly Tyr Ser Phe Tyr Asn Glu Asn Phe 50 55 60

Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Thr Thr Ala Tyr 65 70 75 80

Met Gin Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 85 90 95

Ala Thr Tyr Tyr Asn Tyr Pro Phe Ala Tyr Trp Gly Gin Gly Thr Leu 100 105 110

Val rrhr Val Ser Ala Ala Lys Thr Thr Gly Pro Ser Val Phe Pro Leu 115 120 125

Ala Pro Cys Ser Arg Ser Thr Scr Glu Ser Thr Ala Ala Leu Gly Cys 130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser 165 m 3 75

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 180 185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Fro Ser. Asn 195 200 205

Thr Lys Va! Asp Lys Arg Val Glu Scr Lys Tyr Gly Pro Pro Cys Pro 210 215 220

Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe 225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val 245 250 255 15813 8·序列表.doc •108· s 201208696

Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val Gin Phe 260 265 270

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 275 280 285

Arg Glu Glu Gin Phe Asn Ser Thr Tyr Arg Val Val Ser Va〗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 Scr 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 Val Ser Leu Ihr Cys Leu Val Lys Gly 355 360 365

Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Scr Asn Gly Gin Pro 370 375 380

Glu Asn Asn Tyr Lys Thi Thr Pro Pro Val Leu Asp Ser Asp Gly Scr 385 390 395 400

Phe Phe Leu Tyr Scr Arg Leu Thr Val Asp Lys Ser Arg Trp Gin Glu 405 410 415

Giy Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 420 425 430

Tyr Thr Gin Lys Ser Leu Ser Leu Scr Leu Gly Lys Ala Ser 435 440 445 <21Q> 106 <211> 717 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 106 atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat gttgtgatga cccaaactcc actctccctg cctgtccgtc ttggagaica agcctccatc tettgeagat etagteagag ccttgtacac agtaatggaa acacctattt acattggtac ctgcagaagc caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct ggggtcccag acaggttcag tggcagtgga tcagggacaa atttcacact caagatcagc agagtggagg ctgaggatct gggactttat ttctgctctc aaaglacaca tgttccgtac aegtteggag gggggaccaa getegagate aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg aataactict atcccagaga ggccaaagta cagtggaagg tggataaege cctccaatcg 109- 158138·序列表.doc 201208696 600 660 717 ggtaactccc aggagagtgt cacagagcag sacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg gcctgagcic gcccgtcaca aagagctica acaggggaga gtgttag <210> 107 <21i> 219 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 107

Asp Val Val Met Thr Gin Thr Pro Leu Ser Leu Pro Va) Arg Leu Gly 15 10 15

Asp Gin Ala Ser lie Ser Cys Arg Ser Ser Gin Ser Leu Val His Ser 20 25 30

Asn Gly Asn Thr Tyr Leu His Trj) Tyr Leu Gin Lys Pro Gly Gin Ser 35 40 45

Pro Lys Leu Leu He Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asn Phe Thr Leu Lys 11c 65 70 75 80

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

Arg Thr Val Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu 115 120 125

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 145 150 155 160

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 165 170 175

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 108 <211> 1410 158138-序列表.doc •110- s 201208696 <212〉麗 <213>人工序列 <220> <223>合成募核苷酸。 <400> 108 atgacatlga acatgctgtt ggggctgagg tgggttttct ttgltfiUtt ttatcaaggt 60 gtgcattgtg aggtgcagct tgttgagtcl ggtggaggat tggtgcagcc taaagggtca 120 ttgaaactct catgtgcagc ctctggatta accttcaata tctacgccat gaactgggtc 180 ， cgccaggcu 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 gccaaaacga agggcccatc cgtcttcccc ctggcgccc丨 gctccaggag cacctccgag 4S0 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 540 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgEcct acagtcctca.- 600 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 660 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 720 aaatatggtc ccccatgccc accctgccca gcacctgagt tcaaaggggS accatcagtc 780 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 840 tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat 900 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 960 cgigtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag 1020 tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa 1080 gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag 1140 aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 1200 (gggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1260 gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg 1320 aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 1380 ctctccctgt ctctgggtaa agctagctga 1410 0>1>2>3> <21<21<21<21 109 469

PRT 人工序列 <220> <223>合成肽》 <400>· 109

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 GIu 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 • 111· 158138·序列表.doc 201208696 35 40 45

Gly Leu Thr Phe Asn lie Tyr Ala Met Asn Trp Val Arg Gin Ala Pro 50 55 60

Gly Lys Gly Leu Glu Trp Val Ala Arg lie Arg Asn Lys Scr Asn Asn 65 70 75 80

Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr He Ser 85 90 95

Arg Asp Asp Ser Gin Ser Leu Leu Tyr Leu Gin Met Asn Asn Leu Lys 100 105 110

Thr Glu Asp Thr Ala Met Tyr Tyr Cys Val Gly Arg Asp Trp Phe 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 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 18*0 185 190

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

He 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 Va] GJu 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 Asp Trp Leu Asn Gly 325 330 335 158138-序列表.doc - 112- s 201208696

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 Scr 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 He Ala Val Glu 385 390 395 400

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

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

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

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

Leu Gly Lys Ala Ser 465 <210> 110 <211> 708 <2I2> DNA <213>人工序列 <220> <223>合成肽。 <400> 110 atggcctgga tttcacttat actctctctc ctggctctca gctcaggggc catttcccag gctgttgtga ctcaggaatc tgcactcacc acatcacctg gtgaaacagt cacactcact. tgtcgctcaa gtactggggc tgttacaact agtaactatg ccaactgggt ccaagaaaaa ccagatcatt tattcactgg tetaataggt ggtaccaaca accgagtttc aggtgttcct gccagattct caggctccct gattggagac aaggctgccc tcaccatcac aggggcacag actgaggatg aggcaatata tttctgtgct ctatggtaca gcaaccattg ggtgttcggt ggaggaacca aactcgagat caaacgaact gtegctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atciggaact gcctctgttg tgtgcctgct gaataaette tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg aegetgagea aagcagacta cgagaaacac aaagtctatg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagette aacaggggag agtgttag <210> 111 <2ll> 235 <212> PRT <213>人工序列 158138-序列表.doc -113- 201208696 <220> <223>合成肽。 <400> 111

Met Ala Trp lie Ser Leu lie Leu Ser Leu Leu Ala Leu Scr Scr Gly 1 5 10 15

Ala lie Ser Gin Ala Val Val Thr Gin Glu Ser Ala Leu Thr Thr Ser 20 25 30

Pro Gly Glu Thr Val Thr 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 Pro Asp His Leu 50 55 60

Phe Thr Gly Leu lie Gly Gly Thr Asn Asn Arg Val Ser 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 Tyr 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 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 Gin Trp Lys Val Asp Asn Ala Lea 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 Scr 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 210 235 220

Pro Val Tlir Lys Ser Phe Asn Arg Gly Glu Cys 225 230 235 <210> 112 <211> 1386 <212> MsA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 112 atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag •114- 158138·序列表.doc 201208696 gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120 tgcaaggcta ctggctacac attcggtagc tactggatag agtgggtaaa gcagaggcct ]80 ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtaatac taactacaat 240 gagaacttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300 caactcacca £tctgacatc tgaggactct gccgtctatt actgtgctag ggcggggatt 360 tattggggcc aagggactct ggtcactgtc tctgcagcca aaacgaaggg cccatccgtc 420 ttccccctgg cgccctgctc caggagcacc tccgagagca cagccgccct gggctgcctg 4S0 gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 540 ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tclaciccct cagcagcgtg 600 gtgaccgtgc cctccagcag cttgggcacg aagacctaca cctgcaacgt agatcacaag 660 cccagcaaca ccaaggtgga caagagagtt gagtccaaat atggtccccc atgcccaccc 720 tgcccagcac ctgagttcga agggggacca tcagtcttcc tgttcccccc aaaacccaag 780 gacactctca tgatctcccg gacccctgag gtcacgtgcg tggtggtgga cgtgagccag 840 gaagaccccg aggtccagtt caactggtac gtggatggcg tggaggtgca laatgccaag 900 acaaagccgc gggaggagca gttcaacagc acgtaccgtg tggtcagcgt cctcaccgtc 960 ctgcaccagg actggctgaa cggcaaggag tacaagtgca aggtctccaa caaaggcctc 1020 ccgtcctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga gccacaggtg 1080 ta.caccctgc ccccatccca ggaggagatg accaagaacc aggtcagcct gacctgcctg 1!40 gtcaaaggct tctaccccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1200 aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1260 aggctaaccg tggacaagag caggtggcag gaggggaatg tcttctcatg ctccgtgatg 1320 catga^gctc tgcacaacca ctacacacag aagagcctct ccctgtctct gggtaaagct 】380 agctga 1386 <210> 113 <211> 461 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 113

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Scr 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 Aia Ser Val Lys lie Ser Cys Lys Ala Thr Gly Tyr Thr Phe 35 40 45

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

Glu Trp lie Gly Glu lie Leu Pro Gly Ser Gly Asn Thr Asn Tyr Asn -115- 158138-序列表.doc 201208696 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 Thr 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 Ser 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 Leu Gin Ser Ser 180 185 190

Gly Leu Tyr Ser Leu 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 Ser 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 Glu 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 lie 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 158138-序列表.doc · 116- s 201208696

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 Va】Leu Asp Ser Asp Gly Ser Phe 405 410 415

Phe Leu Tyr Scr 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 Ser Leu Sei Leu Ser Leu Gly Lys Ala Ser 450 455 460 <210> 114 <211> 717 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸^ <400> 114 atggagaaag acacactcct gctatgggtc ctgcttctct gggttccagg ttccacaggt gacattgtgc tgacccaatc tccagctttt ttggctgtgt ctctagggca gagggccacc atctcctgca gagccagcga aagtgttgat aattatggca ttagttttat gaactggttc caacagaaac caggacagcc acccaaactc ctcatctatg ttgcatccaa gcaaggatcc ggggtccctg ccaggtttag tggcagtggg tctgggacag acttcagcct caacatccat cctatggagg aggatgatac tgcaatgtat ttctgtcagc aaagtaagga ggttcctcgg acgttcggtg gaggcaccaa getegagate aaacgaactg tggctgcacc atctgtcttc atcttcccgc catctgatga gcagitgaaa tctggaactg cctcigttgt gtgcctgctg aataaettet atcccagaga ggccaaagta cagtggaagg tggataaege cctccaatcg ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc acccatcagg gcctgagctc gcccgtcaca aagagettea acaggggaga gt&ttag <210> 115 <211> 238 <212> PRT <213>人工序列 <220> <M3>合成肽。 <400> 115

Met Glu Lys 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 Phe Leu Ala 20 25 30 -117- 60 120 180 240 300 360 420 480 540 600 660 717 158138·序列表.doc 201208696

Val Ser Leu Gly G.n Arg A,a Thr I.c Ser Cys Ar£ Ala Ser Glu Ser

Val Asp Asn Tyr Gly lie Ser Phe Met Asn Trp Phc Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Leu Leu He Tyr Val Ala Ser Lys Gin Gly Ser 65 70 75 80

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

Leu Asn lie His Pro Met Glu Glu Asp Asp Thr Ala Met Tyr Phe Cys 100 105 110

Gin Gin Scr Lys Glu Val Pro Arg 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> 116 <211> 1392 <2】2> DNA <2】3>人工序列 <220> <223>合成寡核苷酸。 <400> 116 atggaatgta actggatact tccttttatt ctgtcggtaa cttcaggggt ctactcagag 60 gttcagctcc agcagtctgg gactgtgctg gcaaggcctg gggcttcagt gaagatgtcc 120 tgcaaggctl ctggctacac ctttaccagc tactggatgc actgggtaaa acagaggcct 180 ggacagggtc tggaatggat iggcgctatt tatcctggaa aiagtgatac tacctacaac 240 cagaagttca agggcaafigc caaactgact gcagtcacat ccaccagcac tgcctacatg 300 gagctcagca £cctgacaaa tsasgactct geggtetatt actgtacacc tacttactac 360 tttgactact ggggccaagg cacctctctc acagtctcct cagccaaaac gaagggccca . 420 158138·序列表.doc -118· s 201208696 tccgtcttcc ccctggcgcc ctgctccagg agcacctccg agagcacagc cgccctgggc 480 tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 540 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 600 agcgtggtga ccgtgccctc cagcagcttg ggcacgaaga cctacacctg caacgtagat 660 cacaagccca gcaacaccaa ggtggacaag agagttgagt ccaaatatgg tcccccatgc 720 ccaccctgcc cagcacctga gttcgaaggg ggaccatcag tcttcctgtt ccccccaaaa 780 cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 840 agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat 900 gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc 960 accgtcctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 1020 ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagagcca 1080 caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc 1140 tgcctggtca aaggcttcta ccccagcgac atcgccgigg agtgggagag caatgggcag 1200 ccggagaaca aclacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1260 tacagcaggc taaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc 1320 gtgatgcatg aggctctgca caaccactac acacagaaga gcctctccct gtctctgggt 1380 aaagctagct ga 1392 <210> 117 <21l> 463 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 117

Met Glu Cys Asn Trp He Leu Pro Phe lie Leu Ser Val Thr Ser Gly 15 10 15

Val Tyr Ser Glu Val Gin Leu Gin GJn Ser Gly 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 Gin Arg Pro Gly Gin Gly Leu 50 55 60

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

Gin Lys Phe Lys Gly Lys Ala Lys Leu Thr Ala Val Thr Ser 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 Hir Tyr Tyr Phe Asp Tyr Trp Gly Gin Gly Thr -119* 158138-序列表.doc 201208696 115 120 125

Ser Leu Thr Va) Ser Ser Ala Lys Thr Lys Giy Pro Ser Val Phc 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 Pro 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 Fro Ser Ser 195 200 205

Ser Leu Gly Thr Lys Thr Tyr ITir 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

Val Thr Cys Val Val Val Asp Val Ser Gin Glu Asp Pro Glu Val 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 Val Ser Val Leu 305 310 315 320

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

Val Ser Asn Lys Gly 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 Thr Leu Pro Pro Ser 355 360 365

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

Gly Phe Tyr Pro Ser Asp He 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 158138·序列表.doc -120- s 201208696

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val 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> 118 <21l> 717 <212〉瞧 <213>人工序列 <220> <223>合成寡核苷酸。 <400> 118 atgagtcctg cccaattcct gtttctgtta gtgctctgga ttcgggaaac caacggtgat 60 gttgtgatga cccagactcc actcactttg tcggttacca ttggacaacc agcctccatc 120 tcttgcaagt caagtcagag cctcttagat agtgatggaa agacatattt gaattggttc 180 ttacagaggc caggccagtc tccaaagcgc ctaatctatc tggtgtctaa actggactct 240 ggagtccctg acaggttcac iggcagtgga tcagggacag atttcacact gaaaatcagc 300 agagtggagg ctgaggattt gggagtttat tattgctggc aaggtacaca ttttccgtgg 360 acgttcgetg gaggcaccaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg 480 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 <210> 119 <211> 238 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 119

Met Ser Pro Ala Gin Phe Leu Phe Leu Leu Val Leu Trp lie Arg Glu 15 10 15

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

Thr lie Gly Gin Pro Ala Ser Tie Ser Cys Lys Sex 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 80 -121 - 158138-序列表.doc 201208696

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

Trp Gin Gly Thr His Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Uu 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 TTir 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> 120 <211> 1415 <212> DNA <213>人工序列 <220> <223>合成募核苷酸e <40Q> 120 atgggaggga tctggaictt tcicttcctc ctgtcaggaa ctgcaggtgc ccactctgag 60 atocagetge agcagactgg acctgagctg gtgaagcctg gggcttcagt gaagatatcc 120 tgcaaggctt ctggttatcc attcactgac tacatcatgg tctgggtgaa gcagagccat 180 ggaaagagcc ttgagtggat tggaaatatt agtccttact atggtactac taactacaat 240 ctgaagttca agggcaaggc cacattgact gtagacaaat cttccagcac agcctacatg 300 cagctcaaca gtctgacatc tgaggactct gcagtetatt actgtgcaag atcccctaac 360 tgggacgggg cclggtttgc tcactggggc caaggggctc tggtcactgt ctctgcagcc 420 aaaacaaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480 acagccgccc t£g£ctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540 aactcasgcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca stccicagga 600 ctctactccc teageagegt ggtgaccgtg ccctccagca ecttgsgcac gaagacctac 660 iicctgcaacg tagatcacaa gcccagcaac accaaggtge acaagagagt tgagtccaaa 720 tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780 158138·序列表.doc -122- s 201208696 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 900 fitggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt 960 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 1020 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1080 oagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat 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 tagctgatta attaa 1415 <210> 121 <211> 468 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 121

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

Ala His Ser Glu He Gin Leu Gin G]n Thr Gly Pro GIu Leu Val Lys 20 25 30

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

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

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

Leu Lys Phe Lys Gly Lys Ala 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

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

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

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val -123 - 158138-序列表,doc 201208696 165 170 175

Thr Val Ser Trp Asn Ser Gly Ala Leu Thi 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 Set Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 260 265 270

Ser Arg Tlir 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 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 Uu Pro Pro Ser Gin Glu Glu Met Hu Lys Asn Gin Val Ser Leu 370 375 380

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 Ti*p 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 158138·序列表.doc •124· s 201208696

Gly Lys Ala Ser 465 <210> 122 <211> 717 <212> m <213>人工序列 <220> <223>合成寡核苷酸众 <400> 122 atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60 gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120 atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggttc 180 caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240 gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 300 cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtaatga ggatccattc 360 acgttcggct cggggacaaa gctcgagatc aaacgaactg tggctgcacc atctgtcttc 420 atcttcccgc catctsatga gcagttgaaa tctggaactg cctctgttgt gtgcclgctg 480 aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg 540 ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc 600 agcaccctga cgctgagcaa agcagactac gasaaacaca aagtctatgc ctgcgaagtc 660 acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttag 717 <210> 123 <211> 238 <212> PRT <213>人工序列 <220> <W3>合成肽。 <400> 123

Met Glu Thr Asp Thr lie Leu Leu Trp Val Leu Leu Leu Trp Val Pro 15 10 15

Gly Ser Thr Gly Asp lie Val Leu ThT Gin Scr Pro Ala Scr Leu Ala 20 25 30

Val Ser Lea dy Gin Arg Ala ?〇r I.e Ser Cys Lys Ala Scr Gin Ser

Val Asp Tyr Asp Gly Asp Scr Tyr Met Asn Trp Phe Gin Gin Lys Pro 50 55 60

Gly Gin Pro Pro Lys Uu Uu He Tyr Ala Ala Ser Asn Leu Glu Ser

Gly lie Pro Ala Arg Phe Ser Gly Ser Gly Scr Gly Thr Asp Phe Thr 85 90 95

Leu Asn lie His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys 100 105 HO -125- 158138-序列表.doc 201208696

Gin Gin Ser Asn Glu Asp Pro Phe Thr i^e Gly Ser 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 Asa 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 Vai 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> 124 <211> 1403 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 124 atggctgtcc tggggctgct tctctgcctg gtgacgttcc caagctgtgt cctgtcccag 60 gtgcagctga aggagteagg acctggcctg gtggcaccct cacagagcct gtccatcaca 120 tgcactgtct ctgggttctc attatccaga tatagtgtat tttgggttcg ccagcctcca 180 ggaaagggtc tggagtggct gggattgata tggggtggtg gaagcacaga ctataalica 240 gctctcaaat ccagactgag catcagcaas gacaactcca agagccaagt tttcttaaaa 300 atgaacagtc tgcaaactga tgacacagcc atgtactact gtgccagaat etaetttgat 360 tacgacgggg ctatggacta ctg^ggtcaa ggaacctcag tcaccgtctc ctcagccaaa 420 acaacgggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg 780 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 840 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgts 900 gaggtgcata atgccaagac aaageegegg gaggageagt tcaacagcac gtaccgtgtg 960 gtcagcgtcc tcaccgtcci gcaccaggac tggctgaacg gcaaggasta caagtgcaag 1020 158138·序列表.doc -126-

S 201208696 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctcceacggc tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga sgggaatgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc ctgtctclgg gtaaagctag ctg <210> 125 <211> 467 <212> PRT <213>人工序列 <220> <223>合成肽》 <400> 125

Met Ala Val Leu Gly Leu Leu Leu Cys Leu Vai Thr Phe Pro Scr 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 Val Ser Gly Phe Ser Leu 35 40 45

Ser Arg Tyr Ser Val Phe Trp Va丨 Arg Gin Pro Pro Gly Lys Gly Leu 50 55 60

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

Ala Leu Lys Ser Arg Leu Ser lie Ser Lys Asp Asn Ser Lys Ser Gin, 85 90 95

Val Phe Leu Lys Met Asn Ser Leu Gin Thr Asp Asp Thr Ala Met Tyr 100 105 no

Tyr Cys Ala Arg lie Tyr Phe Asp Tyr Asp Gly Ala Met Asp Tyr Trp

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 Scr 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 Scr Gly Ala Leu Thr Scr Gly Val His Thr Phe Pro 180 185 190

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Ixu Ser Scr Val Val Thr -127· 1080 1140 1200 1260 1320 1380 1403 158138-序列表.doc 201208696 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 G】u 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

Scr 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 Val Ser Gin Glu Asp 275 280 285

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

Ala Lys Tlir 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 G]u 325 330 335

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

Thr He 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 Va] Glu Trp Glu 385 390 395 400

Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 405 430 415

Asp Ser Asp Gly Scr Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430 Γ 3 T4 re A Γ 6 s ,e 15 3 4 V4 Γ 6 s s cy Γ se c ph lo 3 4 V4 n As y

Asi s Hi uo Le45 na

Le Γ c s u Le r o e 6 S4 u Le Γ se s Ly n G1 Γ 5 Th45 Γ Ty e: s & A1 S5 LV46 列 序 6 2 Ax 1273DN人 0>1>2>3> 11 111 ·_ 4* <2<2<2<2 -128- 158138-序列表.doc 201208696 <220> <223>合成寡核苷酸。 <400> 126 atgcatcgca ccagcatggg catcaagatg gagtcacgga ttcaggcatt tgtattcgtg 60 tttctctggt tgtciggtgt tggcggagac attgtgatga cccagtctca caaattcatg 120 tccacatcag taggagacag ggtcagcgtc acctgcaagg ccagtcagga tgtgacttct 180 gctgtagcct ggtatcaaca aaaaccaggg caatctccta aactactgat ttactgggca 240 tccacccggc acactggagt ccctgatcgc t.tcacaggca gtggatctgg gacagattat 300 actctcacca tcagcagtgg gcaggctgaa gacctggcac tttattactg tcaccaatat 360 tatagcgctc clcggacgtt cggtggaggc accaagctcg agatcaaacg aactgtggct 420 gcaccatctg tcltcatctt cccgccatct gatgagcagt tgaaatctgg aactgcctct 480 gttgtgtgcc tgctgaataa cttotatccc agagaggcca aagtacagtg gaaggtggat 540 aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc 600 acctacagcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc 660 tatgcctgcg aagtcaccca tcagggcctg agctcgcccg tcacaaagag cttcaacagg 720 ggagagtgtt ag 732 <210> 127 <211> 243 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 127

Met His Arg Thr Ser Met Gly lie Lys Met Glu Ser Arg lie Gin Ala 15 10 15

Phe Val Phe Val Phe Leu Trp Leu Ser Gly Val Gly Gly Asp He Val 20 25 30

Met Thr Gin Ser His Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val 35 40 4S

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 lie Tyr Trp Ala 65 70 75 80

Scr Thi 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 100 105 110

Ala Leu Tyr Tyr Cys His Girt 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 -129- 158138-序列表.doc 201208696 130 135 140

Phe lie Phe Pro Pro Scr Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser 145 150 155 160

Val Val 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 Scr Val 180 185 190

Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu' 195 200 205

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

Va! Tbr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 225 230 235 240

Gly Glu Cys <210> 128 <211> 1404 <212> DNA <213>人工序列 <220> <223>合成寡核苷酸。 <400> 128 atggaatgga actgggtcgt tctcttcctc cigtcattaa ctgcaggtgt clatgcccag 60 ggtcagatgc agcagtctgg agctgagctg gtgaagcctg gggcttcagt gaagctstcc 120 tgcaagactt ctggcttcac cttcagcagt aactatataa gttggttgaa gcaaaagcct 180 ggacagagtc ttgagtggat tgcatggatt tatgctggaa ctggtggtat tacctataat 240 cagaagttca gaggeaggge ccaactgact gtagacacat cctccagcac agcctacatg 300 cagttcagca gcctgacaac tgatgactct gccatctatt actgtgcaag acacgtgagg 360 £gttaccatc ctatggacta ctggggtcaa ggaacctcag tcaccgtclc ctcagccaaa 420 aegaagggee catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 480 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc 660 tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat 720 ggtcccccat gcccaccctg cccagcacct gagttegaag ggggaccatc agtcttcctg 780 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgasgt cacgtgcgtg 840 gtggtggacg tgagccagga agaccccgas gtccagttca actggtacgt ggatggcgtg 900 gag£t£〇ata atgccaasac aaageegegg gaggageagt tcaacagcac gtaccgtgtg 960 gtcagcgtcc tcaccgtcct scaccaggac tggctgaacg gcaaggagta caagtgcaag 1020 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1080 •130- 158138·序列表.doc 1140 201208696 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> 129 <211> 467 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 129

Met Glu Trp Asn Trp Val Val Leu Phc Leu Leu Ser Leu Thr Ala Gly 15 10 15

Val Tyr Ala Gin Gly Glu Met Gin Gin Ser Gly Ala Glu Leu 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 Ser Asn Tyr lie Ser Trp Leu Lys Gin Lys Pro Gly Gin Scr Leu 50 55 60

Glu Trp lie Ala Trp He Tyr Ala Gly Thr Gly Gly lie Thr Tyr Asn 65 70 75 80

Gin Lys Phe Arg Gly Atg Ala Gin Leu Tbr Val Asp Thr Ser Ser Ser 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 His Val Arg Gly Tyr His Pro Met Asp Tyr Trp 115 120 125

Gly Gin Gly Thr Ser Val Thr Val Ser Scr 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 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 195 200 205 131 - 1200 1260 1320 1380 1404 158138-序列表.doc 201208696

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 lie Ser 260 265 270

Arg Thr Pro G]u Val Thr Cys Val Va] Val Asp Va] Ser Gin G]u 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 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

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 Pile Leu Tyr Ser Arg Leu Thr Val Asp Lys 420 425 430

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

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

Lys Ala Ser 465 > > > > 0123 11 1J 11 1* <2<2<2<2 130 705 m 人工序列 <220> 132· 158138-序列表.doc 201208696 <223>合成寡核苷酸。 <400> 130 atggagtcac agactcaggt ctttgtatac atgttgctgt ggttgtctgg tgttgatgga gacattgtga tgacccagtc tcaaaaattc atgtccgcat cagtagggga cagggtcagc gtcacctgca gggccagtca gaatgtggtt actaatgtag gctggtatca acagaaacca Sggcaatctc ctaaagtact gatttacicg gcatccttcc ggtacagtg£ agtccctgat cgcttcacag gcagtfigatc tgggacagat ttcactctca ccatcaccaa tgtgcagtct • gaagacttgg cagagtattt ctgtcagcaa tataacaact atccgtacac gttcggaggg gggaccaagc tcgagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca ， tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc ctgagctcgc ccgtcacdaa gagcttcaac aggggagagt gtlag <210> 131 <211> 234 <212> PRT <213>人工序列 <2,2〇> <223>合成肽。 <400> 131

Met Glu Ser Gin Thr Gin Val Phc Val Tyr Met Leu Leu Trp Leu Scr 15 10 15

Gly Va] Asp Gly Asp lie Val Met Thr Gin Ser Gin Lys Phe Met Ser 20 25 30

Ala Ser 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 Scr Fro 50 55 60

Lys Val Leu lie Tyr Ser Ala Scr Phe Arg Tyr Ser Gly Val Pro Asp 65 70 75 80

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

Asn Val Gin Ser Glu 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 US 120 125 T，rVa，A.a Ala Pr〇 Ser Val Phe lie Phe Pro Prose. Asp Glu G,„

Leu Lys Ser Giy Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 158138-序列表.doc - 133 - 201208696 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 Set 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> 132 <211> 1407 <212> DNA <213>人工序列 <220> <223>合成募核苷酸。 <400> 132 atgggatgga gctatatcat cctctttttg gtagcaacag ctacagatgt ccactcccag 60 gtccaactgc agcagcctgg ggctgaactg gtgaagcctg gggcttcagt gaagctgtcc 120 tgcaaggctt ctggctacac cttcaccagc tactggatgc actgggtgaa gcagaggcct 180 ggagaaggee ttgagtggat tggagagatt aatcctagct acggtcgtac tgactacaat 240 gggaagttca agaacaaggc cacactgact gtagccaaat cctccagcac agcctacatg 300 caactcagca gcctgacatc tgaggactct geggtetatt actgtgcaag aggagattac 360 tacggtagta gctcgtttgc ttactggggc caagggactc tggtcactgt ctctgcagcc 420 aaaacaaagg gcccatccgt cttccccctg gcgccctgct ccaggagcac ctccgagagc 480 acagccgccc tgggc(gcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 540 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 600 ctctactccc teageagegt ggtgaccgtg ccctccagca gcttgggcac gaagacctac 660 acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa 720 tatggtcccc catgcccacc ctgcccagca cctgagttcg aagggggacc atcagtcttc 780 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 840 gtggtggtgg acgtgagcca ggaagacccc gagstccagt tcaactggta cgtggatggc 900 gtggaggtgc ataatgccaa gacaaagccg egggaggage agticaacag 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 figtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1200 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1260 ggctccttct tcctctacag caggctaacc gtggacaaga gcaggtggca ggaggggaat 1320 • 134· 158138-序列表.doe 201208696 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc tccctgtctc tgggtaaagc tagctga <210> 133 <211> 468 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 133

Met Gly Trp Ser Tyr lie lie Leu Phe Leu Val Ala Thr Ala Thr Asp 1 5 10 15

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

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

Gly Lys Phe Lys Asn Lys Ala Thr Leu Thr Val Ala 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 Gly Asp Tyr Tyr Gly Ser Ser Ser Phe Ala Tyr 115 120 125

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

Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Scr 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 Ma 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 Scr Asn Thi Lys Val Asp Lys Arg Val Glu Ser Lys 225 230 235 240 -135- 158138·序列表.doc 201208696

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 Val Val Asp Val Ser Gin Glu 275 280 285

Asp Pro Glu Val Gin Phe Asn Trp Tyr Val Asp Gly Val Giu 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 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 Lea 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 He 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 Ήιγ Val Asp 420 425 430

Lys Scr Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser 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 465 <21Q> 134 <211> 705 <212> Wk <213>人工序列 <220> <223>合成寡核苷酸。 <400> 134 atggagtcac agactcaset ctttgtatac atgttgctgt ggttgtctgg tgttgatgga gacattgtga tgacccagtc tcaaaaattc atgtccacat cattaggaga cagggtcagc gtcacctgca aggccagtca gaatgtgggt actaatgtdg cctggtatca acagaaacca -136- 60 120 lg〇 158丨38·序列表_doc 201208696 gggcactctc ctaaagcact gatttactcg gcatcctacc ggtacagtgg agtccctgat 240 cgcttcacag gcagtggatc tgggacagat ttcactctca ccatcagcaa tgtgcagtct 300 gaagacitgg cagagttttt ctgtcagcaa tataacaact atccgtacac gttcggaggg 360 gggaccacgc tcgagatcaa aegaactgig gctgcaccat ctgtcttcat cttcccgcca 420 tetgatgage agttgaaatc tg£aactgcc tctgttgtgt gcctgctgaa taaettetat 480 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 540 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 600 ctgagcaaag cagactacga gaaacacaaa gtctatgcct gegaagteae ccatcagggc 660 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 705 ^ > > > > > ^U123 03 1111* 1Λ ΛΖ2ΛΛ2 22 VvV < < < 135 234

PRT 人工序列 合成肽 <400> 135

Met G]u 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 Phc 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 Asa Val Ala Trp Tyr Gin Gin Lys Pro Gly His Ser Pro 50 55 60

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

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

Asn Val Gin Ser GIu Asp Leu Ala Glu Phc Phe Cys Gin Gin 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 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 137- 158138-序列表.doc 201208696 180 185 190

Tyr Ser Leu Ser Scr 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> 136 <211> 32 <212> PRT <213>人工序列 <220> <223>合成肽》 <400> 136

Val Gly Phe Pro Val Thr Pro Gin Val Pro Leu Arg Pro Met Thr Tyr 1 5 10 15 β s u Le p s a o V2 fl fl s Ly

Le y G, y io G3 s Ly u G1 s Ly u Le € ph25 列序37oRT^ 13P /客多 <220> <223>合成肽。 <400> 137

His Thr Gin Gly Tyr Phe Pro Asp Trp Gin Asn Tyr Thr Pro Gly Pro 15 30 15

Gly Val Arg Tyr Pro Leu Thr Phe Gly Trp Leu Tyr Lys Leu 20 25 30 <210> 138 <211> 19 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 138

Glu Lys lie Arg Leu Arg Pro Gly Gly Lys Lys Lys Tyr Lys Leu Lys 15 10 15

His lie Val <210> 139 <211> 32 <212> PRT <213>人工序列 <220> 158138·序列表.doc 138· s 201208696 <223>合成肽。 <400> 139

Asn Pro Pro lie Pro Val Gly Glu lie Tyr Lys Arg Trp lie He i.eu 15 10 15

Gly Leu Asn Lys He Val Arg Met Tyr Ser Pro Thr Ser lie Leu Asp 20 25 30 <210> 140 <211> 31 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 140

Ala lie Phe Gin Ser Ser Met Thr Lys lie Leu Glu Pro Phe Arg Lys 1 5 10 15

Gin Asn Pro Asp lie Val lie Tyr Gin Tyr Met Asp Asp Leu Tyr 20 25 30 <210> !41 <2I1> 60 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 141

Met Trp Val Pro Val Val Phe Leu Thr Leu Ser Val 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 Gly Gly Val Leu Val His Pro Gin Trp Val 50 55 60 <210> 142 <211> 60 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 142

Leu Tlir Ala Ala His Cys lie Arg Asn Lys Sex Val lie Leu Leu Gly 1 5 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 139- 158138·序列表.doc 201208696 35 40 45

Arg Phe Leu Arg Pro Gly Asp Asp Ser Ser His Asp 50 55 60 <210> 143 <21L> 60 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 143

Leu Met Leu Leu Arg Leu Ser Glu Pro Ala Glu Leu Thr Asp Ala Val 15 10 15

Lys Val Met Asp Leu Pro Thr Gin Glu Pro Ala Leu Gly Thr Tlir 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 lie Ser 50 55 60 <210> 144 <211> 60 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 144

Asn Asp Val Cys Ala Gin Val His Pro Gin Lys Val Thr Lys Phe 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 lie Thr Ser 35 40 45

Trp Gly Ser Glu Pro Cys Ala Leu Pro Glu Arg Pro 50 55 60 <210> 145 <211> 21 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 145

Ser Leu Tyr Thr Lys Val Val His Tyr Arg Lys Trp He Lys Asp Thr 15 10 15 lie Val Ala Asn Pro 20 158138-序列表.doc -140- s 201208696 <210> 146 <2L1> 9 <212> PRT <213>人工序列 <220> <223>合成肽。 <400〉】46 lie Met Asp Gin Val Pro Phe Ser Val <210> 147 <211> 9 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 147 lie Thr Asp Gin Val Pro Phe Ser Val <210> 148 <211> 9 <212> PRT <213>人工序列 <220> <i23>合成肽。 <400> 148

Pro Val Thr Val

Tyr Leu Glu Pro Gly <2：10> 149 <211> 9 <212> PRT <2丨3>人工序列 <220> <22,3>合成肽❶ <400> 149

Tyr Leu Glu Pro Gly Pro Val Thr A3a <210> 150 <211> 9 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 150

Lys Thr Trp Gly Gin Tyr Trp Gin Val

<210> 151 <211> 230 <212> PRT -141 - 158138·序列表.doc 201208696 <213>人工序列 <220> <223>合成肽。 <400> 151 Asp ITir Thr Glu Pro Ala Thr Pro Thr Thr Pro Val Tht Thr Pro Thr 15 10 15 TTir 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

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 lie He Asn Gly Ser Gin Val Trp Gly Gly 100 105 110

Gin Pro Val Tyr Pro Gin Glu Thr Asp Asp Ala Cys lie Phe Pro Asp 115 120 125

Gly Gly Pro Cys Pro Ser Gly Ser Trp Ser Gin Lys Arg Ser Phe Val 130 135 ]40

Tyr Val Trp Lys Thr Trp Gly Gin Tyr Trp Gin Val Leu Gly Gly Pro 145 150 155 160

Val Ser Gly Leu Ser Jle Gly Thr Gly Arg Ala Met 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

Pro 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 0 12 3 <21<21<21<21 152 73 PRT 人工序列 <220> <223> 合成肽。 158138-序列表.doc 142- 201208696 <220> <221> misc feature <222> (38)7.(3S) <223> xaa可為任何天然存在之胺基酸 <400> 152

Pro Leu Thr Phe Ala Leu Gin Leu His Asp Pro Ser Gly Tyr Leu Ala 1 5 10 15

Glu Ala Asp Leu Ser Tyr Thr Trp Asp Phe Gly Asp Ser Ser Gly Thr 20 25 30

Leu lie Ser Arg Ala Xaa Val Val Thr His Thr Tyr Leu Glu Pro Gly 35 40 45

Pro Val Thr Ala Gin Val Val Leu Gin Ala Ala lie Pro Leu Thr Ser 50 55 60

Cys Gly Ser Ser Pro Val Pro Ala Ser 65 70 <210〉 153 <211> 109 <212> PRT <Sl3>人工序列 <220> <223>合成肽。 <400> 153

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 rrhr Ala Glu Pro Ser Gly Thr Thr Ser Val Gin Val Pro Thr 35 40 45

Thr Glu Val lie Ser Thr Ala Pro Val Gin Met Pro Thr Ala Glu 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 Ala 85 90 95

Glu Val Ser lie Val Val Leu Ser Gly Thr Thr Ala Ala 100 105 <210> 154 <211> 75 <212> PRT <2]3>人工序列 <220> <223>合成肽。 <400> 154 -143 - 158138-序列表.doc 201208696

Gin Val Thr Thr Thr GIu Trp Val Glu Thr Thr Ala Arg GIu Leu Pro 15 10 15 lie Pro Glu Pro Glu Gly Pro Asp Ala Ser Ser lie Met Ser Thr Glu 20 25 30

Ser lie Thr Gly 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

Gly Ser Phe Ser Val Thr Leu Asp He Val Gin 65 70 75 <210> 155 <211> 109 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 155

Gly lie 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 Pro Lys Glu 20 25 30

Ala Cys Met Clu lie Ser Ser Pro Gly Cys Gin Pro Pro Ala Gin Arg 35 40 45

Leu Cys Gin Pro Val Leu Pro Ser Pro Ala Cys Gin Leu Val Leu His 50 55 60

Gin lie Leu Lys Gly Gly Ser Gly Thr Tyr Cys Leu Asn Val Ser Leu 65 70 75 80

Ala Asp Thr Asn Ser Leu Ala Val Val Ser Thr Gin Leu lie Val Pro 85 90 95

Gly lie Leu Leu Thr Gly Gin Glu Ala Gly Leu Gly Gin 100 105 <210> 156 <211> 50 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 156

Met Glu Met Lys lie Leu Arg Ala Leu Asn Phe Gly Leu Gly Arg Pro 15 10 15

Leu Pro Leu His Phe Leu Arg Arg Ala Ser Lys lie Gly Glu Val Asp 20 25 30 158138-序列表.doc -144- s 201208696

Val Glu Gin His Thr Leu Ala Lys Tyr Leu Met Glu Leu Thr Met Leu 35 40 45

Asp Tyr 50 <210> 157 <2I1> 36 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 157

Asp Trp Leu Val Gin Val Gin Met Lys Phc Arg Leu Leu Gin Glu Thr ]. 5 10 15

Met Tyr Met Thr Val Ser lie lie Asp Arg Phe Met Gin Asn Asn Cys 20 25 30

Va】Pro Lys Lys 35 <210> 158 <211> 48 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 158

Met Glu His Gin Leu Leu Cys Cys Glu Val Glu Thr lie Arg Arg Ala 1 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 Tlir Cys Ala Pro Ser Val Ser Tyi Phe Lys Cys Val 35 40 45 <210> 159 <2I1> 95 <212> PRT <213>人工序列 <220> <223>合成肽。 <_> 159

Gin Lys Glu Val Leu Pro Ser Met Arg Lys lie Val Ala Thr Trp Met 1 5 }〇 IS

Leu Glu Val Cys Glu Glu Gin Lys Cys Gla Glu Glu Val Phc Pro Leu 20 25 30

Ala Met Asn Tyr Lea Asp Arg Phe Leu Ser Leu Glu Pro Val Lys Lys 35 40 45 -145- 158138-序列表.doc 201208696

Ser Arg Leu Gin Leu SO

Leu Gly Ala Thr Cys Met Phe Val Ala Ser Lys 55 60

Met Lys Glu Thr lie 65

Pro Leu Thr Ala Glu Lys Leu Cys lie Tyr Thr 70 75 80

Asp Asn Ser lie Arg 85

Pro Glu Glu Leu Leu Gin Met Glu Leu Leu 90 95 <210> 160 <211> 60 <212> PRT <213>人工序列 <220> <223>合成肽。 <400> 160 Leu Val Asn Lys Leu

Lys Trp Asn Leu Ala Ala Met Thr Pro His Asp 10 15

Phe lie Glu His Phe 20

Leu Ser Lys Met Pro Glu Ala Glu Glu Asn Lys 25 30

Gin He lie Arg Lys 35

His Ala Gin Thr Phe Val Ala Leu Cys Ala Thr 40 45

Asp Val Lys Phe lie SO

Ser Asn Pro Pro Ser Met Val 55 60 > > >pf\ ^G, 0123 ¢3 & 1111 2 2 o a <2<C2<2<2<2<2<4All 161 91 PRT 人工序列 合成肽。 161 Ser Val Val

Ala Ala Val Gin Gly Leu Asn Leu Arg Ser Pro 10 15

Asn Asn Phe Leu Ser 20

Tyr Tyr Arg Leu Thr Arg Phe Leu Ser Arg Vai 25 30 lie Lys Cys Asp Pro 35

Asp Cys Leu Arg Ala Cys Gin Glu Gin lie Glu 40 45

Ala Leu Leu Glu Ser 50

Ser Leu Arg Gin Ala Gin Gin Asn Mel Asp Pro 55 60

Lys Ala Ala Glu Glu 65

Glu Glu Glu Glu Glu Glu Glu Val Asp Leu Ala 70 75 80

Cys Thr Pro Thr Asp 85

Val Arg Asp Val Asp lie 90 158丨38_序列表.doc •146· s

Claims (1)

1. 201208696 七、申請專利範圍： 1. 一種佐劑組合物，其包含： 寒TLR7促效劑之至少一部分結合之抗樹突狀細胞（dc) 特異性抗體或其片段；及醫藥學上可接受之載劑，其中 • 該結合物及促效劑各包含與另一者組合可在需要免疫刺 ， 激之人類或動物個體中有效引起免疫反應的量。 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 (樹突狀細胞相關C型植物凝集 素-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，其中該組合物進一步包含抗原性 肽，其選自人類免疫缺乏病毒（HIV)抗原及選自由gag、 pol及env基因組成之群的基因產物、Nef蛋白、逆轉錄 酶、線性HIV肽（Hipo5)、PSA(KLQCVDLHV)四聚物、來 源於 HIVgag之 p24-PLA HIV gag p24(gag)及其他 HIV組 分、肝炎病毒抗原、流感病毒抗原，及選自由以下組成 之群的肽：血球凝集素、神經胺糖酸苷酶、H1N1流感病 毒株之A型流感血球凝集素HA-1、HLA-A201-F1uMP(58- 158138.doc 201208696 06)肽（GILGFVFTL)四聚物及禽流感（HA5-1)、嗜熱梭狀 芽孢桿菌（C. thermocellum)之錨定蛋白（d〇ckerin)域、麻 疹病毒抗原、風疹病毒抗原、輸狀病毒抗原、巨細胞病 毒抗原、呼吸道融合病毒抗原、單純疱疹病毒抗原、水 痘帶狀疱疹病毒抗原、日本躺炎病毒抗原、狂犬病病毒 抗原，或其組合及修飾。 4. 如請求項1之組合物，其中該·组合物進一步包含選自癌 肽之抗原性肽，該等癌肽係遽自腫瘤相關抗原，包含來 自以下之抗原：白血病及淋巴瘤，神經腫瘤，諸如星形 細胞瘤或神經膠母細胞瘤；黑色素瘤、乳癌、肺癌、頭 頸癌、胃腸腫瘤、胃癌、結腸癌、肝癌、胰臟癌；泌尿 生殖器腫瘤，諸如子宮頸癌、子宮癌、卵巢癌、陰道 癌、睾丸癌、前列腺癌或陰荽癌，骨腫瘤、血管瘤，或 唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽管樹 (biliary tree)、喉、肺及支氣管、膀胱、腎臟、服及神經 系統之其他部分、曱狀腺之癌症；霍奇金氏病 (Hodgkin's disease)、非霍奇金氏淋巴瘤（non_Hodgkin’s lymphoma)、多發性骨髓瘤及白丘病。 5. 如請求項1之組合物，其中該組合物進一步包含選自腫 瘤相關抗原之抗原性肽，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、6及 12、MUC(黏蛋白）（例如 MUC-1、MUC-2等）、GM2及GD2神經節普脂、ras 、myc、路 胺酸酶、MART(黑色素瘤抗原）、MARCO-MART、週期 158138.doc S 201208696 素B1、週期素D、Pmel 17(gpl00)、GnT-V内含子v序列 (N-乙醯葡萄糖胺基轉移酶V内含子V序列）、前列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗原）、 β-索烴素（catenin)、MUM-1-B(黑色素瘤普遍性突變基因 • 產物）、GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗原）2_ ' 10、c-ERB2(Her2/neu)、EBNA(EB 病毒核抗原作卩316111- Barr Virus nuclear antigen))l-6、gp75、人類乳頭狀瘤病 毒（HPV)E6 及 E7、p53、肺抗性蛋白（LRP)、Bcl-2及 Ki- 6Ί。 6. 如請求項1之組合物，其中該DC特異性抗體經人類化° 7. 如請求項1之組合物，其中該組合物係經口途徑、鼻途 徑、局部或注射投與人類或動物個體。 8. 如請求項7之組合物，其中該注射係選自由皮下、靜脈 内、腹膜内、肌内及靜脈内組成之群。 9. 如請求項1之組合物，其中該促效劑為鞭毛蛋白。 10. —種疫苗組合物，其包含： 抗原；及 佐劑：其中該佐劑包含與TLR7促效劑之至少一部分結 合之抗樹突狀細胞（DC)特異性抗體或其片段；及醫藥學 上可接受之載劑，其中該結合物及促效劑各包含與另一 者組合可在需要免疫刺激之人類或動物個體中有效引起 免疫反應的量。 11. 如請求項10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、 158138.doc 201208696 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。 12. 如請求項10之組合物，其中該組合物進一步包含抗原性 肽，其選自人類免疫缺乏病毒（HIV)抗原及選自由gag、 pol及env基因組成之群之基因產物、Nef蛋白、逆轉錄 酶、線性 HIV 肽（Hipo5)、PSA(KLQCVDLHV)四聚物、來 源於 HIVgag之 p24-PLA HIV gag p24(gag)及其他 HIV 組 分、肝炎病毒抗原、流感病毒抗原，及選自由以下組成 之群的肽：血球凝集素、神經胺糠酸苷酶、H1N1流感病 毒株之A型流感血球凝集素HA-1、HLA-A201-F1uMP(58-66)肽（GILGFVFTL)四聚物及禽流感（HA5-1)、嗜熱梭狀 芽孢桿菌之錨定蛋白域、麻疹病毒抗原、風疹病毒抗 原、輪狀病毒抗原、巨細胞病毒抗原、呼吸道融合病毒 抗原、單純疱疹病毒抗原、水痘帶狀疱疹病毒抗原、曰 本腦炎病毒抗原、狂犬病病毒抗原，或其組合及修飾。 13. 如請求項10之組合物，其中該組合物進一步包含選自癌 肽之抗原性肽，該等癌肽係選自腫瘤相關抗原，包含來 自以下之抗原：白血病及淋巴瘤；神經腫瘤，諸如墓形 細胞瘤或神經膠母細胞瘤；黑色素瘤、乳癌、肺癌、頭 158138.doc S 201208696 頸癌、胃腸腫瘤、胃癌、結腸癌、肝癌、胰臟癌；泌尿 生殖器腫瘤，諸如子宮頸癌、子宮癌、卵巢癌、陰道 癌、睾丸癌、前列腺癌或陰莖癌；骨腫瘤、血管瘤；或 唇、鼻咽、咽及口腔、食道、直腸、膽囊、膽管樹、 喉、肺及支氣管、膀胱、腎臟、腦及神經系統之其他部 分、曱狀腺之癌症；霍奇金氏病、非霍奇金氏淋巴瘤、 多發性骨髓瘤及白血病。 14. 如請求項13之組合物，其中該組合物進一步包含選自腫 瘤相關抗原之抗原性肽，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、6及 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、週期 素B1、週期素D、Pmel 17(gpl00)、GnT-V内含子V序列 (N_乙醯葡萄糖胺基轉移酶V内含子V序列）、前列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗原）、 β-索烴素、MUM-1-B(黑色素瘤普遍性突變基因產物）、 GAGE(黑色素瘤抗原）1、BAGE(黑色素瘤抗原）2-10、c-ERB2(Her2/neu)、EBNA(EB 病毒核抗原）1-6、gp75、人 類乳頭狀瘤病毒（HPV)E6及E7、p53、肺抗性蛋白 (LRP)、Bcl-2及Ki-67。 15. 如請求項10之組合物，其中該DC特異性抗體經人類化。 16. 如請求項10之組合物，其中該組合物係經口途徑、鼻途 徑、局部或注射投與人類或動物個體》 158138.doc 201208696 17. 如請求項16之組合物，其中該注射係選自由皮下、靜脈 内、腹膜内、肌内及靜脈内組成之群。 18. 如請求項1〇之組合物，其中該促效劑為鞭毛蛋白。 19. 一種活體外增強抗原呈現細胞之抗原呈現有效性的方 法，其包含使該抗原呈現細胞與如請求項丨〇至丨8中任一 項之組合物接觸。 20. —種如凊求項1〇至18中任一項之組合物的用途係用於 製造針對人類個體之一或多種癌症進行治療、預防或其 組合的藥物。 21. —種如睛求項1〇至18中任一項之組合物的用途係用於 製造針對一或多種病毒性、細菌性、真菌性、寄生蟲 性、原蟲性及過敏性病症進行治療、預防或其組合的藥 物，其中該或該等DC係自人類個體分離，且該等經活化 之DC再引入該人類個體中。 22. —種佐劑組合物，其包含： 與TLR7促效劑之至少_部分結合之抗樹突狀細胞（dc) 特異性抗體或其片段；及醫藥學上可接受之載劑，其中 該結合物及促效料包含與另—者組合可在需要免疫刺 激之人類或動物個體中有效引起免疫反應的量，其中該 抗沉特異性抗體係選自成對之SEQ ID NO: 7與9、_ 13 15與17、19與21、23與25、27與29、31 與33、35與 37 39與41、43與45、47與49、51 與53、55與57、59與 63 與 65 67與 69、71 與 73、75與 77、79與 81、83與 85 87與 89、91 與 93、95 與 97、99與 101、103 與 105、 158138.doc S -6 - 201208696 107 與 109、111 與 113、115 與 117、119 與 121、123 與 125、 127與129、 131與132、 133與134。 23. 如請求項22之組合物’其中該組合物進一步包含抗原性 肽，其選自人類免疫缺乏病毒（HIV)抗原及選自由gag、 pol及env基因組成之群的基因產物、Nef蛋白、逆轉錄 酶、線性HIV肽（Hipo5)、PSA(KLQCVDLHV)四聚物、來 源於 HIVgag 之 p24-PLA HIV gag p24(gag)及其他 HIV 組 分、肝炎病毋抗原、流感病毒抗原’及選自由以下組成 之群的肽：血球凝集素、神經胺糖酸苷酶、H1N1流感病 毒株之A型流感金球凝集素HA-1、HLA-A201-FluMP(58-66)肽（GILGFVFTL)四聚物及禽流感（HA5-1)、嗜熱梭狀 芽抱桿菌之錯定蛋白域、麻療病毒抗原、風療病毒抗 原、輪狀病毒抗原、巨細胞病毒抗原、呼·吸道融合病毒 抗原、單純疮療病毒抗原、水痘帶狀疮療病毒抗原、曰 本腦炎病毒抗原、狂犬病病毒抗原，或其組合及修飾。 24. 如清求項22之組合物’其中該組合物進>__步包含選自癌 肽之抗原性肽’該等癌肽係選自腫瘤相關抗原，包含來 自以下之抗原：白血病及淋巴瘤；神經腫瘤，諸如星形 細胞瘤或神經膠母細胞瘤；黑色素瘤、乳癌、肺癌、頭 頸癌、胃腸腫瘤、胃癌、結腸癌、肝癌、騰臟癌；泌尿 生殖器腫瘤，諸如子宮頸癌、子宮癌、印巢癌、陰道 癌、睾丸癌、前列腺癌或陰莖癌；骨腫瘤、金管瘤；或 唇'鼻咽、咽及口腔、食道、直腸、膽囊、膽管樹、 喉、肺及支氣管 '膀胱、腎臟、腦及神經系統之其他部 158138.doc 201208696 分、曱狀腺之癌症；霍奇金氏病、非霍奇金氏淋巴瘤、 多發性骨髓瘤及白血病。 25 ·如請求項22之組合物，其中該組合物進一步包含選自腫 瘤相關抗原之抗原性肽，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、MApE 1-4、6及 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、週期 素B1、週期素D、Pmel 17(gpl00)、GnT-V内含子V序列 (N-乙醯葡萄糖胺基轉移酶V内含子V序列）、前列腺Ca psm、前列腺血清抗原（PSA)、PRAME(黑色素瘤抗原）、 β-索烴素、MUM-1-B(黑色素瘤普遍性突變基因產物）、 GAGE(黑色，素瘤抗原）1、BAGE(黑色素瘤抗原）2-10、c_ ERB2(Her2/peu)、EBNA(EB病毒核抗原）1-6、gp75、人 類乳頭狀摩病毒（HPV)E6及E7、p53、肺抗性蛋白 (LRP)、Bd-2及Ki-67。 26. 如請求項22,之組合物，其中該DC特異性抗體經人類化。 27. 如請求項22之組合物，其中該組合物係經口途徑、鼻途 徑、局部或注射投與人類或動物個體。 28. 如請求項22之組合物，其中該TLR7促效劑為鞭毛蛋白。 29. —種活體外增強抗原呈現細胞之抗原呈現有效性的方 法，其包含:使該抗原呈現細胞與如請求項22至28中任— 項之組合物接觸。 158138.doc S