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TW202317625A - 新穎三特異性結合分子 - Google Patents

新穎三特異性結合分子 Download PDF

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TW202317625A
TW202317625A TW111122174A TW111122174A TW202317625A TW 202317625 A TW202317625 A TW 202317625A TW 111122174 A TW111122174 A TW 111122174A TW 111122174 A TW111122174 A TW 111122174A TW 202317625 A TW202317625 A TW 202317625A
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保羅 亞當
史蒂芬 Ｒ 克米澳
菲利普 尼可拉斯 加爾曼
班卡 古塔
普利彥卡 古塔
卡爾 漢茲 海德
史琳那 卡斯圖藍根
瑞納特 克諾皮茲基
克勞斯 彼得 坤克勒
珊迪普 庫瑪
塔妮莎 安 塔娜拉 馬克
伊琳伯葛 卡特琳 奧斯特曼
阿卜杜勒薩拉姆 沙巴
大衛 魏斯曼
安地列斯 威尼茲尼
大衛 Ｓ 楊
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德商百靈佳殷格翰國際股份有限公司
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Abstract

本發明係關於新穎三特異性結合分子。本發明亦關於編碼此類結合分子之核酸；用於製備此類結合分子之方法；表現或能夠表現此類結合分子之宿主細胞；包含此類結合分子之組合物；及此類結合分子或此類組合物尤其用於在癌症疾病領域中達成治療目的之用途。

Description

新穎三特異性結合分子
本發明係關於新穎三特異性結合分子。本發明亦關於編碼此類結合分子之核酸；用於製備此類結合分子之方法；表現或能夠表現此類結合分子之宿主細胞；包含此類結合分子之組合物；及此類結合分子或此類組合物尤其用於在癌症疾病領域中達成治療目的之用途。
癌症為一組通常基於異常細胞增殖及癌細胞可能侵入或擴散在整個身體中的疾病。其為嚴重疾病及全球死亡之主要原因。
已嘗試使用多種治療方法管理或在一些情況下治療癌症，包括手術、化學療法、放射線療法及激素療法。另外，抗體提供作為用於治療癌症之強力治療劑的可能性。抗體經設計以識別及結合於細胞表面上之特定蛋白質，亦即其目標抗原。此結合可激起多個不同生物反應，視例如表現目標抗原之細胞類型、目標抗原蛋白質之功能或抗體本身之結構而定。
舉例而言，一些抗體直接結合於癌細胞，且可例如藉由干擾細胞路徑來中止或減少此等細胞之細胞分裂，藉此減緩或防止異常細胞增殖。或者，此類靶向癌細胞之抗體亦可附接有藥物或放射性粒子，藉此將此等治療劑遞送至癌細胞，從而獨立於細胞內源路徑起作用。與此等靶向癌細胞之方法不同的方法係基於能夠誘導免疫系統進攻及殺滅癌細胞之抗體。此可藉由將免疫細胞、諸如細胞毒性T細胞重新引導至癌細胞或藉由直接影響免疫系統本身之活性來達成。
雖然靶向癌細胞之方法以及重新引導免疫細胞之方法提供治療癌症之有效作用模式(MoA)，但其通常依賴於癌細胞特異性標記物，亦即非癌細胞幾乎不表現之目標蛋白的表現。此類腫瘤特異性目標蛋白為罕見的，且此稀缺仍然是在研發癌症特異性治療劑中通常面臨的主要缺點。
雖然已嘗試將免疫細胞重新引導至更廣泛表現之譜系抗原，但此等療法之價值受到此等抗原在某些正常組織中之表現，諸如(例如) Epcam在胃腸道中之表現所引起的毒性限制(Kebenko等人, Oncoimmunology 2018, 第7卷, 第8期)。儘管當前實行減少與位點外(off-site)抗原表現相關之毒性的各種方法，但對於許多化合物，毒性仍然為劑量限制性的。
因此，雖然近年來某些癌症之治療已取得進展，且儘管當前實行大量不同方法，但仍需要提供新穎的治療學上適合用於治療癌症之化合物。因此，本發明之目標在於提供可用於各種癌症疾病之治療中的此類藥理學活性劑。
詳言之，本發明之目標在於提供相較於當前所用及/或此項技術中已知之藥劑、組合物及/或方法，提供特定優點之此類藥理學活性劑、組合物及/或治療方法。此等優點包括尤其相較於此項技術中已知之候選藥物的活體內功效、改良之治療特性及藥理學特性、較少副作用及其他有利特性，諸如改良之易於製備性或降低之商品成本。
此需求由本文中所提供之實施例解決。
本發明係基於將三個抗原結合位點組合在單一結合分子內之概念，亦即特異性結合於滋養層細胞表面抗原2 (TROP2)之第一抗原結合位點、特異性結合於鈣黏素-17 (CDH17)之第二抗原結合位點及特異性結合於分化簇3 (CD3)之第三抗原結合位點。如下文更詳細地論述，本發明之分子之一個優點為其低親和力、高親合力設計，此提供優良的對目標細胞之特異性。
因此，本發明之第一態樣提供一種結合分子，其包含：(a)至少一個以Kd ≥ 1 nM特異性結合於滋養層細胞表面抗原2 (TROP2)之抗原結合位點；(b)至少一個特異性結合於鈣黏素-17 (CDH17)之抗原結合位點，其中該至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群：(i)抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:33 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:35 (CDR1)、SEQ ID NO.:36 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR；及(ii)抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:38 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:39 (CDR1)、SEQ ID NO.:40 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR；及(c)至少一個特異性結合於分化簇3 (CD3)之抗原結合位點。
在本發明之結合分子之一較佳實施例中，至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(vi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO.:1 (CDR1)、SEQ ID NO.:2 (CDR2)及SEQ ID NO.:3 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:4 (CDR1)、SEQ ID NO.:5 (CDR2)及SEQ ID NO.:6 (CDR3)之胺基酸序列之輕鏈CDR； (ii)      抗原結合位點，其包括包含SEQ ID NO.:7 (CDR1)、SEQ ID NO.:8 (CDR2)及SEQ ID NO.:9 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:10 (CDR1)、SEQ ID NO.:11 (CDR2)及SEQ ID NO.:12 (CDR3)之胺基酸序列之輕鏈CDR； (iii)     抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:14 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:16 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (iv)     抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:19 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:20 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (v)      抗原結合位點，其包括包含SEQ ID NO.:21 (CDR1)、SEQ ID NO.:22 (CDR2)及SEQ ID NO.:23 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:24 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:26 (CDR3)之胺基酸序列之輕鏈CDR； 及 (vi)     抗原結合位點，其包括包含SEQ ID NO.:27 (CDR1)、SEQ ID NO.:28 (CDR2)及SEQ ID NO.:29 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:30 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:31 (CDR3)之胺基酸序列之輕鏈CDR。
在本發明之結合分子之一較佳實施例中，至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(xii)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:83之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:84之胺基酸序列之免疫球蛋白輕鏈可變域； (ii)      抗原結合位點，其包括包含SEQ ID NO:85之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:86之胺基酸序列之免疫球蛋白輕鏈可變域； (iii)     抗原結合位點，其包括包含SEQ ID NO:87之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:88之胺基酸序列之免疫球蛋白輕鏈可變域； (iv)     抗原結合位點，其包括包含SEQ ID NO:89之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:90之胺基酸序列之免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含SEQ ID NO:91之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:92之胺基酸序列之免疫球蛋白輕鏈可變域； (vi)     抗原結合位點，其包括包含SEQ ID NO:93之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (vii)    抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (viii)   抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域； (ix)     抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (x)      抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)     抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:99之胺基酸序列之免疫球蛋白輕鏈可變域； 或 (xii)    抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域。 在本發明之結合分子之一較佳實施例中，至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:100之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:101之胺基酸序列之免疫球蛋白輕鏈可變域； 及 (ii)      抗原結合位點，其包括包含SEQ ID NO:102之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:103之胺基酸序列之免疫球蛋白輕鏈可變域。 在本發明之結合分子之一較佳實施例中，至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xxxi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (ii)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:46 (CDR3)之胺基酸序列之輕鏈CDR； (iii)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (iv)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:50 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (v)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vi)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vii)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:53 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (viii)   抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:55 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (ix)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (x)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xi)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:58 (CDR2)及SEQ ID NO.:59 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:60 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xii)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiii)   抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:62 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiv)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:63 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xv)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvi)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:64 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xviii)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xix)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:72 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xx)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxi)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:74 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiii)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:75 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiv)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxv)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:76 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvi)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:77 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvii) 抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:78 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxviii) 抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxix)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxx)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； 及 (xxxi)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR。
在本發明之結合分子之一較佳實施例中，至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xvi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:104之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:109、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:123及SEQ ID NO:129組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (ii)      抗原結合位點，其包括包含SEQ ID NO:110之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:111之胺基酸序列之免疫球蛋白輕鏈可變域； (iii)     抗原結合位點，其包括包含SEQ ID NO:112之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:113之胺基酸序列之免疫球蛋白輕鏈可變域； (iv)     抗原結合位點，其包括包含SEQ ID NO:118之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:119及SEQ ID NO:122組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含SEQ ID NO:124之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:125、SEQ ID NO:126及SEQ ID NO:127組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含選自由SEQ ID NO:128及SEQ ID NO:130組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:127之胺基酸序列之免疫球蛋白輕鏈可變域； (vi)     抗原結合位點，其包括包含SEQ ID NO:131之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:132之胺基酸序列之免疫球蛋白輕鏈可變域； (vii)    抗原結合位點，其包括包含SEQ ID NO:133之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:134及SEQ ID NO:135組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (viii)   抗原結合位點，其包括包含SEQ ID NO:136之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:137之胺基酸序列之免疫球蛋白輕鏈可變域； (ix)     抗原結合位點，其包括包含選自由SEQ ID NO:138及SEQ ID NO：156組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:139之胺基酸序列之免疫球蛋白輕鏈可變域； (x)      抗原結合位點，其包括包含選自由SEQ ID NO:140、SEQ ID NO:142、SEQ ID NO:143及SEQ ID NO:161組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:141之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)     抗原結合位點，其包括包含選自由SEQ ID NO:144及SEQ ID NO:146組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:145之胺基酸序列之免疫球蛋白輕鏈可變域； (xii)    抗原結合位點，其包括包含選自由SEQ ID NO:147、SEQ ID NO:151、SEQ ID NO:153及SEQ ID NO:162組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:148之胺基酸序列之免疫球蛋白輕鏈可變域； (xiii)   抗原結合位點，其包括包含選自由SEQ ID NO:149及SEQ ID NO:152組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:150之胺基酸序列之免疫球蛋白輕鏈可變域； (xiv)    抗原結合位點，其包括包含SEQ ID NO:154之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:155之胺基酸序列之免疫球蛋白輕鏈可變域； (xv)     抗原結合位點，其包括包含SEQ ID NO:157之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:158之胺基酸序列之免疫球蛋白輕鏈可變域；及 (xvi)    抗原結合位點，其包括包含SEQ ID NO:159之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:160之胺基酸序列之免疫球蛋白輕鏈可變域。
在本發明之結合分子之一個較佳實施例中，結合分子為經修飾之免疫球蛋白(Ig)分子，較佳經修飾之IgG分子，其中該至少一個特異性結合於TROP2之抗原結合位點及該至少一個特異性結合於CDH17之抗原結合位點存在於該Ig分子之可變區，且其中該至少一個特異性結合於CD3之抗原結合位點為與該TROP2-CDH17特異性Ig分子融合的scFv。
在本發明之結合分子之一個較佳實施例中，scFv與Ig分子之重鏈之C端融合，較佳與包含至少一個特異性結合於CDH17之抗原結合位點的Ig分子之部分之重鏈融合。
在本發明之結合分子之一較佳實施例中，結合分子包含：(a)選自(a-i)至(a-xii)之第一免疫球蛋白輕鏈及免疫球蛋白重鏈組合，較佳藉由肽連接子連接在一起： (a-i)    包含SEQ ID NO:169之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:170之胺基酸序列之免疫球蛋白重鏈； (a-ii)   包含SEQ ID NO:171之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:172之胺基酸序列之免疫球蛋白重鏈； (a-iii)  包含SEQ ID NO:173之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:174之胺基酸序列之免疫球蛋白重鏈； (a-iv)   包含SEQ ID NO:175之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:176之胺基酸序列之免疫球蛋白重鏈； (a-v)    包含SEQ ID NO:177之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:178之胺基酸序列之免疫球蛋白重鏈； (a-vi)   包含SEQ ID NO:179之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:180之胺基酸序列之免疫球蛋白重鏈； (a-vii)  包含SEQ ID NO:181之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:182之胺基酸序列之免疫球蛋白重鏈； (a-viii) 包含SEQ ID NO:183之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:184之胺基酸序列之免疫球蛋白重鏈； (a-ix)   包含SEQ ID NO:185之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:186之胺基酸序列之免疫球蛋白重鏈； (a-x)    包含SEQ ID NO:187之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:188之胺基酸序列之免疫球蛋白重鏈； (a-xi)   包含SEQ ID NO:189之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:190之胺基酸序列之免疫球蛋白重鏈；或 (a-xii)  包含SEQ ID NO:191之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:192之胺基酸序列之免疫球蛋白重鏈； 及(b)選自(b-i)至(b-ii)之第二免疫球蛋白重鏈及免疫球蛋白輕鏈組合，較佳藉由肽連接子連接在一起： (b-i)    包含SEQ ID NO:196之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:197之胺基酸序列之免疫球蛋白重鏈；或 (b-ii)   包含SEQ ID NO:198之胺基酸序列之免疫球蛋白重鏈及包含SEQ ID NO:199之胺基酸序列之免疫球蛋白輕鏈； 及(c)包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列的單鏈可變片段(scFv)，較佳連接於該第二免疫球蛋白重鏈及免疫球蛋白輕鏈組合之該免疫球蛋白重鏈的C端。
在本發明之結合分子之一較佳實施例中，結合分子包含以下或由以下組成： (a-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (b-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (c-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (d-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (e-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (f-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (g-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (h-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (i-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (j-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:427之胺基酸序列；或 (k)      SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。
本發明之另一態樣提供一種結合分子，其包含以下或由以下組成： (a-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (b-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (c-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (d-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (e-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (f-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (g-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (h-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (i-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (j-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:427之胺基酸序列；或 (k)      SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。
本發明進一步關於一種核酸分子，其編碼本發明之結合分子或其一部分。本發明進一步關於一種表現載體，其包含一或多種本發明之核酸分子。本發明進一步關於一種宿主細胞，其經本發明之表現載體轉染。
本發明進一步關於一種產生本發明之結合分子之方法，該方法包含以下步驟： (a)  在允許根據技術方案1至11中任一項之結合分子表現之條件下培養技術方案12之宿主細胞； (b)  視情況回收該分子；及視情況， (c)  進一步純化及/或修飾及/或調配該結合分子。
本發明進一步關於一種醫藥組合物，其包含一或多種本發明之結合分子及視情況選用之醫藥學上可接受之載劑或由其組成。
本發明進一步關於用於藥物中之本發明之結合分子或本發明之醫藥組合物。本發明進一步關於本發明之結合分子或本發明之醫藥組合物，其用於治療、改善或預防癌症之方法中。
本發明進一步關於一種治療、預防或改善癌症之方法，其包含向有需要之患者投與治療有效量之本發明之結合分子或本發明之醫藥組合物。
本發明進一步關於本發明之結合分子用於製備供治療、預防或改善癌症之醫藥組合物的用途。
在本發明之結合分子或本發明之醫藥組合物或本發明之方法或本發明之用途的一個較佳實施例中，癌症為大腸直腸癌(CRC)、胃癌(GC)或胰臟癌(PAC)。
在本發明之結合分子或本發明之醫藥組合物或本發明之方法或本發明之用途的一個較佳實施例中，結合分子將與免疫檢查點抑制劑、較佳抗PD-1或抗PD-1-L1抗體組合使用。
在本說明書中，引用多個文獻，包括專利申請案及製造商手冊。儘管認為與本發明專利性不相關，但此等文獻之揭示內容在此以全文引用的方式併入本文中。更特定而言，所有參考文獻均以引用的方式併入，其併入程度如同各個別文獻經特定且個別指示以引用的方式併入一般。 定義  本發明之上文概述之態樣以及本發明之其他態樣及實施例將自本文中之進一步描述變得清楚，其中：
a) 熟習此項技術者將清楚，除非另外指示或定義，否則所用全部術語均具有其在此項技術中之常用含義。倘若有衝突，將以專利說明書(包括定義)為準。
例如參考標準手冊，諸如Sambrook等人, 「Molecular Cloning: A Laboratory Manual」 (第2版), 第1-3卷, Cold Spring Harbor Laboratory Press (1989)；Lewin, 「Genes IV」, Oxford University Press, New York, (1990)及Roitt等人, 「Immunology」 (第2版), Gower Medical Publishing, London, New York (1989)，以及本文中所引用之一般背景技術。此外，熟習此項技術者將清楚，除非另外指示，否則所有未特定詳細描述之方法、步驟、技術及操作可以本身已知之方式進行且已以本身已知之方式進行。例如再次提及標準手冊及上文提及之一般背景技術及其中所引用之其他參考文獻。
b) 除非另外指示或定義，否則術語「抗體」根據此項技術中之定義使用。抗體通常為免疫球蛋白(縮寫為Ig)，較佳為γ球蛋白(IgG；亦進一步參見下文)。可在脊椎動物之血液或其他體液中發現天然存在之抗體，其中免疫系統使用該等抗體來鑑別及中和異物，諸如細菌及病毒，該功能由其與稱為抗原之其他分子或結構藉由非共價相互作用進行的結合所介導。此結合為特異性的，意為抗體將僅以高親和力結合於特異性結構。由抗體識別之抗原之獨特部分稱為抗原決定基或抗原決定子。
天然存在之抗體(包括例如經典Y形免疫球蛋白分子)通常由基礎結構單元製成：各具有兩條大的重鏈及兩條小的輕鏈，或如駱駝科物種或軟骨魚中，僅具有兩條重鏈(亦即，分別為V HH及V NAR片段)，且形成例如具有一個單元之單體、具有兩個單元之二聚體或具有五個單元之五聚體。各條重鏈在N端處具有可變域(VH)，之後為三個或四個(就IgE而言)恆定域(CH1、CH2、CH3及CH4)，以及在CH1與CH2之間的鉸鏈區。各條輕鏈具有兩個域：N端可變域(VL)及C端恆定域(CL)。介導與抗原決定基之結合之抗體部分有時稱為互補位且存在於抗體之可變域或可變區(Fv)中。可變域包含三個所謂互補決定區(CDR)，該等CDR由構架區(FR)隔開。構架區採用β-摺疊構形，且CDR可形成連接β-摺疊結構之環。各條鏈中之CDR藉由構架區保持其三維結構且通常與來自其他鏈(若存在/當存在時)之CDR一起介導與抗原之結合。如本申請案中使用之術語「恆定域」或「恆定區」表示抗體除可變區以外之域的總和。此類恆定域及恆定區為目前先進技術所熟知且例如由Kabat等人(「Sequence of proteins of immunological interest」, US Public Health Services, NIH Bethesda, MD, 公開案第91號)描述。
抗體之「Fc部分」不直接參與抗體與抗原之結合，但展現各種效應功能。「抗體之Fc部分」係熟練技術人員熟知之術語且基於抗體之木瓜蛋白酶裂解而定義。視重鏈之恆定區之胺基酸序列而定，抗體或免疫球蛋白分成以下類別：IgA、IgD、IgE、IgG及IgM。根據重鏈恆定區，不同類別之免疫球蛋白分別稱為α、δ、ε、γ及μ。此等中之若干者可進一步分成子類(同型)，例如IgG1、IgG2、IgG3及IgG4、IgA1及IgA2。基於補體活化、C1q結合及Fc受體結合，抗體之Fc部分直接參與ADCC (抗體依賴性細胞介導之細胞毒性)及CDC (補體依賴性細胞毒性)。補體活化(complement activation；CDC)藉由補體因子C1q與大多數IgG抗體子類之Fc部分之結合來啟動。雖然抗體對補體系統之影響視某些條件而定，但C1q結合係由Fc部分內之界定結合位點引起。此類結合位點為目前先進技術所已知且例如描述於Kellner等人 Transfus Med Hemother. 44(5) (2017) 327-336。此類結合位點之非限制性實例為例如L234、L235、D270、N297、E318、K320、K322、P331及P329 (根據Kabat之EU索引編號)。在IgG1中此等殘基中介導C1q及Fcγ受體結合最關鍵的殘基為L234及L235 (Hezareh等人, J. Virology 75 (2001) 12161-12168)。子類別抗體IgG1及IgG3通常顯示補體活化及C1q及C3結合，而IgG2及IgG4不活化補體系統且不結合C1q及C3。
如本文所用，術語「抗體」亦包括保留抗原結合特性之免疫球蛋白片段，如Fab、Fab'或F(ab')2片段。此類片段可藉由免疫球蛋白之片段化，例如藉由蛋白水解消化，或藉由此類片段之重組表現來獲得。舉例而言，免疫球蛋白消化可藉助於常規技術，例如使用木瓜蛋白酶或胃蛋白酶(WO 94/29348)實現。抗體之木瓜蛋白酶消化通常產生兩個一致抗原結合片段，所謂Fab片段，各自具有單個抗原結合位點；及殘餘Fc片段。胃蛋白酶處理產生F(ab')2。在Fab分子中，可變域各自與較佳地人類來源之免疫球蛋白恆定域融合。因此，重鏈可變域可與CH1域(所謂Fd片段)融合，且輕鏈可變域可與CL域融合。此類分子可藉由使用此項技術中已知之方法在宿主細胞中重組表現各別核酸來產生。
此項技術中已描述大量用於修飾天然存在之抗體以及用於在不同分子背景下置放免疫球蛋白之可變域或源自此類可變域之分子的方法，參見例如Holliger, P., Hudson, P. Nat Biotechnol 23, 1126-1136 (2005)或Nilvebrant, J.等人 Current pharmaceutical design 第22卷, 43 (2016): 6527-6537。通常，此等修飾旨在使抗體成為在藥物及技術中更通用之工具。此等方法產生結構上經修飾之分子，在本文中亦稱為「抗體衍生物」或「經修飾之免疫球蛋白」，該等分子通常不同於天然存在之抗體之基礎組成(亦即，由兩條大的重鏈及兩條小的輕鏈組成或如駱駝科物種或軟骨魚中僅由兩條重鏈組成之抗體)。通常，與天然存在之抗體相比，此等分子之尺寸較小，且可包含單一胺基酸鏈或若干胺基酸鏈。例如，單鏈可變片段(scFv)為免疫球蛋白之重鏈及輕鏈之可變區的融合，用短連接子，通常絲胺酸(S)或甘胺酸(G)連接在一起(參見例如WO 88/01649；WO 91/17271)。「單域抗體」或「nanobodies®」在單一Ig樣域中具有抗原結合位點(參見例如WO 94/04678；WO 03/050531)。對相同或不同抗原具有結合特異性之單域抗體可連接在一起。雙功能抗體為由包含兩個可變域之兩條胺基酸鏈組成之二價抗體分子(WO 94/13804)。抗體樣分子之其他實例為免疫球蛋白超家族抗體(IgSF；Srinivasan及Roeske, Current Protein Pept. Sci. 2005, 6(2): 185-96)。不同概念產生所謂小模組免疫藥物(SMIP)，其包含Fv域連接於單鏈鉸鏈及效應域，缺乏恆定域CH1 (WO 02/056910)。然而，在一些情況下，修飾亦可產生大於天然存在之抗體的分子，例如當經典Ig格式與額外抗原結合位點組合時，例如呈scFv形式等。如本文所使用，更通用之術語「抗體」亦涵蓋所有此類抗體衍生物或經修飾之免疫球蛋白。
因為對於在人中之應用，常常需要降低最初源自其他物種、如小鼠之抗體之免疫原性，所以已開發出改良方法，如構築嵌合抗體或所謂抗體「人類化」。在此背景下，「嵌合抗體」應理解為包含來源於一種物種(例如小鼠)之序列部分(例如可變域)與來源於不同物種(例如人類)之序列部分(例如恆定域)融合的抗體。「人類化抗體」為包含最初來源於非人類物種之可變域的抗體，其中已使某些胺基酸突變，使得可變域之總序列更近似於人類可變域之序列。抗體嵌合及人類化之方法為此項技術中所熟知(Billetta R, Lobuglio AF. 「Chimeric antibodies」. Int Rev Immunol. 1993;10(2-3):165-76；Riechmann L, Clark M, Waldmann H, Winter G (1988). 「Reshaping human antibodies for therapy」. Nature: 332:323.)。如本文所用，術語「人類抗體」係指基於來源於人類基因體之序列，例如藉由噬菌體呈現或使用轉殖基因動物建立的抗體(參見例如WO 90/05144)。如本文所用，術語「抗體」明確包括此類人類化抗體、嵌合抗體以及人類抗體。
抗體可進一步經融合(為融合蛋白)或者連接(藉由共價鍵或非共價鍵)至對抗體特性具有期望影響之其他分子實體。例如，可能需要改善抗體分子之藥物動力學特性，例如在諸如血液之體液中之穩定性，尤其在單鏈抗體或域抗體之情況下。關於此，特別是為延長此類抗體之循環半衰期，已研發出大量技術，諸如聚乙二醇化(WO 98/25971；WO 98/48837；WO 2004081026)，抗體與對如白蛋白之血清蛋白具有親和力之另一抗體融合或共價附接(WO 2004041865；WO 2004003019)，或抗體表現為與如白蛋白或運鐵蛋白之血清蛋白之全部或部分的融合蛋白(WO 01/79258)。用於抗體設計中之主要鑑別及主要優化的手段及方法為此項技術中所熟知且已例如評述於Goulet, D.R.及Atkins, W.M. J Pharm Sci 2020;109(1):74-103或Tiller, K. E.及Tessier, P. M. (2015). Annual review of biomedical engineering, 17, 191-216。
c) 亦已開發「抗體模擬物」，其通常僅與免疫球蛋白可變域具有遙遠的結構關係，或毫無此類關係，但顯示與免疫球蛋白可變域相當的一定結合特異性及親和力。此類非免疫球蛋白「抗體模擬物」有時稱為「支架蛋白」，可例如基於蛋白A、脂質運載蛋白、纖維結合蛋白域、錨蛋白共同重複域及硫化還原蛋白之基因(Skerra, Current Opinion in Biotechnology 2007, 18(4): 295-304)。
d) 如本文所用，術語「免疫球蛋白可變域」意謂基本上由四個「構架區」組成之免疫球蛋白域，該等「構架區」在此項技術中且在下文中分別稱為「構架區1」或「FR1」；「構架區2」或「FR2」；「構架區3」或「FR3」；及「構架區4」或「FR4」；該等構架區間雜有三個「互補決定區」或「CDR」，該等「互補決定區」在此項技術中且在下文中分別稱為「互補決定區1」或「CDR1」；「互補決定區2」或「CDR2」；及「互補決定區3」或「CDR3」。因此，免疫球蛋白可變域之通用結構或序列可如下表示：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。免疫球蛋白可變域藉由攜載抗原結合位點而賦予抗體對抗原之特異性。
e) 可「結合」、「結合於」、「特異性結合」或「特異性結合於」一定抗原決定基、抗原或蛋白質(或其至少一個部分、片段或抗原決定基)、「對其具有親和力」及/或「對其具有特異性」之分子(諸如本發明之結合分子或其片段)稱為「抗」或「針對」該抗原決定基、抗原或蛋白質，或為關於此類抗原決定基、抗原或蛋白質之「結合」分子。
f)  如本文所用，術語「抗原結合位點」係指賦予與特定抗原之結合的結合分子之域。抗原結合位點最初來源於抗體，不過此領域中之發展已使得在不需要產生針對所關注之目標的天然存在之抗體下亦可設計及/或獲得抗原結合位點。無論來源如何，根據本發明之「抗原結合位點」至少包含允許與其特定目標抗原結合之最小結構元件，亦即必需及足夠結構元件。因此，根據本發明之「抗原結合位點」包含至少三個重鏈CDR序列(在單域抗體之情況下)，更佳至少三個輕鏈及三個重鏈CDR序列。如上文所論述，此等CDR通常存在於抗體之所謂可變域或可變區(Fv)中。應瞭解，儘管抗原結合位點至少包含最小結構元件，但其通常涵蓋額外元件(諸如例如構架區)。因此，如根據本發明所用，抗原結合位點亦可經由重鏈可變域與輕鏈可變域之各別組合的序列界定。根據本發明，尤其較佳地，「抗原結合位點」包含於多肽中及/或該等CDR或該等可變域中之各者為多肽或肽。
g) 術語結合分子或抗原結合位點之「特異性結合」可描述根據其交叉反應性來描述。較佳地，本發明之結合分子之抗原結合位點不與或基本上不與不同於目標抗原但結構類似於目標抗原之抗原決定基交叉反應。較佳地，「特異性結合於」係指抗原結合位點不結合於與特定敍述之目標，亦即分別抗原TROP2、CDH17及CD3具有小於65%、較佳小於70%、小於75%、小於80%、小於85%、小於90%、小於95%且最佳小於98%一致性(使用此項技術中已知之方法計算)的目標。所研究之一組分子之交叉反應性可例如藉由評估該組分子在習知條件下與所關注之抗原決定基以及與多個大體上(結構上及/或功能上)緊密相關之抗原決定基的結合來測試。僅認為彼等與相關背景下所關注之抗原決定基(例如蛋白質結構中之特定模體)結合但不結合於或基本上不結合於任何其他抗原決定基的分子特異性結合。對應方法描述於教科書文獻以及例如Brooks BD. Curr Drug Discov Technol. 2014年6月;11(2):109-12或Abdiche YN等人, PLoS One. 2014年3月20日;9(3):e92451。
然而，「特異性」亦可根據其親和力及/或親合力來描述或說明。
由抗原與結合分子之解離平衡常數(Kd)表示之親和力係抗原決定基與結合分子上的抗原結合位點之間的結合強度之量度：Kd值愈小，抗原決定基與結合分子之間的結合強度愈強(或者，親和力亦可表示為親和力常數(Ka)，其為1/Kd)。
尤其較佳地，特異性結合於其目標之抗原結合位點對各別目標，亦即抗原TROP2、CDH17或CD3之結合親和力顯著高於結構上不相關之分子。因此，TROP2之抗原結合位點對TROP2之結合親和力顯著高於任何其他結構上不相關之分子；CDH17之抗原結合位點對CDH17之結合親和力顯著高於任何其他結構上不相關之分子；且CD3之抗原結合位點對CD3之結合親和力顯著高於任何其他結構上不相關之分子。根據本發明，若在一致條件下抗原結合位點與其目標抗原之結合親和力比對不相關抗原之親和力大至少兩倍、較佳大至少十倍、更佳大至少20倍且最佳大至少100倍，則認為該抗原結合位點對該目標抗原具有顯著較高結合親和力。
較佳結合親和力視結合分子而變化，但包括解離常數(Kd)為至少10E-4莫耳/公升或更低之結合分子，例如經由此項技術中已知之任何標準方法，較佳經由下文及隨附實例中所述之Biacore分析量測。一般認為大於10E-4 M之任何Kd值指示非特異性結合。較佳地，抗原結合位點將以小於500 nM、較佳小於200 nM、更佳小於100 nM且最佳小於20 nM之Kd特異性結合於期望抗原。對於某些結合劑，諸如本文所述之CD3之抗原結合位點，且除非本文中另外定義，否則較佳地，解離常數(Kd)小於10 nM，更佳小於5 nM且甚至更佳小於2 nM。
親合力為結合分子(諸如本發明之結合分子或其片段)與相關抗原之間的結合強度之量度。親合力與抗原決定基與結合分子上之其抗原結合位點之間的親和力及結合分子上存在之相關結合位點數目兩者有關。
如熟練技術人員清楚的(例如基於本文中之進一步揭示內容)，可使用此項技術中本身已知之手段及方法測定特異性結合，視所關注之特定相關抗原而定。此類手段及方法包括不限於史卡查分析(Scatchard analysis)及/或競爭結合分析，諸如放射免疫分析(RIA)、酶免疫分析(EIA)及夾心競爭分析，及電漿子共振分析(Malmqvist M., Curr Opin Immunol. 1993年4月;5(2):282-6.)，利用例如經純化之野生型抗原。亦可使用動力學排除分析(KinExA)技術(Darling, R.J.及Brault P-A., ASSAY and Drug Development Technologies. 2004年12月2(6): 647-657)來量測抗體親和力。較佳地，特異性結合藉由電漿子共振分析，利用經純化之野生型抗原來測定。更佳地，用於測定Kd值之方法係基於Biacore分析，如例如以下實例3.2中所描述。因此，較佳地，本文所提及之任何Kd值為在Biacore 4000上經由表面電漿子共振(SPR)獲得之Kd值，其中所關注之結合分子經由蛋白A/G捕捉至傳感器表面上，在10 µl/min下持續60秒，接著各別目標分子(例如人類Trop2、CDH17或CD3)較佳以100 nM之濃度施加，在30 µl/min下締合180秒，接著在HBS-EP緩衝液中解離120秒。
h) 如此項技術中通常已知且同意，將根據標準三字母或單字母胺基酸代碼指示胺基酸殘基。當比較兩個胺基酸序列時，術語「胺基酸差異」係指相較於第二序列，在參考序列之某一位置處插入、缺失或取代指定數目個胺基酸殘基。在取代之情況下，該(等)取代將較佳為保守胺基酸取代，此意謂胺基酸殘基經具有相似化學結構之另一胺基酸殘基取代，且幾乎不會或基本上不會對多肽之功能、活性或其他生物特性造成影響。此類保守胺基酸取代為此項技術中所熟知，例如WO 98/49185，其中保守胺基酸取代較佳為以下組(i)-(v)內之一個胺基酸經同一組內之另一個胺基酸殘基取代的取代：(i)小型脂族、非極性或略微極性殘基：Ala、Ser、Thr、Pro及GIy；(ii)極性、帶負電荷之殘基及其(不帶電荷)之醯胺：Asp、Asn、GIu及GIn；(iii)極性、帶正電荷之殘基：His、Arg及Lys；(iv)大型脂族、非極性殘基：Met、Leu、Ile、VaI及Cys；及(v)芳族殘基：Phe、Tyr及Trp。尤其較佳之保守胺基酸取代如下： Ala取代成GIy或取代成Ser； Arg取代成Lys； Asn取代成GIn或取代成His； Asp取代成GIu; Cys取代成Ser； GIn取代成Asn； GIu取代成Asp； GIy取代成Ala或取代成Pro； His取代成Asn或取代成GIn； Ile取代成Leu或取代成VaI； Leu取代成Ile或取代成VaI； Lys取代成Arg、取代成GIn或取代成GIu； Met取代成Leu、取代成Tyr或取代成Ile； Phe取代成Met、取代成Leu或取代成Tyr； Ser取代成Thr； Thr取代成Ser； Trp取代成Tyr； Tyr取代成Trp或取代成Phe； VaI取代成Ile或取代成Leu。
i)  如本文所用，術語「分離」係指物質脫離其原始或原生環境(例如天然環境(若其為天然存在的))。例如，活動物中存在的天然存在之核酸分子或多肽未經分離，但藉由人為干預與天然系統中之共同存在之材料中的一些或全部分離的相同核酸分子或多肽係經分離的。此類核酸分子可為載體之一部分及/或此類核酸分子或多肽可為組合物之一部分，且仍為經分離的，此係因為此類載體或組合物不為核酸分子或多肽天然存在之環境的一部分。舉例而言，當與核酸分子或多肽所獲自之天然生物來源及/或反應介質或培養介質相比，該核酸分子或多肽已與在該來源或培養基中通常相關聯之至少一種其他組分，諸如另一核酸分子、另一多肽、另一生物組分或大分子或至少一種污染物、雜質或次要組分分離時，該核酸分子或多肽視為「(呈)基本上分離(形式)」。詳言之，當以至少2倍，尤其至少10倍、更尤其至少100倍且高達1000倍或更大程度純化核酸分子或多肽時，其視為「基本上分離」的。使用合適技術，諸如合適層析技術，諸如聚丙烯醯胺-凝膠電泳測定，「呈基本上分離形式」之核酸分子或多肽較佳為基本上均質的。本發明之結合分子及核酸較佳經分離。
j)  除非另外指示，否則如本文所用，術語「序列」(例如，在如「免疫球蛋白序列」、「結合分子序列」或「多肽序列」之術語中)通常應理解為包括相關胺基酸序列，以及編碼其之核酸序列或核苷酸序列，除非上下文需要更具限制性之解釋。
k) 在兩種或更多種核酸或多肽序列之情況下，如本文所用，術語「一致」或「一致性百分比」係指當出於最大對應性進行比較及比對時相同或具有指定百分比之相同核苷酸或胺基酸殘基的兩種或更多種序列或子序列。為確定一致性百分比，出於最佳比較目的而比對序列(例如，可在第一胺基酸或核酸序列之序列中引入間隙以與第二胺基酸或核酸序列最佳比對)。接著比較對應胺基酸位置或核苷酸位置處之胺基酸殘基或核苷酸。當第一序列中之位置與第二序列中之相應位置由相同胺基酸殘基或核苷酸殘基佔據，則分子在該位置處一致。兩個序列之間的一致性百分比為該等序列共有的一致位置數的函數(亦即，一致性%=一致位置數/位置總數(例如重疊位置)×100)。在一些實施例中，適當時，在序列內引入間隙之後，進行比較之兩個序列長度相同(例如不包括延伸超過比較序列之額外序列)。舉例而言，當比較可變區序列時，不考慮前導及/或恆定域序列。對於兩個序列之間的序列比較，「對應」CDR係指兩個序列中相同位置之CDR (例如各序列之CDR-H1)。
可使用數學演算法測定兩個序列之間的一致性百分比或相似性百分比。用於比較兩個序列之數學演算法之較佳非限制性實例為Karlin及Altschul, 1990, Proc. Natl. Acad. Sci. USA 87:2264-2268之算法，修改為Karlin及Altschul, 1993, Proc. Natl. Acad. Sci. USA 90:5873-5877。將此類演算法併入Altschul等人, 1990, J. Mol. Biol. 215:403-410之NBLAST及XBLAST程式中。BLAST核苷酸檢索可用NBLAST程式(得分=100，字長=12)進行以獲得與編碼所關注蛋白質之核酸同源之核苷酸序列。BLAST蛋白質檢索可用XBLAST程式(得分=50，字長=3)進行以獲得與所關注蛋白質同源之胺基酸序列。為實現間隙比對以達成比較目的，可如Altschul等人, 1997, Nucleic Acids Res. 25:3389-3402中所述使用間隙BLAST。替代地，PSI-Blast可用於進行偵測分子間的遠緣關係之迭代檢索(同上)。利用BLAST、間隙BLAST及PSI-Blast程式時，可使用各別程式(例如XBLAST及NBLAST)之預設參數。用於比較序列之數學演算法之另一較佳非限制性實例為Myers及Miller, CABIOS (1989)之演算法。將此類演算法併入ALIGN程式(版本2.0)中，該程式為GCG序列比對套裝軟體之部分。當利用ALIGN程式來比較胺基酸序列時，可使用PAM120權重殘基表、間隙長度罰分12及間隙罰分4。用於序列分析之額外演算法為此項技術中所已知且包括如Torellis及Robotti, 1994, Comput. Appl. Biosci. 10:3-5中所描述之ADVANCE及ADAM；及Pearson及Lipman, 1988, Proc. Natl. Acad. Sci. USA 85:2444-8中描述之FASTA。在FASTA內，ktup為設定檢索之敏感性及速度的控制選項。若ktup = 2，則藉由觀察比對殘基對發現兩個比較序列中之相似區域；若ktup = 1，則檢查單一比對胺基酸。對於蛋白質序列，ktup可設定為2或1，或對於DNA序列設定為1至6。若ktup未規定，則對於蛋白質預設值為2，且對於DNA為6。或者，可使用CLUSTAL W演算法進行蛋白質序列比對，如Higgins等人, 1996, Methods Enzymol. 266:383-402所描述。較佳地，使用上述CLUSTAL W演算法。
l)  如本文所用，術語「包含」表示除特定敍述之組分及/或步驟外可包括之進一步組分及/或步驟。然而，此術語亦涵蓋所主張之主題完全由所敍述組分及/或步驟組成。
m) 如本文所用，術語「至少」係指包括特定敍述之數目及高於其之任何數目的任何數目。舉例而言，「至少一個」涵蓋確切一個，以及超過一個，包括不限於兩個，諸如(例如)三個或四個。進一步包括例如五個、六個、七個、八個、九個、10個、15個，諸如20個、30個、40個、50個、75個、100個、150個、200個、300個、400個或500個，以及此等特定敍述之數目之間或高於此等數目的任何整數。關於術語「至少一個抗原結合位點」，尤其較佳地，該術語涵蓋一、二、三或四個抗原結合位點。最佳地，該術語係指確切一個抗原結合位點。在選擇超過一個針對目標之抗原結合位點的彼等情況下，此等多個抗原結合位點可獨立地加以選擇，亦即其可一致或其可彼此不同。
n) 如本文所用，術語「多肽」描述含有超過30個胺基酸之線性胺基酸分子鏈，包括單鏈多肽或其片段。另一方面，如本發明中所用，術語「肽」描述含有至多30個胺基酸之線性胺基酸鏈。如根據本發明使用之術語「(多)肽」係指包含由至多30個胺基酸組成之肽之群以及由超過30個胺基酸組成之多肽之群的一組分子。
o) 如本文所用，術語「連接子」涵蓋肽連接子，亦即胺基酸序列，以及非肽連接子，其共價或非共價連接分子之個別部分。如本文所用，術語「非肽連接子」係指具有兩個或更多個反應性基團但排除如下所定義之肽連接子的連接基團。舉例而言，非肽連接子可為在兩端具有反應性基團之聚合物，該等反應性基團個別結合於本發明之分子之結合部分的反應性基團，例如胺基端、離胺酸殘基、組胺酸殘基或半胱胺酸殘基。聚合物之反應性基團包括醛基、丙醛基、丁醛基、順丁烯二醯亞胺基、酮基、乙烯基碸基、硫醇基、醯肼基、羰基咪唑(CDI)基團、硝苯基碳酸酯(NPC)基團、三氟乙基磺酸酯基(trysylate)、異氰酸酯基及丁二醯亞胺衍生物。丁二醯亞胺衍生物之實例包括丁二醯亞胺基丙酸酯(SPA)、丁二醯亞胺基丁酸(SBA)、丁二醯亞胺基羧甲基酯(SCM)、丁二醯亞胺基丁二醯胺(SSA)、丁二醯亞胺基丁二酸酯(SS)、丁二醯亞胺基碳酸酯及N-羥基丁二醯亞胺(NHS)。非肽聚合物之兩個末端處的反應性基團可相同或不同。舉例而言，非肽聚合物可在一個末端具有順丁烯二醯亞胺基且在另一末端具有醛基。
如本文所設想，肽連接子為長度為至少1個胺基酸之(多)肽連接子。較佳地，連接子為1至100個胺基酸長。更佳地，連接子為5至50個胺基酸長，更佳10至40個胺基酸長，且甚至更佳地，連接子為15至30個胺基酸長。通常使用之小連接子之非限制性實例包括甘胺酸及絲胺酸胺基酸之序列，稱為GS微型連接子。此等連接子中之胺基酸之數目可變化，例如，其可為4個(GGGS) (SEQ ID NO:273)或6個(GGSGGS) (SEQ ID NO:274)，或其倍數，諸如此四個/六個胺基酸之兩個或三個或更多個重複序列。最佳地，此類GS微型連接子具有20個胺基酸及序列GGGGSGGGGSGGGGSGGGGS (SEQ ID NO:275)。
熟練技術人員應瞭解，當所關注分子為單一多肽鏈時，連接子為肽連接子。
此項技術中已知，連接子之性質，亦即長度及/或組合物，諸如胺基酸序列，可調節或增加含有連接子之分子之穩定性及/或溶解性。通常，連接子之長度及序列視各別所關注分子之組成而選擇。熟練技術人員十分瞭解設計及測試不同連接子之適合性的方法，參見例如Völkel, T.等人 Protein Engineering, Design and Selection, 第14卷, 第10期, 2001, 第815-823頁。舉例而言，容易藉由比較本發明之分子之結合部分的結合親和力來測試分子之特性。在本發明之三特異性分子的情況下，可分別進行各結合部分之各別量測。可使用基於ELISA之方法測定在人類血清中在37℃下培育若干時段之後分子之殘餘結合力來量測所得分子之穩定性。其他適合之測試可見於例如Brian R. Miller, B.R.等人 Protein Engineering, Design and Selection, 第23卷, 第7期, 2010, 第549-557頁或Kügler, M.等人 Protein Engineering, Design and Selection, 第22卷, 第3期, 2009, 第135-147頁。
(p)根據本發明，術語「核酸分子」可在本文中與術語「聚核苷酸」互換使用，包括DNA，諸如(例如)cDNA或基因體DNA，及RNA，例如mRNA。進一步包括此項技術中已知之核酸模擬分子，諸如(例如)DNA或RNA之合成或半合成衍生物及混合聚合物。根據本發明之此類核酸模擬分子或核酸衍生物包括硫代磷酸酯核酸、胺基磷酸酯核酸、2'-O-甲氧基乙基核糖核酸、N-嗎啉基核酸、己糖醇核酸(HNA)及鎖核酸(LNA)。LNA為一種RNA衍生物，其中核糖環受2'-氧與4'-碳之間的亞甲基鍵約束。如熟習此項技術者將容易瞭解，其可含有額外非天然或衍生核苷酸鹼基。 本發明之三特異性結合分子  本發明係關於一種結合分子，其包含：(a)至少一個以Kd ≥ 1 nM特異性結合於滋養層細胞表面抗原2 (TROP2)，較佳人類TROP2之抗原結合位點；(b)至少一個以Kd ≥ 10 nM，較佳以Kd ≥ 100 nM特異性結合於鈣黏素-17 (CDH17)，較佳人類CDH17之抗原結合位點；及(c)至少一個特異性結合於分化簇3 (CD3)，較佳人類CD3之抗原結合位點。
因此，本發明之結合分子(在本文中亦稱為「本發明之蛋白質」或「本發明之結合劑」)至少包含特定敍述之三個不同抗原結合位點，亦即至少一個TROP2結合位點、至少一個CDH17結合位點及至少一個CD3結合位點。由於此三種特異性，本發明之結合分子在本文中亦稱為本發明之「三特異性結合分子」。
如本文所用，術語TROP2係指「滋養層細胞表面抗原2」。TROP2屬於腫瘤相關之鈣信號轉導子(TACSTD)家族且為緊密連接蛋白-7及緊密連接蛋白-1之穩定性所需。人類TROP2由SEQ ID NO: 419以及資料庫寄存編號UniProt P09758表示。
如本文所用，術語CDH17係指「鈣黏素-17」。CDH17為鈣依賴性膜相關醣蛋白之鈣黏素超家族的一員。編碼蛋白質類似於鈣黏素，由含有7個鈣黏素域之細胞外區及跨膜區組成，但缺乏保守細胞質域。已報導該蛋白質在胃腸道及胰管中表現。人類CDH17由SEQ ID NO: 420以及資料庫寄存編號UniProt Q12864表示。
如本文所用，術語CD3係指「分化簇3」。CD3為參與活化細胞毒性T細胞(亦即CD8+未處理T細胞)與T輔助細胞(亦即CD4+未處理T細胞)之蛋白質複合物及T細胞共受體。CD3由四個獨特鏈構成，其中在哺乳動物中該複合物含有一條CD3γ鏈、一條CD3δ鏈及兩條CD3ε鏈。與T細胞受體(TCR)及ζ-鏈(ζ鏈)一起，CD3在T淋巴球中產生活化信號。人類CD3中CD3 δ鏈由SEQ ID No: 421以及資料庫寄存編號UniProtKB-P04234表示，CD3 ε鏈由SEQ ID No: 422以及資料庫寄存編號UniProtKB-P07766表示，CD3 γ鏈由SEQ ID No: 423以及資料庫寄存編號UniProtKB-P09693表示，且CD3 ζ鏈由SEQ ID No: 424以及資料庫寄存編號UniProtKB-P20963表示。
抗原結合位點之通用結構為此項技術中所熟知且可為例如單域，諸如抗原決定基結合域、單鏈Fv (ScFv)域或成對VH/VL域，如上文所論述。在一較佳實施例中，抗原結合位點至少包含輕鏈可變域及重鏈可變域。
如關於一般定義所論述，需要抗原結合位點與其各別目標抗原特異性結合。另外，本發明之結合分子的進一步特徵在於特異性結合於TROP2及CDH17之抗原結合位點在TROP2情況下及在CDH17情況下分別以不低於1 nM之Kd及不低於10 nM (較佳不低於100 nM)之Kd結合。換言之，雖然需要該等抗原結合位點對其目標抗原具有特異性，但並不針對強結合親和力來選擇其，而實際上需要以較低親和力結合，從而允許僅在兩個目標存在下強結合本發明之結合分子。如下文更詳細地論述且如實例(尤其實例6至8)中所示，發現此兩個抗原結合位點對其各別抗原具有降低之親和力的要求導致單價結合低，但在兩個目標存在下由親合力引起本發明之所得三特異性結合分子的結合增強。尤其較佳地，TROP2之抗原結合位點具有1 nM與20 nM之間、更佳1 nM與10 nM之間、甚至更佳1 nM與4 nM之間的Kd。最佳地，特異性結合於TROP2之抗原結合位點具有2 nM與5 nM之間的Kd。此外，CDH17之抗原結合位點尤其較佳具有10 nM與200 nM之間、更佳50 nM與150 nM之間、甚至更佳75 nM與125 nM之間的Kd。最佳地，特異性結合於CDH17之抗原結合位點具有100 nM與120 nM之間的Kd。較佳地，該Kd如上文關於Biacore 4000上之SPR所述測定。
根據本發明，對親和力降低之結合劑的此類要求對於結合於CD3之抗原結合位點而言並非必需的。因此，且如上文中所陳述，對於靶向CD3之抗原結合位點，尤其較佳地，結合劑以小於500 nM、較佳小於200 nM、更佳小於10 nm之Kd且最佳以小於2 nM之Kd結合。特異性結合於CD3之許多抗原結合位點已描述於此項技術中，例如WO2004106383中，其中描述衍生自選自由以下組成之群之抗體的熟知抗原結合位點：X35-3、VIT3、BMA030 (BW264/56)、CLB-T3/3、CRIS7、YTH12.5、F111-409、CLB-T3.4.2、TR-66、WT32、SPv-T3b、11 D8、XIII-141、XIII-46、XIII-87、12F6、T3/RW2-8C8、T3/RW2-4B6、OKT3D、M-T301、SMC2、WT31及F101.01.e，以及SP34。詳言之，WO2004106383描述VH及VL區來源於能夠在其他TCR次單元之背景下，例如在針對人類CD3-ε鏈進行轉殖基因之小鼠細胞中，特異性識別人類CD3-ε鏈之抗體/抗體衍生物及其類似物。合適CD3特異性抗原結合位點之進一步非限制性實例提供於US20180118848、W02011090762 (例如CRIS-7、OKT3、HU291、G19-4)、US9782478、US20180118827 (SP34修飾)、US20160145340 (SP34修飾)、US9212225 (例如SP34 CDR之修飾)、US10174124 (CD3融合瘤純系，包括純系40G5C及38E4.V1)、US9914776及WO2020127619 (SP34修飾)、US7,728,114、US5929212、WO2014047231 (基於OKT3或CRIS-7)、WO2004108158 (基於OKT3)、WO200703320 (CD3純系28F11、27H5、23F10、15C3)、US10066015 (SP34修飾)、WO2018201051 (SP34修飾)、WO201911871、US99759662、US20180326058、WO2019131988 (包括SP34 (mu、hu)、OKT3、UCHT1.v9、UCHT1、v1、UCHT1.vM1、HU40G5C、38E4.V1、抗CD3純系AN104、AN119、AN121、AN395)、US20180161428、WO2019075378 (SP34 CDR變異體)、WO2016187594 (例如與莫羅單抗(muromonab)-CD3相關之CDRS (OKT3)、奧昔珠單抗(otelixizumab) (TRX4)、替利珠單抗(teplizumab) (MGA031)、維西珠單抗(visilizumab) (Nuvion)、SP34、X35、VIT3、BMA030 (BW264/56)、CLB-T3/3、CRIS7、YTH12.5、F111-409、CLB-T3.4.2、TR-66、WT32、SPv-T3b、11D8、XIII-141、XIII-46、XIII-87、12F6、T3/RW2-8C8、T3/RW2-4B6、OKT3D、M-T301、SMC2、F101.01、UCHT-1及WT-31)、US10066016 (SP34 CDR變異體)、WO20180209298 (tritac)或US10544221 (SP34 CDR變異體)。
熟練技術人員可自本文所述之抗原結合位點，自此項技術中描述之抗原結合位點(諸如此項技術中已知之CD3之抗原結合位點，如上文所詳述)或自新開發之抗原結合位點選擇所敍述目標之抗原結合位點，在各種情況下限制條件為滿足上述關於特異性(亦即，特異性結合各別目標，但對於TROP2及CDH17，限制條件為Kd不過低，如上所定義)之先決條件。上文已提供測試此等要求之手段及方法且可藉由熟練技術人員立即應用。
儘管本發明之結合分子之抗原結合位點作為(a)、(b)及(c)列出，但此清單並不意欲規定特定次序或排列。因此，抗原結合位點可以任何次序排列在本發明之結合分子內，諸如(例如)(a)-(b)-(c)、(b)-(c)-(a)、(c)-(a)-(b)、(b)-(a)-(c)等。下文將進一步詳述本發明之結合分子內抗原結合位點之較佳排列。
重要地，本發明之結合分子能夠(實質上)同時結合所有三個目標(TROP2、CDH17及CD3)。因此，假定所有三個目標均存在，本發明之結合分子將結合於其中所有三者，藉此充當T細胞接合分子(TcE)：其將結合於T細胞上之CD3，因此，將使T細胞接近表現TROP2與CDH17兩者之腫瘤細胞。所關注之結合分子是否能夠結合於目標細胞表面上之Trop2及CDH17兩者且可誘導T細胞活性可如隨附實例中所描述，例如使用重組HEK293細胞或內源性表現抗原之癌細胞株，諸如大腸直腸癌DLD-1細胞株(已在實例9中描述兩者)來確定。
在一較佳實施例中，本發明之結合分子除特定敍述之TROP2、CDH17及CD3之三個抗原結合位點外不含進一步抗原結合位點。甚至更佳地，本發明之結合分子為三特異性及三價的，亦即其含有三個抗原目標中之各者的一個結合位點。
本發明之結合分子的格式不受特定限制，限制條件為其至少包含特定敍述之三個不同抗原結合位點(TROP2、CDH17及CD3)且如本文所定義，能夠同時(實質上)結合此三個目標。因此，格式可基於天然存在之抗體或抗體衍生物或此類抗體之片段以及抗體模擬物的格式。此類格式可根據需要經修飾以容納所有三個抗原結合位點，例如藉由額外包含另一抗體片段(詳言之，Fv、Fab、Fab'或F(ab') 2片段)、單鏈抗體(詳言之，單鏈可變片段(scFv))、小模組免疫藥物(SMIP)、域抗體或奈米抗體。可採用之個別或所有抗原結合位點之合適格式的進一步非限制性實例包括上文所定義之抗體模擬物。
較佳地，本發明之結合分子為經修飾之免疫球蛋白(在本文中亦稱為經修飾之免疫球蛋白分子)。舉例而言，在一較佳實施例中，TROP2及CDH17之抗原結合位點存在於具有(經典Y形)免疫球蛋白格式之結合分子之可變區中。在此類格式中，第一組免疫球蛋白輕鏈及重鏈在其可變區中含有TROP2之抗原結合位點且第二組免疫球蛋白輕鏈及重鏈在其可變區中含有CDH17之抗原結合位點，且兩組鏈彼此例如經由二硫橋連接，形成免疫球蛋白分子。
用於製造此類免疫球蛋白分子之技術為此項技術中所熟知且包括不限於具有不同特異性之兩個免疫球蛋白重鏈-輕鏈對之重組共表現(例如Milstein及Cuello, Nature 305: 537 (1983))、WO 93/08829及Traunecker等人, EMBO J. 10: 3655 (1991))；「杵-臼」工程改造(例如美國專利第5,731, 168號)；用於製造抗體Fc-雜二聚體分子之工程靜電導向作用(WO 2009/089004A1)；兩個或更多個免疫球蛋白或片段之交聯(例如美國專利第4,676,980號，及Brennan等人, Science, 229: 81 (1985))；使用白胺酸拉鏈產生雙特異性抗體(參見例如Kostelny等人, Immunol., 148(5): 1547-1553 (1992))等。熟練技術人員十分瞭解此類方法，該等方法亦評述於此項技術中，例如Liu H.等人(2017) Front. Immunol. 8:38. doi: 10.3389/fimmu.2017.00038或Moore, G.L., Methods, 第154卷, 2019, 第38-50頁。
該免疫球蛋白分子藉由包含CD3之抗原結合位點之額外組分的融合而進一步修飾，藉此產生經修飾之免疫球蛋白。較佳地，CD3之該抗原結合位點為與免疫球蛋白分子之重鏈中之一或兩者之C端融合的scFv。各個組分彼此之融合為此項技術中所熟知。該融合可例如經由肽連接子，或經由非肽連接子進行。較佳地，該融合經由肽連接子進行。
更佳地，該免疫球蛋白分子及/或該經修飾之免疫球蛋白分子為單株、嵌合、人類化或人類免疫球蛋白(例如抗體)分子。更佳地，該免疫球蛋白分子之重鏈恆定區係選自由以下組成之群：IgG1、IgG2、IgG3、IgG4、IgM、IgA及IgE恆定區。在另一較佳實施例中，該免疫球蛋白分子之輕鏈恆定區為κ或λ。
根據本發明，構成本發明之結合分子的個別元件彼此可經由一或多種連接子連接。較佳地，此等連接子為肽連接子且更佳地，其經由共價連接個別元件。本文中尤其較佳地，各別輕鏈經由連接子連接於其各別重鏈。
在本發明之結合分子含有超過一種連接子之彼等實施例中，設想該等連接子可具有相同或不同長度且可由相同或不同結構構成，例如包含相同或不同胺基酸序列或相同或不同非肽聚合物。在一較佳實施例中，本發明之結合分子中存在之連接子彼此的長度及/或結構不同(例如胺基酸序列或非肽聚合物之性質)。
較佳地，連接子為肽連接子。更佳地，連接子為使用例如胺基酸丙胺酸及絲胺酸或甘胺酸及絲胺酸之可撓性連接子，諸如SEQ ID NO:275中所示之連接子，或為SEQ ID No: 265及266中所示之連接子中之一者。因此，尤其較佳地，本發明之結合分子完全由胺基酸構成，亦即其為多肽。
據本發明人所瞭解，迄今為止未報導過連接癌細胞上之Trop2及CDH17及免疫細胞上之CD3之三特異性抗體與重組三特異性抗體衍生物，其中Trop2及CDH17特異性結合劑分別以高於1 nM及10 nM之Kd結合其目標。WO21113748為描述各種格式多特異性抗體之專利申請案，該等格式包括稱為「TriAx-E」之結合於Trop2、CDH17及/或CD3之分子，然而，本發明人再現該分子之任何嘗試均因穩定性不夠而失敗。經典抗體選擇活動通常適合產生高親和力結合劑。此亦為WO21113748中遵循之方法。然而，本發明人意外地發現對此兩個目標具有高親和力之抗原結合位點之併入引起治療窗狹窄。如實例、尤其實例6至8中所示，較高親和力之使用產生對僅表現一個或另一目標之細胞的單價結合及活性，因此增加不希望副作用之風險。另外，多價格式之使用亦減小治療窗。此等發現顯示對兩個目標中之任一者之親和力增加導致特異性喪失，此為在價數增加之情況下進一步增強的作用。因此，選擇專注於獲得低親和力結合劑之不同選擇策略。如自以下實例顯而易見，本發明之三特異性結合分子提供對目標細胞之優良特異性。如下文實例中所示，獲得低親和力及單價結合劑組合之結合分子的最佳結果。
在本發明之結合分子之另一較佳實施例中，至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(vi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO.:1 (CDR1)、SEQ ID NO.:2 (CDR2)及SEQ ID NO.:3 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:4 (CDR1)、SEQ ID NO.:5 (CDR2)及SEQ ID NO.:6 (CDR3)之胺基酸序列之輕鏈CDR； (ii)      抗原結合位點，其包括包含SEQ ID NO.:7 (CDR1)、SEQ ID NO.:8 (CDR2)及SEQ ID NO.:9 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:10 (CDR1)、SEQ ID NO.:11 (CDR2)及SEQ ID NO.:12 (CDR3)之胺基酸序列之輕鏈CDR； (iii)     抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:14 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:16 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (iv)     抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:19 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:20 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (v)      抗原結合位點，其包括包含SEQ ID NO.:21 (CDR1)、SEQ ID NO.:22 (CDR2)及SEQ ID NO.:23 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:24 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:26 (CDR3)之胺基酸序列之輕鏈CDR； 及 (vi)     抗原結合位點，其包括包含SEQ ID NO.:27 (CDR1)、SEQ ID NO.:28 (CDR2)及SEQ ID NO.:29 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:30 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:31 (CDR3)之胺基酸序列之輕鏈CDR。
本文揭示及SEQ ID NO: 1至31中描繪之CDR根據Kabat命名法呈現，且展示於下表1中。如本文所用，HCDR表示重鏈CDR且LCDR表示輕鏈CDR。
由於此項技術中已知額外命名法，因此基於此等命名法中最常用者之CDR序列亦展示於下表1中，但僅針對此等替代命名法之應用產生不同胺基酸序列的彼等情況。此等編號系統係基於(i) CCG (Almagro等人, Proteins 2011; 79:3050-3066及Maier等人, Proteins 2014; 82:1599-1610所說明之Chemical Computing Group)；(ii) Chothia (Chothia and Lesk, 1987, J. Mol. Biol. 196: 901-917)、(iii) IMGT (Lefranc MP, Dev Comp Immunol. 2003年1月;27(1):55-77)及(iv) North (North B, J Mol Biol. (2011) 406:228-56)。
本文中(參見表1)根據Kabat、CCG、Chothia、IMGT及North位置指示CDR之胺基酸位置為線性的，亦即各別全長分子鏈之胺基酸在N端自編號1開始連續編號，且以與該分子中胺基酸之總數目相對應之編號結束。舉例而言，由長度為118個胺基酸組成之重鏈將在N端以編號1開始，且將在最C端胺基酸以編號118結束。因此，自所提及之此分子之N端計數，對例如位置25之任何提及意謂胺基酸編號25。
在本發明之結合分子之一更佳實施例中，至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(xii)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:83之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:84之胺基酸序列之免疫球蛋白輕鏈可變域； (ii)      抗原結合位點，其包括包含SEQ ID NO:85之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:86之胺基酸序列之免疫球蛋白輕鏈可變域； (iii)     抗原結合位點，其包括包含SEQ ID NO:87之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:88之胺基酸序列之免疫球蛋白輕鏈可變域； (iv)     抗原結合位點，其包括包含SEQ ID NO:89之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:90之胺基酸序列之免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含SEQ ID NO:91之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:92之胺基酸序列之免疫球蛋白輕鏈可變域； (vi)     抗原結合位點，其包括包含SEQ ID NO:93之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (vii)    抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (viii)   抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域； (ix)     抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (x)      抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)     抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:99之胺基酸序列之免疫球蛋白輕鏈可變域； 或 (xii)    抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域。
根據本發明，術語「免疫球蛋白重鏈可變域」及「免疫球蛋白輕鏈可變域」係根據此項技術中之定義使用。
在本發明之結合分子之另一較佳實施例中，至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群： (i)             抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:33 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:35 (CDR1)、SEQ ID NO.:36 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR； (ii)            及 (ii)      抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:38 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:39 (CDR1)、SEQ ID NO.:40 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR。
本文揭示及SEQ ID NO: 32至40中描繪之CDR亦根據Kabat命名法呈現，且展示於下表1中。同樣，由於此項技術中已知額外命名法，因此基於此等命名法中最常用者之CDR序列亦展示於下表1中，但僅針對此等替代命名法之應用產生不同胺基酸序列的彼等情況。
在本發明之結合分子之一更佳實施例中，至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:100之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:101之胺基酸序列之免疫球蛋白輕鏈可變域； 及 (ii)      抗原結合位點，其包括包含SEQ ID NO:102之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:103之胺基酸序列之免疫球蛋白輕鏈可變域。
在本發明之結合分子之一較佳實施例中， (a)    該至少一個特異性結合於TROP2之抗原結合位點包含於包含第一免疫球蛋白重鏈恆定CH1域、第一免疫球蛋白重鏈可變域、視情況存在之第一連接子、第一免疫球蛋白輕鏈恆定域及第一免疫球蛋白輕鏈可變域之第一多肽中，及/或 (b)    該至少一個特異性結合於CDH17之抗原結合位點包含於包含第二免疫球蛋白重鏈恆定CH1域、第二免疫球蛋白重鏈可變域、視情況存在之第二連接子、第二免疫球蛋白輕鏈恆定域及第二免疫球蛋白輕鏈可變域之第二多肽中。
根據本發明，術語「免疫球蛋白重鏈恆定CH1域」及「免疫球蛋白輕鏈恆定域」亦係根據此項技術中之定義使用。較佳地，上文所述之次序為自N端至C端。
如本文在某些多肽及免疫球蛋白鏈之情況下所用，術語「第一」及「第二」以及下文進一步之術語「第三」僅意欲指示此等分子為不同分子(因為其結合於不同目標抗原)。因此，此等術語不應理解為係指多肽或免疫球蛋白鏈在本發明之結合蛋白內的準確次序或序列。實際上，當提及與結合於TROP2相關之態樣時，使用術語「第一」，當提及與結合於CDH17相關之態樣時，使用術語「第二」，且當提及與結合於CD3相關之態樣時，使用術語「第三」。
術語連接子已在上文進行定義，且合適連接子已描述於此項技術中。在本發明之結合分子之一較佳實施例中，第一及/或第二連接子包含SEQ ID NO:265、SEQ ID NO:266、SEQ ID NO:273、SEQ ID NO:274或SEQ ID NO:275中之任一者之胺基酸序列。更佳地，第一及/或第二連接子包含SEQ ID NO:266之胺基酸序列。
根據本發明之結合分子之此實施例，TROP2及/或CDH17之抗原結合位點係選自上文所描述之抗原結合位點，而CD3之抗原結合位點係由熟練技術人員自此項技術中可獲得之彼等CD3特異性抗原結合位點或自本文揭示之彼等抗原結合位點選擇。更佳地，CD3特異性抗原結合位點係選自下文所定義之scFv序列(SEQ ID No:222至264，較佳SEQ ID No:222至245，更佳SEQ ID No:222至224)中之一者。
本發明之結合分子可含有且較佳含有Fc部分。術語Fc部分為此項技術中所已知且已在上文定義。天然存在之免疫球蛋白分子之Fc區通常與多種Fc受體相互作用，此產生多種重要的功能能力(稱為「效應功能」)。根據本發明，較佳地，本發明之結合分子含有Fc區或Fc區之一部分，其不干擾本發明之結合分子與目標抗原之相關部分的特異性結合。此外，熟練技術人員十分瞭解恆定區之類型及長度之選擇視如補體結合或抗體依賴性細胞介導之細胞毒性之效應功能是否為期望特徵以及抗體蛋白質之期望藥理學特性而定。
因此，在本發明之結合分子之一個較佳實施例中，結合分子具有經工程改造以避免與可溶性Fcγ受體及/或補體C1q發生不希望之交聯的Fc區或其相關部分。較佳地，此類結合分子對Fcγ受體及/或補體C1q之親和力比未經工程改造之結合分子(亦即，突變(經工程改造)分子來源於之Fc未經工程改造之結合分子)低得多。此類免疫球蛋白分子通常亦稱為Ig(KO)。
在本發明之結合分子之一尤其較佳實施例中，藉由利用引導位置234及235之L至A突變誘發(所謂「LA-LA突變」；Hezareh等人, J. Virology 75 (2001) 12161- 12168)的IgG4恆定區或IgG1恆定區，去除本發明中之結合分子與補體產物C1q或Fcγ受體的結合。較佳地，本發明之結合分子含有該L至A突變誘發。
在本發明之結合分子之另一個較佳實施例中，結合分子包含經工程改造以藉由例如使CH2域中位置H310A (根據EU編號方案)處發生點突變而優化與新生兒Fc受體(FcRn)之相互作用來調節血清含量(半衰期)的Fc區或其相關部分。此類Ig分子在本文中稱為IgFcRnmut。
多聚體結合分子設計之一個挑戰為在無隨機鏈配對及其他錯配下在工業規模上生產其。熟練技術人員瞭解大量嘗試阻止尤其重鏈均二聚體形成之方法，包括例如所謂杵-臼(KiH)策略，使用相反電荷建立靜電導向作用，或促進重鏈雜二聚化之疏水性突變，CH3股交換工程改造域(SEED技術)及CH3域C端中諸如可裂解白胺酸拉鏈之雜二聚體模組的融合(LUZ-Y技術))，Amaral等人(J Appl Bioanal 6(1), 26-51 (2020))中近來概述。
因此，尤其較佳地，本發明之結合分子至少含有促使杵-臼形成之突變。較佳地，本發明之結合分子係基於經修飾之免疫球蛋白分子，其中Ig分子部分之重鏈包含以下突變： (i)    第一重鏈包含在位置366處之色胺酸(W) [T366W]，且第二重鏈包含在位置366處之絲胺酸(S) [T366S]、在位置368處之丙胺酸(A) [L368A]及在位置407處之纈胺酸(V) [Y407V]； (ii)   第一重鏈包含在位置366處之酪胺酸(Y) [T366Y]，且第二重鏈包含在位置407處之蘇胺酸(T) [Y407T]； (iii) 第二重鏈包含在位置366處之色胺酸(W) [T366W]，且第一重鏈包含在位置366處之絲胺酸(S) [T366S]、在位置368處之丙胺酸(A) [L368A]及在位置407處之纈胺酸(V) [Y407V]；或 (iv)   第二重鏈包含在位置366處之酪胺酸(Y) [T366Y]，且第一重鏈包含在位置407處之蘇胺酸(T) [Y407T]， 且更佳地，其中免疫球蛋白分子之含有第一重鏈之部分為亦含有特異性結合於TROP2之抗原結合位點之部分(本文中亦稱為Ig分子之TROP2結合部分)且免疫球蛋白分子之含有第二重鏈之部分為亦含有特異性結合於CDH17之抗原結合位點之部分(本文中亦稱為Ig分子之CDH17結合部分)。
根據此較佳實施例，編號係基於各別重鏈，其中在重鏈之該恆定區N端之第一胺基酸為根據EU編號方案之位置118。換言之，位置366處之色胺酸為重鏈恆定區內之第366個胺基酸，自位置118之N端開始。此編號為熟練技術人員所熟知，且亦描述於文獻中，關於CH1之EU編號系統，參見例如IMGT Scientific圖，其中根據Edelman, G.M.等人, Proc. Natl. Acad. USA, 63, 78-85 (1969)，對於IgG1，恆定區在胺基酸118處之「A」開始。
較佳地，本發明之結合分子包含上文(i)中列舉之突變，亦即Ig分子之一個結合部分含有杵突變(T366W)，而Ig分子之其他結合部分含有臼突變(T366S、L368A及Y407V)。更佳地，Ig分子之TROP2結合部分含有杵突變(T366W)，而Ig分子之CDH17結合部分含有臼突變(T366S、L368A及Y407V)。熟練技術人員知道如何將本文所述之目標特異性抗原結合位點(較佳地，包含單鏈Fab或由其組成之目標特異性結合位點)與包含此類杵或臼突變之Fc域組合；例如，SEQ ID No: 434及435中所示之Fc域可用於將所關注之任何抗原結合位點，較佳Fab置放至期望杵或臼背景中。
在本發明之結合分子之一甚至更佳實施例中，含有臼突變之重鏈另外進一步包含以下突變： v)     在位置435處之精胺酸[H435R]及在位置436處之苯丙胺酸[Y436F] (移除蛋白A結合位點)；及/或 vi)    在位置234處之丙胺酸[L234A]及在位置235處之丙胺酸[L235A]，如上文所論述。
關於如上所定義之編號的相同考慮因素在細節上作必要修改後適用。熟練技術人員可應用之進一步突變為此項技術中所熟知且已描述於例如Saunders KO (2019). Front. Immunol. 10:1296。
在本發明之結合分子之一甚至更佳實施例中，結合分子包含 (a-i)    包含SEQ ID NO:169之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:170之胺基酸序列之免疫球蛋白重鏈； (a-ii)   包含SEQ ID NO:171之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:172之胺基酸序列之免疫球蛋白重鏈； (a-iii)  包含SEQ ID NO:173之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:174之胺基酸序列之免疫球蛋白重鏈； (a-iv)   包含SEQ ID NO:175之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:176之胺基酸序列之免疫球蛋白重鏈； (a-v)    包含SEQ ID NO:177之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:178之胺基酸序列之免疫球蛋白重鏈； (a-vi)   包含SEQ ID NO:179之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:180之胺基酸序列之免疫球蛋白重鏈； (a-vii)  包含SEQ ID NO:181之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:182之胺基酸序列之免疫球蛋白重鏈； (a-viii) 包含SEQ ID NO:183之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:184之胺基酸序列之免疫球蛋白重鏈； (a-ix)   包含SEQ ID NO:185之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:186之胺基酸序列之免疫球蛋白重鏈； (a-x)    包含SEQ ID NO:187之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:188之胺基酸序列之免疫球蛋白重鏈； (a-xi)   包含SEQ ID NO:189之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:190之胺基酸序列之免疫球蛋白重鏈；或 (a-xii)  包含SEQ ID NO:191之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:192之胺基酸序列之免疫球蛋白重鏈； 及/或 (b-i)    包含SEQ ID NO:196之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:197之胺基酸序列之免疫球蛋白重鏈；或 (b-ii)   包含SEQ ID NO:198之胺基酸序列之免疫球蛋白重鏈及包含SEQ ID NO:199之胺基酸序列之免疫球蛋白輕鏈。
根據本發明，術語「免疫球蛋白重鏈」及「免疫球蛋白輕鏈」係根據此項技術中之定義使用。因此，此等術語係指IgG，例如IgG1、IgG2或IgG4之各別鏈或域。
詳言之，免疫球蛋白重鏈通常包含呈所述次序之重鏈可變域VH、第一重鏈恆定CH1域及Fc域，包含鉸鏈區及兩個恆定域(CH 2及CH 3)，而免疫球蛋白輕鏈通常包含呈所述次序之輕鏈可變域VL及第一輕鏈恆定CL1域。
根據本發明之結合分子之此實施例，TROP2及/或CDH17之抗原結合位點包含於上文所敍述之特定序列中，而CD3之抗原結合位點係由熟練技術人員自此項技術中可獲得之彼等CD3特異性抗原結合位點或自本文揭示之彼等抗原結合位點選擇。更佳地，CD3特異性抗原結合位點係選自下文所定義之scFv序列(SEQ ID No:222至264，較佳SEQ ID No:222至245，更佳SEQ ID No:222至224)中之一者。
在本發明之結合分子之又一更佳實施例中，結合分子包括包含至少第一及第二多肽之免疫球蛋白分子，其中 (a)  該第一多肽特異性結合於TROP2且包含如上文在(a-i)至(a-xii)中定義之免疫球蛋白重鏈及免疫球蛋白輕鏈組合，視情況藉由第一連接子連接，及 (b)  該第二多肽特異性結合於CDH17且包含如上文在(b-i)至(b-ii)中定義之免疫球蛋白重鏈及免疫球蛋白輕鏈組合，視情況藉由第二連接子連接。
術語連接子已在上文進行定義，且合適連接子已描述於此項技術中。在本發明之結合分子之一較佳實施例中，包含SEQ ID NO:265、SEQ ID NO:266、SEQ ID NO:273、SEQ ID NO:274或SEQ ID NO:275中之任一者之胺基酸序列。更佳地，第一及/或第二連接子包含SEQ ID NO:266之胺基酸序列。
亦根據本發明之結合分子之此實施例，TROP2及CDH17之抗原結合位點包含於上文所敍述之特定序列中，而CD3之抗原結合位點係由熟練技術人員自此項技術中可獲得之彼等CD3特異性抗原結合位點或自本文揭示之彼等抗原結合位點選擇。更佳地，CD3特異性抗原結合位點係選自下文所定義之scFv序列(SEQ ID No:222至264，較佳SEQ ID No:222至245，更佳SEQ ID No:222至224)中之一者。
在本發明之結合分子之又一更佳實施例中，結合分子包含 (a-i)    SEQ ID NO:200之胺基酸序列； (a-ii)   SEQ ID NO:207之胺基酸序列； (a-iii)  SEQ ID NO:208之胺基酸序列； (a-iv)   SEQ ID NO:209之胺基酸序列； (a-v)    SEQ ID NO:210之胺基酸序列； (a-vi)   SEQ ID NO:211之胺基酸序列； (a-vii)  SEQ ID NO:212之胺基酸序列； (a-viii) SEQ ID NO:213之胺基酸序列； (a-ix)   SEQ ID NO:214之胺基酸序列； (a-x)    SEQ ID NO:215之胺基酸序列； (a-xi)   SEQ ID NO:216之胺基酸序列；或 (a-xii)  SEQ ID NO:217之胺基酸序列； 及/或 (b-i)    SEQ ID NO:220之胺基酸序列；或 (b-ii)   SEQ ID NO:221之胺基酸序列。
亦根據本發明之結合分子之此實施例，TROP2及CDH17之抗原結合位點包含於上文所敍述之特定序列中，而CD3之抗原結合位點係由熟練技術人員自此項技術中可獲得之彼等CD3特異性抗原結合位點或自本文揭示之彼等抗原結合位點選擇。更佳地，CD3特異性抗原結合位點係選自下文所定義之scFv序列(SEQ ID No:222至264)中之一者。甚至更佳地，CD3特異性抗原結合位點係選自SEQ ID No:222至245之scFV序列中之一者。甚至更佳地，CD3特異性抗原結合位點係選自SEQ ID No:222至224之scFV序列中之一者。
在本發明之結合分子之另一較佳實施例中，至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xxxi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (ii)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:46 (CDR3)之胺基酸序列之輕鏈CDR； (iii)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (iv)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:50 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (v)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vi)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vii)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:53 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (viii)   抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:55 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (ix)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (x)      抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xi)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:58 (CDR2)及SEQ ID NO.:59 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:60 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xii)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiii)   抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:62 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiv)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:63 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xv)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvi)    抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:64 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xviii)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xix)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:72 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xx)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxi)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:74 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiii)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:75 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiv)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxv)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:76 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvi)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:77 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvii) 抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:78 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxviii) 抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxix)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxx)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； 及 (xxxi)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR。
除非另外明確說明，否則上文在TROP2及/或CDH17之抗原結合位點之背景下敍述的定義及較佳實施例亦適用於特異性結合於CD3之此至少一個抗原結合位點。詳言之，抗原結合位點內某些元件之次序，非TROP2或CDH17特異性之術語之定義及本發明之結合分子之元件之通用設計及結構的態樣亦適用於此CD3特異性抗原結合位點。此外，對於此CD3特異性抗原結合位點，亦較佳地，其完全由胺基酸構成，亦即其包含於多肽中及/或CDR為肽或多肽。應瞭解，此亦意謂任何連接子若存在，則較佳為肽連接子，較佳如上文所定義之可撓性連接子。較佳地，任何此類連接子包含SEQ ID NO:265、SEQ ID NO:266、SEQ ID NO:273、SEQ ID NO:274或SEQ ID NO:275中之任一者之胺基酸序列。更佳地，連接子包含SEQ ID NO:265之胺基酸序列。
本文揭示及SEQ ID NO: 41至82中描繪之CDR亦根據Kabat命名法呈現，且展示於下表1中。同樣，由於此項技術中已知額外命名法，因此基於此等命名法中最常用者之CDR序列亦展示於下表1中，但僅針對此等替代命名法之應用產生不同胺基酸序列的彼等情況。
在本發明之結合分子之另一更佳實施例中，該至少一個特異性結合於CD3之抗原結合位點包含第三免疫球蛋白重鏈可變域及第三免疫球蛋白輕鏈可變域，視情況藉由第三連接子連接。
在本發明之結合分子之一更佳實施例中，至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xvi)組成之群： (i)       抗原結合位點，其包括包含SEQ ID NO:104之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:109、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:123及SEQ ID NO:129組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (ii)      抗原結合位點，其包括包含SEQ ID NO:110之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:111之胺基酸序列之免疫球蛋白輕鏈可變域； (iii)     抗原結合位點，其包括包含SEQ ID NO:112之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:113之胺基酸序列之免疫球蛋白輕鏈可變域； (iv)     抗原結合位點，其包括包含SEQ ID NO:118之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:119及SEQ ID NO:122組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含SEQ ID NO:124之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:125、SEQ ID NO:126及SEQ ID NO:127組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)      抗原結合位點，其包括包含選自由SEQ ID NO:128及SEQ ID NO:130組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:127之胺基酸序列之免疫球蛋白輕鏈可變域； (vi)     抗原結合位點，其包括包含SEQ ID NO:131之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:132之胺基酸序列之免疫球蛋白輕鏈可變域； (vii)    抗原結合位點，其包括包含SEQ ID NO:133之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:134及SEQ ID NO:135組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (viii)   抗原結合位點，其包括包含SEQ ID NO:136之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:137之胺基酸序列之免疫球蛋白輕鏈可變域； (ix)     抗原結合位點，其包括包含選自由SEQ ID NO:138及SEQ ID NO：156組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:139之胺基酸序列之免疫球蛋白輕鏈可變域； (x)      抗原結合位點，其包括包含選自由SEQ ID NO:140、SEQ ID NO:142、SEQ ID NO:143及SEQ ID NO:161組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:141之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)     抗原結合位點，其包括包含選自由SEQ ID NO:144及SEQ ID NO:146組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:145之胺基酸序列之免疫球蛋白輕鏈可變域； (xii)    抗原結合位點，其包括包含選自由SEQ ID NO:147、SEQ ID NO:151、SEQ ID NO:153及SEQ ID NO:162組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:148之胺基酸序列之免疫球蛋白輕鏈可變域； (xiii)   抗原結合位點，其包括包含選自由SEQ ID NO:149及SEQ ID NO:152組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:150之胺基酸序列之免疫球蛋白輕鏈可變域； (xiv)    抗原結合位點，其包括包含SEQ ID NO:154之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:155之胺基酸序列之免疫球蛋白輕鏈可變域； (xv)     抗原結合位點，其包括包含SEQ ID NO:157之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:158之胺基酸序列之免疫球蛋白輕鏈可變域；及 (xvi)    抗原結合位點，其包括包含SEQ ID NO:159之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:160之胺基酸序列之免疫球蛋白輕鏈可變域。
亦較佳地，該特異性結合於CD3之抗原結合位點為單鏈可變片段(scFV)。更佳地，該scFv經配置以使得重鏈可變域在其N端處且輕鏈可變域在其C端處。
連接包括scFv分子之所關注之多肽與例如IgG分子之重鏈之C端的方法為此項技術中熟知。應瞭解，該scFv與Ig分子之融合可為直接融合或可經由連接子，較佳長度為5至40個胺基酸之肽連接子。更佳地，該肽連接子包含SEQ ID NO:265、SEQ ID NO:266、SEQ ID NO:273、SEQ ID NO:274或SEQ ID NO:275中之任一者之胺基酸序列。更佳地，該連接子包含SEQ ID NO:275之胺基酸序列。實際上，通常連接藉由將編碼所關注之IgG之核酸分子與編碼期望多肽，例如scFv之核酸組合來達成，必要時藉由編碼連接序列之核酸分子隔開，藉此形成包含所有三個元件之單個核酸分子。隨後，此完整HC-scFv編碼核酸分子置放於表現載體內且引入至適當宿主細胞中，以便形成完整IgG重鏈-scFv單一多肽。
在本發明之結合分子之一甚至更佳實施例中，至少一個特異性結合於CD3之抗原結合位點包含選自由SEQ ID NO: 222至264組成之群的胺基酸序列。甚至更佳地，CD3特異性抗原結合位點係選自SEQ ID No:222至245之scFv序列之一。甚至更佳地，CD3特異性抗原結合位點係選自SEQ ID No:222至224之scFv序列之一。
如上文所指示，本發明之結合分子之抗原結合位點的編號(a)、(b)及(c)並不意欲指示任何特定次序或格式。
然而，較佳地，特異性結合於TROP2之第一抗原結合位點及特異性結合於CDH17之第二抗原結合位點皆包含於一個免疫球蛋白(Ig)分子內，亦即其配置成習知IgG抗體格式，形成Y形結構，如例如圖3中所示，其中Ig分子之一半(例如包含連接於第一重鏈之第一輕鏈)含有TROP2之抗原結合位點且Ig分子之第二半(例如包含連接於第二重鏈之第二輕鏈)含有CDH17之抗原結合位點。較佳地，該Ig分子為IgG或具有來源於IgG之格式。更佳地，該免疫球蛋白分子經修飾，其中至少一個特異性結合於CD3之抗原結合位點較佳呈單鏈可變片段(scFv)與之融合。
因此，在本發明之結合分子之一尤其較佳實施例中，結合分子為經修飾之免疫球蛋白(Ig)分子，較佳經修飾之IgG分子，其中該至少一個特異性結合於TROP2之抗原結合位點及該至少一個特異性結合於CDH17之抗原結合位點存在於該Ig分子之可變區，且其中該至少一個特異性結合於CD3之抗原結合位點為與該TROP2-CDH17特異性Ig分子融合的至少一個scFv。更佳地，該scFv與Ig分子之重鏈之C端融合，較佳與兩條重鏈中僅一者之C端融合，且更佳與Ig分子之包含至少一個特異性結合於CDH17之抗原結合位點的部分的重鏈，亦如圖3中描繪。
在本發明之結合分子之另一更佳實施例中，結合分子包含： (a)       選自(a-i)至(a-xii)之第一免疫球蛋白輕鏈及免疫球蛋白重鏈組合： (a-i)    包含SEQ ID NO:169之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:170之胺基酸序列之免疫球蛋白重鏈； (a-ii)   包含SEQ ID NO:171之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:172之胺基酸序列之免疫球蛋白重鏈； (a-iii)  包含SEQ ID NO:173之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:174之胺基酸序列之免疫球蛋白重鏈； (a-iv)   包含SEQ ID NO:175之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:176之胺基酸序列之免疫球蛋白重鏈； (a-v)    包含SEQ ID NO:177之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:178之胺基酸序列之免疫球蛋白重鏈； (a-vi)   包含SEQ ID NO:179之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:180之胺基酸序列之免疫球蛋白重鏈； (a-vii)  包含SEQ ID NO:181之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:182之胺基酸序列之免疫球蛋白重鏈； (a-viii) 包含SEQ ID NO:183之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:184之胺基酸序列之免疫球蛋白重鏈； (a-ix)   包含SEQ ID NO:185之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:186之胺基酸序列之免疫球蛋白重鏈； (a-x)    包含SEQ ID NO:187之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:188之胺基酸序列之免疫球蛋白重鏈； (a-xi)   包含SEQ ID NO:189之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:190之胺基酸序列之免疫球蛋白重鏈；或 (a-xii)  包含SEQ ID NO:191之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:192之胺基酸序列之免疫球蛋白重鏈； 及 (b)      選自(b-i)至(b-ii)之第二免疫球蛋白重鏈及免疫球蛋白輕鏈組合： (b-i)    包含SEQ ID NO:196之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:197之胺基酸序列之免疫球蛋白重鏈；或 (b-ii)   包含SEQ ID NO:198之胺基酸序列之免疫球蛋白重鏈及包含SEQ ID NO:199之胺基酸序列之免疫球蛋白輕鏈； 及 (c)       單鏈可變片段(scFv)，其包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群。
較佳地，該第一免疫球蛋白重鏈經由第一連接子，較佳SEQ ID NO:266之連接子與第一免疫球蛋白輕鏈融合，及/或該第二免疫球蛋白重鏈經由第二連接子，較佳SEQ ID NO:266之連接子與第二免疫球蛋白輕鏈融合，及/或該scFv經由第三連接子，較佳SEQ ID NO:275之連接子與第二免疫球蛋白重鏈之C末端融合。
在本發明之結合分子之又一甚至更佳實施例中，結合分子包含： (i)       包含SEQ ID NO.:200之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (ii)      包含SEQ ID NO.:200之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (iii)     包含SEQ ID NO.:207之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (iv)     包含SEQ ID NO.:207之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (v)      包含SEQ ID NO.:208之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (vi)     包含SEQ ID NO.:208之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (vii)    包含SEQ ID NO.:209之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (viii)   包含SEQ ID NO.:209之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (ix)     包含SEQ ID NO.:210之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (x)      包含SEQ ID NO.:210之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xi)     包含SEQ ID NO.:211之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xii)    包含SEQ ID NO.:211之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xiii)   包含SEQ ID NO.:212之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xiv)    包含SEQ ID NO.:212之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xv)     包含SEQ ID NO.:213之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xvi)    包含SEQ ID NO.:213之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xvii)   包含SEQ ID NO.:214之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xviii)  包含SEQ ID NO.:214之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xix)    包含SEQ ID NO.:215之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xx)     包含SEQ ID NO.:215之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xxi)    包含SEQ ID NO.:216之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xxii)   包含SEQ ID NO.:216之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈； (xxiii)  包含SEQ ID NO.:217之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:220之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈；或 (xxiv)  包含SEQ ID NO.:217之胺基酸序列之第一多肽鏈、包含SEQ ID NO.:221之胺基酸序列之第二多肽鏈及包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列、更佳選自由SEQ ID NO:222至245組成之群且甚至更佳選自由SEQ ID No:222至224組成之群的第三多肽鏈。
在本發明之結合分子之一甚至更佳實施例中，結合分子包含以下或由以下組成：選自由SEQ ID NO:200、207至217及436組成之群的第一胺基酸序列及選自由SEQ ID NO:267至272、424至427及437組成之群的第二胺基酸序列。
在本發明之結合分子之又一更佳實施例中，該結合分子包含以下或由以下組成： (a-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (b-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (c-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (d-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (e-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (f-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (g-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (h-i)    SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ii)   SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iii)  SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (i-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (j-i)     SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ii)    SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iii)   SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iv)   SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-v)    SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vi)   SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vii)  SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-viii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ix)   SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-x)    SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xi)   SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xii)  SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:427之胺基酸序列；或 (k)      SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。
在一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列。在另一尤其較佳實施例中，本發明之結合分子包含SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。
如隨附實例中所示，本發明之此等尤其較佳之結合分子結合於所有三個目標抗原，藉此，使T細胞與攜帶Trop2與CDH17之腫瘤細胞緊鄰。意外地，發現併入高親和力抗原結合位點在僅表現此兩個目標中之一者之細胞上產生單價結合及活性，因此增加不希望副作用之風險。因此，本發明提供包含腫瘤細胞抗原之低親和力結合劑的三特異性結合分子。如自以下實例顯而易見，本發明之此等低親和力高親合力三特異性結合分子提供對目標細胞之優良特異性。
本發明進一步關於一種三特異性結合分子，其包含以下或由以下組成：(i) SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列；(ii) SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列；(iii) SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列；(iv) SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列；(v) SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列；(vi) SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列；(vii) SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列；(viii) SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列；(ix)  SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列；(x)本發明包含SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列；(xi) SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列；(xii) SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列；(xiii) SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列；(xiv) SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列；(xv) SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列；(xvi) SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列；(xvii) SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列；或(xviii) SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。 下表1中概述本發明之結合分子之較佳胺基酸序列或其部分。
表 1 ： 本發明之結合分子中所包含的 CDR 、可變重鏈 (VH) 、可變輕鏈 (VL) 、輕鏈 (LC) 、重鏈 (HC) 、單鏈 Fv (scFv) 以及其尤其較佳之組合的胺基酸序列及 SEQ ID NO ：
SEQ ID 編號 序列簡單描述 序列
SEQ ID NO: 1 Trop2#1 HCDR1 DYTMH
SEQ ID NO:2 Trop2#1 HCDR2 GIYPNYGDTNYNEKFKD
SEQ ID NO:3 Trop2#1 HCDR3 KTVLLRLRYFDV
SEQ ID NO:4 Trop2#1 LCDR1 RASGNIHNYLA
SEQ ID NO:5 Trop2#1 LCDR2 NAITLAD
SEQ ID NO:6 Trop2#1 LCDR3 QHFWSTPFT
SEQ ID NO:7 Trop2#8 HCDR1 RYSVH
SEQ ID NO:8 Trop2#8 HCDR2 MIWGGGSTDYNSDFKP
SEQ ID NO:9 Trop2#8 HCDR3 KGSYYTNYGAMDY
SEQ ID NO:10 Trop2#8 LCDR1 KASQDINKYIA
SEQ ID NO:11 Trop2#8 LCDR2 YTSTLQP
SEQ ID NO:12 Trop2#8 LCDR3 LQYDNLWT
SEQ ID NO:13 Trop2#11、#12、#13、#14、#15、#16、#17、#18 HCDR1 SGYYWN
SEQ ID NO:14 Trop2#11 HCDR2 YISYDGRNNYNPSLKN
SEQ ID NO:15 Trop2#11、#12、#13、#14、#15、#16、#17、#18 HCDR3 DTTAYFDY
SEQ ID NO:16 Trop2#11 LCDR1 RASESVDSSVNRFMH
SEQ ID NO:17 Trop2#11、#12、#13、#14、#15、#16、#17、#18 LCDR2 RASNLES
SEQ ID NO:18 Trop2#11、#12、#13、#14、#15、#16、#17、#18 LCDR3 QQSNEDPYT
SEQ ID NO:19 Trop2#12、#13、#14、#15、#16、#17、#18 HCDR2 YISYSGRNLYNPSLKS
SEQ ID NO:20 Trop2#12、#13、#14、#15、#16、#17、#18 LCDR1 RASESVSSSVNRFLH
SEQ ID NO:21 Trop2#9 HCDR1 DYYMN
SEQ ID NO:22 Trop2#9 HCDR2 YIYPNNGATGYNQKFKG
SEQ ID NO:23 Trop2#9 HCDR3 EDSYYYAMDY
SEQ ID NO:24 Trop2#9 LCDR1 KSSQSLVHSNGNTFLH
SEQ ID NO:25 Trop2#9、#10 LCDR2 KVSNRFS
SEQ ID NO:26 Trop2#9 LCDR3 SQSTHVYT
SEQ ID NO:27 Trop2#10 HCDR1 NYYIH
SEQ ID NO:28 Trop2#10 HCDR2 YIYPGNGATAYNQKFKG
SEQ ID NO:29 Trop2#10 HCDR3 EDYYYAMDY
SEQ ID NO:30 Trop2#10 LCDR1 RSSQSLVHSNGNTYLH
SEQ ID NO:31 Trop2#10 LCDR3 SQSTHVWT
SEQ ID NO:32 CDH17#1、#8 HCDR1 DHTIH
SEQ ID NO:33 CDH17#1 HCDR2 YIYPRDGSTKYNEKFKG
SEQ ID NO:34 CDH17#1、#8 HCDR3 WGYYYGSSRYYFDY
SEQ ID NO:35 CDH17#1 LCDR1 KSSQSLLYSSNQKNYLA
SEQ ID NO:36 CDH17#1 LCDR2 WASTRES
SEQ ID NO:37 CDH17#1、#8 LCDR3 QQYYSYPWT
SEQ ID NO:38 CDH17#8 HCDR2 YIYPRLGSTKYAEKFQG
SEQ ID NO:39 CDH17#8 LCDR1 RASQSVLYSSNQKQYLA
SEQ ID NO:40 CDH17#8 LCDR2 GASTRET
SEQ ID NO:41 所有CD3#1至#25 HCDR1 TYAMN
SEQ ID NO:42 所有CD3#1至#5、CD3#8至#16、#21、#24、#25 HCDR2 RIRSKYNNYATYYADSVKD
SEQ ID NO:43 所有CD3#1至#11、#13、#14、#16、#21、#24、#25 HCDR3 HGNFGNSYVSWFAY   
SEQ ID NO:44 所有CD3#1至#11、#13、#14、#15 LCDR1 RSSTGAVTTSNYAN
SEQ ID NO:45    所有CD3#1至#13、#17、#19、#20、#22、#23、#24 LCDR2 GTNKRAP
SEQ ID NO:46 CD3#2、#11 LCDR3 ALWYSNKWV
SEQ ID NO:47 CD3#1、所有CD3#3至#10、#13至#16 LCDR3 ALWYSNLWV
SEQ ID NO:48 CD3#6、#7、#17、#18、#19 HCDR2 RIRSKYNNYATYYADSVKG
SEQ ID NO:49 CD3#12、#15 HCDR3 HGNFLNSYVSWFAY
SEQ ID NO:50 CD3#12 LCDR1 RSSTGAVTTSYYAN
SEQ ID NO:51 CD3#12 LCDR3 ALWYSNHWV
SEQ ID NO:52 CD3#14、#15、#16、#18、#21、#25 LCDR2 GTNIRAP
SEQ ID NO:53 CD3#16 LCDR1 ISSTGAVTTSNYAN
SEQ ID NO:54 CD3#17、#18、#19、#22、#23 HCDR3 HGNFIDSYVSWFAY
SEQ ID NO:55 CD3#17 LCDR1 GRSTGAVTTSNYAN
SEQ ID NO:56 CD3#18、#23 LCDR1 GSSTGAVTTSWYAN
SEQ ID NO:57 CD3#19、#22、#25 LCDR1 GSSTGAVTTSNYAN
SEQ ID NO:58 CD3#20 HCDR2 RIRSIYNNYATYYADSVKG
SEQ ID NO:59 CD3#20 HCDR3 HGNFGDSYVSWFAY
SEQ ID NO:60 CD3#20 LCDR1 VSSTGAVTTSNYAN
SEQ ID NO:61 CD3#21、#24 LCDR1 GSSTGAVTTSYYAN
SEQ ID NO:62 CD3#22 HCDR2 RIRSIYNNYATYYADIVKG
SEQ ID NO:63 CD3#23 HCDR2 RIRSKYNNYATYYADIVKG
SEQ ID NO:64 CD3#26、#27 HCDR2 NINADTGSTNYNEKFKN
SEQ ID NO:65 CD3#26、#27 HCDR3 DGYSFYYFDY
SEQ ID NO:66 CD3#所有26至#30、#33、#35、#37、#39、#42、#43 LCDR1 KSSQSLLNSRTRKNYLA
SEQ ID NO:67 所有CD3#26至#43 LCDR2 WASTRKS
SEQ ID NO:68 所有CD3#26至#43 LCDR3 IQSFILRT
SEQ ID NO:69 CD3#28、#34 HCDR2 NINASTGSTNYNQKFKG
SEQ ID NO:70 CD3#28、#32、#39、#42、#43 HCDR3 DAYSFYYFDY
SEQ ID NO:71 CD3#31、#32、#34、#36 LCDR1 KSSQSLLNARTRKNYLA
SEQ ID NO:72 CD3#29 HCDR2 NINASTGSTSYAEKFKG
SEQ ID NO:73 CD3#30、#32 HCDR2 NINASTGSTNYAQKFQG
SEQ ID NO:74 CD3#31 HCDR2 NINASTGSTNYAQKFKG
SEQ ID NO:75 CD3#33 HCDR2 NINASTGSTSYNQKFKG
SEQ ID NO:76 CD3#35 HCDR2 NINASTGSTSYNQKFQN
SEQ ID NO:77 CD3#36 HCDR2 NINASTGSTNYNQKFQN
SEQ ID NO:78 CD3#37 HCDR2 NINASTGSTSYAQKFKG
SEQ ID NO:79 CD3#38、#40、#41 HCDR2 NINADTGSTKYNQKFKG
SEQ ID NO:80 CD3#38、#40、#41 LCDR1 RSSQSLLNSRTRKNYLA
SEQ ID NO:81 CD3#39、#42、#43 HCDR2 NINADTGSTNYNQKFQG
SEQ ID NO:82 所有CD3#26至#43 HCDR1 SYWMH
SEQ ID NO:83 Trop2#1 VH EVQLQQSGPELLKPGASVKISCKASGYTFTDYTMHWVKQSHGKSLEWIGGIYPNYGDTNYNEKFKDKATLTVDESSSTAYMELRSLTSEDSAVYYCSRKTVLLRLRYFDVWGTGTTVTVSS
SEQ ID NO:84 Trop2#1 VL DIQMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAITLADGVPSRFSGSGSGTQYSLKINSLQPEDFGSYYCQHFWSTPFTFGSGTKLEIK
SEQ ID NO:85 Trop2#8 VH QVQLKESGPGLVAPSQSLSITCTVSGLSLSRYSVHWVRQPPGKGLEWLGMIWGGGSTDYNSDFKPRLSISKDNSKSQVFLKMNSLQTDDTAMYYCARKGSYYTNYGAMDYWGQGTSVTVSS
SEQ ID NO:86 Trop2#8 VL DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIATYYCLQYDNLWTFGGGTKLEIK
SEQ ID NO:87 Trop2#9 VH EVQLQQSGPEPVKPGASVKMSCKASGYTFTDYYMNWVKQSHGKSLEWIGYIYPNNGATGYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCAREDSYYYAMDYWGQGTSVTVSS
SEQ ID NO:88 Trop2#9 VL DVVMTQTPLSLPVSLGDQASISCKSSQSLVHSNGNTFLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKINRVEAEDLGVYFCSQSTHVYTFGGGTKLEIK
SEQ ID NO:89 Trop2#10 VH QIQLQQSGPELVKPGAPVKISCKASGYTFTNYYIHWVKQRPGQGLEWIGYIYPGNGATAYNQKFKGKATLTADNPSSTAYMQLSSLTSEDSAVYFCAREDYYYAMDYWGQGTSVTVSS
SEQ ID NO:90 Trop2#10 VL VVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVWTFGGGTKLEIK
SEQ ID NO:91 Trop2#11 VH DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYDGRNNYNPSLKNRISITRDTSENQFFLKLNSVTPEDTATYYCARDTTAYFDYWGQGTTLTVSS
SEQ ID NO:92 Trop2#11 VL DIVLTQSPPSLAVSLGQRATISCRASESVDSSVNRFMHWYQQKPGQPPKLLIYRASNLESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGGTKLEIK
SEQ ID NO:93 Trop2#12 VH DVLMTQTPLSLPVSLGDQASISCRSSQNIVHSNGNTYLDWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPPTFGAGTKLELK
SEQ ID NO:94 Trop2#12及#13 VL DIQMTQSPSSLSASVGDRVTITCRASESVSSSVNRFLHWYQQKPGKAPKLLIYRASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPYTFGQGTKLEIK
SEQ ID NO:95 Trop2#13、#14、#15及#17 VH QVQLQESGPGLVKPSQTLKLTCTVSGYSISSGYYWNWIRQPPGKGLEWIGYISYSGRNLYNPSLKSRVTISRDTSKNQFSLKLSSVTAADTAVYYCARDTTAYFDYWGQGTLVTVSS
SEQ ID NO:96 Trop2#14及#18 VL DIQMTQSPSSLSASVGDRVTITCRASESVSSSVNRFLHWYQQKPGKAPKLLIYRASNLESGVPSRFSGKGSGTDFTLTISSLQPEDFATYYCQQSNEDPYTFGQGTKLEIK
SEQ ID NO:97 Trop2#15及#16 VL DIQMTQSPSSLSASVGDRVTITCRASESVSSSVNRFLHWYQQKPGKAPKLLIYRASNLESGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQSNEDPYTFGQGTKLEIK
SEQ ID NO:98 Trop2#16及#18 VH QVQLQESGPGLVKPSQTLSLTCTVSGYSISSGYYWNWIRQPPGKGLEWIGYISYSGRNLYNPSLKSRVTISRDTSKNQFSLKLSRVTAADTAVYYCARDTTAYFDYWGQGTLVTVSS
SEQ ID NO:99 Trop2#17 VL DIRMTQSPSSLSASVGDRVTITCRASESVSSSVNRFLHWYQQKPGKAPKLLIYRASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPYTFGQGTKLEIK
SEQ ID NO:100 CDH17#1 VH QVQLQQSDAELVKPGASVKISCKVSGYTFTDHTIHWMKQRPEQGLEWIGYIYPRDGSTKYNEKFKGKATLTADKSSSTAYMQLNSLTSEDSAVYFCARWGYYYGSSRYYFDYWGQGTTLTVSS
SEQ ID NO:101 CDH17#1 VL DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPWTFGGGTKLEIK
SEQ ID NO:102 CDH17#8 VH QVQLVQSGAEVKKPGSSVKVSCKASGYTFSDHTIHWVRQAPGQGLEWMGYIYPRLGSTKYAEKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARWGYYYGSSRYYFDYWGQGTLVTVSS
SEQ ID NO:103 CDH17#8 VL EIVMTQSPATLSVSPGERATLSCRASQSVLYSSNQKQYLAWYQQKPGQAPRLLIYGASTRETGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYYSYPWTFGQGTKLEIK
SEQ ID NO:104 所有CD3#1至#4、#8至#11、#13、#14、#16、#21 VH EVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:105 CD3#1 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPGQLPRGLIGGTNKRAPWVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNLWVFGGGTKLTVL
SEQ ID NO:106 CD3#2 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNKWVFGGGTKLTVL
SEQ ID NO:107 CD3#3、#4 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFGGGTKLTVL
SEQ ID NO:108 CD3#5 VH EVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKCLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:109 CD3#5 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFGCGTKLTVL
SEQ ID NO:110 CD3#6 VH EVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:111 CD3#6 VL QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFGGGTKLTVL
SEQ ID NO:112 CD3#7 VH EVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKCLEWVARIRSKYNNYATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:113 CD3#7 VL QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFGCGTKLTVL
SEQ ID NO:114 CD3#8 VL QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPWVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNLWVFGGGTKLTVL
SEQ ID NO:115 CD3#9 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPWVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNLWVFGGGTKLTVL
SEQ ID NO:116 CD3#10 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNLWVFGGGTKLTVL
SEQ ID NO:117 CD3#11 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQLPRGLIGGTNKRAPGVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNKWVFGGGTKLTVL
SEQ ID NO:118 CD3#12 VH EVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFLNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:119 CD3#12 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSYYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:120 CD3#13 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNLWVFGVGTKLTVL
SEQ ID NO:121 CD3#14 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNLWVFGYGTKLTVL
SEQ ID NO:122 CD3#15 VL EAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEAWYFCALWYSNLWVFGGGTKLTVL
SEQ ID NO:123 CD3#16 VL QAVVTQEPSLTVSPGGTVTLTCISSTGAVTTSNYANWVQQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNLWVFGGGTKLTVL
SEQ ID NO:124 CD3#17、#18、#19 VH EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSKYNNYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFIDSYVSWFAYWGQGTLVTVSS
SEQ ID NO:125 CD3#17 VL QAVVTQEPSLTVSPGGTVTLTCGRSTGAVTTSNYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:126 CD3#18 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSWYANWVQQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:127 CD3#19、#20、#22 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:128 CD3#20 VH EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSIYNNYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGDSYVSWFAYWGQGTLVTVSS
SEQ ID NO:129 CD3#21 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSYYANWVKQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:130 CD3#22 VH EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSIYNNYATYYADIVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFIDSYVSWFAYWGQGTLVTVSS
SEQ ID NO:131 CD3#23 VL EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSKYNNYATYYADIVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFIDSYVSWFAYWGQGTLVTVSS
SEQ ID NO:132 CD3#23 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSWYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:133 CD3#24、#25 VH EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSS
SEQ ID NO:134 CD3#24 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSYYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:135 CD3#25 VL QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNIRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL
SEQ ID NO:136 CD3#26 VH QVQLQQPGAELGKPGTSVKLSCKASGYTFTSYWMHWVKQRPGQGLEWIGNINADTGSTNYNEKFKNRATLTVDKSSSTAYMQLSTLTSEDSAVYYCTRDGYSFYYFDYWGQGTTLTVSS
SEQ ID NO:137 CD3#26 VL DIVMSQSPSSLAVSAGEKVTMFCKSSQSLLNSRTRKNYLAWYQQKPGQSPKLLIYWASTRKSGVPDRFTGSGSGTDFTLTISSVQAEDLAIYYCIQSFILRTFGGGTKLEIK
SEQ ID NO:138 CD3#27 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINADTGSTNYNEKFKNRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:139 CD3#27、#39 VL DIVMTQSPDSLAVSLGERATINCKSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:140 CD3#28 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINASTGSTNYNQKFKGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDAYSFYYFDYWGQGTTLTVSS
SEQ ID NO:141 CD3#28、#29、#30、#42 VL DIVMTQSPDSLAVSLGERATIFCKSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAIYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:142 CD3#29 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINASTGSTSYAEKFKGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDGYSFYYFDYWGQGTTLTVSS   
SEQ ID NO:143 CD3#30 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINASTGSTNYAQKFQGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDGYSFYYFDYWGQGTTLTVSS
SEQ ID NO:144 CD3#31 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINASTGSTNYAQKFKGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDGYSFYYFDYWGQGTTLTVSS
SEQ ID NO:145 CD3#31、#32 VL DIVMTQSPDSLAVSLGERATIFCKSSQSLLNARTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAIYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:146 CD3#32 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINASTGSTNYAQKFQGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDAYSFYYFDYWGQGTTLTVSS
SEQ ID NO:147 CD3#33 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINASTGSTSYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:148 CD3#33、#35、#37、#43 VL DIVMTQSPDSLAVSLGERATMFCKSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:149 CD3#34 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINASTGSTNYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:150 CD3#34 VL DIVMTQSPDSLAVSLGERATMFCKSSQSLLNARTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:151 CD3#35 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINASTGSTSYNQKFQNRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:152 CD3#36 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINASTGSTNYNQKFQNRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:153 CD3#37 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINASTGSTSYAQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:154 CD3#38 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINADTGSTKYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:155 CD3#38 VL DIVMTQSPDSLAVSLGERATINCRSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:156 CD3#39 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINADTGSTNYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAYSFYYFDYWGQGTTVTVSS
SEQ ID NO:157    CD3#40 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINADTGSTKYNQKFKGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDGYSFYYFDYWGQGTTLTVSS
SEQ ID NO:158 CD3#40 VL DIVMTQSPDSLAVSLGERATIFCRSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAIYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:159 CD3#41 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINADTGSTKYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSFYYFDYWGQGTTVTVSS
SEQ ID NO:160 CD3#41 VL DIVMTQSPDSLAVSLGERATMFCRSSQSLLNSRTRKNYLAWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCIQSFILRTFGQGTKLEIK
SEQ ID NO:161 CD3#42 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGNINADTGSTNYNQKFQGRVTMTVDTSTSTVYMELSSLRSEDTAVYYCTRDAYSFYYFDYWGQGTTLTVSS
SEQ ID NO:162 CD3#43 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWIGNINADTGSTNYNQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAYSFYYFDYWGQGTTVTVSS
SEQ ID NO:163 Trop2#5 VL    DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSHGNIYLHWYLQKPGLSPKLLIFKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVWTFGGGTKLEIK
SEQ ID NO:164 Trop2#5 VH EVQLQQSGPDLVKPGASVKMSCKASGFIFTDYYMNWVKQSHGKSLEWIGYIYPNNGATAYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARESDFYAMDYWGQGTSVTVSS
SEQ ID NO:165 Trop2#7 VL    DIQMTQSSSSFSVSLGDRVTITCKASEDIYNRLAWFQQKPGNAPRLLISGATSLETGVPSRFRGSRSGKDYTLSITSLQTEDVATYYCQQYWSTWTFGGGTKLEIK
SEQ ID NO:166 Trop2#7 VH EVQLQQSGPELVKPGASVKMSCRASGYTFTSYAMHWVKQKPGQGLEWIGYINPYNGGTKYNEKFKGRATLTSDKSSSTAYMELSSLTSEDSAVYYCAREGIYYGAWFAYWGQGTLVTVSA
SEQ ID NO:167 TNP VH QIQLVQSGPELKKPGETVKISCKTSGYTFTNYGMNWVKQAPGKGLKWVGWINTYTGEPKYADDFKGRFAFSVETSASTAYLQINNLKNEDTATYFCARGIYDGYHWYFDVWGAGTTVTVSS
SEQ ID NO:168 TNP VL DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSIGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKITRVEAEDLGVYFCSQSTHVPFTFGSGTKLEIK
SEQ ID NO:169 Trop2#1 LC    DIQMTQSPASLSASVGETVTITC RASGNIHNYLA WYQQKQGKSPQLLVY NAITLAD GVPSRFSGSGSGTQYSLKINSLQPEDFGSYYC QHFWSTPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:170 Trop2#1 HC (杵) EVQLQQSGPELLKPGASVKISCKASGYTFT DYTMH WVKQSHGKSLEWIG GIYPNYGDTNYNEKFKD KATLTVDESSSTAYMELRSLTSEDSAVYYCSR KTVLLRLRYFDV WGTGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:171 Trop2#8 LC    DIQMTQSPSSLSASLGGKVTITC KASQDINKYIA WYQHKPGKGPRLLIH YTSTLQP GIPSRFSGSGSGRDYSFSISNLEPEDIATYYC LQYDNLWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:172 Trop2#8 HC (杵) QVQLKESGPGLVAPSQSLSITCTVSGLSLS RYSVH WVRQPPGKGLEWLG MIWGGGSTDYNSDFKP RLSISKDNSKSQVFLKMNSLQTDDTAMYYCAR KGSYYTNYGAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:173 Trop2#9 LC    DVVMTQTPLSLPVSLGDQASISC KSSQSLVHSNGNTFLH WYLQKPGQSPKLLIY KVSNRFS GVPDRFSGSGSGTDFTLKINRVEAEDLGVYFC SQSTHVYT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:174 Trop2#9 HC (杵) EVQLQQSGPEPVKPGASVKMSCKASGYTFT DYYMN WVKQSHGKSLEWIG YIYPNNGATGYNQKFKG KATLTVDKSSSTAYMELRSLTSEDSAVYYCAR EDSYYYAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:175    Trop2#10 LC    DVVMTQTPLSLPVSLGDQASISC RSSQSLVHSNGNTYLH WYLQKPGQSPKLLIY KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDLGVYFC SQSTHVWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:176 Trop2#10 HC (杵) QIQLQQSGPELVKPGAPVKISCKASGYTFT NYYIH WVKQRPGQGLEWIG YIYPGNGATAYNQKFKG KATLTADNPSSTAYMQLSSLTSEDSAVYFCAR EDYYYAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:177 Trop2#11 LC    DIVLTQSPPSLAVSLGQRATISC RASESVDSSVNRFMH WYQQKPGQPPKLLIY RASNLES GIPARFSGSGSRTDFTLTINPVEADDVATYYC QQSNEDPYT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:178 Trop2#11 HC (杵) DVQLQESGPGLVKPSQSLSLTCSVTGYSIT SGYYWN WIRQFPGNKLEWMG YISYDGRNNYNPSLKN RISITRDTSENQFFLKLNSVTPEDTATYYCAR DTTAYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:179 Trop2#12 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:180 Trop2#12 HC (杵) QVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:181 Trop2#13 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:182 Trop2#13 HC (杵) QVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:183 Trop2#14 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGKGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:184 Trop2#14 HC (杵) QVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:185 Trop2#15 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTIRSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:186 Trop2#15 HC (杵) QVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:187 Trop2#16 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTIRSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:188 Trop2#16 HC (杵) QVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSRVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:189 Trop2#17 LC    DIRMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:190 Trop2#17 HC (杵) QVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:191 Trop2#18 LC    DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGKGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:192 Trop2#18 HC (杵) QVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSRVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:193 TNP LC    DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSIGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKITRVEAEDLGVYFCSQSTHVPFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:194 TNP HC (臼) QIQLVQSGPELKKPGETVKISCKTSGYTFTNYGMNWVKQAPGKGLKWVGWINTYTGEPKYADDFKGRFAFSVETSASTAYLQINNLKNEDTATYFCARGIYDGYHWYFDVWGAGTTVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:195 TNP HC (杵) QIQLVQSGPELKKPGETVKISCKTSGYTFTNYGMNWVKQAPGKGLKWVGWINTYTGEPKYADDFKGRFAFSVETSASTAYLQINNLKNEDTATYFCARGIYDGYHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:196 CDH17#1 LC    DIVMSQSPSSLAVSVGEKVTMSC KSSQSLLYSSNQKNYLA WYQQKPGQSPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVKAEDLAVYYC QQYYSYPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:197 CDH17#1 HC (臼) QVQLQQSDAELVKPGASVKISCKVSGYTFT DHTIH WMKQRPEQGLEWIG YIYPRDGSTKYNEKFKG KATLTADKSSSTAYMQLNSLTSEDSAVYFCAR WGYYYGSSRYYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:198 CDH17#8 LC    EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:199 CDH17#8 HC (臼) QVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:200 Trop2#1全長(杵) DIQMTQSPASLSASVGETVTITC RASGNIHNYLA WYQQKQGKSPQLLVY NAITLAD GVPSRFSGSGSGTQYSLKINSLQPEDFGSYYC QHFWSTPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSEVQLQQSGPELLKPGASVKISCKASGYTFT DYTMH WVKQSHGKSLEWIG GIYPNYGDTNYNEKFKD KATLTVDESSSTAYMELRSLTSEDSAVYYCSR KTVLLRLRYFDV WGTGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:201 Trop2#2全長(杵) DIQMTQSPASQSASLGDSVTITC LASQTIGTWLA WYQRKPGKSPQLLIY GATSLAD GVPSRFSGNGSGTKFSFKISGLQAEDFVSYFC QQLYSTPYT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSEVQLQQSGPELVKPGASVKISCKASGYTFT DYFMD WVKLSHEKSLEWIG DINPHNGGSDYNQKFKG KATLTVDRSSSTAYMELRSLTSEDSAVYYCAK GPYYYGGGPYWYFDV WGTGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:202 Trop2#3全長(杵) DILLTQSPAILSVSPGERVSFSC RASQNIGTSIH WYQQRTNGSPRLLIK YASESIY GIPSRFSGSGSGTDFTLNINSVESEDIGDYYC QQSNSWPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQPGAELVKPGASVKLSCKASGYTFT SYWIN WVRQRPGQGLEWIG NIYPGNSITNYNENFKS KATLTADKSSSTAYMQLSSLTSEDSAVYYCTS SSSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:203 Trop2#4全長(杵) DILLIQSPAILSVSPGERVSFSC RASQSIGTHIH WFQQRKNGSPRLLID YASESIS GIPSRFSGSGSGTDFILTINSVESEDIADYYC QHSHSWPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQPGAELVKPGASVKMSCKTSGYTFT IYWIN WVKQRPGQGLEWIG NIFPGRGITNYNEKFKT KASLTLDTSSSTVYMQLSSLTFEDSAVYYCSR GSNSDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:204 Trop2#5全長(杵) DVVMTQTPLSLPVSLGDQASISC RSSQSLVHSHGNIYLH WYLQKPGLSPKLLIF KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDLGVYFC SQSTHVWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSEVQLQQSGPDLVKPGASVKMSCKASGFIFT DYYMN WVKQSHGKSLEWIG YIYPNNGATAYNQKFKG KATLTVDKSSSTAYMELRSLTSEDSAVYYCAR ESDFYAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:205 Trop2#6全長(杵) DILLTQSPAILSVSPGERVSFSC RASQSIGTSIH WFQQRTNGSPRLLIK YASESIS GIPSRFSGSGSGTDFTLTINSVESEDIADYYC QQTNTWPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSGTELVRPGTSVKMSCKAAGYTFT NYWIN WVKQRPGHGLEWIG NIYPGGGYTNYNEKFKG KASLTADTSSSTAYMQLSSLTSEDSAIYYCAR GINDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:206 Trop2#7全長(杵) DIQMTQSSSSFSVSLGDRVTITC KASEDIYNRLA WFQQKPGNAPRLLIS GATSLET GVPSRFRGSRSGKDYTLSITSLQTEDVATYYC QQYWSTWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSEVQLQQSGPELVKPGASVKMSCRASGYTFT SYAMH WVKQKPGQGLEWIG YINPYNGGTKYNEKFKG RATLTSDKSSSTAYMELSSLTSEDSAVYYCAR EGIYYGAWFAY WGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:207 Trop2#8全長(杵) DIQMTQSPSSLSASLGGKVTITC KASQDINKYIA WYQHKPGKGPRLLIH YTSTLQP GIPSRFSGSGSGRDYSFSISNLEPEDIATYYC LQYDNLWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLKESGPGLVAPSQSLSITCTVSGLSLS RYSVH WVRQPPGKGLEWLG MIWGGGSTDYNSDFKP RLSISKDNSKSQVFLKMNSLQTDDTAMYYCAR KGSYYTNYGAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:208 Trop2#9全長(杵) DVVMTQTPLSLPVSLGDQASISC KSSQSLVHSNGNTFLH WYLQKPGQSPKLLIY KVSNRFS GVPDRFSGSGSGTDFTLKINRVEAEDLGVYFC SQSTHVYT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSEVQLQQSGPEPVKPGASVKMSCKASGYTFT DYYMN WVKQSHGKSLEWIG YIYPNNGATGYNQKFKG KATLTVDKSSSTAYMELRSLTSEDSAVYYCAR EDSYYYAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:209 Trop2#10全長(杵) DVVMTQTPLSLPVSLGDQASISC RSSQSLVHSNGNTYLH WYLQKPGQSPKLLIY KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDLGVYFC SQSTHVWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQIQLQQSGPELVKPGAPVKISCKASGYTFT NYYIH WVKQRPGQGLEWIG YIYPGNGATAYNQKFKG KATLTADNPSSTAYMQLSSLTSEDSAVYFCAR EDYYYAMDY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:210 Trop2#11全長(杵) DIVLTQSPPSLAVSLGQRATISC RASESVDSSVNRFMH WYQQKPGQPPKLLIY RASNLES GIPARFSGSGSRTDFTLTINPVEADDVATYYC QQSNEDPYT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSDVQLQESGPGLVKPSQSLSLTCSVTGYSIT SGYYWN WIRQFPGNKLEWMG YISYDGRNNYNPSLKN RISITRDTSENQFFLKLNSVTPEDTATYYCAR DTTAYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:211 Trop2#12全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:212 Trop2#13全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:213 Trop2#14全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGKGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:214 Trop2#15全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTIRSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:215 Trop2#16全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTIRSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSRVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:216 Trop2#17全長(杵) DIRMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLKLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSSVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:217 Trop2#18全長(杵) DIQMTQSPSSLSASVGDRVTITC RASESVSSSVNRFLH WYQQKPGKAPKLLIY RASNLES GVPSRFSGKGSGTDFTLTISSLQPEDFATYYC QQSNEDPYT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGYSIS SGYYWN WIRQPPGKGLEWIG YISYSGRNLYNPSLKS RVTISRDTSKNQFSLKLSRVTAADTAVYYCAR DTTAYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:218 TNP全長(臼) DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSIGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKITRVEAEDLGVYFCSQSTHVPFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQIQLVQSGPELKKPGETVKISCKTSGYTFTNYGMNWVKQAPGKGLKWVGWINTYTGEPKYADDFKGRFAFSVETSASTAYLQINNLKNEDTATYFCARGIYDGYHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:219 TNP全長(杵) DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSIGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKITRVEAEDLGVYFCSQSTHVPFTFGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQIQLVQSGPELKKPGETVKISCKTSGYTFTNYGMNWVKQAPGKGLKWVGWINTYTGEPKYADDFKGRFAFSVETSASTAYLQINNLKNEDTATYFCARGIYDGYHWYFDVWGAGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:220 CDH17#1全長(臼) DIVMSQSPSSLAVSVGEKVTMSC KSSQSLLYSSNQKNYLA WYQQKPGQSPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVKAEDLAVYYC QQYYSYPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSDAELVKPGASVKISCKVSGYTFT DHTIH WMKQRPEQGLEWIG YIYPRDGSTKYNEKFKG KATLTADKSSSTAYMQLNSLTSEDSAVYFCAR WGYYYGSSRYYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:221 CDH17#8全長(臼) EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:222 CD3#1 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQEKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:223 CD3#2 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNKWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:224 CD3#3 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:225 CD3#4 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:226 CD3#5 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:227 CD3#6 scFv QAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:228 CD3#7 scFv QAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:229 CD3#8 scFv QAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:230 CD3#9 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:231 CD3#10 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:232 CD3#11 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNKWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:233 CD3#12 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSYYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFLNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:234 CD3#13 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNLWV FGVGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:235 CD3#14 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNLWV FGYGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:236 CD3#15 scFv EAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEAWYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFLNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:237 CD3#16 scFv QAVVTQEPSLTVSPGGTVTLTC ISSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:238 CD3#17 scFv QAVVTQEPSLTVSPGGTVTLTC GRSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSKYNNYATYYADSVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFIDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:239 CD3#18 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSWYAN WVQQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSKYNNYATYYADSVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFIDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:240 CD3#19 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSKYNNYATYYADSVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFIDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:241 CD3#20 scFv QAVVTQEPSLTVSPGGTVTLTC VSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSIYNNYATYYADSVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFGDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:242 CD3#21 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSYYAN WVKQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:243 CD3#22 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSIYNNYATYYADIVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFIDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:244 CD3#23 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSWYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFS TYAMN WVRQAPGKGLEWVG RIRSKYNNYATYYADIVKG RFTISRDDSKNTLYLQMNSLRAEDTAVYYCVR HGNFIDSYVSWFAY WGQGTLVTVSS
SEQ ID NO:245 CD3#24 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSYYAN WVQQKPGKSPRGLIG GTNKRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSS
SEQ ID NO:246 CD3#25 scFv QAVVTQEPSLTVSPGGTVTLTC GSSTGAVTTSNYAN WVQQKPGKSPRGLIG GTNIRAP GVPARFSGSLLGGKAALTISGAQPEDEADYYC ALWYSNHWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSS
SEQ ID NO:247 CD3#26 scFv DIVMSQSPSSLAVSAGEKVTMFC KSSQSLLNSRTRKNYLA WYQQKPGQSPKLLIY WASTRKS GVPDRFTGSGSGTDFTLTISSVQAEDLAIYYC IQSFILRT FGGGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLQQPGAELGKPGTSVKLSCKASGYTFT SYWMH WVKQRPGQGLEWIG NINADTGSTNYNEKFKN RATLTVDKSSSTAYMQLSTLTSEDSAVYYCTR DGYSFYYFDY WGQGTTLTVSS
SEQ ID NO:248 CD3#27 scFv DIVMTQSPDSLAVSLGERATINC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINADTGSTNYNEKFKN RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:249 CD3#28 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINASTGSTNYNQKFKG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DAYSFYYFDY WGQGTTLTVSS
SEQ ID NO:250 CD3#29 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINASTGSTSYAEKFKG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DGYSFYYFDY WGQGTTLTVSS
SEQ ID NO:251 CD3#30 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINASTGSTNYAQKFQG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DGYSFYYFDY WGQGTTLTVSS
SEQ ID NO:252 CD3#31 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNARTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINASTGSTNYAQKFKG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DGYSFYYFDY WGQGTTLTVSS
SEQ ID NO:253 CD3#32 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNARTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINASTGSTNYAQKFQG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DAYSFYYFDY WGQGTTLTVSS
SEQ ID NO:254 CD3#33 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINASTGSTSYNQKFKG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:255 CD3#34 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNARTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINASTGSTNYNQKFKG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:256 CD3#35 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINASTGSTSYNQKFQN RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:257 CD3#36 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNARTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINASTGSTNYNQKFQN RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:258 CD3#37 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINASTGSTSYAQKFKG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:259 CD3#38 scFv DIVMTQSPDSLAVSLGERATINC RSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINADTGSTKYNQKFKG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:260 CD3#39 scFv DIVMTQSPDSLAVSLGERATINC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINADTGSTNYNQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DAYSFYYFDY WGQGTTVTVSS
SEQ ID NO:261 CD3#40 scFv DIVMTQSPDSLAVSLGERATIFC RSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINADTGSTKYNQKFKG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DGYSFYYFDY WGQGTTLTVSS
SEQ ID NO:262 CD3#41 scFv DIVMTQSPDSLAVSLGERATMFC RSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINADTGSTKYNQKFKG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DGYSFYYFDY WGQGTTVTVSS
SEQ ID NO:263 CD3#42 scFv DIVMTQSPDSLAVSLGERATIFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAIYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWMG NINADTGSTNYNQKFQG RVTMTVDTSTSTVYMELSSLRSEDTAVYYCTR DAYSFYYFDY WGQGTTLTVSS
SEQ ID NO:264 CD3#43 scFv DIVMTQSPDSLAVSLGERATMFC KSSQSLLNSRTRKNYLA WYQQKPGQPPKLLIY WASTRKS GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC IQSFILRT FGQGTKLEIKGGSEGKSSGSGSESKSTGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT SYWMH WVRQAPGQGLEWIG NINADTGSTNYNQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR DAYSFYYFDY WGQGTTVTVSS
SEQ ID NO:265 連接子，例如介於CD3 scFv內之VH與VL之間 GGSEGKSSGSGSESKSTGGS
SEQ ID NO:266 連接子，例如介於LC與HC之間 GGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGS
SEQ ID NO:267 CDH17#1(臼) / CD3#1 全長 DIVMSQSPSSLAVSVGEKVTMSC KSSQSLLYSSNQKNYLA WYQQKPGQSPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVKAEDLAVYYC QQYYSYPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSDAELVKPGASVKISCKVSGYTFT DHTIH WMKQRPEQGLEWIG YIYPRDGSTKYNEKFKG KATLTADKSSSTAYMQLNSLTSEDSAVYFCAR WGYYYGSSRYYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQEKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:268 CDH17#1 (臼) / CD3#2 全長 DIVMSQSPSSLAVSVGEKVTMSC KSSQSLLYSSNQKNYLA WYQQKPGQSPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVKAEDLAVYYC QQYYSYPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSDAELVKPGASVKISCKVSGYTFT DHTIH WMKQRPEQGLEWIG YIYPRDGSTKYNEKFKG KATLTADKSSSTAYMQLNSLTSEDSAVYFCAR WGYYYGSSRYYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQEKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:269 CDH17#1 (臼) / CD3#3 全長 DIVMSQSPSSLAVSVGEKVTMSC KSSQSLLYSSNQKNYLA WYQQKPGQSPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVKAEDLAVYYC QQYYSYPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSDAELVKPGASVKISCKVSGYTFT DHTIH WMKQRPEQGLEWIG YIYPRDGSTKYNEKFKG KATLTADKSSSTAYMQLNSLTSEDSAVYFCAR WGYYYGSSRYYFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQEKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:270 CDH17#8 (臼) / CD3#1 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:271 CDH17#8 (臼) / CD3#2 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNKWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:272 CDH17#8 (臼) / CD3#3 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO: 273 4aa連接子 GGGS
SEQ ID NO:274 6aa連接子 GGSGGS
SEQ ID NO:275 20aa連接子；例如介於Fc與CD3 scFv之間 GGGGSGGGGSGGGGSGGGGS
SEQ ID NO:276 Trop2#1 HCDR1 (CCG) GYTFTDYTMH
SEQ ID NO:277 Trop2#8 HCDR1 (CCG) GLSLSRYSVH
SEQ ID NO:278 Trop2#11 HCDR1 (CCG) GYSITSGYYWN
SEQ ID NO:279 Trop2#12至#18 HCDR1 (CCG) GYSISSGYYWN
SEQ ID NO:280 Trop2#9 HCDR1 (CCG) GYTFTDYYMN
SEQ ID NO:281 Trop2#10 HCDR1 (CCG) GYTFTNYYIH
SEQ ID NO:282 CDH17#1 HCDR1 (CCG) GYTFTDHTIH
SEQ ID NO:283 CDH17#8 HCDR1 (CCG) GYTFSDHTIH
SEQ ID NO:284 CD3#1至#15、#20、#23、#24 HCDR1 (CCG) GFTFNTYAMN
SEQ ID NO:285 CD3#16至#19、#21、#22 HCDR1 (CCG) GFTFSTYAMN
SEQ ID NO:286 CDH17#25至#42 HCDR1 (CCG) GYTFTSYWMH
SEQ ID NO:287 Trop2#1及#9 HCDR1 (Chothia) GYTFTDY
SEQ ID NO:288 Trop2#1 HCDR2 (Chothia) YPNYGD
SEQ ID NO:289 Trop2#8 HCDR1 (Chothia) GLSLSRY
SEQ ID NO:290 Trop2#8 HCDR2 (Chothia) WGGGS
SEQ ID NO:291 Trop2#11 HCDR1 (Chothia) GYSITSGY
SEQ ID NO:292 Trop2#11 HCDR2 (Chothia) SYDGR
SEQ ID NO:293 Trop2#12至#18 HCDR1 (Chothia) GYSISSGY
SEQ ID NO:294 Trop2#12至#18 HCDR2 (Chothia) SYSGR
SEQ ID NO:295 Trop2#9 HCDR2 (Chothia) YPNNGA
SEQ ID NO:296 Trop2#10 HCDR1 (Chothia) GYTFTNY
SEQ ID NO:297 Trop2#10 HCDR2 (Chothia) YPGNGA
SEQ ID NO:298 CDH17#1 HCDR1 (Chothia) GYTFTDH
SEQ ID NO:299 CDH17#1 HCDR2 (Chothia) YPRDGS
SEQ ID NO:300 CDH17#8 HCDR1 (Chothia) GYTFSDH
SEQ ID NO:301 CDH17#8 HCDR2 (Chothia) YPRLGS
SEQ ID NO:302 CD3#1至#15、#20、#23、#24 HCDR1 (Chothia) GFTFNTY
SEQ ID NO:303 CD3#1至#18、#20、#22、#23、#24 HCDR1 (Chothia) RSKYNNYA
SEQ ID NO:304 CD3#16至#19、#21、#22 HCDR1 (Chothia) GFTFSTY
SEQ ID NO:305 CD3#19、#21、HCDR1 (Chothia) RSIYNNYA
SEQ ID NO:306 CD3#25至#42 HCDR1 (Chothia) GYTFTSY
SEQ ID NO:307 CD3#25、#26、#37至#42 HCDR1 (Chothia) NADTGS
SEQ ID NO:308 CD3#27至#36 HCDR1 (Chothia) NASTGS
SEQ ID NO:309 Trop2#1 HCDR1 (IMGT) GYTFTDYT
SEQ ID NO:310 Trop2#1 HCDR2 (IMGT) IYPNYGDT
SEQ ID NO:311 Trop2#1 HCDR3 (IMGT) SRKTVLLRLRYFDV
SEQ ID NO:312 Trop2#1 LCDR1 (IMGT) GNIHNY
w/o Trop2#1 LCDR2 (IMGT) NAI
SEQ ID NO:314 Trop2#8 HCDR1 (IMGT) GLSLSRYS
SEQ ID NO:315 Trop2#8 HCDR2 (IMGT) IWGGGST
SEQ ID NO:316 Trop2#8 HCDR3 (IMGT) ARKGSYYTNYGAMDY
SEQ ID NO:317 Trop2#8 LCDR1 (IMGT) QDINKY
w/o Trop2#8 LCDR2  (IMGT) YTS
SEQ ID NO:319 Trop2#11 HCDR1 (IMGT) GYSITSGYY
SEQ ID NO:320 Trop2#11 HCDR2 (IMGT) ISYDGRN
SEQ ID NO:321 Trop2#11至#18 HCDR3 (IMGT) ARDTTAYFDY
SEQ ID NO:322 Trop2#11 LCDR1 (IMGT) ESVDSSVNRF
w/o Trop2#11至#18 LCDR2  (IMGT) RAS
SEQ ID NO:324 Trop2#12至#18 HCDR1 (IMGT) GYSISSGYY
SEQ ID NO:325 Trop2#12至#18 HCDR2 (IMGT) ISYSGRN
SEQ ID NO:326 Trop2#12至#18 LCDR1 (IMGT) ESVSSSVNRF
SEQ ID NO:327 Trop2#9 HCDR1 (IMGT) GYTFTDYY
SEQ ID NO:328 Trop2#9 HCDR2 (IMGT) IYPNNGAT
SEQ ID NO:329 Trop2#9 HCDR3 (IMGT) AREDSYYYAMDY
SEQ ID NO:330 Trop2#9 LCDR1 (IMGT) QSLVHSNGNTF
w/o Trop2#9及# 10 LCDR2  (IMGT) KVS
SEQ ID NO:332 Trop2#10 HCDR1 (IMGT) GYTFTNYY
SEQ ID NO:333 Trop2#10 HCDR2 (IMGT) IYPGNGAT
SEQ ID NO:334 Trop2#10 HCDR3 (IMGT) AREDYYYAMDY
SEQ ID NO:335 Trop2#10 LCDR1 (IMGT) QSLVHSNGNTY
SEQ ID NO:336 CDH17#1 HCDR1 (IMGT) GYTFTDHT
SEQ ID NO:337 CDH17#1 HCDR2 (IMGT) IYPRDGST
SEQ ID NO:338 CDH17#1及#8 HCDR3 (IMGT) ARWGYYYGSSRYYFDY
SEQ ID NO:339 CDH17#1  LCDR1 (IMGT) QSLLYSSNQKNY
w/o CDH17#1及CD3#25至#42 LCDR2 (IMGT) WAS
SEQ ID NO:341 CDH17#8 HCDR1 (IMGT) GYTFSDHT
SEQ ID NO:342 CDH17#8 HCDR2 (IMGT) IYPRLGST
SEQ ID NO:343 CDH17#8 LCDR1 (IMGT) QSVLYSSNQKQY
w/o CDH17#8  LCDR2  (IMGT) GAS
SEQ ID NO:345 CD3#1至# 15、#20、#23、#24 HCDR1 (IMGT) GFTFNTYA
SEQ ID NO:346 CD3#1至# 18、#20、#22、#23、#24 HCDR2 (IMGT) IRSKYNNYAT
SEQ ID NO:347 CD3#1至# 10、#12、#13、#15、#20、#23、#24 HCDR3 (IMGT) VRHGNFGNSYVSWFAY
SEQ ID NO:348 CD3#1至# 10、#12至#16、#18、#19、#21、#24 LCDR1 (IMGT) TGAVTTSNY
w/o CD3#1至#24 LCDR2 (IMGT) GTN
SEQ ID NO:350 CD3#11、#14 HCDR3 (IMGT) VRHGNFLNSYVSWFAY
SEQ ID NO:351 CD3#11、#20、#23 LCDR1 (IMGT) TGAVTTSYY
SEQ ID NO:352 CD3#16至# 19、#21、#22 HCDR1 (IMGT) GFTFSTYA
SEQ ID NO:353 CD3#16至# 18、#21、#22、HCDR2 (IMGT) VRHGNFIDSYVSWFAY
SEQ ID NO:354 CD3#17及# 22 LCDR1 (IMGT) TGAVTTSWY
SEQ ID NO:355 CD3#19及#21 HCDR2 (IMGT) IRSIYNNYAT
SEQ ID NO:356 CD3#19 HCDR3 (IMGT) VRHGNFGDSYVSWFAY
SEQ ID NO:357 CD3#25至#42 HCDR1 (IMGT) GYTFTSYW
SEQ ID NO:358 CD3#25、#26、#37至#42 HCDR2 (IMGT) INADTGST
SEQ ID NO:359 CD3#25、#28至#30、#39 HCDR3 (IMGT) TRDGYSFYYFDY
SEQ ID NO:360 CD3#25至#29、#32、#34、#36至#42 LCDR1 (IMGT) QSLLNSRTRKNY
SEQ ID NO:361 CD3#26、#32至#37、#40 HCDR3 (IMGT) ARDGYSFYYFDY
SEQ ID NO:362 CD3#27至#36 HCDR2 (IMGT) INASTGST
SEQ ID NO:363 CD3#27、#31、#41 HCDR3 (IMGT) TRDAYSFYYFDY
SEQ ID NO:364 CD3#30、#31、#33、#35 LCDR1 (IMGT) QSLLNARTRKNY
SEQ ID NO:365 CD3#38、#42 HCDR3 (IMGT) ARDAYSFYYFDY
SEQ ID NO:366 Trop2#1 HCDR1 (North) KASGYTFTDYTMH
SEQ ID NO:367 Trop2#1 HCDR2 (North) GIYPNYGDTN
SEQ ID NO:368 Trop2#1 HCDR3 (North) SRKTVLLRLRYFDV
SEQ ID NO:369 Trop2#1 LCDR2 (North) YNAITLAD
SEQ ID NO:370 Trop2#8 HCDR1 (North) TVSGLSLSRYSVH
SEQ ID NO:371 Trop2#8 HCDR2 (North) MIWGGGSTD
SEQ ID NO:372 Trop2#8 HCDR3 (North) ARKGSYYTNYGAMDY
SEQ ID NO:373 Trop2#8 LCDR2 (North) HYTSTLQP
SEQ ID NO:374 Trop2#11 HCDR1 (North) SVTGYSITSGYYWN
SEQ ID NO:375 Trop2#11 HCDR2 (North) YISYDGRNN
SEQ ID NO:376 Trop2#11至#18 HCDR3 (North) ARDTTAYFDY
SEQ ID NO:377 Trop2#11至#18 LCDR2 (North) YRASNLES
SEQ ID NO:378 Trop2#12至#18 HCDR1 (North) TVSGYSISSGYYWN
SEQ ID NO:379 Trop2#12至#18 HCDR2 (North) YISYSGRNL
SEQ ID NO:380 Trop2#9 HCDR1 (North) KASGYTFTDYYMN
SEQ ID NO:381 Trop2#9 HCDR2 (North) YIYPNNGATG   
SEQ ID NO:382 Trop2#9 HCDR3 (North) AREDSYYYAMDY
SEQ ID NO:383 Trop2#9及#10 LCDR2 (North) YKVSNRFS
SEQ ID NO:384 Trop2#10 HCDR1 (North) KASGYTFTNYYIH
SEQ ID NO:385 Trop2#10 HCDR2 (North) YIYPGNGATA
SEQ ID NO:386 Trop2#10 HCDR3 (North) AREDYYYAMDY
SEQ ID NO:387 CDH17#1 HCDR1 (North) KVSGYTFTDHTIH
SEQ ID NO:388 CDH17#1 HCDR2 (North) YIYPRDGSTK
SEQ ID NO:389 CDH17#1及#8 HCDR3 (North) ARWGYYYGSSRYYFDY
SEQ ID NO:390 CDH17#1  LCDR2 (North) YWASTRES
SEQ ID NO:391 CDH17#8 HCDR1 (North) KASGYTFSDHTIH
SEQ ID NO:392 CDH17#8 HCDR2 (North) YIYPRLGSTK
SEQ ID NO:393 CDH17#8  LCDR2 (North) YGASTRET
SEQ ID NO:394 CD3#1至#15、#20、#23、#24 HCDR1 (North) AASGFTFNTYAMN
SEQ ID NO:395 CD3#1至#18、#20、#22、#23、#24 HCDR2 (North) RIRSKYNNYATY
SEQ ID NO:396 CD3#1至#10、#12、#13、#15、#20、#23、#24 HCDR3 (North) VRHGNFGNSYVSWFAY
SEQ ID NO:397 CD3#1至#12、#16、#18、#19、#21、#22、#23 LCDR2 (North) GGTNKRAP
SEQ ID NO:398 CD3#11及#14 HCDR3 (North) VRHGNFLNSYVSWFAY
SEQ ID NO:399 CD3#13至#15、#17、#20、#24 LCDR2 (North) GGTNIRAP
SEQ ID NO:400 CD3#16至#18、#21、#22 HCDR1 (North) AASGFTFSTYAMN
SEQ ID NO:401 CD3#16至#18、#21、#22 HCDR3 (North) VRHGNFIDSYVSWFAY
SEQ ID NO:402 CD3#19及#21 HCDR2 (North) RIRSIYNNYATY
SEQ ID NO:403 CD3#19 HCDR3 (North) VRHGNFGDSYVSWFAY
SEQ ID NO:404 CD3#25至#42 HCDR1 (North) KASGYTFTSYWMH
SEQ ID NO:405 CD3#25、#26、#38、# 41、#42 HCDR2 (North) NINADTGSTN
SEQ ID NO:406 CD3#25、#28至#30、#39 HCDR3(North) TRDGYSFYYFDY
SEQ ID NO:407 CD3#25至# 42 LCDR2 (North) YWASTRKS
SEQ ID NO:408 CD3#26、#32至#37、#40 HCDR3(North) ARDGYSFYYFDY
SEQ ID NO:409 CD3#27、#29至#31、#33、# 35 HCDR2 (North) NINASTGSTN
SEQ ID NO:410 CD3#27、#31、#41 HCDR3(North) TRDAYSFYYFDY
SEQ ID NO:411 CD3#28、#32、#34、#36 HCDR2 (North) NINASTGSTS
SEQ ID NO:412 CD3#37、#39、#40 HCDR2 (North) NINADTGSTK
SEQ ID NO:413 CD3#38 #42 HCDR3(North) ARDAYSFYYFDY
SEQ ID NO:414 IgG1野生型HC ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SEQ ID NO:415    IgG1 KO HC ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:416 IgG4 Pro野生型HC ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO:417 IgG1 FcRnmut ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLAQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:418 人類輕鏈恆定域(κ) RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO:419 人類Trop2 MARGPGLAPPPLRLPLLLLVLAAVTGHTAAQDNCTCPTNKMTVCSPDGPGGRCQCRALGSGMAVDCSTLTSKCLLLKARMSAPKNARTLVRPSEHALVDNDGLYDPDCDPEGRFKARQCNQTSVCWCVNSVGVRRTDKGDLSLRCDELVRTHHILIDLRHRPTAGAFNHSDLDAELRRLFRERYRLHPKFVAAVHYEQPTIQIELRQNTSQKAAGDVDIGDAAYYFERDIKGESLFQGRGGLDLRVRGEPLQVERTLIYYLDEIPPKFSMKRLTAGLIAVIVVVVVALVAGMAVLVITNRRKSGKYKKVEIKELGELRKEPSL
SEQ ID NO:420 人類CDH17 MILQAHLHSLCLLMLYLATGYGQEGKFSGPLKPMTFSIYEGQEPSQIIFQFKANPPAVTFELTGETDNIFVIEREGLLYYNRALDRETRSTHNLQVAALDANGIIVEGPVPITIKVKDINDNRPTFLQSKYEGSVRQNSRPGKPFLYVNATDLDDPATPNGQLYYQIVIQLPMINNVMYFQINNKTGAISLTREGSQELNPAKNPSYNLVISVKDMGGQSENSFSDTTSVDIIVTENIWKAPKPVEMVENSTDPHPIKITQVRWNDPGAQYSLVDKEKLPRFPFSIDQEGDIYVTQPLDREEKDAYVFYAVAKDEYGKPLSYPLEIHVKVKDINDNPPTCPSPVTVFEVQENERLGNSIGTLTAHDRDEENTANSFLNYRIVEQTPKLPMDGLFLIQTYAGMLQLAKQSLKKQDTPQYNLTIEVSDKDFKTLCFVQINVIDINDQIPIFEKSDYGNLTLAEDTNIGSTILTIQATDADEPFTGSSKILYHIIKGDSEGRLGVDTDPHTNTGYVIIKKPLDFETAAVSNIVFKAENPEPLVFGVKYNASSFAKFTLIVTDVNEAPQFSQHVFQAKVSEDVAIGTKVGNVTAKDPEGLDISYSLRGDTRGWLKIDHVTGEIFSVAPLDREAGSPYRVQVVATEVGGSSLSSVSEFHLILMDVNDNPPRLAKDYTGLFFCHPLSAPGSLIFEATDDDQHLFRGPHFTFSLGSGSLQNDWEVSKINGTHARLSTRHTEFEEREYVVLIRINDGGRPPLEGIVSLPVTFCSCVEGSCFRPAGHQTGIPTVGMAVGILLTTLLVIGIILAVVFIRIKKDKGKDNVESAQASEVKPLRS
SEQ ID NO:421 人類CD3 δ鏈 MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGVFCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK
SEQ ID NO:422 人類CD3 ε鏈 MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRDLYSGLNQRRI
SEQ ID NO:423 人類CD3 γ鏈 MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGKMIGFLTEDKKKWNLGSNAKDPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGFLFAEIVSIFVLAVGVYFIAGQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLRRN
SEQ ID NO:424 人類CD3 ζ鏈 MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIYGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR
SEQ ID NO:424 CDH17#8 (臼) / CD3#4 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:425 CDH17#8 (臼) / CD3#5 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:426 CDH17#8 (臼) / CD3#6 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:427 CDH17#8 (臼) / CD3#7 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:428 CDH17#8 (杵) / CD3#2 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNKWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
SEQ ID NO:429 CDH17#8 (杵) / CD3#3 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:430 CDH17#8 (杵) / CD3#4 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:431 CDH17#8 (杵) / CD3#5 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:432 CDH17#8 (杵) / CD3#6 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP GVPARFSGSLLGGKAALTLSGAQPEDEAEYYC ALWYSNLWV FGCGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKCLEWVA RIRSKYNNYATYYADSVKG RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:433 CDH17#8 (杵) / CD3#7 全長 EIVMTQSPATLSVSPGERATLSC RASQSVLYSSNQKQYLA WYQQKPGQAPRLLIY GASTRET GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC QQYYSYPWT FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGYTFS DHTIH WVRQAPGQGLEWMG YIYPRLGSTKYAEKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR WGYYYGSSRYYFDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSQAVVTQEPSLTVSPGGTVTLTC RSSTGAVTTSNYAN WVQQKPGQLPRGLIG GTNKRAP WVPARFSGSLLGGKAALTLSGAQPEDEAEYFC ALWYSNLWV FGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFN TYAMN WVRQAPGKGLEWVA RIRSKYNNYATYYADSVKD RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVR HGNFGNSYVSWFAY WGQGTLVTVSA
SEQ ID NO:434 Fc域杵 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
SEQ ID NO:435 Fc域臼 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:436 Trop2#11全長(臼) DIVLTQSPPSLAVSLGQRATISCRASESVDSSVNRFMHWYQQKPGQPPKLLIYRASNLESGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSDVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMGYISYDGRNNYNPSLKNRISITRDTSENQFFLKLNSVTPEDTATYYCARDTTAYFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG
SEQ ID NO:437 CDH17#1 (杵) / CD3#1 全長 DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSSNQKNYLAWYQQKPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSEGKSSGSGSESKSTEGKSSGSGSESKSTGGGGSQVQLQQSDAELVKPGASVKISCKVSGYTFTDHTIHWMKQRPEQGLEWIGYIYPRDGSTKYNEKFKGKATLTADKSSSTAYMQLNSLTSEDSAVYFCARWGYYYGSSRYYFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSGGGGSGGGGSEAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPGQLPRGLIGGTNKRAPWVPARFSGSLLGGKAALTLSGAQPEDEAEYFCALWYSNLWVFGGGTKLTVLGGSEGKSSGSGSESKSTGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTLVTVSA
本文揭示為Trop2#1、Trop2#8至Trop2#18、CDH17#1、CDH17#8以及CD3#1至CD3#43之較佳抗原結合位點均由本發明人鑑別且作為適用於本發明之三特異性結合分子之抗原結合位點測試。詳言之，該等抗原結合位點藉由多肽鏈或連接子之可撓性元件連接，該等可撓性元件不干擾該等抗原結合位點之結構及功能完整性。 TROP2之單特異性結合分子  本文進一步提供特異性結合於TROP2之抗體分子(例如具有具兩條重鏈及兩條輕鏈之Y形結構之全長抗體/免疫球蛋白分子，或其片段，諸如Fv、Fab、Fab'或F(ab')2片段、單鏈抗體、單鏈可變片段(scFv))。在一些實施例中，對TROP2具有特異性之抗體分子為重組單株抗體、嵌合、人類化或人類抗體分子。
在一些實施例中，對TROP2具有特異性之抗體分子包含(i)至(vi)中所示之以下CDR組合中的任一者： (i)    包含SEQ ID NO.:1 (CDR1)、SEQ ID NO.:2 (CDR2)及SEQ ID NO.:3 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:4 (CDR1)、SEQ ID NO.:5 (CDR2)及SEQ ID NO.:6 (CDR3)之胺基酸序列之輕鏈CDR； (ii)   包含SEQ ID NO.:7 (CDR1)、SEQ ID NO.:8 (CDR2)及SEQ ID NO.:9 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:10 (CDR1)、SEQ ID NO.:11 (CDR2)及SEQ ID NO.:12 (CDR3)之胺基酸序列之輕鏈CDR； (iii)  包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:14 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:16 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (iv)   包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:19 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:20 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (v)    包含SEQ ID NO.:21 (CDR1)、SEQ ID NO.:22 (CDR2)及SEQ ID NO.:23 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:24 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:26 (CDR3)之胺基酸序列之輕鏈CDR； 或 (vi)   包含SEQ ID NO.:27 (CDR1)、SEQ ID NO.:28 (CDR2)及SEQ ID NO.:29 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:30 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:31 (CDR3)之胺基酸序列之輕鏈CDR。
在一些實施例中，對TROP2具有特異性之抗體分子包含： i)     包含SEQ ID NO:83之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:84之胺基酸序列之免疫球蛋白輕鏈可變域； (ii)   包含SEQ ID NO:85之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:86之胺基酸序列之免疫球蛋白輕鏈可變域； (iii)  包含SEQ ID NO:87之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:88之胺基酸序列之免疫球蛋白輕鏈可變域； (iv)   包含SEQ ID NO:89之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:90之胺基酸序列之免疫球蛋白輕鏈可變域； (v)    包含SEQ ID NO:91之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:92之胺基酸序列之免疫球蛋白輕鏈可變域； (vi)   包含SEQ ID NO:93之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (vii)  包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (viii) 包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域； (ix)   包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (x)    包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)   包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:99之胺基酸序列之免疫球蛋白輕鏈可變域； 或 (xii)  包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域。
在一些實施例中，如上所定義之TROP2特異性抗體進一步包含人類重鏈恆定域(例如，IgG恆定域)及人類輕鏈恆定域(例如，κ或λ輕鏈恆定域)。在一些實施例中，重鏈恆定域為人類IgG1野生型(例如，如SEQ ID NO:414中提供)、IgG1 KO (例如，如SEQ ID NO:415中提供)、IgG4 Pro野生型(例如，如SEQ ID NO:416中提供)或IgG1 FcRnmut (例如，如SEQ ID NO:417中提供)。在一些實施例中，人類輕鏈恆定域為人類κ (例如，如SEQ ID NO:418)中提供。
在一些實施例中，TROP2特異性抗體具有包含SEQ ID NO: 83、85、87、89、91、93、95或98中之任一者之序列與SEQ ID No：414、415、416或417中之任一者之序列融合的重鏈及包含SEQ ID NO: 84、86、88、90、92、94、96、97或99中之任一者之序列與SEQ ID NO:418之序列融合的輕鏈。
本文所提供之TROP2特異性抗體可藉由附接對不同抗原具有結合特異性之染料、藥物或另一分子而用於活體外、活體內或離體標記、定位、鑑別或靶向表現TROP2之細胞(例如在ELISA分析、FACS分析、免疫組織學或其類似方面中)。本文所述之TROP2特異性抗體單獨時對表現TROP2之細胞之細胞活力無作用。在一些實施例中，TROP2特異性抗體特異性結合於表現TROP2之細胞之表面且用於定位及/或鑑別此類細胞。在一些實施例中，本文所提供之TROP2抗體用於鑑別表現TROP2之細胞(例如腫瘤細胞)。在一些實施例中，本文所提供之TROP2抗體藉由將藥物或細胞毒性劑附接至該TROP2抗體用於遞送此類藥物或細胞毒性劑至目標細胞(例如表現TROP2之腫瘤細胞)，藉此例如殺滅該目標細胞。
本文亦提供一種偵測樣品中之滋養層細胞表面抗原2 (TROP2)之方法，該方法包含以下步驟： (a)    使該樣品與如上文所定義之抗TROP2抗體分子接觸； (b)    允許在該樣品中形成抗體-抗原複合物；及 (c)    偵測抗TROP2抗體。
用於偵測抗體之手段及方法為此項技術中所熟知且包括例如免疫組織化學、免疫墨點及ELISA。
本文進一步提供一種偵測滋養層細胞表面抗原2 (TROP2)之套組，其中該套組包含如上文所定義之抗TROP2抗體分子及使用說明書。 CDH17之單特異性結合分子  本文進一步提供特異性結合於CDH17之抗體分子(例如具有具兩條重鏈及兩條輕鏈之Y形結構之全長抗體/免疫球蛋白分子，或其片段，諸如Fv、Fab、Fab'或F(ab')2片段、單鏈抗體、單鏈可變片段(scFv))。在一些實施例中，對CDH17具有特異性之抗體分子為重組單株抗體、嵌合、人類化或人類抗體分子。
在一些實施例中，對CDH17具有特異性之抗體分子包含(i)至(ii)中所示之以下CDR組合中的任一者： (i)    包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:33 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:35 (CDR1)、SEQ ID NO.:36 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR； 及 (ii)   包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:38 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:39 (CDR1)、SEQ ID NO.:40 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR。
在一些實施例中，對CDH17具有特異性之抗體分子包含 (i)    包含SEQ ID NO:100之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:101之胺基酸序列之免疫球蛋白輕鏈可變域； 或 (ii)   包含SEQ ID NO:102之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:103之胺基酸序列之免疫球蛋白輕鏈可變域。
在一些實施例中，如上所定義之CDH17特異性抗體進一步包含人類重鏈恆定域(例如，IgG恆定域)及人類輕鏈恆定域(例如，κ或λ輕鏈恆定域)。在一些實施例中，重鏈恆定域為人類IgG1野生型(例如，如SEQ ID NO:414中提供)、IgG1 KO (例如，如SEQ ID NO:415中提供)、IgG4 Pro野生型(例如，如SEQ ID NO:416中提供)或IgG1 FcRnmut (例如，如SEQ ID NO:417中提供)。在一些實施例中，人類輕鏈恆定域為人類κ (例如，如SEQ ID NO:418中提供)。
在一些實施例中，CDH17特異性抗體具有包含SEQ ID NO: 100或102中之任一者之序列與SEQ ID NO: 414、415、416或417中之任一者之序列融合的重鏈及包含SEQ ID NO: 101或103中之任一者之序列與SEQ ID NO:418之序列融合的輕鏈。
本文所提供之CDH17特異性抗體可藉由附接對不同抗原具有結合特異性之染料、藥物或另一分子而用於活體外、活體內或離體標記、定位、鑑別或靶向表現CDH17之細胞(例如在ELISA分析、FACS分析、免疫組織學或其類似方面中)。本文所述之CDH17特異性抗體單獨時對表現CDH17之細胞之細胞活力無作用。在一些實施例中，CDH17特異性抗體特異性結合於表現CDH17之細胞之表面且用於定位及/或鑑別此類細胞。在一些實施例中，本文所提供之CDH17抗體用於鑑別表現CDH17之細胞(例如腫瘤細胞)。在一些實施例中，本文所提供之CDH17抗體藉由將藥物或細胞毒性劑附接至該CDH17抗體用於遞送此類藥物或細胞毒性劑至目標細胞(例如表現CDH17之腫瘤細胞)，藉此例如殺滅該目標細胞。
本文亦提供一種偵測樣品中之鈣黏素-17 (CDH17)之方法，該方法包含以下步驟： (a)    使該樣品與如上文所定義之抗CDH17抗體分子接觸； (b)    允許在該樣品中形成抗體-抗原複合物；及 (c)    偵測該抗CDH17抗體。
用於偵測抗體之手段及方法為此項技術中所熟知且包括例如免疫組織化學、免疫墨點及ELISA。
本文進一步提供一種偵測滋養層細胞表面抗原2 (TROP2)之套組，其中該套組包含如上文所定義之抗TROP2抗體分子及使用說明書。 本發明之核酸分子、表現載體及宿主細胞  本發明進一步關於一種核酸分子，其編碼本發明之結合分子或其一部分。本發明進一步涵蓋一組編碼本發明之結合分子之核酸分子。
根據本發明，該核酸分子「編碼」本發明之結合分子或其一部分，此意謂核酸分子呈可表現形式，亦即呈確保本發明之結合分子(或其各別部分)可自其表現之形式提供。
術語「其一部分」反映如下事實：如熟練技術人員瞭解，並非本發明之結合分子之所有元件均需要在單個核酸分子上編碼。實情為，可依賴於兩個或更多個核酸分子以單獨地編碼本發明之結合分子之某些部分。因此，本發明亦涵蓋一組經分離之核酸分子，其中該組一起編碼本發明之結合分子之所有部分，使得此組經分離之核酸分子之表現產生本發明之完整結合分子。換言之本文提供一或多種核酸分子，其編碼本發明之結合分子之個別多肽鏈，包括重鏈、輕鏈、scFv以及其組合，在個別核酸分子上分開編碼或組合在一個核酸分子中。
較佳地，本發明之結合分子由兩種不同的經分離之核酸分子編碼，其中第一核酸分子編碼包含特異性結合於TROP2之抗原結合位點的全長鏈(包括單鏈Fab及Fc域)且第二核酸分子編碼包含特異性結合於CDH17之抗原結合位點的全長鏈(包括單鏈Fab及Fc域)，兩者連接於包含特異性結合於CD3之抗原結合位點的全長鏈(較佳呈scFv形式)。在表現之後，表現之多肽將例如經由恆定域之間的二硫鍵等形成本發明之完整結合分子。
較佳地，核酸分子為包含編碼序列之DNA分子。更佳地，該DNA分子另外包含調控序列，及視情況存在之天然或人工內含子(諸如來自具有嵌入之miRNA-557表現卡匣之智人的β-球蛋白內含子)。其可具有其初始密碼子或可具有最佳化密碼子使用，特別適用於在所需宿主細胞或宿主生物體中表現。本發明之此類核酸分子容易藉由熟練技術人員依靠本身已知之方法，諸如藉由自動化DNA合成、自天然來源分離及/或重組DNA技術，基於本文中所給出的關於本發明之結合分子之胺基酸序列的資訊製備或獲得。
本發明之核酸分子包括但不限於編碼序列表中所示之多肽序列的DNA分子。此外，本發明涵蓋與上文所定義之DNA分子互補之核酸分子，以及在如WO 2007/042309中所定義之高度嚴格結合及洗滌條件下與其雜交之核酸分子。較佳分子(自mRNA視角)為與本文所述之DNA分子中之一者具有至少75%或80% (較佳地至少85%，更佳地至少90%且最佳地至少95%)同源性或序列一致性的彼等分子。舉例而言，若目標為在真核細胞中表現本發明之結合分子，則DNA序列將必須經設計以匹配真核細胞中之密碼子使用。若需要在大腸桿菌或其他原核系統中表現抗體，則此等序列將必須經設計以匹配大腸桿菌或各別原核系統中之密碼子使用。可以若干種不同方式構築本發明之DNA分子之變異體，如例如WO 2007/042309中所描述。
較佳地，分離核酸，術語「分離」在上文進一步定義。
本發明進一步關於一種表現載體，其包含本發明之核酸分子。
根據本發明，載體為表現載體，亦即可在活體外及/或活體內(例如在合適宿主細胞、宿主生物體及/或表現系統中)使各別多肽自編碼核酸分子表現之載體。表現載體包括質體、逆轉錄病毒、黏質體、EBV來源之游離基因體及其類似物。通常選擇與宿主細胞相容之表現載體及表現控制序列。表現載體一般包含可操作地連接於一或多種適合之調控元件(諸如啟動子、強化子、終止子及其類似物)的至少一種本發明之核酸分子。適用於表現本發明之多肽或表現本發明之多肽所需的此類調控元件及其他元件，諸如整合因子、選擇標記物、信號或前導序列、報導基因及其類似者之特定實例揭示於例如WO2006/040153之第131頁至第133頁上。
啟動子序列之非限制性實例(針對在哺乳動物細胞中表現所例示)係來源於CMV (諸如人類細胞巨大病毒之CMV啟動子/強化子或CMV猿猴病毒40 (SV40)啟動子/強化子)、腺病毒(例如腺病毒主要晚期啟動子(AdMLP))、多瘤病毒之啟動子及/或強化子，及強哺乳動物啟動子，諸如天然免疫球蛋白及肌動蛋白啟動子。聚腺苷酸化信號之實例為倉鼠生長激素或牛生長激素polyA、SV40晚期或早期polyA；或者，可使用免疫球蛋白基因之3´UTRs等。
重組表現載體亦可攜帶調控載體在宿主細胞中複製之序列(例如複製起點，諸如ColE1 (pUC)複製起點)及可選擇標記物基因(諸如賦予安比西林(ampicillin)抗性以在大腸桿菌中擴增質體之ß-內醯胺酶基因)。重組表現載體亦可編碼促進所得多肽分泌之信號肽。編碼各別多肽鏈之核酸分子可選殖至載體中，以使得信號肽與成熟全長核酸分子鏈之胺基端同框連接。信號肽可為免疫球蛋白信號肽或來自非免疫球蛋白蛋白質之異源信號肽。或者，編碼本發明之蛋白質之全長鏈的DNA序列可能已含有信號肽序列。
如上所指出，插入載體中之編碼序列可例如藉由標準方法合成，或自天然來源分離，或以半合成方式，亦即藉由組合化學合成與重組技術產生。可使用已確立之方法將編碼序列與轉錄調控元件及/或其他胺基酸編碼序列接合。通常採用之一種方法為例如使用編碼功能完整之人類CH (恆定重鏈)免疫球蛋白序列之載體，其中適當限制位點經工程改造以使得可容易插入及表現任何抗原結合位點，諸如單鏈Fab序列或任何重鏈/輕鏈可變域。對於抗體重鏈，其可為但不限於任何IgG同型(IgG1、IgG2、IgG3、IgG4)或其他免疫球蛋白，包括對偶基因變異體。
在構成本發明之結合分子需要超過一種核酸分子之彼等情況下，此等超過一種核酸分子可插入至不同表現載體中或插入至相同表現載體中。在後一情況下，其可在相同調控元件(例如啟動子、強化子、終止子及其類似物)的控制下，或其可各自具有其自身的一組調控元件。根據本發明，尤其較佳地，在超過一種核酸分子編碼本發明之結合分子之個別元件的彼等情況下(亦即，包含特異性結合於TROP2之抗原結合位點之多肽鏈、包含特異性結合於CHD17之抗原結合位點之多肽鏈及包含特異性結合於CD3之抗原結合位點之多肽鏈)，形成本發明之結合分子所需之所有個別核酸分子存在於單一表現載體且較佳地，各核酸分子具有其自身的一組調控元件。
包含此等DNA分子之表現載體可根據此項技術中熟知之轉染方法引入至宿主細胞，例如細菌細胞或(高等)真核細胞(例如哺乳動物細胞)中，該等轉染方法包括脂質體介導之轉染、聚陽離子介導之轉染、原生質體融合、顯微注射、磷酸鈣沈澱、電穿孔或藉由病毒載體轉移。
因此，本發明亦關於一種用本發明之表現載體轉染之宿主細胞。
宿主細胞可為此項技術中已知之任何適合細胞，包括原核細胞，諸如細菌，以及真核細胞，諸如酵母細胞或哺乳動物細胞。哺乳動物細胞之非限制性實例包括但不限於人類、小鼠、大鼠、猴及嚙齒類動物細胞株。可用作宿主細胞進行表現之特定哺乳動物細胞株為此項技術中所熟知且尤其包括中國倉鼠卵巢(CHO)細胞、NS0、SP2/0細胞、HeLa細胞、幼倉鼠腎(BHK)細胞、猴腎細胞(COS)、人類癌瘤細胞(例如Hep G2及A549細胞)、3T3細胞或任何此類細胞株之衍生物/後代。用於上述宿主細胞之適當培養基及條件為此項技術中所已知。 用於產生本發明之結合分子的方法  本發明亦關於一種產生本發明之結合分子之方法，該方法包含以下步驟： (a)    在允許本發明之結合分子表現之條件下培養本發明之宿主細胞； (b)    視情況回收該分子；及視情況， (c)    進一步純化及/或修飾及/或調配該結合分子。
本發明之蛋白質藉由將宿主細胞培養一段足以允許宿主細胞表現該蛋白質的時間來製備。
適用於培養原核或真核宿主之條件為熟習此項技術者所熟知。為提高表現產物之產率及溶解度，培養基可經緩衝或補充有已知增強或促進兩者之適合添加劑。一般而言，熟習此項技術者亦瞭解，此等條件可能必須適於宿主之需求及所表現之分子之要求。在誘導型啟動子在宿主細胞中存在之載體中控制本發明之核酸分子的情況下，所關注分子之表現可藉由添加適當誘導劑來誘導。適合之表現方案及策略為熟練技術人員所已知。
隨後，回收本發明之結合分子，且必要時進一步純化。較佳地，以分泌分子形式自培養基回收其。然而，若例如在無分泌信號之情況下表現，則亦可自宿主細胞溶解物回收其。應瞭解，術語「回收該分子」係指分離由本發明之核酸分子編碼之本發明之結合分子，亦即由於該宿主細胞經本發明之核酸分子或載體轉型或轉染而存在於本發明之宿主細胞中之結合分子。
純化本發明之結合分子之視情況選用之步驟進一步幫助獲得分子之基本上均勻之製劑。用於純化所關注分子之手段及方法為所熟知，且熟練技術人員可例如使用用於重組蛋白及宿主細胞蛋白質之標準蛋白質純化方法且以適合於各別分子之方式對其進行調整。舉例而言，適用於獲得本發明之結合分子之目前先進技術純化方法包括自培養基或溶解物移除細胞及/或顆粒細胞碎片作為第一步驟，接著例如藉由在免疫親和力或離子交換管柱上分級分離、乙醇沈澱、逆相HPLC、Sephadex層析、二氧化矽或陽離子交換樹脂上層析來自污染性可溶蛋白質、多肽及核酸純化。
作為獲得本發明之結合分子之方法中的最終視情況選用之步驟，純化之蛋白質分子可經乾燥，例如凍乾，如下文針對治療性應用所述，或按需要以其他方式調配。此外，本發明之所得結合分子可經受進一步修飾，例如移除非所需轉譯後修飾及其類似修飾。 醫藥組合物及本發明之結合分子或醫藥組合物之醫學用途  本發明進一步關於一種醫藥組合物，其包含一或多種本發明之結合分子或由其組成。在一個實施例中，該(等)結合分子為唯一醫藥活性劑。在一替代實施例中，除該(等)結合分子以外，該組合物包含一或多種其他醫藥活性劑，例如如下文進一步定義。
根據本發明，術語「醫藥組合物」係指用於向患者、較佳地人類患者投與之組合物。本發明之醫藥組合物包含上文所述之單獨或組合之化合物。其可視情況包含能夠改變本發明之化合物之特徵的其他分子，藉此例如穩定化、調節及/或活化其功能。組合物可呈固體、液體或氣體形式，且可尤其呈粉末形式，例如凍乾粉末、溶液、錠劑或氣溶膠。較佳地，組合物為凍乾粉末或溶液。
為用於療法中，將本發明之結合分子或抗體調配成適於促進向動物或人類投與之醫藥組合物。因此，本發明之醫藥組合物較佳亦包含醫藥學上可接受之載劑。包含此類載劑之組合物可藉由熟知之習知方法調配。通常，包含本發明之結合分子之醫藥組合物可藉由將結合分子與此類醫藥學上可接受之載劑以及(視情況)賦形劑或穩定劑混合來調配。此外，「醫藥學上可接受之載劑」意謂任何類型之無毒固體、半固體或液體填充劑、稀釋劑、囊封材料或調配助劑。其他賦形劑、調節劑或穩定劑在所採用之劑量及濃度下亦無毒。醫藥學上可接受之載劑、賦形劑、調節劑及穩定劑包括但不限於緩衝系統，諸如磷酸鹽、檸檬酸鹽、乙酸鹽及其他無機酸或有機酸及其鹽；抗氧化劑，包括抗壞血酸及甲硫胺酸；防腐劑，諸如氯化十八烷基二甲基苯甲基銨；氯化六羥季銨；氯苄烷銨、苄索氯銨；苯酚、丁醇或苯甲醇；對羥苯甲酸烷基酯，諸如對羥基苯甲酸甲酯或對羥基苯甲酸丙酯；兒茶酚；間苯二酚；環己醇；3-戊醇；及間甲酚；蛋白質，諸如血清白蛋白、明膠或免疫球蛋白；親水性聚合物，諸如聚乙烯吡咯啶酮或聚乙二醇(PEG)；胺基酸，諸如甘胺酸、麩醯胺酸、天冬醯胺、組胺酸、精胺酸或離胺酸；單醣、雙醣、寡醣或多醣及其他碳水化合物，包括葡萄糖、甘露糖、蔗糖、海藻糖、糊精或聚葡萄糖；螯合劑，諸如EDTA；糖醇，諸如甘露糖醇或山梨糖醇；成鹽相對離子，諸如鈉；金屬錯合物(例如Zn-蛋白質錯合物)；及/或離子或非離子界面活性劑，諸如TWEEN™ (聚山梨醇酯)、PLURONICS™或脂肪酸酯、脂肪酸醚或糖酯。有機溶劑亦可含於調配物中，諸如乙醇或異丙醇。賦形劑亦可具有調節釋放或調節吸收之功能。
通常，水溶液或懸浮液將為較佳的。一般而言，用於治療性蛋白質(諸如本發明之結合分子)之適合調配物為緩衝蛋白質溶液，諸如包括適合濃度(諸如0.001至400 mg/ml，較佳0.005至200 mg/ml，更佳0.01至200 mg/ml，更佳1.0-100 mg/ml，諸如1.0至10.0 mg/ml (靜脈內投與)或100 mg/ml (皮下投與))之蛋白質及水性緩衝液之溶液，該水性緩衝液諸如： -  磷酸鹽緩衝鹽水，pH 7.4， -  其他磷酸鹽緩衝液，pH 6.2至pH 8.2， -  乙酸鹽緩衝液，pH 3.2至pH 7.5，較佳pH 4.8至pH 5.5 -  組胺酸緩衝液，pH 5.5至pH 7.0， -  丁二酸鹽緩衝液，pH 3.2至pH 6.6，或 - 檸檬酸鹽緩衝液，pH 2.1至pH 6.2， 及視情況選用之用於提供溶液之等張性的鹽(例如NaCl)及/或穩定劑(諸如蔗糖、海藻糖、離胺酸)及/或其他多元醇(諸如甘露糖醇及甘油)，及視情況選用之洗滌劑，例如以防止聚集(例如0.02% Tween-20或Tween-80)。
較佳的用於靜脈內投與之緩衝蛋白質溶液為包括約10 mg/ml溶解於10 mM檸檬酸鹽緩衝液(pH 5.5)、207 mM蔗糖、25 mM離胺酸HCl及0.02%聚山梨醇酯20中之本發明之結合分子的溶液。皮下施用之調配物可包括顯著較高濃度，諸如高達100 mg/ml或甚至大於100 mg/ml的本發明之抗體。然而，熟習此項技術者將清楚，如上所給出的成分及其量僅表示一種較佳選擇。其替代方案及變體將為熟習此項技術者直接顯而易知，或可易於自以上揭示內容開始進行構想。
本發明之醫藥組合物可使用任何適合之投與模式向個體投與，包括例如藉由輸注或注射(靜脈內、關節內、肌肉內、皮下、胸骨內、腹膜內、皮內)非經腸投與，以及經皮、鼻內、經頰或經口投與或藉由吸入投與。為投與溶液或復原凍乾粉末，非經腸投與模式為較佳的。
一般而言，為治療、預防及/或緩解本文所提及之疾病、病症及病狀且視待治療之特定疾病、病症或病狀而定，待使用之本發明之特異性結合分子的效力、特定投與途徑及所使用之特定醫藥調配物或組合物對待投與之實際劑量具有影響。此外，實際醫藥學上有效量或治療劑量亦將視熟習此項技術者已知之因素而定，諸如患者之年齡及體重。在任何情況下，本發明之結合分子或本發明之醫藥組合物將基於患者獨特病狀以允許遞送醫藥學上有效量之劑量及方式投與。較佳地，本發明之結合分子或本發明之醫藥組合物將以每公斤體重0.005與20.0 mg之間的量及較佳0.05與10.0毫克/公斤/劑之間且更佳0.5與5毫克/公斤/劑之間的劑量連續(例如藉由輸注)或更佳作為單次劑量投與。投與時間間隔可為例如一週兩次、每週一次或每月一次劑量，但可顯著變化，尤其視前面提及之參數而定。因此，在一些情況下，使用小於上文給出之最小劑量可為足夠的，而在其他情況下必須超過上限。當投與較大量時，在一天內將其分成多個較小劑量係可取的。較佳地，每週一次，以每公斤體重0.005與20.0 mg之間的劑量範圍，及較佳0.05與10.0毫克/公斤/劑之間，且更佳0.5與5毫克/公斤/劑之間的劑量投與。
可使用任何適合之活體外分析、基於細胞之分析、本身已知之活體內分析及/或動物模型或其任何組合測試本發明之結合分子及包含其之組合物的功效，視所涉及之特定疾病而定。適合之分析及動物模型為熟習此項技術者所清楚，且例如包括以下實例中所用之分析及動物模型。
本發明之結合分子或本發明之醫藥組合物可獨立地或與其他藥理學活性成分組合使用，該等其他藥理學活性成分諸如目前先進技術或標準照護化合物，諸如細胞生長抑制或細胞毒性物質、細胞增殖抑制劑、抗血管生成物質、類固醇、免疫調節劑/檢查點抑制劑及其類似物。
因此，本發明之另一態樣提供本發明之結合分子或包含本發明之結合分子以及一或多種其他活性成分及視情況選用之醫藥學上可接受之載劑的醫藥組合物。
根據本發明可作為組合搭配物投與之細胞生長抑制及/或細胞毒性活性物質包括但不限於激素、激素類似物及抗激素、芳香酶抑制劑、LHRH促效劑及拮抗劑、生長因子(諸如血小板衍生生長因子(PDGF)、纖維母細胞生長因子(FGF)、血管內皮生長因子(VEGF)、表皮生長因子(EGF)、胰島素樣生長因子(IGF)、人類表皮生長因子(HER，例如HER2、HER3、HER4)及肝細胞生長因子(HGF)之生長因子)抑制劑、例如(抗)生長因子抗體、(抗)生長因子受體抗體之抑制劑及酪胺酸激酶抑制劑(諸如西妥昔單抗(cetuximab)、吉非替尼(gefitinib)、阿法替尼(afatinib)、尼達尼布(nintedanib)、伊馬替尼(imatinib)、拉帕替尼(lapatinib)、伯舒替尼(bosutinib)及曲妥珠單抗(trastuzumab))；抗代謝物(例如抗葉酸鹽，諸如甲胺喋呤(methotrexate)、雷替曲塞(raltitrexed)；嘧啶類似物，諸如5-氟尿嘧啶(5-fluorouracil，5-FU)、吉西他濱(gemcitabine)、伊立替康(irinotecan)、多柔比星(doxorubicin)、TAS-102、卡培他濱(capecitabine)及吉西他濱(gemcitabine)；嘌呤及腺苷類似物，諸如巰基嘌呤(mercaptopurine)、硫鳥嘌呤(thioguanine)、克拉屈濱(cladribine)及噴司他汀(pentostatin)、阿糖胞苷(cytarabine)(ara C)、氟達拉濱(fludarabine))；抗腫瘤抗生素(例如蒽環黴素(anthracyclin))；鉑衍生物(例如順鉑(cisplatin)、奧沙利鉑(oxaliplatin)、卡鉑(carboplatin))；烷基化劑(例如雌莫司汀(estramustin)、甲基二(氯乙基)胺(meclorethamine)、美法侖(melphalan)、苯丁酸氮芥(chlorambucil)、白消安(busulphan)、達卡巴嗪(dacarbazin)、環磷醯胺(cyclophosphamide)、異環磷醯胺(ifosfamide)、替莫唑胺(temozolomide)、亞硝基脲(諸如卡莫司汀(carmustin)及洛莫司汀(lomustin))、噻替派(thiotepa))；抗有絲分裂劑(例如長春花生物鹼，諸如長春花鹼(vinblastine)、長春地辛(vindesin)、長春瑞濱(vinorelbin)及長春新鹼(vincristine)；及紫杉烷(taxane)，諸如太平洋紫杉醇(paclitaxel)、多西他賽(docetaxel))；血管生成抑制劑，包括貝伐珠單抗(bevacizumab)、雷莫蘆單抗(ramucirumab)及阿柏西普(aflibercept)；微管蛋白抑制劑；DNA合成抑制劑、PARP抑制劑、拓樸異構酶抑制劑(例如表鬼臼毒素(epipodophyllotoxin)(諸如依託泊苷(etoposide)及依託泊苷磷酸鹽(etopophos))、替尼泊苷(teniposide)、安吖啶(amsacrin)、托泊替康(topotecan)、伊立替康(irinotecan)、米托蒽醌(mitoxantrone))、絲胺酸/蘇胺酸激酶抑制劑(例如PDK1抑制劑、Raf抑制劑、A-Raf抑制劑、B-Raf抑制劑、C-Raf抑制劑、mTOR抑制劑、mTORC1/2抑制劑、PI3K抑制劑、PI3Kα抑制劑、雙重mTOR/PI3K抑制劑、STK33抑制劑、AKT抑制劑、PLK1抑制劑(諸如伏拉塞替(volasertib))、CDK抑制劑(包括CDK9抑制劑)、Aurora激酶抑制劑)、酪胺酸激酶抑制劑(例如PTK2/FAK抑制劑)、蛋白質蛋白質相互作用抑制劑、MEK抑制劑、ERK抑制劑、FLT3抑制劑、BRD4抑制劑、IGF-1R抑制劑、Bcl-xL抑制劑、Bcl-2抑制劑、Bcl-2/Bcl-xL抑制劑、ErbB受體抑制劑、BCR-ABL抑制劑、ABL抑制劑、Src抑制劑、雷帕黴素(rapamycin)類似物(例如依維莫司(everolimus)、替西羅莫司(temsirolimus)、地磷莫司(ridaforolimus)、西羅莫司(sirolimus))、雄激素合成抑制劑、雄激素受體抑制劑、DNMT抑制劑、HDAC抑制劑、ANG1/2抑制劑、CYP17抑制劑、放射性藥物、免疫治療劑(諸如免疫檢查點抑制劑(例如CTLA4、PD1、PD-L1、LAG3及TIM3結合分子/免疫球蛋白，諸如伊匹單抗(ipilimumab)、納武利尤單抗(nivolumab)、帕博利珠單抗(pembrolizumab))及各種化學治療劑(諸如阿米福汀(amifostin)、阿那格雷(anagrelid)、氯膦酸鹽(clodronat)、非格司亭(filgrastin)、干擾素、干擾素α、甲醯四氫葉酸(leucovorin)、利妥昔單抗(rituximab)、丙卡巴肼(procarbazine)、左旋咪唑(levamisole)、美司鈉(mesna)、米托坦(mitotane)、帕米膦酸鹽(pamidronate)及卟吩姆(porfimer)))；蛋白酶體抑制劑(諸如硼替佐米(Bortezomib))；Smac及BH3模擬物；恢復p53功能性之藥劑，包括mdm2-p53拮抗劑；Wnt/β-連環蛋白信號傳導路徑抑制劑；基質調節劑，諸如靶向CD137及FAP之分子(較佳雙特異性)；及/或細胞週期蛋白依賴性激酶9抑制劑。
根據本發明，較佳為用本發明之結合分子或本發明之醫藥組合物與選自以下之藥物組合進行之治療： (i)例如尤其在乳癌患者中，有或無化學療法組合(包括新輔助背景下之多柔比星/環磷醯胺組合及/或卡培他濱/多西他賽組合；第一線及後續路線治療之紫杉烷/鉑方案)的抗VEGF抗體(貝伐珠單抗(bevacizumab)及其他抗血管生成物質)； (ii)用於治療CRC之化學治療劑(包括5-氟尿嘧啶、伊立替康、多柔比星及TAS-102)； (iii)例如用於治療CRC患者之有或無化學療法組合(包括伊立替康)、抗VEGF抗體組合(貝伐珠單抗及其他抗血管生成物質)或瑞戈非尼(regorafenib)組合的抗EGFR抗體(KRAS野生型腫瘤中之西妥昔單抗及帕尼單抗(panitumumab))；及/或 (iv)例如用於治療CRC患者之免疫治療劑，包括抗PD-1及抗PD-L1藥劑及抗LAG3藥劑，諸如埃本利單抗(ezabenlimab)、帕博利珠單抗及納武利尤單抗以及如WO2017/198741所揭示之其他抗體；及/或 (v)基質調節劑，諸如靶向CD137及FAP之分子(較佳雙特異性)。
在尤其較佳實施例中，本發明之結合分子或本發明之醫藥組合物用於與免疫檢查點抑制劑組合，較佳與PD-1拮抗劑，諸如抗PD-1抗體或抗PDL-1抗體組合治療癌症。較佳地，該抗PD-1抗體係選自由以下組成之群：帕博利珠單抗、納武利尤單抗、皮立珠單抗(pidilizumab)、PD1-1、PD1-2、PD1-3、PD1-4及PD1-5，如WO2017/198741 (以引用之方式併入本文中)中所述，更佳地，該抗PD-1抗體為埃本利單抗。較佳地，該抗PDL-1抗體係選自由阿特珠單抗(atezolizumab)、阿維魯單抗(avelumab)及德瓦魯單抗(durvalumab)組成之群。
本發明進一步關於用於藥物中之本發明之結合分子或本發明之醫藥組合物。本發明進一步關於用於製備藥劑之本發明之結合分子或本發明之醫藥組合物。
此外，本發明亦關於本發明之結合分子或本發明之醫藥組合物，其用於治療、改善或預防癌症之方法中。本發明進一步關於一種治療、預防或改善癌症之方法，其包含向有需要之患者投與治療有效量之本發明之結合分子或本發明之醫藥組合物。
待投與分子之「治療有效量」為預防、改善或治療癌症臨床症狀所必需之最小量，特定言之對所治療之特定癌症有效的最小量。
如本文所用，術語「癌症」意謂包括所有類型之癌腫生長或致癌過程、轉移性組織或惡性轉型細胞、組織或器官(無論組織病理型或侵襲階段)。因此，藉由在體內之特定位置/源表徵的下文提及之所有癌症、腫瘤、贅瘤等意謂包括原發腫瘤及來源於其之轉移性腫瘤。
生長可使用本文所述之多特異性結合分子抑制的癌症為任何表現TROP2/CDH17之腫瘤，包括(但不限於) T細胞淋巴瘤、骨髓白血病、乳癌；卵巢癌、口腔鱗狀癌瘤及胃腸癌。胃腸癌包括但不限於食道癌(例如胃食管結合部癌)、胃部(胃)癌、肝細胞癌、膽道癌(例如膽管癌)、膽囊癌、胰臟癌或大腸直腸癌(CRC)。在一些實施例中，以下癌症、腫瘤及其他增生性疾病可用本發明之多特異性結合分子治療：頭頸癌，較佳HNSCC；肺癌；較佳NSCLC；乳癌；甲狀腺癌；子宮頸癌；卵巢癌；子宮內膜癌；肝癌(肝母細胞瘤或肝細胞癌)；胰臟癌；前列腺癌；胃肉瘤；胃腸基質瘤、食道癌；大腸癌；大腸直腸癌；腎癌；皮膚癌；腦瘤；神經膠母細胞瘤；非霍奇金氏淋巴瘤(Non-Hodgkin lymphoma) (T或B細胞淋巴瘤)；白血病(慢性或急性骨髓性白血病、非淋巴球性白血病)或多發性骨髓瘤。
在根據本發明使用之結合分子或醫藥組合物或者本發明之治療、預防或改善癌症之方法或者本發明之用途的一較佳實施例中，癌症為大腸直腸癌(CRC)，包括轉移性CRC (mCRC)、胃癌(GC)、胰臟癌(PAC)或食道癌。在本發明之一尤其較佳實施例中，癌症為mCRC。
大腸直腸癌(CRC)為ICD-10中列出之獨特惡性疾病，且為全世界癌症發病率及死亡率之主要原因之一。大約25% CRC患者呈現明顯癌轉移且在40-50%新診斷之患者中產生轉移性疾病。雖然近來化學療法之改良已延長轉移性CRC之存活持續時間，但大部分患者將死於其病。因此對治療此疾病之其他治療劑存在巨大需求。
已知大約30%-50%大腸直腸癌具有突變(異常) KRAS基因。在贅瘤中頻繁發現之KRAS突變包括外顯子2 (密碼子12及13)及外顯子3 (密碼子61)處之突變且可由腫瘤生檢分析。其包括活化突變，該等突變導致持續信號轉導，刺激參與細胞生長、增殖、侵襲及癌轉移之下游信號傳導路徑。因此，在一個實施例中，本發明之結合分子用於治療KRAS突變型大腸直腸癌(亦即，患有KRAS突變腫瘤之患者)。在一替代實施例中，本發明之結合分子用於治療KRAS野生型大腸直腸癌(亦即，患有KRAS野生型腫瘤之患者)。
胃部癌，亦稱為胃癌，為癌症相關死亡之第三大原因。雖然由於食物保存得到改善，使得20世紀早期以來發生率已降低，但胃部癌仍為具有不良預後之適應症，因為大部分患者呈現出已為晚期之疾病且療法選擇限於手術、化學療法、放射及有限量之靶向療法。
胰臟癌(PAC)為一種惡性疾病，其造成全世界每年＞400,000例死亡。其係工業化國家中癌症相關死亡的最常見病因之一。儘管進行如手術及化學療法之治療性干預，佔所有胰臟癌病例之約90%的胰腺癌通常具有極其不良預後，大約25%的人存活一年且僅5%之患者存活五年。
食道癌為全世界最常診斷出的癌症之一。類似於胰臟癌，其診斷困難且往往在已晚期階段方診斷出，從而導致此適應症之預後極其不良。因此，其佔癌症相關死亡之大約5%，因此使其成為第六最常見之癌症相關死亡病因。
兩種主要類型之食道癌，亦即食道鱗狀細胞細胞癌(ESCC，60-70%之病例)及食道腺癌(EAC，20-23%之病例)之發生率在不同地理區域之間極大地變化，其中ESCC在發展中國家中更常見，而EAC在工業化國家中為主型。當前治療選擇基本上限於手術及化學放射線療法。僅局部腫瘤在治癒性意向下治療，而轉移性疾病之療法基本上為姑息性的。
如上文所陳述，本發明者已鑑別出本文所述之結合分子對靶向癌細胞具有許多效用且因此可用於表現TROP2及CDH17兩者之癌症的療法中。鑑別特定腫瘤是否表現TROP2及CDH17之方法為此項技術中所熟知。舉例而言，免疫組織化學可用於判定腫瘤組織是否表現TROP2及CDH17 (例如使用如本文所述之TROP2及/或CDH17抗體)且因此將適合於用本發明之結合分子治療。
本發明之結合分子可用於第一線、第二線或任何其他路線治療及維持治療之情形中的治療方案中。
在另一態樣中，本發明之結合分子與適用於投與結合分子之裝置，諸如注射器、注射筆、微型泵或其他裝置組合使用。在另一態樣中，本發明之結合分子包含於分裝部分之套組中，例如亦包括具有結合分子之使用說明的藥品說明書。 實例：  本發明現藉助於以下非限制性實例描述。  實例1：鑑別Trop2及CDH17為在GI癌組織上共表現但不在正常組織上共表現的膜蛋白  用Affymetrix Chipset HGU133a及HGU133b量測自GeneLogic獲得之腫瘤及關鍵正常組織中之Trop2及CDH17之基因表現，且證實在某些適應症，諸如胃、胰臟、食管及大腸直腸癌之腫瘤組織中的共表現，如圖1中所示。在正常組織中未偵測到共表現。
在人類腫瘤組織切片中，在單染色及雙染色方案中，藉由免疫組織化學，使用與Trop2 (ENZ-ABS380，Enzo)及CDH17 (760-4865，Roche Ventana)結合之抗體來進一步評估CDH17及Trop2蛋白之表現。此另外證實此等目標在胃、胰臟及大腸直腸來源之腫瘤細胞上之共表現(圖2)。 實例2：本發明之三特異性結合蛋白之示意圖  為實現T細胞介導之共表現Trop2及CDH17之腫瘤細胞的溶解，設計結合Trop2、CDH17及CD3之多特異性結合蛋白。所使用之一種示例性分子設計具有IgG抗體支架及IgG樣結構，如圖3中所示。其特徵在於此項技術中已知之用於異二聚之Fc域中之杵-臼技術，其中杵部分位於抗Trop2結合臂上且臼部分位於抗CDH17結合臂上。另外，結合蛋白在各臂中之輕鏈與相應重鏈之間具有可撓性肽序列。在此示例性設計中，CD3結合單鏈可變區附接至臼鏈之Fc部分。因此，結合蛋白包含三個抗原結合位點，一個結合於Trop2，另一個結合於CDH17，其中各臂包含單鏈Fab及Fc區，且第三抗原結合位點呈scFv結合於CD3。在較佳分子設計中，結合分子為三特異性及三價的(亦即，對於三個目標中之各者分別為單價的)。 實例3：抗原結合位點及三特異性結合分子之設計、構築及驗證 實例 3.1 ： 使用自融合瘤及培養之單 B 細胞 回收之高通量 V 基因製備識別 Trop2 及 CDH17 之 抗原結合位點 .為獲得抗Trop2結合劑，在活體外培養來源於經Trop2免疫接種之野生型及AlivaMab人類化小鼠(Ablexis, San Francisco, CA, USA：具有人類免疫球蛋白基因座之AlivaMab基因轉殖小鼠平台)的融合瘤或單B細胞。藉由AlphaLISA (PerkinElmer, Waltham, MA, USA)關於針對重組人類Trop2之反應性來篩選上清液，且藉由流動式細胞測量術證實與表現人類Trop2之原發癌細胞株的結合。
為獲得抗CDH17結合劑，在Abpro (Abpro SOW#4)對野生型小鼠進行免疫接種。在活體外培養來源於經免疫接種之小鼠之融合瘤或單一B細胞。藉由AlphaLISA (PerkinElmer, Waltham, MA, USA)，關於針對重組人類CDH17，且藉由流動式細胞測量術，針對表現人類CDH17之AsPC-1胰臟腫瘤細胞株(ATCC®，CRL-1682)及/或NCI-H716大腸腫瘤細胞株(ATCC®，CCL-251)之細胞篩選上清液。淋巴結根據標準Abpro融合瘤程序加工。藉由ELISA，使用hCDH17-His (如下文實例4.5中所描述來製備)進行初級篩選。藉由流動式細胞測量術，針對上列2種細胞株篩選所有ELISA陽性孔。擴大所有ELISA及細胞株陽性孔且藉由兩種方法再測試。使用ForteBio Octet對擴增之陽性融合瘤進行親和力排序。
對於Trop2與CDH17，隨後自鑑別之陽性純系擴增免疫球蛋白(Ig) VH及VL基因。為自融合瘤分離RNA，將約2×10 6個來自單一純系之細胞粒化且用作源材料。對於單一B細胞，將自單獨分離之B細胞擴增之100至500個細胞用作源材料。使用RNeasy Plus (Qiagen, Hilden, Germany)分離RNA。隨後根據製造商說明書使用Smarter cDNA合成套組(Clontech, Mountain View, CA)合成cDNA。
為促進cDNA合成，使用oligodT引發所有信使RNA之逆轉錄，之後用Smarter IIA寡核苷酸進行「5'封端」。使用靶向Smarter IIA端帽之5'引子及靶向CH1中之共有區之3'引子，使用2步PCR擴增進行VH及VL片段之後續擴增。簡言之，各50 μl PCR反應物由20 µM正向及反向引子混合物、25 μl PrimeStar Max DNA聚合酶預混合物(Clontech)、2 μl未純化之cDNA及21 μl雙蒸餾H 2O組成。循環程式在94℃下開始，持續3分鐘，接著35個週期(94℃持續30秒，50℃持續1分鐘，68℃持續1分鐘)，且在72℃下持續7分鐘結束。用VL及VH第2輪引子進行第二輪PCR，該等引子含有「重疊」其各別pTT5母載體中之各別區域(VH及VL)之15 bp互補延伸。用以下程式進行第二輪PCR：94℃持續3分鐘；35個週期(94℃持續30秒，50℃持續1分鐘，68℃持續1分鐘)，及在72℃下持續7分鐘結束。
使用In-Fusion® HD選殖套組(Clontech, U.S.A.)將VL基因定向選殖於pTT5 huIgK載體中且將VH基因定向選殖於pTT5 huIgG1KO載體中。為促進In-Fusion® HD選殖，PCR產物在In-Fusion HD選殖之前經純化且用選殖增強劑處理。根據製造商之方案(Clontech, U.S.A.)進行選殖及轉型。使Mini-prep DNA進行桑格定序(Sanger sequencing)以證實獲得完整的V基因片段。
使用此方法，製備編碼對Trop2及CDH17具有特異性之抗原結合位點之Ig VH與VL基因對。藉由用相應的重鏈及輕鏈編碼質體瞬時轉染CHO-E37細胞製備重組抗體。 實例 3.2 ： 重組抗體之證實篩選藉由流動式細胞測量術，分別針對與表現人類或食蟹獼猴Trop2及CDH17之細胞株的結合分析含有所表現重組抗體之上清液。簡言之，將細胞與重組上清液一起培育，洗滌，且用抗人類-IgG-APC (Jackson ImmunoResearch 109-136-098)偵測來自上清液之結合單株抗體(mAb)。藉由以樣品之中值螢光強度(MFI)除以同型對照之中值螢光強度來計算信號/背景比(S/B) (針對不相關蛋白質及不同恆定區主鏈之可變區)。
在Biacore 4000上對重組上清液進行表面電漿子共振(SPR)。簡言之，經由蛋白A/G將HTP上清液中之非最佳化IgG捕捉於感測器表面上，在10 ul/min下持續60秒。監測100 nM人類Trop2或100 nM人類CDH17與捕捉之IgG的結合，在30 ul/min下締合180秒，隨後在HBS-EP緩衝液中解離120秒。在各結合循環之間用甘胺酸pH 2.1進行蛋白A/G表面之再生。
在此分析中使用以下材料：蛋白質試劑：重組表現之人類Trop2及CDH17。系統操作緩衝液：HBS-EP緩衝液(10 mM HEPES pH 7.4、150 mM NaCl、3 mM EDTA及0.005% v/v聚山梨醇酯P20)。捕捉試劑：蛋白A/G G (ThermoFisher Scientific, Waltham, MA, USA)，對所有人類IgG同型具有特異性。
選擇所關注之純系(Kd在nM範圍內)用於多特異性格式化。隨後產生多特異性結合蛋白且進一步在如下所述之機制及功能性篩選中評估(諸如細胞結合、細胞毒性及T細胞活化)。 實例 3.3 ： Trop2 及 CDH17 結合劑之人類化及最佳化如上文所述之Trop2及CDH17結合劑之序列經人類化及/或最佳化。抗體之序列最佳化/人類化係一種用於工程改造在非人類物種中產生(針對特異性抗原/抗原決定基)之用作治療劑之抗體的方法，該等抗體與在人類中產生之抗體類似且藉此在保留特異性的同時消除可能不良影響，諸如免疫原性。本文利用之序列最佳化/人類化方法係由Singh等人, 2015 (Singh S等人, mAbs 2015: 7(4):778-91)描述。簡言之，電腦模擬鑑別緊密匹配之人類生殖系，且使用噬菌體篩選方法評估最佳化/人類化變異體。基於結合、人類評分百分比及Epivax (潛在免疫原性之電腦模擬預測工具)評分選擇最終主要候選序列。 實例 3.4 ： CD3 結合劑之 scFv 轉變為構築編碼CD3 scFv之基因區段，編碼CD3結合可變域之VL與VH基因對來源於文獻(Pessano等人, EMBO J. 1985年2月; 4(2): 337-44；Salmerón A等人, J Immunol. 1991年11月1日;147(9):3047-52)中描述之CD3結合劑之人類化，且藉由編碼肽序列GGSEGKSSGSGSESKSTGGS (SEQ ID NO:265)之可撓性連接子之基因區段接合。 實例 3.5 ： 結合 Trop2 、 CDH17 及 CD3 之三特異性蛋白質及對照之構築使用常用分子生物學技術，將Trop2、CDH17結合劑及CD3 scFv以及對應對照之可變區選殖至表現載體pTT5 (National Research Council, Canada)中以形成具有一個Trop2特異性結合單元及CDH17特異性結合單元及CD3 scFv的三特異性結合蛋白，該Trop2特異性結合單元包含結合於Trop2之單鏈Fab及Fc區(此類結合單元在本文中亦稱為「Trop2臂」或「Trop2鏈」)，該CDH17特異性結合單元包含結合於CDH17之單鏈Fab及Fc區(此類結合單元在本文中亦稱為「CDH17臂」或「CDH17鏈」)，CD3 scFv附加至該等臂中之一者，較佳CDH17臂之C端。使用20胺基酸之間隔子將scFv與Fc分開。Trop2及CDH17臂之Fc區包括「杵」或「臼」突變(Atwell等人, JMB, 1997, 270, 26-35)且相應鏈稱為杵或臼鏈。對於多片段DNA組裝，根據製造商之方案，使用Gibson組裝及NEBuilder HiFi DNA組裝方法(New England Biolabs, Ipswich, MA, USA)。對DNA mini-prep定序。
各表現載體含有鏈編碼基因(Trop2或CDH17臂/鏈)，亦即編碼信號序列及輕鏈及重鏈之基因之真核啟動子元件，原核選擇標記基因(諸如安比西林)之表現卡匣及複製起點。使此等DNA質體在抗安比西林性大腸桿菌菌落中繁殖且純化。
使用如上所述之Gibson組裝及NEBuilder HiFi DNA組裝方法，選殖包括Trop2/Trop2/CD3、CDH17/CDH17/CD3、Trop2/TNP/CD3、TNP/CDH17/CD3及TNP/TNP/CD3之各種組件中之對照分子，且選殖至pTT5載體中以進行短暫表現。 實例 4 ： 結合 Trop2 、 CDH17 及 CD3 之三特異性三價結合蛋白之表現及純化 藉由用攜帶Trop2/CDH17/CD3-鏈編碼基因之pTT5載體瞬時轉染CHO-E細胞來產生結合Trop2、CDH17及CD3之三特異性分子以及對應對照。簡言之，在搖瓶中在140 rpm攪拌下在37℃及5% CO 2下培養在無血清培養基中懸浮生長之經轉染之CHO-E細胞且保持在指數生長之條件下。在轉染當天，用杵鏈質體及臼鏈質體以1:3質量比以化學方式轉染細胞。隨後以1至2×10 6個細胞/毫升將其接種於1 L Gibco® FreeStyle™ CHO表現培養基(LifeTechnologies, NY, US)中。隨後在軌道震盪下將細胞培育10天，一次饋送200 ml市售進料溶液以允許表現蛋白質。根據製造商說明書，使用Octet®儀器(Pall ForteBio, CA, US)及protA生物感測器尖端測定細胞培養上清液中之抗體力價。
以兩步法自培養上清液純化重組Trop2/CDH17/CD3結合蛋白：首先藉由蛋白A親和層析使用MabSelect™管柱(GE Healthcare)；其次，藉由陽離子交換層析使用Poros 50 HS管柱(Applied Biosystems, Carlsbad, CA, USA)。將經兩步純化之材料儲存於50 mM醋酸鈉及100 mM NaCl pH 5.0之最終緩衝液中，藉由分析型尺寸排阻層析、質譜分析及分析型超速離心評估樣品之純度及異質性程度。進行功能性測試之樣品包含經兩步純化之材料，單體含量＞98%。 實例 4.1 ： 抗 Trop2 抗體之構架工程改造以降低等電點不平衡隨後對含有抗Trop2、抗CDH17及抗CD3之三特異性分子進一步修飾以將觀測到之聚集之量減至最少(在單步ProA純化之後單體約65%)。個別Fv臂之電腦模擬分析顯示，抗Trop2抗體之pI (pI=7.7)比抗CDH17 (pI=8.5)及抗CD3臂(pI=8.8)低1個單位。此工程改造策略之假設為，抗Trop2臂之pI升高至與抗CDH17及抗CD3臂一致將減少聚集及增加單體百分比。突變係選自在至少一條天然存在之重鏈或κ輕鏈(無論家族如何)中之構架位置中具有離胺酸或精胺酸的殘基子集。重鏈(+親本)中存在總共7個所選擇之點突變且輕鏈(+親本)中存在總共4個點突變。電荷變異體之模型化顯示單點突變之併入使抗Trop2 Fv之pI提高至8.3之平均值，且雙突變體(重鏈上之一個，輕鏈上之一個)使pI提高至8.8。
以下突變經選擇適合於提高抗Trop2 Fv之pI：VH：S19K、T23K、G43R、S61K、T72R、S83R、T85R，及VL：Q3R、S65K、S76R、Q79K。編號係基於Kabat編號方案且VH或VL域之第一個胺基酸分別計為編號1 (亦即，突變S19K為VH域之第19個胺基酸中之突變等)。 實例 4.2 ：抗 CD3 scFv 之最佳化以提高穩定性為提高抗CD3 scFv之穩定性，使用基於結構建模之方法。經由MOE (Chemical Computing Group, ULC)中之Antibody Modeler進行的高通量抗體建模，建立CD3#1之Fv部分(SEQ ID NO:222)之分子模型。使用該結構模型計算Fv區中之VL及VH界面穩定性以及其溶液及分子表面的描述符。鑑別經電腦模擬確定影響生物物理學特性之位置，且產生變異體之文庫且針對三特異性格式中之提高之血清穩定性進行篩選。鑑別輕鏈中之八個突變(R23G、E40Q、L45A、G59W、V60T、L77I、E87D及F89Y)及重鏈中之9個突變(K19R、S30N、G49A、D68G、T80S、A81L、N87S、K89R及T90A)，該等突變個別(參見例如CD3#8，SEQ ID NO: 229中)或組合地(參見例如CD3#2 (SEQ ID NO:223)、3 (SEQ ID NO:224)、5 (SEQ ID NO:226)、7 (SEQ I DNO:228)中)影響生物物理學特性。同樣，編號係基於Kabat編號方案且VH或VL域之第一個胺基酸分別計為編號1 (亦即，突變R23G為VL域之第23個胺基酸中之突變等)。 實例 4.3 ： Trop2/CDH17/CD3 結合蛋白之單體含量百分比藉由分析型尺寸排阻層析(aSEC)，確定示例性Trop2/CDH17/CD3結合蛋白之單體百分比，如表2中所示。在Waters (Milfrod, MA, USA) Acquity UPLC系統上使用蛋白質BEH SEC管柱200 Å，1.7 µm，4.6×150 mm (目錄號186005225)進行aSEC。操作條件如下：移動相：50 mM磷酸鈉，200 mM精胺酸及0.05%疊氮化鈉；流動速率：0.5 ml/min；運轉時間：5分鐘；樣品負載量：10 µg；峰值偵測：A280nm；層析圖之自動化處理方法。
Trop2 CDH17 CD3 在第1步純化之後的單體百分比 在第2步純化之後的單體百分比
         (Prot. A) (CEX)
              
Trop2#8 CDH17#1 CD3#1 86.16 ＞98%
Trop2#9 CDH17#1 CD3#1 62.07 ＞98%
Trop2#10 CDH17#1 CD3#1 80.58 ＞98%
Trop2#11 CDH17#1 CD3#1 84.13 ＞98%
Trop2#5 CDH17#1 CD3#1 76.27 ＞98%
Trop2#7 CDH17#1 CD3#1 86.37 ＞98%
Trop2#12 CDH17#8 CD3#9 73.92 ＞98%
Trop2#12 CDH17#8 CD3#10 55.96 ＞98%
Trop2#12 CDH17#8 CD3#2 64.81 ＞98%
Trop2#12 CDH17#8 CD3#7 73.68 ＞98%
Trop2#12 CDH17#8 CD3#3 61.68 ＞98%
Trop2#12 CDH17#8 CD3#8 60.63 ＞98%
Trop2#13 CDH17#8 CD3#2 75.8 ＞98%
Trop2#14 CDH17#8 CD3#2 85 ＞98%
Trop2#15 CDH17#8 CD3#2 77.32 ＞98%
Trop2#16 CDH17#8 CD3#2 74.21 ＞98%
Trop2#17 CDH17#8 CD3#3 74.06 ＞98%
Trop2#14 CDH17#8 CD3#3 74.8 ＞98%
Trop2#18 CDH17#8 CD3#3 73.32 ＞98%
Trop2#15 CDH17#8 CD3#3 76.28 ＞98%
表2：含有Trop2、CDH17及CD3之三特異性分子之第一及第二純化步驟之後的單體百分比。各別結合劑之序列可見於表1。 實例 4.4 ： 熱穩定性藉由熱偏移分析(TSA)測定熱穩定性且代表性Trop2/CDH17/CD3結合蛋白之第一熔融轉變(Tm1)結果展示於表3中。使用QuantStudio 6 Flex即時PCR系統(Applied Biosystems, Waltham, MA)，利用SYPRO Orange (Invitrogen, Carlsbad, CA)作為外源性螢光團獲得隨溫度而變的螢光強度概況。將樣品在具有40 mM氯化鈉及0.02%疊氮化鈉之10 mM組胺酸pH 6.0中稀釋至0.4 mg/ml。以2℃/min之速率用25℃至95℃之熱斜變生成熔融曲線，經由『ROX』過濾器組(Ex：580 ±10 nm，Em：623 ±14 nm)大約每0.4℃收集資料。使用蛋白質熱偏移軟體版本1.3 (ThermoFisher Scientific, Waltham, MA)分析資料。
Trop2# CDH17# CD3# Tm1 ( ℃ )
Trop2#5 CDH17#1 CD3#1 59.5
Trop2#7 CDH17#1 CD3#1 59.3
Trop2#8 CDH17#1 CD3#1 59.1
Trop2#9 CDH17#1 CD3#1 58.6
Trop2#10 CDH17#1 CD3#1 59.7
Trop2#11 CDH17#1 CD3#1 59.9
Trop2#12 CDH17#8 CD3#9 58.3
Trop2#12 CDH17#8 CD3#10 61.5
Trop2#12 CDH17#8 CD3#2 61.8
Trop2#12 CDH17#8 CD3#7 57.6
Trop2#12 CDH17#8 CD3#3 58.8
Trop2#12 CDH17#8 CD3#8 56.6
Trop2#13 CDH17#8 CD3#2 62.5
Trop2#14 CDH17#8 CD3#2 64.4
Trop2#14 CDH17#8 CD3#3 59.3
Trop2#15 CDH17#8 CD3#2 62.1
Trop2#15 CDH17#8 CD3#3 59.2
Trop2#16 CDH17#8 CD3#2 64.6
Trop2#17 CDH17#8 CD3#3 58.9
Trop2#18 CDH17#8 CD3#3 59.1
表3：藉由代表性Trop2/CDH17/CD3結合蛋白之第一熔融轉變(Tm1)量測的熱穩定性 實例 4.5 ： 產生重組蛋白 人類 Trop2-His 及人類 CDH17-His 使用HEK-293細胞(Thermo Fisher)、Lenti-X慢病毒系統(Clontech)及編碼人類Trop2-His (人類Trop2寄存編號P09758)及人類CDH17-His (人類CDH17寄存編號Q12864)之質體生成產生人類Trop2-His及人類CDH17-His之細胞株。為了表現，在37℃、5% CO2及140 rpm震盪下培養及擴增細胞。在表現第0天，粒化細胞且再懸浮於Expi 293培養基中。在表現第3天，藉由在4700 rpm下將細胞粒化40分鐘來收穫經調節之培養上清液。在純化之前將蛋白酶抑制劑添加至生物質。藉由西方墨點法證實表現。用0.5 mM TCEP、0.02% CHAPS、10 mM咪唑調整經調節之培養上清液。在HisTrap Ni excel管柱及緩衝液A：50 mM MES、50 mM NaCl、0.5 mM TCEP、0.02% CHAPS pH 6.5上進行純化。在補充有0.5M咪唑之緩衝液A pH 8.5中，使用自20 mM咪唑至500 mM咪唑之溶離梯度溶離所關注蛋白質。將經彙集之溶離份在以下緩衝液中滲析：50 mM MES、50 mM NaCl、1 mM TCEP、0.02% CHAPS、0.2M精胺酸、3%甘油pH 6.5。藉由質譜分析及分析型超速離心檢核純化材料。 Cyno Trop2-His 及 Cyno CDH17-His 使用HEK-293細胞(Thermo Fisher)、Lenti-X慢病毒系統(Clontech)及編碼Cyno Trop2-His (Cyno Trop2寄存編號：寄存編號XP_001114599.1 (RefSeq))及Cyno CDH17-His (Cyno CDH17寄存編號: XP_005563762.1 (RefSeq))之質體生成產生Cyno Trop2-His及Cyno CDH17-His之細胞株。為了表現，在37℃、5% CO2及140 rpm震盪下培養及擴增細胞。在表現第0天，粒化細胞且再懸浮於Expi 293培養基中。在表現第3天，藉由在4700 rpm下將細胞粒化40分鐘來收穫經調節之培養上清液。在純化之前將蛋白酶抑制劑添加至生物質。藉由西方墨點法證實表現。用0.5 mM TCEP、0.02% CHAPS、10 mM咪唑調整經調節之培養上清液。在HisTrap Ni excel管柱及緩衝液A：50 mM MES、50 mM NaCl、0.5 mM TCEP、0.02% CHAPS pH 6.5上進行純化。在補充有0.5M咪唑之緩衝液A pH 8.5中，使用自20 mM咪唑至500 mM咪唑之溶離梯度溶離所關注蛋白質。將經彙集之溶離份在以下緩衝液中滲析：50 mM MES、50 mM NaCl、1 mM TCEP、0.02% CHAPS、0.2M精胺酸、3%甘油pH 6.5。藉由質譜分析及分析型超速離心檢核純化材料。 實例5：用於選擇結合劑之細胞株的產生  為產生表現單獨或與Trop2組合之全長人類CDH17的穩定HEK293細胞，將CDH17 (蛋白質寄存編號Q12864)之編碼序列選殖至pCMV6 (Origene)中。為產生表現單獨或與CDH17組合之全長人類Trop2的穩定HEK293細胞，自Origene (#RC202519)獲得包含具有C端Myc-DDK標籤之Trop2之編碼序列的pCMV6。使用細胞株核酸轉染套組V (Amaxa)根據製造商說明書轉染HEK293細胞且分別使用遺傳黴素(geneticin)及嘌呤黴素(puromycin)選擇確立穩定純系。
藉由流動式細胞測量術，使用抗Trop2 (R&D# MAB650)及抗CDH17 (R&D# MAB1032)初級抗體，接著經PE標記之抗小鼠二級抗體(Dako# R0480)驗證重組蛋白之表現。 實例6：選擇具有親合力潛能之CDH17結合劑及證實三特異性格式之親合力潛能  測試二價及單價格式之四種不同CDH17結合蛋白(亦即，CDH17#6、CDH17#4、CDH17#7及CDH17#1；均如實例3中所述產生；各別結合劑之序列可見於表1)之結合。為此，藉由流動式細胞測量術分析其與如實例5中所述製備的重組表現人類CDH17之HEK293細胞株之結合。
將HEK293細胞在FACS緩衝液(PBS/0.5% BSA/0.05%疊氮化鈉)中以增加濃度之經兩步純化之二價或單價CDH17結合蛋白染色。用FITC結合之抗人類二級抗體(Invitrogen 05-4211)偵測結合分子。各CDH17結合蛋白之親合力潛能藉由比較各別單價格式之結合曲線與二價形式之結合曲線來評估(圖4)。選擇展示自單價至二價格式之顯著親和力轉變的結合蛋白用於後續實驗。
為進一步測試此等CDH17結合劑活化T細胞之潛能，各種CDH17結合劑組裝成三特異性Trop2/CDH17/CD3結合分子且在單獨表現CDH17或表現CDH17與Trop2之組合的Hek293細胞存在下評估T細胞活化。在此分析中，以10:1之效應:目標細胞比率，將Trop2/CDH17陽性細胞株與作為效應細胞之人類T細胞及增加濃度之Trop2/CDH17/CD3結合分子共培養72小時。藉由用攜帶鏈編碼基因之pTT5載體瞬時轉染CHO-E細胞產生Trop2/CDH17/CD3結合分子，如實例4中所描述。
自Stemcell Technologies獲得冷凍人類周邊血液單核細胞(PBMC)。洗滌細胞且再懸浮於分析培養基中，該分析培養基含有無酚紅之RPMI-1640 (Gibco/Lonza # BE 12-918-F)、5% HiFBS (FBS、HyClone (Thermo Scientific，目錄號：SH30071.03)，加熱不活化，56℃，30分鐘)、Glutamax (Gibco# 35050-061)、27.5 µM β-巰基乙醇(Gibco #21985-023)。使用全T細胞分離套組II (Miltenyi Biotec #130-091-156)藉由陰性選擇自洗滌之PBMC分離T細胞。簡言之，將周邊血液單核細胞再懸浮於40 μl緩衝液PBS/0.5% BSA (Gibco ref#041-94553 M)/2 mM EDTA (Invitrogen ref# 15575-038)/10個Mio細胞中且與10 μl生物素-抗體混合物/10個Mio細胞一起在4℃下培育5分鐘。接著，添加30 µl緩衝液及20 µl抗生物素MicroBeds/1千萬個細胞且在4℃下培育10分鐘。接著，在適合MACS分離器(Miltenyi Biotec)之磁場中將混合物置放於預沖洗之25LS管柱(Miltenyi Biotec #130-042-401)中。收集包含T細胞之流過物且在分析培養基中洗滌。
隨後，將目標細胞及T細胞以1:10之比率與指定濃度(參見圖5)之Trop2/CDH17/CD3結合蛋白一起培育72小時。
為測定T細胞活化，將細胞離心且用針對CD4 (Biolegend #31744)、CD8 (BD #562428)及CD69 (BD#557745)之抗體染色，且藉由流動式細胞測量術量測螢光。結果描繪於圖5中。
藉由比較在僅表現人類CDH17 (圖5A)或表現CDH17與Trop2之組合(圖5B)之HEK293細胞存在下誘導的CD8+ T細胞活化之量來分析親合力潛能。僅選擇在僅表現CDH17之HEK293細胞存在下在100 nM下引起小於20% T細胞活化之結合劑用於進一步評估。 實例7：選擇具有親合力潛能之Trop2結合劑及證實三特異性格式之親合力潛能  測試二價(IgG)或單價(具有虛擬結合臂之杵-臼格式)形式之七種不同Trop2結合劑(Trop2#1至Trop2#7；各別結合劑之序列可見於表1)的結合。在單價格式中，結合位點中之一者置換為與四硝基苯酚(TNP；包括SEQ ID No:167及168之VH及VL域)結合之結合位點，四硝基苯酚係真核情形中不存在之不相關抗原。為此，藉由流動式細胞測量術分析其與如實例5中所述製備的重組表現人類Trop2之HEK293細胞株之結合。如實例4中所描述，產生Trop2結合蛋白。
將HEK293細胞在FACS緩衝液(PBS/0.5% BSA/0.05%疊氮化鈉)中以增加濃度之經兩步純化之二價或單價Trop2結合蛋白染色。用FITC結合之抗人類二級抗體(Invitrogen 05-4211)偵測結合分子。各Trop2結合蛋白之親合力潛能藉由比較各別單價格式之結合曲線與二價形式之結合曲線來評估(圖6)。選擇展示自單價至二價格式之顯著親和力轉變的結合蛋白用於以下實驗。
為進一步測試此等Trop2結合劑活化T細胞之潛能，各種Trop2結合劑組裝成三特異性Trop2/CDH17/CD3結合分子且在單獨表現CDH17或單獨表現Trop2或表現CDH17與Trop2之組合的Hek293細胞存在下評估T細胞活化。在此分析中，以10:1之效應:目標細胞比率，將Trop2/CDH17陽性HEK293細胞株與作為效應細胞之人類T細胞及增加濃度之Trop2/CDH17/CD3結合分子共培養72小時。將具有不同抗原親和力之三種不同Trop2結合劑以三特異性格式與實例6中鑑別之CDH17結合劑組合(圖5A)以在僅表現CDH17之HEK293細胞存在下誘導最低T細胞活化。藉由用攜帶鏈編碼基因之pTT5載體瞬時轉染CHO-E細胞產生Trop2/CDH17/CD3結合分子，如實例4中所描述。如實例6中所述分離人類T細胞。
隨後，將目標細胞及T細胞以1:10之比率與指定濃度(參見圖7)之Trop2/CDH17/CD3結合分子一起培育72小時。
如實例6中所述確定T細胞活化狀態。
藉由比較在僅表現人類Trop2 (圖7B)、僅表現人類CDH17 (圖7C)或表現人類CDH17與人類Trop2之組合(圖7A)之HEK293細胞存在下誘導的CD8+ T細胞上CD69上調之量來分析親合力潛能。同樣，選擇在單價結合情形下，亦即在表現CDH17 (僅)或Trop2 (僅)之細胞上在10 nM下引起小於20% T細胞活化之結合劑用於後續實驗。
藉由基於流動式細胞測量術之史卡查方法(Scatchard method)評估對HEK293細胞上表現之Trop2的結合親和力且揭露對Trop2#1之Kd為2.2nM，對Trop2#5之Kd為0.6且對Trop2#7之Kd為0.4。親合力潛能與經由此方法確定之親和力反相關，此表明僅二價格式之低親和力結合劑允許區分單陽性細胞與雙陽性細胞。 實例8：在細胞結合分析中分析各種三特異性Trop2/CDH17/CD3結合劑組合之親合力潛能  為證實基於親合力之效力增加，將三種不同Trop2/CDH17/CD3三特異性結合分子(Trop2#1/CDH17#1/CD3#1、Trop2#5/CDH17#1/CD3#1、Trop2#7/CDH17#1/CD3#1，參見圖8)之目標結合與雙特異性Trop2/Trop2/CD3結合分子以及三特異性Trop2/TNP/CD3結合分子之結合相比較。為此，藉由流動式細胞測量術測試此等分子與重組表現人類Trop2 (圖8A)或共表現人類Trop2及人類CDH17 (圖8B)之HEK293細胞株之結合。如實例4中所述產生Trop2/CDH17/CD3、Trop2/TNP/CD3及Trop2/Trop2/CD3結合蛋白。
將重組表現人類Trop2或共表現人類Trop2及人類CDH17之HEK293細胞在FACS緩衝液(PBS/0.5% BSA/0.05%疊氮化鈉)中以增加濃度之經兩步純化之Trop2/CDH17/CD3、Trop2/Trop2/CD3及Trop2/TNP/CD3結合分子染色。用FITC結合之抗人類二級抗體(Invitrogen 05-4211)偵測結合分子。藉由比較單價及二價結合曲線來評估各三特異性結合分子之親合力潛能。不選擇僅展示與Trop2之顯著結合之結合蛋白用於親合力最佳化之雙特異性結合方法。結果展示於圖8中。各別結合劑之序列可見於表1。 實例9：表現CDH17、Trop2或共表現兩者之細胞中介導T細胞誘導之溶解的效力。  為解決Trop2/CDH17/CD3結合蛋白對共表現Trop2及CDH17兩種蛋白之人類細胞之選擇性，測試藉由重新引導未經刺激之T細胞至表現人類CDH17及/或人類Trop2之細胞來誘導溶解的能力。
如下所述，使用乳酸去氫酶(LDH)釋放作為細胞溶解之讀取，確定T細胞介導之Trop2/CDH17陽性細胞株之溶解的效力。在此分析中，以10:1之效應:目標細胞比率，將表現Trop2或CDH17或兩者之細胞株與作為效應細胞之人類T細胞及增加濃度之Trop2/CDH17/CD3結合分子共培養72小時。藉由用攜帶鏈編碼基因之pTT5載體瞬時轉染CHO-E細胞產生Trop2/CDH17/CD3結合分子，如實例4中所描述。
如實例6中所述，自冷凍PBMC分離人類T細胞。
使用細胞毒性偵測套組PLUS (Roche)，根據製造商說明書測定細胞毒活性。簡言之，此方法係基於LDH自死亡或細胞質膜受損細胞之釋放。將細胞培養上清液與來自套組之反應混合物一起培育30分鐘且在分光光度計中在500 nm下量測作為細胞溶解之替代的因LDH活性而引起之甲臢形成。根據下式計算相對於最大溶解對照之細胞毒性百分比：
Figure 02_image001
背景：目標細胞+效應細胞 最大溶解：目標細胞+5% Triton X-100 最小溶解：目標細胞
使用GraphPad Prism 5軟體，針對相應Trop2/CDH17/CD3結合分子濃度繪製細胞毒性相對於最大溶解對照之百分比。用四參數邏輯斯諦方程(logistic equation)模型分析劑量反應曲線以評估S形劑量-反應曲線。
雖然三特異性Trop2/CDH17/CD3結合分子以良好功效介導Trop2+/CDH17+細胞之溶解，但僅表現Trop2或僅表現CDH17之細胞株的情況分別並非如此，因此證實該等三特異性分子之親合力增強之生物活性(參見圖9A)。親合力方法之特異性藉由以下事實進一步證實：單價結合Trop2 (Trop2/TNP/CD3)或CDH17 (TNP/CDH17/CD3)之對照分子不能誘導顯著目標細胞溶解。相同格式之Trop2及CDH17之二價結合劑用作對照。
為在癌症背景下證實親合力方法(參見圖9B)，在共表現Trop2/CDH17之大腸直腸癌細胞株DLD-1以及經工程改造缺乏CDH17，因此僅表現Trop2之DLD-1純系中評估重新引導之T細胞之細胞毒性。自ATCC獲得DLD-1細胞且產生引入報導蛋白GFP之缺乏CDH17之DLD-1純系。48小時之後，藉由流動式細胞測量術(Sonysorter)分離GFP陽性轉染物且藉由限制稀釋來分離純系。藉由使用CDH17特異性抗體用西方墨點法分析純系蛋白質提取物之CDH17含量來證實CDH17之缺乏。
Trop2+CDH17-純系之細胞溶解與對Trop2+CDH17+親本細胞株之作用相比顯著減少，藉此證實基於親合力之效力增加。Trop2/CDH17/CD3結合分子對Trop2+CDH17-純系之活性對應於單價Trop2結合劑(Trop2/TNP/CD3)之活性，因此證實對Trop2+/CDH17-目標細胞之作用係Trop2介導的。
圖9展示用代表Trop2結合劑(Trop2#1、#8、#9、#10、#11、#12、#13、#14、#15、#16、#17、#18)與CDH17結合劑(CDH17#1、#8)及CD3結合劑(CD3#1、#2、#3)之若干示例性組合之一系列分子獲得的功能資料，其中顯示基於親合力之效力增加。各別結合劑之序列可見於表1。 實例10：證實CDH17結合對親合力誘導之效力增加的影響  為證實CDH17結合對親合力誘導之效力增加的影響，將五種不同Trop2結合劑與CDH17結合臂或針對不相關目標四硝基苯酚(TNP)之結合劑分別組合成Trop2/CDH17/CD3或Trop2/TNP/CD3結合分子。在此分析中，以10:1之效應:目標細胞比率，將Trop2/CDH17陽性大腸直腸癌細胞株SK-CO1與作為效應細胞之未經刺激之人類T細胞及增加濃度之Trop2/CDH17/CD3或Trop2/TNP/CD3結合分子共培養72小時。藉由用攜帶鏈編碼基因之pTT5載體瞬時轉染CHO-E細胞產生Trop2/CDH17/CD3結合分子，如實例4中所描述。細胞毒性活性如實例9中所述來測定。如實例6中所描述，自健康供體PBMC分離T細胞。CDH17結合臂引起效力顯著增加，Trop2/CDH17/CD3之EC50相對於Trop2/TNP/CD3增加40-60倍；如圖10中所示(各別結合劑之序列可見於表1)。 實例11：比較杵-臼格式  以兩種不同杵-臼格式(亦即，臼臂上為Trop2且杵臂上為CDH17/CD3或反過來)產生三特異性分子，且如實例9中所述來評估其對T細胞介導之細胞毒性的作用。儘管兩種類型之格式均很好地起作用，但意外地發現CD3與CDH17結合部分均位於分子之臼部分上的構築體一致地具有較高效能，與所用結合劑無關(示例性結果參見圖11；相應結合劑之序列可見於表1中)。 實例12：證實活體內腫瘤生長抑制  使用用人類T細胞重組之人類異種移植小鼠模型進行功效研究。詳言之，將人類HPAF-II胰臟癌細胞(5×10 7)皮下注射(s.c.)至NOG小鼠之右背側腹。平行地，如上所述，使用全T細胞分離套組II (Miltenyi Biotec #130-091-156)藉由陰性選擇自PBMC分離人類T細胞。
隨後，使用T細胞活化/擴增套組人類(Miltenyi Biotec目錄號130-091-441，批號5170720843)將T細胞擴增20天。簡言之，抗生物素MACSiBeadTM粒子負載有CD2生物素、CD3生物素、CD28生物素且以每個粒子2個細胞之比率轉移至經純化之T細胞且在20個單位重組IL-2 (R&D#202-IL-050/CF)存在下以0.5-1×10 6個細胞/毫升之密度培育20天。細胞每三天補充20個單位新鮮IL-2。在注射於動物中之前的三天，用裝載有CD2生物素、CD3生物素、CD28生物素之抗生物素MACSiBeadTM粒子以每4個細胞1個珠粒之比率再刺激T細胞額外三天。最後，用MACSiMAG分離器(Miltenyi Biotec)移除珠粒且在PBS中洗滌T細胞。
第14天，基於腫瘤體積將動物隨機分為處理組且腹膜內(i.p.)注射2×10 7個人類T細胞。第17天開始用三特異性分子進行處理。以每週一次給藥方案，藉由靜脈內(i.v.)推注注射至側尾靜脈中，投與Trop2/CDH17/CD3結合蛋白、Trop2/TNP/CD3結合蛋白、TNP/CDH17/CD3結合蛋白或媒劑緩衝液(50 mM NaOAc、100 mM NaCl，pH 5.0)。藉由外部測徑規量測監測腫瘤生長且使用標準半橢球公式計算腫瘤體積。
在研究結束時，藉由對人類CD3進行免疫組織化學(IHC)染色在脾中證實人類T細胞植入。僅將在研究結束時展示人類T細胞植入之彼等動物包括於統計分析中。在研究期間早期出於道德原因對達到處死準則之動物施以安樂死。
如圖12中所示，每週一次用三特異性Trop2/CDH17/CD3結合分子(由SEQ ID NO:436與437之組合或SEQ ID NO:214與271之組合表示)處理負載腫瘤小鼠誘導顯著腫瘤消退，但用相同劑量及處理時間間隔之對照Trop2/TNP/CD3或TNP/CDH17/CD3結合分子處理無顯著腫瘤消退。
圖 1 ： CDH17 及 Trop2 在 GI 癌組織 上共表現 ， 但不在正常組織上共表現。腫瘤及關鍵正常組織中之基因表現。標度為MAS5正規化之表現值的經log2轉換之任意單位。軸標記為基因符號(TACSTD2.202286_s_at = Trop2，CDH17.209847_at = CDH17)及Affymetrix探針組。 圖 2 ： 證實 GI 腫瘤中之目標表現。在選定人類癌症組織上使用結合於Trop2 (ENZ-ABS380，Enzo)及CDH17 (760-4865，Roche Ventana)之抗體的免疫組織化學。 圖 3 ： 本發明之示例性三特異性結合分子之示意圖。 圖 4 ： 選擇具有親合力潛能之 CDH17 結合劑。藉由流動式細胞測量術測試，所示四種不同CDH17結合蛋白(二價與單價格式)結合於重組表現人類CDH17之HEK293細胞株。抗TNP結合臂為針對四硝基酚之不相關(非結合)對照。 圖 5 ：證實呈三特異性格式之 CDH17 結合劑的親合力潛能。在僅表現CDH17 (左圖)或共表現Trop2/CDH17 (右圖)之HEK293細胞存在下具有不同CDH17抗原結合位點之Trop2/CDH17/CD3分子介導的CD8+ T細胞上之T細胞活化標記物CD69的上調。 圖 6 ： 選擇具有親合力潛能之 Trop2 結合劑。藉由流動式細胞測量術測試，所示七種不同Trop2結合劑(二價與單價格式)結合於重組表現人類Trop2之HEK293細胞株。抗TNP結合臂為針對四硝基酚之不相關(非結合)對照。 圖 7 ： 證實呈三特異性格式之 Trop2 結合劑的親合力潛能。在僅表現CDH17 (C)、僅表現Trop2 (B)或共表現Trop2/CDH17 (A)之HEK293細胞存在下具有不同CDH17抗原結合位點之Trop2/CDH17/CD3分子介導的CD8+ T細胞上之T細胞活化標記物CD69的上調。 圖 8 ：在細胞結合分析中分析各種三特異性 Trop2/CDH17/CD3 結合劑組合之親合力潛能。藉由流動式細胞測量術測試，呈三特異性格式之Trop2與CDH17結合劑之不同組合結合於重組表現人類Trop2 (A)或共表現人類Trop2及CDH17 (B)之HEK293細胞株。抗TNP結合臂為針對四硝基酚之不相關(非結合)對照。 圖 9 ： 表現 CDH17 、 Trop2 或共表現兩者之細胞中介導 T 細胞誘導之溶解 的效力。使用各種Trop2/CDH17/CD3結合劑(A中展示一種示例性Trop2/CDH17/CD3結合劑)以及單價或二價結合於僅一個目標之各種對照分子評估重組表現CDH17 (左)、Trop2 (中)或兩者(右)之HEK293細胞的重新引導之T細胞介導之溶解(A)。使用不同Trop2/CDH17/CD3結合劑組合以及單價Trop2結合對照評估僅表現Trop2 (左)或表現CDH17與Trop2兩者(右)之DLD-1來源細胞株的重新引導之T細胞介導之溶解(B)。 圖 10 ： 證實 CDH17 結合對親合力誘導之效力增加的影響。使用不同Trop2/CDH17/CD3分子以及Trop2/TNP/CD3對照分子評估SK-CO1細胞的重新引導之T細胞介導之溶解。 圖 11 ： 杵 - 臼格式比較。使用呈兩種不同杵-臼格式之三特異性分子評估SK-CO1細胞的重新引導之T細胞介導之溶解。圖例中之括號中的參考「臼」或「杵」指示CDH17/CD3臂之定位，亦即「臼」指示CDH17/CD3在臼臂上(參見SEQ ID No:271、272及424至427)，而「杵」指示CDH17/CD3在杵臂(參見SEQ ID No:428至433)上。 圖 12 ： 證實活體內之腫瘤生長抑制。不同Trop2/CDH17/CD3結合劑以及單價對照結合劑對人類化小鼠模型中HPAF-II來源之異種移植物腫瘤之生長的作用。 
              
          <![CDATA[<110> 德商百靈佳殷格翰國際股份有限公司(Boehringer Ingelheim International GmbH)]]>
          <![CDATA[<120> 新穎三特異性結合分子]]>
          <![CDATA[<130> 12-0454-FF]]>
          <![CDATA[<150> EP 21180033.9]]>
          <![CDATA[<151> 2021-06-17]]>
          <![CDATA[<160> 437]]>
          <![CDATA[<170> BiSSAP 1.3.6]]>
          <![CDATA[<210> 1]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR1]]>
          <![CDATA[<400> 1]]>
          Asp Tyr Thr Met His 
          1               5   
          <![CDATA[<210> 2]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR2]]>
          <![CDATA[<400> 2]]>
          Gly Ile Tyr Pro Asn Tyr Gly Asp Thr Asn Tyr Asn Glu Lys Phe Lys 
          1               5                   10                  15      
          Asp 
          <![CDATA[<210> 3]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR3]]>
          <![CDATA[<400> 3]]>
          Lys Thr Val Leu Leu Arg Leu Arg Tyr Phe Asp Val 
          1               5                   10          
          <![CDATA[<210> 4]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR1]]>
          <![CDATA[<400> 4]]>
          Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Ala 
          1               5                   10      
          <![CDATA[<210> 5]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR2]]>
          <![CDATA[<400> 5]]>
          Asn Ala Ile Thr Leu Ala Asp 
          1               5           
          <![CDATA[<210> 6]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR3]]>
          <![CDATA[<400> 6]]>
          Gln His Phe Trp Ser Thr Pro Phe Thr 
          1               5                   
          <![CDATA[<210> 7]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR1]]>
          <![CDATA[<400> 7]]>
          Arg Tyr Ser Val His 
          1               5   
          <![CDATA[<210> 8]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> P]]>RT
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR2]]>
          <![CDATA[<400> 8]]>
          Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Asp Phe Lys Pro 
          1               5                   10                  15      
          <![CDATA[<210> 9]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR3]]>
          <![CDATA[<400> 9]]>
          Lys Gly Ser Tyr Tyr Thr Asn Tyr Gly Ala Met Asp Tyr 
          1               5                   10              
          <![CDATA[<210> 10]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR1]]>
          <![CDATA[<400> 10]]>
          Lys Ala Ser Gln Asp Ile Asn Lys Tyr Ile Ala 
          1               5                   10      
          <![CDATA[<210> 11]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR2]]>
          <![CDATA[<400> 11]]>
          Tyr Thr Ser Thr Leu Gln Pro 
          1               5           
          <![CDATA[<210> 12]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR3]]>
          <![CDATA[<400> 12]]>
          Leu Gln Tyr Asp Asn Leu Trp Thr 
          1               5               
          <![CDATA[<210> 13]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11、#12、#13、#14、#15、#16、#17、#18 HCDR1]]>
          <![CDATA[<400> 13]]>
          Ser Gly Tyr Tyr Trp Asn 
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          <![CDATA[<210> 14]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR2]]>
          <![CDATA[<400> 14]]>
          Tyr Ile Ser Tyr Asp Gly Arg Asn Asn Tyr Asn Pro Ser Leu Lys Asn 
          1               5                   10                  15      
          <![CDATA[<210>]]> 15
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11、#12、#13、#14、#15、#16、#17、#18 HCDR3]]>
          <![CDATA[<400> 15]]>
          Asp Thr Thr Ala Tyr Phe Asp Tyr 
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          <![CDATA[<210> 16]]>
          <![CDATA[<211> 15]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 LCDR1]]>
          <![CDATA[<400> 16]]>
          Arg Ala Ser Glu Ser Val Asp Ser Ser Val Asn Arg Phe Met His 
          1               5                   10                  15  
          <![CDATA[<210> 17]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11、#12、#13、#14、#15、#16、#17、#18 LCDR2]]>
          <![CDATA[<400> 17]]>
          Arg Ala Ser Asn Leu Glu Ser 
          1               5           
          <![CDATA[<210> 18]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11、#12、#13、#14、#15、#16、#17、#18 LCDR3]]>
          <![CDATA[<400> 18]]>
          Gln Gln Ser Asn Glu Asp Pro Tyr Thr 
          1               5                   
          <![CDATA[<210> 19]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12、#13、#14、#15、#16、#17、#18 HCDR2]]>
          <![CDATA[<400> 19]]>
          Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu Lys Ser 
          1               5                   10                  15      
          <![CDATA[<210> 20]]>
          <![CDATA[<211> 15]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12、#13、#14、#15、#16、#17、#18 LCDR1]]>
          <![CDATA[<400]]>> 20]]&gt;
          <br/><![CDATA[Arg Ala Ser Glu Ser Val Ser Ser Ser Val Asn Arg Phe Leu His 
          1               5                   10                  15  
          <![CDATA[<210> 21]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR1]]>
          <![CDATA[<400> 21]]>
          Asp Tyr Tyr Met Asn 
          1               5   
          <![CDATA[<210> 22]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR2]]>
          <![CDATA[<400> 22]]>
          Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Gly Tyr Asn Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 23]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR3]]>
          <![CDATA[<400> 23]]>
          Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   10  
          <![CDATA[<210> 24]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 LCDR1]]>
          <![CDATA[<400> 24]]>
          Lys Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Phe Leu His 
          1               5                   10                  15      
          <![CDATA[<210> 25]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9、#10 LCDR2]]>
          <![CDATA[<400> 25]]>
          Lys Val Ser Asn Arg Phe Ser 
          1               5           
          <![CDATA[<210> 26]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 LCDR3]]>
          <![CDATA[<400> 26]]>
          Ser Gln Ser Thr His Val Tyr Thr 
          1               5               
          <![CDATA[<210> 27]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR1]]>
          <![CDATA[<400> 27]]>
          Asn Tyr Tyr Ile His 
          1               5   
          <![CDATA[<210> 28]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR2]]>
          <![CDATA[<400> 28]]>
          Tyr Ile Tyr Pro Gly Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 29]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR3]]>
          <![CDATA[<400> 29]]>
          Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   
          <![CDATA[<210> 30]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 LCDR1]]>
          <![CDATA[<400> 30]]>
          Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His 
          1               5                   10                  15      
          <![CDATA[<210> 31]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 LCDR3]]>
          <![CDATA[<400> 31]]>
          Ser Gln Ser Thr His Val Trp Thr 
          1               5               
          <![CDATA[<210> 32]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1、#8 HCDR1]]>
          <![CDATA[<400> 32]]>
          Asp His Thr Ile His 
          1               5   
          <![CDATA[<210> 33]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR2]]>
          <![CDATA[<400> 33]]>
          Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 34]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1、#8 HCDR3]]>
          <![CDATA[<400> 34]]>
          Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
          1               5                   10                  
          <![CDATA[<210> 35]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 LCDR1]]>
          <![CDATA[<400> 35]]>
          Lys Ser Ser Gln Ser Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu 
          1               5                   10                  15      
          Ala 
          <![CDATA[<210> 36]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 LCDR2]]>
          <![CDATA[<400> 36]]>
          Trp Ala Ser Thr Arg Glu Ser 
          1               5           
          <![CDATA[<210> 37]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1、#8 LCDR3]]>
          <![CDATA[<400> 37]]>
          Gln Gln Tyr Tyr Ser Tyr Pro Trp Thr 
          1               5                   
          <![CDATA[<210> 38]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR2]]>
          <![CDATA[<400> 38]]>
          Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu Lys Phe Gln 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 39]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LCDR1]]>
          <![CDATA[<400> 39]]>
          Arg Ala Ser Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Gln Tyr Leu 
          1               5                   10                  15      
          Ala 
          <![CDATA[<210> 40]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LCDR2]]>
          <![CDATA[<400> 40]]>
          Gly Ala Ser Thr Arg Glu Thr 
          1               5           
          <![CDATA[<210> 41]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> ]]>PRT
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#25 HCDR1]]>
          <![CDATA[<400> 41]]>
          Thr Tyr Ala Met Asn 
          1               5   
          <![CDATA[<210> 42]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#5、CD3#8至#16、#21、#24、#25 HCDR2]]>
          <![CDATA[<400> 42]]>
          Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
          1               5                   10                  15      
          Val Lys Asp 
          <![CDATA[<210> 43]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#11、#13、#14、#16、#21、#24、#25 HCDR3]]>
          <![CDATA[<400> 43]]>
          His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  
          <![CDATA[<210> 44]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#11、#13、#14、#15 LCDR1]]>
          <![CDATA[<400> 44]]>
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 45]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#13、#17、#19、#20、#22、#23、#24 LCDR2]]>
          <![CDATA[<400> 45]]>
          Gly Thr Asn Lys Arg Ala Pro 
          1               5           
          <![CDATA[<210> 46]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#2、#11 LCDR3]]>
          <![CDATA[<400> 46]]>
          Ala Leu Trp Tyr Ser Asn Lys Trp Val 
          1               5                   
          <![CDATA[<210> 47]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1、所有CD3#3至#10、#13至#16 LCDR3]]>
          <![CDATA[<400> 47]]>
          Ala Leu Trp Tyr Ser Asn Leu Trp Val 
          1               5                   
          <![CDATA[<210> 48]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#6、#7、#17、#18、#19 HCDR2]]>
          <![CDATA[<400> 48]]>
          Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
          1               5                   10                  15      
          Val Lys Gly 
          <![CDATA[<210> 49]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12、#15 HCDR3]]>
          <![CDATA[<400> 49]]>
          His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  
          <![CDATA[<210> 50]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12 LCDR1]]>
          <![CDATA[<400> 50]]>
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Tyr Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 51]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12 LCDR3]]>
          <![CDATA[<400> 51]]>
          Ala Leu Trp Tyr Ser Asn His Trp Val 
          1               5                   
          <![CDATA[<210> 52]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#14、#15、#16、#18、#21、#25 LCDR2]]>
          <![CDATA[<400> 52]]>
          Gly Thr Asn Ile Arg Ala Pro 
          1               5           
          <![CDATA[<210> 53]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16 LCDR1]]>
          <![CDATA[<400> 53]]>
          Ile Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 54]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17、#18、#19、#22、#23 HCDR3]]>
          <![CDATA[<400> 54]]>
          His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  
          <![CDATA[<210> 55]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17 LCDR1]]>
          <![CDATA[<400> 55]]>
          Gly Arg Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 56]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#18、#23 LCDR1]]>
          <![CDATA[<400> 56]]>
          Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Trp Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 57]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19、#22、#25 LC]]>DR1
          <![CDATA[<400> 57]]>
          Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 58]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#20 HCDR2]]>
          <![CDATA[<400> 58]]>
          Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
          1               5                   10                  15      
          Val Lys Gly 
          <![CDATA[<210> 59]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#20 HCDR3]]>
          <![CDATA[<400> 59]]>
          His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  
          <![CDATA[<210> 60]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#20 LCDR1]]>
          <![CDATA[<400> 60]]>
          Val Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 61]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#21、#2]]>4 LCDR1
          <![CDATA[<400> 61]]>
          Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Tyr Tyr Ala Asn 
          1               5                   10                  
          <![CDATA[<210> 62]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#22 HCDR2]]>
          <![CDATA[<400> 62]]>
          Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ile 
          1               5                   10                  15      
          Val Lys Gly 
          <![CDATA[<210> 63]]>
          <![CDATA[<211> 19]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#23 HCDR2]]>
          <![CDATA[<400> 63]]>
          Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ile 
          1               5                   10                  15      
          Val Lys Gly 
          <![CDATA[<210> 64]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26、#27 HCDR2]]>
          <![CDATA[<400> 64]]>
          Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Glu Lys Phe Lys 
          1               5                   10                  15      
          Asn 
          <![CDATA[<210> 65]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26、#27 HCDR3]]>
          <![CDATA[<400> 65]]>
          Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10  
          <![CDATA[<210> 66]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#26至#30、#33、#35、#37、#39、#42、#43 LCDR1]]>
          <![CDATA[<400> 66]]>
          Lys Ser Ser Gln Ser Leu Leu Asn Ser Arg Thr Arg Lys Asn Tyr Leu 
          1               5                   10                  15      
          Ala 
          <![CDATA[<210> 67]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#26至#43 LCDR2]]>
          <![CDATA[<400> 67]]>
          Trp Ala Ser Thr Arg Lys Ser 
          1               5           
          <![CDATA[<210> 68]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#26至#43 LCDR3]]>
          <![CDATA[<400> 68]]>
          Ile Gln Ser Phe Ile Leu Arg Thr 
          1               5               
          <![CDATA[<210> 69]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#28、#34 HCDR2]]>
          <![CDATA[<400> 69]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 70]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#28、#32、#39、#42、#43 HCDR3]]>
          <![CDATA[<400> 70]]>
          Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10  
          <![CDATA[<210> 71]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#31、#32、#34、#36 LCDR1]]>
          <![CDATA[<400> 71]]>
          Lys Ser Ser Gln Ser Leu Leu Asn Ala Arg Thr Arg Lys Asn Tyr Leu 
          1               5                   10                  15      
          Ala 
          <![CDATA[<210> 72]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#29 HCDR2]]>
          <![CDATA[<400> 72]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Ala Glu Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 73]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#30、#32 HCDR2]]>
          <![CDATA[<400> 73]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Ala Gln Lys Phe Gln 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 74]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#31 HCDR2]]>
          <![CDATA[<400> 74]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Ala Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 75]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#33 HCDR2]]>
          <![CDATA[<400> 75]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Asn Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 76]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> ]]>CD3#35 HCDR2
          <![CDATA[<400> 76]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Asn Gln Lys Phe Gln 
          1               5                   10                  15      
          Asn 
          <![CDATA[<210> 77]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#36 HCDR2]]>
          <![CDATA[<400> 77]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe Gln 
          1               5                   10                  15      
          Asn 
          <![CDATA[<210> 78]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#37 HCDR2]]>
          <![CDATA[<400> 78]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Ala Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 79]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38、#40、#41 HCDR2]]>
          <![CDATA[<400> 79]]>
          Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr Asn Gln Lys Phe Lys 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 80]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38、#40、#41 LCDR1]]>
          <![CDATA[<400> 80]]>
          Arg Ser Ser Gln Ser Leu Leu Asn Ser Arg Thr Arg Lys Asn Tyr Leu 
          1               5                   10                  15      
          Ala 
          <![CDATA[<210> 81]]>
          <![CDATA[<211> 17]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#39、#42、#43 HCDR2]]>
          <![CDATA[<400> 81]]>
          Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe Gln 
          1               5                   10                  15      
          Gly 
          <![CDATA[<210> 82]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#26至#43 HCDR1]]>
          <![CDATA[<400> 82]]>
          Ser Tyr Trp Met His 
          1               5   
          <![CDATA[<210> 83]]>
          <![CDATA[<211> 121]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 VH]]>
          <![CDATA[<400> 83]]>
          Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Leu Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
                      20                  25                  30          
          Thr Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Gly Ile Tyr Pro Asn Tyr Gly Asp Thr Asn Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Asp Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ser Arg Lys Thr Val Leu Leu Arg Leu Arg Tyr Phe Asp Val Trp Gly 
                      100                 105                 110         
          Thr Gly Thr Thr Val Thr Val Ser Ser 
                  115                 120     
          <![CDATA[<210> 84]]>
          <![CDATA[<211> 107]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 VL]]>
          <![CDATA[<400> 84]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
                      20                  25                  30          
          Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val 
                  35                  40                  45              
          Tyr Asn Ala Ile Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn Ser Leu Gln Pro 
          65                  70                  75                  80  
          Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp Ser Thr Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
                      100                 105         
          <![CDATA[<210> 85]]>
          <![CDATA[<211> 121]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 VH]]>
          <![CDATA[<400> 85]]>
          Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
          1               5                   10                  15      
          Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Leu Ser Leu Ser Arg Tyr 
                      20                  25                  30          
          Ser Val His Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu 
                  35                  40                  45              
          Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Asp Phe Lys 
              50                  55                  60                  
          Pro Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu 
          65                  70                  75                  80  
          Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala 
                          85                  90                  95      
          Arg Lys Gly Ser Tyr Tyr Thr Asn Tyr Gly Ala Met Asp Tyr Trp Gly 
                      100                 105                 110         
          Gln Gly Thr Ser Val Thr Val Ser Ser 
                  115                 120     
          <![CDATA[<210> 86]]>
          <![CDATA[<211> 106]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 VL]]>
          <![CDATA[<400> 86]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 
          1               5                   10                  15      
          Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Tyr 
                      20                  25                  30          
          Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile 
                  35                  40                  45              
          His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro 
          65                  70                  75                  80  
          Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Trp Thr 
                          85                  90                  95      
          Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105     
          <![CDATA[<210> 87]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 VH]]>
          <![CDATA[<400> 87]]>
          Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Pro Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
                      20                  25                  30          
          Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Gly Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Ser Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 88]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223]]>> Trop2#9 VL]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 88]]&gt;
          <br/><![CDATA[Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 89]]>
          <![CDATA[<211> 118]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 VH]]>
          <![CDATA[<400> 89]]>
          Gln Ile Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Pro Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
                      20                  25                  30          
          Tyr Ile His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Gly Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Ala Asp Asn Pro Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 
                      100                 105                 110         
          Ser Val Thr Val Ser Ser 
                  115             
          <![CDATA[<210> 90]]>
          <![CDATA[<211> 110]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 VL]]>
          <![CDATA[<400> 90]]>
          Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly Asp 
          1               5                   10                  15      
          Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser Asn 
                      20                  25                  30          
          Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser 
          65                  70                  75                  80  
          Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser Thr 
                          85                  90                  95      
          His Val Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110 
          <![CDATA[<210> 91]]>
          <![CDATA[<211> 117]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 VH]]>
          <![CDATA[<400> 91]]>
          Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 
                  35                  40                  45              
          Met Gly Tyr Ile Ser Tyr Asp Gly Arg Asn Asn Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Glu Asn Gln Phe Phe 
          65                  70                  75                  80  
          Leu Lys Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Thr Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr 
                      100                 105                 110         
          Leu Thr Val Ser Ser 
                  115         
          <![CDATA[<210> 92]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 VL]]>
          <![CDATA[<400> 92]]>
          Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asn 
          65                  70                  75                  80  
          Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 93]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12 VH]]>
          <![CDATA[<400> 93]]>
          Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Asn Ile Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                          85                  90                  95      
          Ser His Val Pro Pro Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
                      100                 105                 110         
          <![CDATA[<210> 94]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12及#13 VL]]>
          <![CDATA[<400> 94]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 95]]>
          <![CDATA[<211> 117]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#13、#14、#15及#17 VH]]>
          <![CDATA[<400> 95]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser 
                  115         
          <![CDATA[<210> 96]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#14及#18 VL]]>
          <![CDATA[<400> 96]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Lys Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 97]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#15及#16 VL]]>
          <![CDATA[<400> 97]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 98]]>
          <![CDATA[<211> 117]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#16及#18 VH]]>
          <![CDATA[<400> 98]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Arg Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser 
                  115         
          <![CDATA[<210> 99]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#17 VL]]>
          <![CDATA[<400> 99]]>
          Asp Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 100]]>
          <![CDATA[<211> 123]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 VH]]>
          <![CDATA[<400> 100]]>
          Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp His 
                      20                  25                  30          
          Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
                      100                 105                 110         
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                  115                 120             
          <![CDATA[<210> 101]]>
          <![CDATA[<211> 113]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 VL]]>
          <![CDATA[<400> 101]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys 
          <![CDATA[<210> 102]]>
          <![CDATA[<211> 123]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 VH]]>
          <![CDATA[<400> 102]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp His 
                      20                  25                  30          
          Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
                      100                 105                 110         
          Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120             
          <![CDATA[<210> 103]]>
          <![CDATA[<211> 113]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 VL]]>
          <![CDATA[<400> 103]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys 
          <![CDATA[<210> 104]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 所有CD3#1至#4、#8至#11、#13、#14、#16、#21 VH]]>
          <![CDATA[<400> 104]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120                 125 
          <![CDATA[<210> 105]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1 VL]]>
          <![CDATA[<400> 105]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 106]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#2 VL]]>
          <![CDATA[<400> 106]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Lys Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 107]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#3、#4 VL]]>
          <![CDATA[<400> 107]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 108]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#5 VH]]>
          <![CDATA[<400> 108]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120                 125 
          <![CDATA[<210> 109]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#5 VL]]>
          <![CDATA[<400> 109]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 110]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#6 VH]]>
          <![CDATA[<400> 110]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120                 125 
          <![CDATA[<210> 111]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#6 VL]]>
          <![CDATA[<400> 111]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 112]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#7 VH]]>
          <![CDATA[<400> 112]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120                 125 
          <![CDATA[<210> 113]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#7 VL]]>
          <![CDATA[<400> 113]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 114]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#8 VL]]>
          <![CDATA[<400> 114]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 115]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#9 VL]]>
          <![CDATA[<400> 115]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 116]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#10 VL]]>
          <![CDATA[<400> 116]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 117]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#11 VL]]>
          <![CDATA[<400> 117]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Lys Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 118]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12 VH]]>
          <![CDATA[<400> 118]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120                 125 
          <![CDATA[<210> 119]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12 VL]]>
          <![CDATA[<400> 119]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 120]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#13 VL]]>
          <![CDATA[<400> 120]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Val Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 121]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#14 VL]]>
          <![CDATA[<400> 121]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Tyr Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 122]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#15 VL]]>
          <![CDATA[<400> 122]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Trp Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 123]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16 VL]]>
          <![CDATA[<400> 123]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Ile Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 124]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17、#18、#19 VH]]>
          <![CDATA[<400> 124]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120                 125 
          <![CDATA[<210> 125]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17 VL]]>
          <![CDATA[<400> 125]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Arg Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 126]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#18 VL]]>
          <![CDATA[<400> 126]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Trp Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 127]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19、#20、#22 VL]]>
          <![CDATA[<400> 127]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 128]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#20 VH]]>
          <![CDATA[<400> 128]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Gly Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120                 125 
          <![CDATA[<210> 129]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#21 VL]]>
          <![CDATA[<400> 129]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Lys Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 130]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#22 VH]]>
          <![CDATA[<400> 130]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Gly Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ile Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120                 125 
          <![CDATA[<210> 131]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#23 VL]]>
          <![CDATA[<400> 131]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ile Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120                 125 
          <![CDATA[<210> 132]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#23 VL]]>
          <![CDATA[<400> 132]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Trp Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 133]]>
          <![CDATA[<211> 125]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#24、#25 VH]]>
          <![CDATA[<400> 133]]>
          Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
          1               5                   10                  15      
          Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr 
                      20                  25                  30          
          Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
                  35                  40                  45              
          Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
              50                  55                  60                  
          Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
          65                  70                  75                  80  
          Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                          85                  90                  95      
          Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
                      100                 105                 110         
          Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                  115                 120                 125 
          <![CDATA[<210> 134]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#24 VL]]>
          <![CDATA[<400> 134]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 135]]>
          <![CDATA[<211> 109]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25 VL]]>
          <![CDATA[<400> 135]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                      100                 105                 
          <![CDATA[<210> 136]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26 VH]]>
          <![CDATA[<400> 136]]>
          Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Gly Lys Pro Gly Thr 
          1               5                   10                  15      
          Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Asn Arg Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Gln Leu Ser Thr Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 137]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26 VL]]>
          <![CDATA[<400> 137]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 138]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27 VH]]>
          <![CDATA[<400> 138]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 139]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27、#39 VL]]>
          <![CDATA[<400> 139]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 140]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#28 VH]]>
          <![CDATA[<400> 140]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 141]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#28、#29、#30、#42 VL]]>
          <![CDATA[<400> 141]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 142]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#29 VH]]>
          <![CDATA[<400> 142]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Ala Glu Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 143]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#30 VH]]>
          <![CDATA[<400> 143]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Ala Gln Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 144]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#31 VH]]>
          <![CDATA[<400> 144]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Ala Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 145]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#31、#32]]>
          <![CDATA[<400> 145]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 146]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#32 VH]]>
          <![CDATA[<400> 146]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Ala Gln Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 147]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#33 VH]]>
          <![CDATA[<400> 147]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 148]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#33、#35、#37、#43 VL]]>
          <![CDATA[<400> 148]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 149]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#34 VH]]>
          <![CDATA[<400> 149]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 150]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#34 VL]]>
          <![CDATA[<400> 150]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 151]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#35 VH]]>
          <![CDATA[<400> 151]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Gln Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 152]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#36 VH]]>
          <![CDATA[<400> 152]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Gln Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 153]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#37 VH]]>
          <![CDATA[<400> 153]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr Ala Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 154]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38 VH]]>
          <![CDATA[<400> 154]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 155]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38 VL]]>
          <![CDATA[<400> 155]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Asn Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 156]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#39 VH]]>
          <![CDATA[<400> 156]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 157]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#40 VH]]>
          <![CDATA[<400> 157]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 158]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#40 VL]]>
          <![CDATA[<400> 158]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 159]]>
          <![CDATA[<211>]]> 119
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#41 VH]]>
          <![CDATA[<400> 159]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 160]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#41 VL]]>
          <![CDATA[<400> 160]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 161]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#42 VH]]>
          <![CDATA[<400> 161]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Leu Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 162]]>
          <![CDATA[<211> 119]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#43 VH]]>
          <![CDATA[<400> 162]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Thr Val Thr Val Ser Ser 
                  115                 
          <![CDATA[<210> 163]]>
          <![CDATA[<211> 111]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#5 VL]]>
          <![CDATA[<400> 163]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          His Gly Asn Ile Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Leu Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Phe Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110     
          <![CDATA[<210> 164]]>
          <![CDATA[<211> 118]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<22]]>3> Trop2#5 VH]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 164]]&gt;
          <br/><![CDATA[Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Ile Phe Thr Asp Tyr 
                      20                  25                  30          
          Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Glu Ser Asp Phe Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 
                      100                 105                 110         
          Ser Val Thr Val Ser Ser 
                  115             
          <![CDATA[<210> 165]]>
          <![CDATA[<211> 106]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#7 VL]]>
          <![CDATA[<400> 165]]>
          Asp Ile Gln Met Thr Gln Ser Ser Ser Ser Phe Ser Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asp Ile Tyr Asn Arg 
                      20                  25                  30          
          Leu Ala Trp Phe Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile 
                  35                  40                  45              
          Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Arg Gly 
              50                  55                  60                  
          Ser Arg Ser Gly Lys Asp Tyr Thr Leu Ser Ile Thr Ser Leu Gln Thr 
          65                  70                  75                  80  
          Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Ser Thr Trp Thr 
                          85                  90                  95      
          Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105     
          <![CDATA[<210> 166]]>
          <![CDATA[<211> ]]>120
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#7 VH]]>
          <![CDATA[<400> 166]]>
          Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Met Ser Cys Arg Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
                      20                  25                  30          
          Ala Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Asn Pro Tyr Asn Gly Gly Thr Lys Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Gly Arg Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Glu Gly Ile Tyr Tyr Gly Ala Trp Phe Ala Tyr Trp Gly Gln 
                      100                 105                 110         
          Gly Thr Leu Val Thr Val Ser Ala 
                  115                 120 
          <![CDATA[<210> 167]]>
          <![CDATA[<211> 121]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP VH]]>
          <![CDATA[<400> 167]]>
          Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 
          1               5                   10                  15      
          Thr Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn Tyr 
                      20                  25                  30          
          Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Val 
                  35                  40                  45              
          Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Lys Tyr Ala Asp Asp Phe 
              50                  55                  60                  
          Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Gly Ile Tyr Asp Gly Tyr His Trp Tyr Phe Asp Val Trp Gly 
                      100                 105                 110         
          Ala Gly Thr Thr Val Thr Val Ser Ser 
                  115                 120     
          <![CDATA[<210> 168]]>
          <![CDATA[<211> 112]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP VL]]>
          <![CDATA[<400> 168]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Ile Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          <![CDATA[<210> 169]]>
          <![CDATA[<211> 214]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LC]]>
          <![CDATA[<400> 169]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
                      20                  25                  30          
          Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val 
                  35                  40                  45              
          Tyr Asn Ala Ile Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn Ser Leu Gln Pro 
          65                  70                  75                  80  
          Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp Ser Thr Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys 
              210                 
          <![CDATA[<210> 170]]>
          <![CDATA[<211> 450]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223]]>> Trop2#1 HC (杵)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 170]]&gt;
          <br/><![CDATA[Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Leu Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
                      20                  25                  30          
          Thr Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Gly Ile Tyr Pro Asn Tyr Gly Asp Thr Asn Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Asp Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ser Arg Lys Thr Val Leu Leu Arg Leu Arg Tyr Phe Asp Val Trp Gly 
                      100                 105                 110         
          Thr Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                  115                 120                 125             
          Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
              130                 135                 140                 
          Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
          145                 150                 155                 160 
          Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                          165                 170                 175     
          Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
                      180                 185                 190         
          Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
                  195                 200                 205             
          Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
              210                 215                 220                 
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          225                 230                 235                 240 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                          245                 250                 255     
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                      260                 265                 270         
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                  275                 280                 285             
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
              290                 295                 300                 
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
          305                 310                 315                 320 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                          325                 330                 335     
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                      340                 345                 350         
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                  355                 360                 365             
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
              370                 375                 380                 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
          385                 390                 395                 400 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                          405                 410                 415     
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                      420                 425                 430         
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                  435                 440                 445             
          Pro Gly 
              450 
          <![CDATA[<210> 171]]>
          <![CDATA[<211> 213]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LC]]>
          <![CDATA[<400> 171]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 
          1               5                   10                  15      
          Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Tyr 
                      20                  25                  30          
          Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile 
                  35                  40                  45              
          His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro 
          65                  70                  75                  80  
          Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Trp Thr 
                          85                  90                  95      
          Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro 
                      100                 105                 110         
          Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
                  115                 120                 125             
          Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
              130                 135                 140                 
          Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
          145                 150                 155                 160 
          Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                          165                 170                 175     
          Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
                      180                 185                 190         
          Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
                  195                 200                 205             
          Asn Arg Gly Glu Cys 
              210             
          <![CDATA[<210> 172]]>
          <![CDATA[<211> 450]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HC (杵)]]>
          <![CDATA[<400> 172]]>
          Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln 
          1               5                   10                  15      
          Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Leu Ser Leu Ser Arg Tyr 
                      20                  25                  30          
          Ser Val His Trp Val Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu 
                  35                  40                  45              
          Gly Met Ile Trp Gly Gly Gly Ser Thr Asp Tyr Asn Ser Asp Phe Lys 
              50                  55                  60                  
          Pro Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu 
          65                  70                  75                  80  
          Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala 
                          85                  90                  95      
          Arg Lys Gly Ser Tyr Tyr Thr Asn Tyr Gly Ala Met Asp Tyr Trp Gly 
                      100                 105                 110         
          Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                  115                 120                 125             
          Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
              130                 135                 140                 
          Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
          145                 150                 155                 160 
          Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                          165                 170                 175     
          Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
                      180                 185                 190         
          Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
                  195                 200                 205             
          Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
              210                 215                 220                 
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          225                 230                 235                 240 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                          245                 250                 255     
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                      260                 265                 270         
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                  275                 280                 285             
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
              290                 295                 300                 
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
          305                 310                 315                 320 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                          325                 330                 335     
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                      340                 345                 350         
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                  355                 360                 365             
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
              370                 375                 380                 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
          385                 390                 395                 400 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                          405                 410                 415     
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                      420                 425                 430         
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                  435                 440                 445             
          Pro Gly 
              450 
          <![CDATA[<210> 173]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 LC]]>
          <![CDATA[<400> 173]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 174]]>
          <![CDATA[<211> 448]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HC (杵)]]>
          <![CDATA[<400> 174]]>
          Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Pro Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
                      20                  25                  30          
          Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Gly Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly 
                      100                 105                 110         
          Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
                  115                 120                 125             
          Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
              130                 135                 140                 
          Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
          145                 150                 155                 160 
          Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                          165                 170                 175     
          Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
                      180                 185                 190         
          Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
                  195                 200                 205             
          Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
              210                 215                 220                 
          Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 
          225                 230                 235                 240 
          Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                          245                 250                 255     
          Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
                      260                 265                 270         
          Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
                  275                 280                 285             
          Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
              290                 295                 300                 
          Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
          305                 310                 315                 320 
          Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                          325                 330                 335     
          Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
                      340                 345                 350         
          Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 
                  355                 360                 365             
          Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
              370                 375                 380                 
          Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
          385                 390                 395                 400 
          Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                          405                 410                 415     
          Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
                      420                 425                 430         
          Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445             
          <![CDATA[<210> 175]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 LC]]>
          <![CDATA[<40]]>0> 175]]&gt;
          <br/><![CDATA[Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 176]]>
          <![CDATA[<211> 447]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HC (杵)]]>
          <![CDATA[<400> 176]]>
          Gln Ile Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Pro Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
                      20                  25                  30          
          Tyr Ile His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Gly Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Ala Asp Asn Pro Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 
                      100                 105                 110         
          Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
                  115                 120                 125             
          Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
              130                 135                 140                 
          Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
          145                 150                 155                 160 
          Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                          165                 170                 175     
          Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
                      180                 185                 190         
          Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
                  195                 200                 205             
          Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
              210                 215                 220                 
          His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 
          225                 230                 235                 240 
          Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                          245                 250                 255     
          Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                      260                 265                 270         
          Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
                  275                 280                 285             
          Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
              290                 295                 300                 
          Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
          305                 310                 315                 320 
          Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                          325                 330                 335     
          Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                      340                 345                 350         
          Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
                  355                 360                 365             
          Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
              370                 375                 380                 
          Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
          385                 390                 395                 400 
          Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                          405                 410                 415     
          Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                      420                 425                 430         
          Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445         
          <![CDATA[<210> 177]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<21]]>2> PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; Trop2#11 LC]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 177]]&gt;
          <br/><![CDATA[Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asn 
          65                  70                  75                  80  
          Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 178]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HC (杵)]]>
          <![CDATA[<400> 178]]>
          Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 
                  35                  40                  45              
          Met Gly Tyr Ile Ser Tyr Asp Gly Arg Asn Asn Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Glu Asn Gln Phe Phe 
          65                  70                  75                  80  
          Leu Lys Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Thr Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr 
                      100                 105                 110         
          Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 179]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12 LC]]>
          <![CDATA[<400> 179]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 180]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12 HC (杵)]]>
          <![CDATA[<400> 180]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 181]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<22]]>3> Trop2#13 LC]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 181]]&gt;
          <br/><![CDATA[Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 182]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#13 HC (杵)]]>
          <![CDATA[<400> 182]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210>]]> 183
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#14 LC]]>
          <![CDATA[<400> 183]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Lys Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 184]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#14 HC (杵)]]>
          <![CDATA[<400> 184]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 185]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#15 LC]]>
          <![CDATA[<400> 185]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 186]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#15 HC (杵)]]>
          <![CDATA[<400> 186]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 187]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#16 LC]]>
          <![CDATA[<400> 187]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 188]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#16 HC (杵)]]>
          <![CDATA[<400> 18]]>8
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Arg Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 189]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#17 LC]]>
          <![CDATA[<400> 189]]>
          Asp Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 190]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PR]]>T
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#17 HC (杵)]]>
          <![CDATA[<400> 190]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 191]]>
          <![CDATA[<211> 218]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#18 LC]]>
          <![CDATA[<400> 191]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Lys Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215             
          <![CDATA[<210> 192]]>
          <![CDATA[<211> 446]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#18 HC (杵)]]>
          <![CDATA[<400> 192]]>
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
          1               5                   10                  15      
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                      20                  25                  30          
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
                  35                  40                  45              
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
              50                  55                  60                  
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
          65                  70                  75                  80  
          Leu Lys Leu Ser Arg Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                      100                 105                 110         
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
                  115                 120                 125             
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
              130                 135                 140                 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
          145                 150                 155                 160 
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                          165                 170                 175     
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                      180                 185                 190         
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
                  195                 200                 205             
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
              210                 215                 220                 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
          225                 230                 235                 240 
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                          245                 250                 255     
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                      260                 265                 270         
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                  275                 280                 285             
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
              290                 295                 300                 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
          305                 310                 315                 320 
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                          325                 330                 335     
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                      340                 345                 350         
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
                  355                 360                 365             
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
              370                 375                 380                 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
          385                 390                 395                 400 
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                          405                 410                 415     
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                      420                 425                 430         
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                  435                 440                 445     
          <![CDATA[<210> 193]]>
          <![CDATA[<211> 219]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP LC]]>
          <![CDATA[<400> 193]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Ile Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
                  115                 120                 125             
          Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
              130                 135                 140                 
          Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
          145                 150                 155                 160 
          Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                          165                 170                 175     
          Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
                      180                 185                 190         
          Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                  195                 200                 205             
          Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215                 
          <![CDATA[<210> 194]]>
          <![CDATA[<211]]>> 450]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; TNP HC (臼)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 194]]&gt;
          <br/><![CDATA[Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 
          1               5                   10                  15      
          Thr Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn Tyr 
                      20                  25                  30          
          Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Val 
                  35                  40                  45              
          Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Lys Tyr Ala Asp Asp Phe 
              50                  55                  60                  
          Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Gly Ile Tyr Asp Gly Tyr His Trp Tyr Phe Asp Val Trp Gly 
                      100                 105                 110         
          Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                  115                 120                 125             
          Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
              130                 135                 140                 
          Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
          145                 150                 155                 160 
          Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                          165                 170                 175     
          Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
                      180                 185                 190         
          Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
                  195                 200                 205             
          Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
              210                 215                 220                 
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          225                 230                 235                 240 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                          245                 250                 255     
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                      260                 265                 270         
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                  275                 280                 285             
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
              290                 295                 300                 
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
          305                 310                 315                 320 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                          325                 330                 335     
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                      340                 345                 350         
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                  355                 360                 365             
          Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
              370                 375                 380                 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
          385                 390                 395                 400 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
                          405                 410                 415     
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                      420                 425                 430         
          His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser 
                  435                 440                 445             
          Pro Gly 
              450 
          <![CDATA[<210> 195]]>
          <![CDATA[<211> 450]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP HC (杵)]]>
          <![CDATA[<400> 195]]>
          Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 
          1               5                   10                  15      
          Thr Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn Tyr 
                      20                  25                  30          
          Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Val 
                  35                  40                  45              
          Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Lys Tyr Ala Asp Asp Phe 
              50                  55                  60                  
          Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Gly Ile Tyr Asp Gly Tyr His Trp Tyr Phe Asp Val Trp Gly 
                      100                 105                 110         
          Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                  115                 120                 125             
          Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
              130                 135                 140                 
          Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
          145                 150                 155                 160 
          Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                          165                 170                 175     
          Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
                      180                 185                 190         
          Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
                  195                 200                 205             
          Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
              210                 215                 220                 
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
          225                 230                 235                 240 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                          245                 250                 255     
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                      260                 265                 270         
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                  275                 280                 285             
          His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
              290                 295                 300                 
          Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
          305                 310                 315                 320 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                          325                 330                 335     
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                      340                 345                 350         
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                  355                 360                 365             
          Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
              370                 375                 380                 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
          385                 390                 395                 400 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                          405                 410                 415     
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                      420                 425                 430         
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                  435                 440                 445             
          Pro Gly 
              450 
          <![CDATA[<210> 196]]>
          <![CDATA[<211> 220]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 LC]]>
          <![CDATA[<400> 196]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215                 220 
          <![CDATA[<210> 197]]>
          <![CDATA[<211> 452]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HC (]]>臼)
          <![CDATA[<400> 197]]>
          Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro Gly Ala 
          1               5                   10                  15      
          Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp His 
                      20                  25                  30          
          Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu Trp Ile 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu Lys Phe 
              50                  55                  60                  
          Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                          85                  90                  95      
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
                      100                 105                 110         
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly 
                  115                 120                 125             
          Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
              130                 135                 140                 
          Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
          145                 150                 155                 160 
          Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                          165                 170                 175     
          Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
                      180                 185                 190         
          Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
                  195                 200                 205             
          Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 
              210                 215                 220                 
          Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 
          225                 230                 235                 240 
          Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                          245                 250                 255     
          Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
                      260                 265                 270         
          Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
                  275                 280                 285             
          Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
              290                 295                 300                 
          Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
          305                 310                 315                 320 
          Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                          325                 330                 335     
          Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
                      340                 345                 350         
          Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 
                  355                 360                 365             
          Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
              370                 375                 380                 
          Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
          385                 390                 395                 400 
          Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 
                          405                 410                 415     
          Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
                      420                 425                 430         
          Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser 
                  435                 440                 445             
          Leu Ser Pro Gly 
              450         
          <![CDATA[<210> 198]]>
          <![CDATA[<211> 220]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LC]]>
          <![CDATA[<400> 198]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
              210                 215                 220 
          <![CDATA[<210> 199]]>
          <![CDATA[<211> 452]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HC (臼)]]>
          <![CDATA[<400> 199]]>
          Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 
          1               5                   10                  15      
          Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asp His 
                      20                  25                  30          
          Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
                  35                  40                  45              
          Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu Lys Phe 
              50                  55                  60                  
          Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 
          65                  70                  75                  80  
          Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                          85                  90                  95      
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
                      100                 105                 110         
          Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
                  115                 120                 125             
          Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
              130                 135                 140                 
          Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
          145                 150                 155                 160 
          Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                          165                 170                 175     
          Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
                      180                 185                 190         
          Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
                  195                 200                 205             
          Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 
              210                 215                 220                 
          Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 
          225                 230                 235                 240 
          Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                          245                 250                 255     
          Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
                      260                 265                 270         
          Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
                  275                 280                 285             
          Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
              290                 295                 300                 
          Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
          305                 310                 315                 320 
          Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                          325                 330                 335     
          Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
                      340                 345                 350         
          Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 
                  355                 360                 365             
          Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
              370                 375                 380                 
          Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
          385                 390                 395                 400 
          Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 
                          405                 410                 415     
          Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
                      420                 425                 430         
          Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser 
                  435                 440                 445             
          Leu Ser Pro Gly 
              450         
          <![CDATA[<210> 200]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1全長(杵)]]>
          <![CDATA[<400> 200]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
                      20                  25                  30          
          Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val 
                  35                  40                  45              
          Tyr Asn Ala Ile Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn Ser Leu Gln Pro 
          65                  70                  75                  80  
          Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp Ser Thr Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser 
              210                 215                 220                 
          Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser 
          225                 230                 235                 240 
          Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Glu Val Gln Leu 
                          245                 250                 255     
          Gln Gln Ser Gly Pro Glu Leu Leu Lys Pro Gly Ala Ser Val Lys Ile 
                      260                 265                 270         
          Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Thr Met His Trp 
                  275                 280                 285             
          Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile Gly Gly Ile Tyr 
              290                 295                 300                 
          Pro Asn Tyr Gly Asp Thr Asn Tyr Asn Glu Lys Phe Lys Asp Lys Ala 
          305                 310                 315                 320 
          Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg 
                          325                 330                 335     
          Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ser Arg Lys Thr 
                      340                 345                 350         
          Val Leu Leu Arg Leu Arg Tyr Phe Asp Val Trp Gly Thr Gly Thr Thr 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 201]]>
          <![CDATA[<211> 705]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#2全長(杵)]]>
          <![CDATA[<400> 201]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Gln Ser Ala Ser Leu Gly 
          1               5                   10                  15      
          Asp Ser Val Thr Ile Thr Cys Leu Ala Ser Gln Thr Ile Gly Thr Trp 
                      20                  25                  30          
          Leu Ala Trp Tyr Gln Arg Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile 
                  35                  40                  45              
          Tyr Gly Ala Thr Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Asn Gly Ser Gly Thr Lys Phe Ser Phe Lys Ile Ser Gly Leu Gln Ala 
          65                  70                  75                  80  
          Glu Asp Phe Val Ser Tyr Phe Cys Gln Gln Leu Tyr Ser Thr Pro Tyr 
                          85                  90                  95      
          Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser 
              210                 215                 220                 
          Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser 
          225                 230                 235                 240 
          Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Glu Val Gln Leu 
                          245                 250                 255     
          Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile 
                      260                 265                 270         
          Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Phe Met Asp Trp 
                  275                 280                 285             
          Val Lys Leu Ser His Glu Lys Ser Leu Glu Trp Ile Gly Asp Ile Asn 
              290                 295                 300                 
          Pro His Asn Gly Gly Ser Asp Tyr Asn Gln Lys Phe Lys Gly Lys Ala 
          305                 310                 315                 320 
          Thr Leu Thr Val Asp Arg Ser Ser Ser Thr Ala Tyr Met Glu Leu Arg 
                          325                 330                 335     
          Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Lys Gly Pro 
                      340                 345                 350         
          Tyr Tyr Tyr Gly Gly Gly Pro Tyr Trp Tyr Phe Asp Val Trp Gly Thr 
                  355                 360                 365             
          Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
              370                 375                 380                 
          Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
          385                 390                 395                 400 
          Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
                          405                 410                 415     
          Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                      420                 425                 430         
          Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
                  435                 440                 445             
          Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
              450                 455                 460                 
          Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 
          465                 470                 475                 480 
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 
                          485                 490                 495     
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                      500                 505                 510         
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                  515                 520                 525             
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
              530                 535                 540                 
          Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
          545                 550                 555                 560 
          Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
                          565                 570                 575     
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                      580                 585                 590         
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                  595                 600                 605             
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
              610                 615                 620                 
          Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
          625                 630                 635                 640 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
                          645                 650                 655     
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                      660                 665                 670         
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                  675                 680                 685             
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
              690                 695                 700                 
          Gly 
          705 
          <![CDATA[<210> 202]]>
          <![CDATA[<211> 696]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#3全長(杵)]]>
          <![CDATA[<400> 202]]>
          Asp Ile Leu Leu Thr Gln Ser Pro Ala Ile Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Asn Ile Gly Thr Ser 
                      20                  25                  30          
          Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 
                  35                  40                  45              
          Lys Tyr Ala Ser Glu Ser Ile Tyr Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile Asn Ser Val Glu Ser 
          65                  70                  75                  80  
          Glu Asp Ile Gly Asp Tyr Tyr Cys Gln Gln Ser Asn Ser Trp Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser 
              210                 215                 220                 
          Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser 
          225                 230                 235                 240 
          Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Gln Val Gln Leu 
                          245                 250                 255     
          Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Leu 
                      260                 265                 270         
          Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Ile Asn Trp 
                  275                 280                 285             
          Val Arg Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Asn Ile Tyr 
              290                 295                 300                 
          Pro Gly Asn Ser Ile Thr Asn Tyr Asn Glu Asn Phe Lys Ser Lys Ala 
          305                 310                 315                 320 
          Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser 
                          325                 330                 335     
          Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Thr Ser Ser Ser 
                      340                 345                 350         
          Ser Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala 
                  355                 360                 365             
          Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 
              370                 375                 380                 
          Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
          385                 390                 395                 400 
          Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
                          405                 410                 415     
          Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
                      420                 425                 430         
          Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
                  435                 440                 445             
          Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 
              450                 455                 460                 
          Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
          465                 470                 475                 480 
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                          485                 490                 495     
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      500                 505                 510         
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  515                 520                 525             
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              530                 535                 540                 
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          545                 550                 555                 560 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          565                 570                 575     
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      580                 585                 590         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                  595                 600                 605             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              610                 615                 620                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          625                 630                 635                 640 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          645                 650                 655     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      660                 665                 670         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  675                 680                 685             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695     
          <![CDATA[<210> 203]]>
          <![CDATA[<211> 696]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#4全長(杵)]]>
          <![CDATA[<400> 203]]>
          Asp Ile Leu Leu Ile Gln Ser Pro Ala Ile Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr His 
                      20                  25                  30          
          Ile His Trp Phe Gln Gln Arg Lys Asn Gly Ser Pro Arg Leu Leu Ile 
                  35                  40                  45              
          Asp Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Asp Phe Ile Leu Thr Ile Asn Ser Val Glu Ser 
          65                  70                  75                  80  
          Glu Asp Ile Ala Asp Tyr Tyr Cys Gln His Ser His Ser Trp Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser 
              210                 215                 220                 
          Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser 
          225                 230                 235                 240 
          Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Gln Val Gln Leu 
                          245                 250                 255     
          Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met 
                      260                 265                 270         
          Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Ile Tyr Trp Ile Asn Trp 
                  275                 280                 285             
          Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Asn Ile Phe 
              290                 295                 300                 
          Pro Gly Arg Gly Ile Thr Asn Tyr Asn Glu Lys Phe Lys Thr Lys Ala 
          305                 310                 315                 320 
          Ser Leu Thr Leu Asp Thr Ser Ser Ser Thr Val Tyr Met Gln Leu Ser 
                          325                 330                 335     
          Ser Leu Thr Phe Glu Asp Ser Ala Val Tyr Tyr Cys Ser Arg Gly Ser 
                      340                 345                 350         
          Asn Ser Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala 
                  355                 360                 365             
          Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 
              370                 375                 380                 
          Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
          385                 390                 395                 400 
          Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
                          405                 410                 415     
          Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
                      420                 425                 430         
          Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
                  435                 440                 445             
          Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 
              450                 455                 460                 
          Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
          465                 470                 475                 480 
          Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                          485                 490                 495     
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                      500                 505                 510         
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                  515                 520                 525             
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
              530                 535                 540                 
          Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
          545                 550                 555                 560 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                          565                 570                 575     
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                      580                 585                 590         
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                  595                 600                 605             
          Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro 
              610                 615                 620                 
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
          625                 630                 635                 640 
          Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                          645                 650                 655     
          Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                      660                 665                 670         
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                  675                 680                 685             
          Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695     
          <![CDATA[<210> 204]]>
          <![CDATA[<211> 703]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#5全長(杵)]]>
          <![CDATA[<400> 204]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          His Gly Asn Ile Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Leu Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Phe Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala 
                      260                 265                 270         
          Ser Val Lys Met Ser Cys Lys Ala Ser Gly Phe Ile Phe Thr Asp Tyr 
                  275                 280                 285             
          Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
              290                 295                 300                 
          Gly Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe 
          305                 310                 315                 320 
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
                          325                 330                 335     
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Glu Ser Asp Phe Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 
                  355                 360                 365             
          Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
              370                 375                 380                 
          Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
          385                 390                 395                 400 
          Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
                          405                 410                 415     
          Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                      420                 425                 430         
          Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
                  435                 440                 445             
          Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
              450                 455                 460                 
          Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
          465                 470                 475                 480 
          His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 
                          485                 490                 495     
          Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                      500                 505                 510         
          Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                  515                 520                 525             
          Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
              530                 535                 540                 
          Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
          545                 550                 555                 560 
          Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
                          565                 570                 575     
          Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                      580                 585                 590         
          Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                  595                 600                 605             
          Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
              610                 615                 620                 
          Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
          625                 630                 635                 640 
          Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
                          645                 650                 655     
          Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                      660                 665                 670         
          Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                  675                 680                 685             
          Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700             
          <![CDATA[<210> 205]]>
          <![CDATA[<211> 695]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#6全長(杵)]]>
          <![CDATA[<400> 205]]>
          Asp Ile Leu Leu Thr Gln Ser Pro Ala Ile Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Ser 
                      20                  25                  30          
          Ile His Trp Phe Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 
                  35                  40                  45              
          Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Val Glu Ser 
          65                  70                  75                  80  
          Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Thr Asn Thr Trp Pro Phe 
                          85                  90                  95      
          Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
                      100                 105                 110         
          Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
                  115                 120                 125             
          Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
              130                 135                 140                 
          Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
          145                 150                 155                 160 
          Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                          165                 170                 175     
          Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
                      180                 185                 190         
          Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
                  195                 200                 205             
          Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser 
              210                 215                 220                 
          Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser 
          225                 230                 235                 240 
          Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Gln Val Gln Leu 
                          245                 250                 255     
          Gln Gln Ser Gly Thr Glu Leu Val Arg Pro Gly Thr Ser Val Lys Met 
                      260                 265                 270         
          Ser Cys Lys Ala Ala Gly Tyr Thr Phe Thr Asn Tyr Trp Ile Asn Trp 
                  275                 280                 285             
          Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Asn Ile Tyr 
              290                 295                 300                 
          Pro Gly Gly Gly Tyr Thr Asn Tyr Asn Glu Lys Phe Lys Gly Lys Ala 
          305                 310                 315                 320 
          Ser Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser 
                          325                 330                 335     
          Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys Ala Arg Gly Ile 
                      340                 345                 350         
          Asn Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser 
                  355                 360                 365             
          Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
              370                 375                 380                 
          Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
          385                 390                 395                 400 
          Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
                          405                 410                 415     
          His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                      420                 425                 430         
          Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
                  435                 440                 445             
          Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
              450                 455                 460                 
          Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
          465                 470                 475                 480 
          Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                          485                 490                 495     
          Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                      500                 505                 510         
          Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                  515                 520                 525             
          Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
              530                 535                 540                 
          Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
          545                 550                 555                 560 
          Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
                          565                 570                 575     
          Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                      580                 585                 590         
          Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
                  595                 600                 605             
          Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
              610                 615                 620                 
          Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
          625                 630                 635                 640 
          Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
                          645                 650                 655     
          Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                      660                 665                 670         
          Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                  675                 680                 685             
          Ser Leu Ser Leu Ser Pro Gly 
              690                 695 
          <![CDATA[<210> 206]]>
          <![CDATA[<211> 700]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#7全長(杵)]]>
          <![CDATA[<400> 206]]>
          Asp Ile Gln Met Thr Gln Ser Ser Ser Ser Phe Ser Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asp Ile Tyr Asn Arg 
                      20                  25                  30          
          Leu Ala Trp Phe Gln Gln Lys Pro Gly Asn Ala Pro Arg Leu Leu Ile 
                  35                  40                  45              
          Ser Gly Ala Thr Ser Leu Glu Thr Gly Val Pro Ser Arg Phe Arg Gly 
              50                  55                  60                  
          Ser Arg Ser Gly Lys Asp Tyr Thr Leu Ser Ile Thr Ser Leu Gln Thr 
          65                  70                  75                  80  
          Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Trp Ser Thr Trp Thr 
                          85                  90                  95      
          Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro 
                      100                 105                 110         
          Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
                  115                 120                 125             
          Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
              130                 135                 140                 
          Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
          145                 150                 155                 160 
          Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                          165                 170                 175     
          Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
                      180                 185                 190         
          Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
                  195                 200                 205             
          Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser Gly 
              210                 215                 220                 
          Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser Gly 
          225                 230                 235                 240 
          Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Glu Val Gln Leu Gln 
                          245                 250                 255     
          Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Met Ser 
                      260                 265                 270         
          Cys Arg Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ala Met His Trp Val 
                  275                 280                 285             
          Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Asn Pro 
              290                 295                 300                 
          Tyr Asn Gly Gly Thr Lys Tyr Asn Glu Lys Phe Lys Gly Arg Ala Thr 
          305                 310                 315                 320 
          Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr Met Glu Leu Ser Ser 
                          325                 330                 335     
          Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Glu Gly Ile 
                      340                 345                 350         
          Tyr Tyr Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr 
                  355                 360                 365             
          Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
              370                 375                 380                 
          Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
          385                 390                 395                 400 
          Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
                          405                 410                 415     
          Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 
                      420                 425                 430         
          Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 
                  435                 440                 445             
          Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 
              450                 455                 460                 
          Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 
          465                 470                 475                 480 
          Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu 
                          485                 490                 495     
          Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
                      500                 505                 510         
          Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
                  515                 520                 525             
          Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
              530                 535                 540                 
          Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
          545                 550                 555                 560 
          Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
                          565                 570                 575     
          Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
                      580                 585                 590         
          Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
                  595                 600                 605             
          Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
              610                 615                 620                 
          Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
          625                 630                 635                 640 
          Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
                          645                 650                 655     
          Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
                      660                 665                 670         
          Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
                  675                 680                 685             
          His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700 
          <![CDATA[<210> 207]]>
          <![CDATA[<211> 701]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223>]]> Trop2#8全長(杵)
          <![CDATA[<400> 207]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 
          1               5                   10                  15      
          Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Tyr 
                      20                  25                  30          
          Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile 
                  35                  40                  45              
          His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly 
              50                  55                  60                  
          Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro 
          65                  70                  75                  80  
          Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Trp Thr 
                          85                  90                  95      
          Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro 
                      100                 105                 110         
          Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
                  115                 120                 125             
          Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
              130                 135                 140                 
          Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
          145                 150                 155                 160 
          Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                          165                 170                 175     
          Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
                      180                 185                 190         
          Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
                  195                 200                 205             
          Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser Gly 
              210                 215                 220                 
          Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser Gly 
          225                 230                 235                 240 
          Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser Gln Val Gln Leu Lys 
                          245                 250                 255     
          Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Ile Thr 
                      260                 265                 270         
          Cys Thr Val Ser Gly Leu Ser Leu Ser Arg Tyr Ser Val His Trp Val 
                  275                 280                 285             
          Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu Gly Met Ile Trp Gly 
              290                 295                 300                 
          Gly Gly Ser Thr Asp Tyr Asn Ser Asp Phe Lys Pro Arg Leu Ser Ile 
          305                 310                 315                 320 
          Ser Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu 
                          325                 330                 335     
          Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala Arg Lys Gly Ser Tyr 
                      340                 345                 350         
          Tyr Thr Asn Tyr Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val 
                  355                 360                 365             
          Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
              370                 375                 380                 
          Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
          385                 390                 395                 400 
          Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
                          405                 410                 415     
          Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                      420                 425                 430         
          Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
                  435                 440                 445             
          Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
              450                 455                 460                 
          Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
          465                 470                 475                 480 
          Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
                          485                 490                 495     
          Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                      500                 505                 510         
          Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
                  515                 520                 525             
          Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
              530                 535                 540                 
          Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
          545                 550                 555                 560 
          Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                          565                 570                 575     
          Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                      580                 585                 590         
          Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
                  595                 600                 605             
          Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
              610                 615                 620                 
          Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
          625                 630                 635                 640 
          Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
                          645                 650                 655     
          Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                      660                 665                 670         
          Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
                  675                 680                 685             
          Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700     
          <![CDATA[<210> 208]]>
          <![CDATA[<211> 704]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9全長(杵)]]>
          <![CDATA[<400> 208]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Phe Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Pro Val Lys Pro Gly Ala 
                      260                 265                 270         
          Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
                  275                 280                 285             
          Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
              290                 295                 300                 
          Gly Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Gly Tyr Asn Gln Lys Phe 
          305                 310                 315                 320 
          Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
                          325                 330                 335     
          Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly 
                  355                 360                 365             
          Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
              370                 375                 380                 
          Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
          385                 390                 395                 400 
          Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
                          405                 410                 415     
          Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                      420                 425                 430         
          Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
                  435                 440                 445             
          Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
              450                 455                 460                 
          Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
          465                 470                 475                 480 
          Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 
                          485                 490                 495     
          Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                      500                 505                 510         
          Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
                  515                 520                 525             
          Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
              530                 535                 540                 
          Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
          545                 550                 555                 560 
          Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
                          565                 570                 575     
          Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                      580                 585                 590         
          Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
                  595                 600                 605             
          Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 
              610                 615                 620                 
          Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
          625                 630                 635                 640 
          Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                          645                 650                 655     
          Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                      660                 665                 670         
          Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
                  675                 680                 685             
          Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700                 
          <![CDATA[<210> 209]]>
          <![CDATA[<211> 703]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10全長(杵)]]>
          <![CDATA[<400> 209]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Ile Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala 
                      260                 265                 270         
          Pro Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
                  275                 280                 285             
          Tyr Ile His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
              290                 295                 300                 
          Gly Tyr Ile Tyr Pro Gly Asn Gly Ala Thr Ala Tyr Asn Gln Lys Phe 
          305                 310                 315                 320 
          Lys Gly Lys Ala Thr Leu Thr Ala Asp Asn Pro Ser Ser Thr Ala Tyr 
                          325                 330                 335     
          Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                      340                 345                 350         
          Ala Arg Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr 
                  355                 360                 365             
          Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
              370                 375                 380                 
          Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
          385                 390                 395                 400 
          Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
                          405                 410                 415     
          Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                      420                 425                 430         
          Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
                  435                 440                 445             
          Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
              450                 455                 460                 
          Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
          465                 470                 475                 480 
          His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser 
                          485                 490                 495     
          Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                      500                 505                 510         
          Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                  515                 520                 525             
          Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
              530                 535                 540                 
          Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
          545                 550                 555                 560 
          Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
                          565                 570                 575     
          Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                      580                 585                 590         
          Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                  595                 600                 605             
          Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
              610                 615                 620                 
          Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
          625                 630                 635                 640 
          Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
                          645                 650                 655     
          Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                      660                 665                 670         
          Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                  675                 680                 685             
          Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700             
          <![CDATA[<210> 210]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11全長(杵)]]>
          <![CDATA[<400> 210]]>
          Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asn 
          65                  70                  75                  80  
          Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 
              290                 295                 300                 
          Met Gly Tyr Ile Ser Tyr Asp Gly Arg Asn Asn Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Glu Asn Gln Phe Phe 
                          325                 330                 335     
          Leu Lys Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Thr Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr 
                  355                 360                 365             
          Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 211]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12全長(杵)]]>
          <![CDATA[<400> 211]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 212]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#13全長(杵)]]>
          <![CDATA[<400> 212]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 213]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#14全長(杵)]]>
          <![CDATA[<400> 213]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Lys Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 214]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#15全長(杵)]]>
          <![CDATA[<400> 214]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 215]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#16全長(杵)]]>
          <![CDATA[<400> 215]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Arg Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 216]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#17]]>全長(杵)
          <![CDATA[<400> 216]]>
          Asp Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 217]]>
          <![CDATA[<211> 702]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#18全長(杵)]]>
          <![CDATA[<400> 217]]>
          Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
          1               5                   10                  15      
          Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
              50                  55                  60                  
          Arg Phe Ser Gly Lys Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
          65                  70                  75                  80  
          Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp 
              290                 295                 300                 
          Ile Gly Tyr Ile Ser Tyr Ser Gly Arg Asn Leu Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser 
                          325                 330                 335     
          Leu Lys Leu Ser Arg Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                  355                 360                 365             
          Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 218]]>
          <![CDATA[<211> 707]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP全長(臼)]]>
          <![CDATA[<400> 218]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Ile Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
                  115                 120                 125             
          Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
              130                 135                 140                 
          Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
          145                 150                 155                 160 
          Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                          165                 170                 175     
          Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
                      180                 185                 190         
          Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                  195                 200                 205             
          Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser 
              210                 215                 220                 
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly 
          225                 230                 235                 240 
          Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly 
                          245                 250                 255     
          Ser Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly 
                      260                 265                 270         
          Glu Thr Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn 
                  275                 280                 285             
          Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp 
              290                 295                 300                 
          Val Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Lys Tyr Ala Asp Asp 
          305                 310                 315                 320 
          Phe Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala 
                          325                 330                 335     
          Tyr Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe 
                      340                 345                 350         
          Cys Ala Arg Gly Ile Tyr Asp Gly Tyr His Trp Tyr Phe Asp Val Trp 
                  355                 360                 365             
          Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
              370                 375                 380                 
          Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
          385                 390                 395                 400 
          Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
                          405                 410                 415     
          Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                      420                 425                 430         
          Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
                  435                 440                 445             
          Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
              450                 455                 460                 
          His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser 
          465                 470                 475                 480 
          Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
                          485                 490                 495     
          Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                      500                 505                 510         
          Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                  515                 520                 525             
          His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
              530                 535                 540                 
          Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
          545                 550                 555                 560 
          Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                          565                 570                 575     
          Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                      580                 585                 590         
          Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                  595                 600                 605             
          Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
              610                 615                 620                 
          Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
          625                 630                 635                 640 
          Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                          645                 650                 655     
          Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
                      660                 665                 670         
          Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                  675                 680                 685             
          Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu 
              690                 695                 700                 
          Ser Pro Gly 
          705         
          <![CDATA[<210> 219]]>
          <![CDATA[<211> 707]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> TNP全長(杵)]]>
          <![CDATA[<400> 219]]>
          Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly 
          1               5                   10                  15      
          Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
                      20                  25                  30          
          Ile Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
                  35                  40                  45              
          Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
              50                  55                  60                  
          Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
          65                  70                  75                  80  
          Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser 
                          85                  90                  95      
          Thr His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
                  115                 120                 125             
          Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
              130                 135                 140                 
          Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
          145                 150                 155                 160 
          Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                          165                 170                 175     
          Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
                      180                 185                 190         
          Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                  195                 200                 205             
          Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser 
              210                 215                 220                 
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly 
          225                 230                 235                 240 
          Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly 
                          245                 250                 255     
          Ser Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly 
                      260                 265                 270         
          Glu Thr Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn 
                  275                 280                 285             
          Tyr Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp 
              290                 295                 300                 
          Val Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Lys Tyr Ala Asp Asp 
          305                 310                 315                 320 
          Phe Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala 
                          325                 330                 335     
          Tyr Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe 
                      340                 345                 350         
          Cys Ala Arg Gly Ile Tyr Asp Gly Tyr His Trp Tyr Phe Asp Val Trp 
                  355                 360                 365             
          Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
              370                 375                 380                 
          Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
          385                 390                 395                 400 
          Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
                          405                 410                 415     
          Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                      420                 425                 430         
          Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
                  435                 440                 445             
          Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
              450                 455                 460                 
          His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser 
          465                 470                 475                 480 
          Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
                          485                 490                 495     
          Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                      500                 505                 510         
          Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                  515                 520                 525             
          His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
              530                 535                 540                 
          Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
          545                 550                 555                 560 
          Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                          565                 570                 575     
          Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                      580                 585                 590         
          Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                  595                 600                 605             
          Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
              610                 615                 620                 
          Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
          625                 630                 635                 640 
          Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                          645                 650                 655     
          Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
                      660                 665                 670         
          Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                  675                 680                 685             
          Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
              690                 695                 700                 
          Ser Pro Gly 
          705         
          <![CDATA[<210> 220]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1全長(臼)]]>
          <![CDATA[<400> 220]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro 
                      260                 265                 270         
          Gly Ala Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr 
                  275                 280                 285             
          Asp His Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Ile Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu 
          305                 310                 315                 320 
          Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 
                      340                 345                 350         
          Phe Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 221]]>
          <![CDATA[<211> 710]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8全長(臼)]]>
          <![CDATA[<400> 221]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly 
          705                 710 
          <![CDATA[<210> 222]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1 scFv]]>
          <![CDATA[<400> 222]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 223]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#2 scFv]]>
          <![CDATA[<400> 223]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Lys Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 224]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#3 scFv]]>
          <![CDATA[<400> 224]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 225]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#4 scFv]]>
          <![CDATA[<400> 225]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 226]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#5 scFv]]>
          <![CDATA[<400> 226]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 227]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#6 scFv]]>
          <![CDATA[<400> 227]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 228]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#7 scFv]]>
          <![CDATA[<400> 228]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Cys Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 229]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#8 scFv]]>
          <![CDATA[<400> 229]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 230]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#9 scFv]]>
          <![CDATA[<400> 230]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 231]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#10 scFv]]>
          <![CDATA[<400> 231]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 232]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#11 scFv]]>
          <![CDATA[<400> 232]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Lys Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 233]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#12 scFv]]>
          <![CDATA[<400> 233]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 234]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#13 scFv]]>
          <![CDATA[<400> 234]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Val Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210]]>> 235]]&gt;
          <br/>&lt;![CDATA[&lt;211&gt; 254]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; CD3#14 scFv]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 235]]&gt;
          <br/><![CDATA[Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Tyr Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 236]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#15 scFv]]>
          <![CDATA[<400> 236]]>
          Glu Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Trp Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 237]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16 scFv]]>
          <![CDATA[<400> 237]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Ile Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 238]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17 scFv]]>
          <![CDATA[<400> 238]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Arg Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 239]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#18 scFv]]>
          <![CDATA[<400> 239]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Trp Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 240]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19 scFv]]>
          <![CDATA[<400> 240]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 241]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#20 scFv]]>
          <![CDATA[<400> 241]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Val Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 242]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#21 scFv]]>
          <![CDATA[<400> 242]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Lys Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala 
                          245                 250                 
          <![CDATA[<210> 243]]>
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          <![CDATA[<223> CD3#22 scFv]]>
          <![CDATA[<400> 243]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ile Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 244]]>
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          <![CDATA[<212> PRT]]>
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          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#23 scFv]]>
          <![CDATA[<400> 244]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Trp Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ile Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 245]]>
          <![CDATA[<211> 254]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#24 scFv]]>
          <![CDATA[<400> 245]]>
          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Tyr Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 246]]>
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          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
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          <![CDATA[<223> CD3#25 scFv]]>
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          Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 
          1               5                   10                  15      
          Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
                      20                  25                  30          
          Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 
                  35                  40                  45              
          Leu Ile Gly Gly Thr Asn Ile Arg Ala Pro Gly Val Pro Ala Arg Phe 
              50                  55                  60                  
          Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
          65                  70                  75                  80  
          Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                          85                  90                  95      
          His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser 
                      100                 105                 110         
          Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly 
                  115                 120                 125             
          Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
              130                 135                 140                 
          Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr 
          145                 150                 155                 160 
          Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                          165                 170                 175     
          Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala 
                      180                 185                 190         
          Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn 
                  195                 200                 205             
          Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val 
              210                 215                 220                 
          Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp 
          225                 230                 235                 240 
          Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                          245                 250                 
          <![CDATA[<210> 247]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26 scFv]]>
          <![CDATA[<400> 247]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Gly 
              130                 135                 140                 
          Lys Pro Gly Thr Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Glu Lys Phe Lys Asn Arg Ala Thr Leu Thr Val Asp Lys Ser Ser 
                  195                 200                 205             
          Ser Thr Ala Tyr Met Gln Leu Ser Thr Leu Thr Ser Glu Asp Ser Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 248]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27 scFv]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Glu Lys Phe Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 249]]>
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          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 250]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#29 scFv]]>
          <![CDATA[<400> 250]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr 
                      180                 185                 190         
          Ala Glu Lys Phe Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 251]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#30 scFv]]>
          <![CDATA[<400> 251]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 252]]>
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          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#31 scFv]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Ala Gln Lys Phe Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 253]]>
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          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#32 scFv]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 254]]>
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          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#33 scFv]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 255]]>
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          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 256]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#35 scFv]]>
          <![CDATA[<400> 256]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Gln Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 257]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#36 scFv]]>
          <![CDATA[<400> 257]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ala 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Gln Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 258]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#37 scFv]]>
          <![CDATA[<400> 258]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser Tyr 
                      180                 185                 190         
          Ala Gln Lys Phe Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 259]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38 scFv]]>
          <![CDATA[<400> 259]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Asn Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 260]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#39 scFv]]>
          <![CDATA[<400> 260]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 261]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#40 scFv]]>
          <![CDATA[<400> 261]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 262]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#41 scFv]]>
          <![CDATA[<400> 262]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Arg Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 263]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#42 scFv]]>
          <![CDATA[<400> 263]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Ile Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Ile Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Met Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 264]]>
          <![CDATA[<211> 251]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#43 scFv]]>
          <![CDATA[<400> 264]]>
          Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Met Phe Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
                      20                  25                  30          
          Arg Thr Arg Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Ile Gln 
                          85                  90                  95      
          Ser Phe Ile Leu Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
                      100                 105                 110         
          Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                  115                 120                 125             
          Thr Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
              130                 135                 140                 
          Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr 
          145                 150                 155                 160 
          Phe Thr Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly 
                          165                 170                 175     
          Leu Glu Trp Ile Gly Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn Tyr 
                      180                 185                 190         
          Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr 
                  195                 200                 205             
          Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala 
              210                 215                 220                 
          Val Tyr Tyr Cys Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          225                 230                 235                 240 
          Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
                          245                 250     
          <![CDATA[<210> 265]]>
          <![CDATA[<211> 20]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 連接子，例如介於CD3 scFv內之VH與VL之間]]>
          <![CDATA[<40]]>0> 265]]&gt;
          <br/><![CDATA[Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
          1               5                   10                  15      
          Thr Gly Gly Ser 
                      20  
          <![CDATA[<210> 266]]>
          <![CDATA[<211> 38]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 連接子，例如介於LC與HC之間]]>
          <![CDATA[<400> 266]]>
          Gly Gly Gly Gly Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser 
          1               5                   10                  15      
          Lys Ser Thr Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser 
                      20                  25                  30          
          Thr Gly Gly Gly Gly Ser 
                  35              
          <![CDATA[<210> 267]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1(臼) / CD3#1全長]]>
          <![CDATA[<400> 267]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro 
                      260                 265                 270         
          Gly Ala Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr 
                  275                 280                 285             
          Asp His Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Ile Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu 
          305                 310                 315                 320 
          Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 
                      340                 345                 350         
          Phe Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 268]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1(臼) / CD3#2全長]]>
          <![CDATA[<400> 268]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro 
                      260                 265                 270         
          Gly Ala Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr 
                  275                 280                 285             
          Asp His Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Ile Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu 
          305                 310                 315                 320 
          Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 
                      340                 345                 350         
          Phe Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 269]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1(臼]]>) / CD3#3全長
          <![CDATA[<400> 269]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro 
                      260                 265                 270         
          Gly Ala Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr 
                  275                 280                 285             
          Asp His Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Ile Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu 
          305                 310                 315                 320 
          Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 
                      340                 345                 350         
          Phe Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 270]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#1全長]]>
          <![CDATA[<400> 270]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 271]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#2全長]]>
          <![CDATA[<400> 271]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Lys Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 272]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#3全長]]>
          <![CDATA[<400> 272]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 273]]>
          <![CDATA[<211> 4]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 4aa連接子]]>
          <![CDATA[<400> 273]]>
          Gly Gly Gly Ser 
          1               
          <![CDATA[<210> 274]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 6aa連接子]]>
          <![CDATA[<400> 274]]>
          Gly Gly Ser Gly Gly Ser 
          1               5       
          <![CDATA[<210> 275]]>
          <![CDATA[<211> 20]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 20aa連接子；例如介於Fc與CD3 scFv之間]]>
          <![CDATA[<400> 275]]>
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
          1               5                   10                  15      
          Gly Gly Gly Ser 
                      20  
          <![CDATA[<210> 276]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213>]]> 人工序列
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR1 (CCG)]]>
          <![CDATA[<400> 276]]>
          Gly Tyr Thr Phe Thr Asp Tyr Thr Met His 
          1               5                   10  
          <![CDATA[<210> 277]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR1 (CCG)]]>
          <![CDATA[<400> 277]]>
          Gly Leu Ser Leu Ser Arg Tyr Ser Val His 
          1               5                   10  
          <![CDATA[<210> 278]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR1 (CCG)]]>
          <![CDATA[<400> 278]]>
          Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr Trp Asn 
          1               5                   10      
          <![CDATA[<210> 279]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR1 (CCG)]]>
          <![CDATA[<400> 279]]>
          Gly Tyr Ser Ile Ser Ser Gly Tyr Tyr Trp Asn 
          1               5                   10      
          <![CDATA[<210> 280]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR1 (CCG)]]>
          <![CDATA[<400> 280]]>
          Gly Tyr Thr Phe Thr Asp Tyr Tyr Met Asn 
          1               5                   10  
          <![CDATA[<210> 281]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR1 (CCG)]]>
          <![CDATA[<400> 281]]>
          Gly Tyr Thr Phe Thr Asn Tyr Tyr Ile His 
          1               5                   10  
          <![CDATA[<210> 282]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR1 ]]>(CCG)
          <![CDATA[<400> 282]]>
          Gly Tyr Thr Phe Thr Asp His Thr Ile His 
          1               5                   10  
          <![CDATA[<210> 283]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR1 (CCG)]]>
          <![CDATA[<400> 283]]>
          Gly Tyr Thr Phe Ser Asp His Thr Ile His 
          1               5                   10  
          <![CDATA[<210> 284]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#15、#20、#23、#24 HCDR1 (CCG)]]>
          <![CDATA[<400> 284]]>
          Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn 
          1               5                   10  
          <![CDATA[<210> 285]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16至#19、#21、#22 HCDR1 (CCG)]]>
          <![CDATA[<400> 285]]>
          Gly Phe Thr Phe Ser Thr Tyr Ala Met Asn 
          1               5                   10  
          <![CDATA[<210> 286]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#25至#42 HCDR1 (CCG)]]>
          <![CDATA[<400> 286]]>
          Gly Tyr Thr Phe Thr Ser Tyr Trp Met His 
          1               5                   10  
          <![CDATA[<210> 287]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1及#9 HCDR1 (Chothia)]]>
          <![CDATA[<400> 287]]>
          Gly Tyr Thr Phe Thr Asp Tyr 
          1               5           
          <![CDATA[<210> 288]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR2 (Chothia)]]>
          <![CDATA[<400> 288]]>
          Tyr Pro Asn Tyr Gly Asp 
          1               5       
          <![CDATA[<210> 289]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR1 (Chothia)]]>
          <![CDATA[<400> 289]]>
          Gly Leu Ser Leu Ser Arg Tyr 
          1               5           
          <![CDATA[<210> 290]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR2 (Chothia)]]>
          <![CDATA[<400> 290]]>
          Trp Gly Gly Gly Ser 
          1               5   
          <![CDATA[<210> 291]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR1 (Chothia)]]>
          <![CDATA[<400> 291]]>
          Gly Tyr Ser Ile Thr Ser Gly Tyr 
          1               5               
          <![CDATA[<210> 292]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR2 (Chothia)]]>
          <![CDATA[<400> 292]]>
          Ser Tyr Asp Gly Arg 
          1               5   
          <![CDATA[<210> 293]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR1 (Chothia)]]>
          <![CDATA[<400> 293]]>
          Gly Tyr Ser Ile Ser Ser Gly Tyr 
          1               5               
          <![CDATA[<210> 294]]>
          <![CDATA[<211> 5]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR2 (Chothia)]]>
          <![CDATA[<400> 294]]>
          Ser Tyr Ser Gly Arg 
          1               5   
          <![CDATA[<210> 295]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR2 (Chothia)]]>
          <![CDATA[<400> 295]]>
          Tyr Pro Asn Asn Gly Ala 
          1               5       
          <![CDATA[<210> 296]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR1 (Chothia)]]>
          <![CDATA[<400> 296]]>
          Gly Tyr Thr Phe Thr Asn Tyr 
          1               5           
          <![CDATA[<210> 297]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR2 (Chothia)]]>
          <![CDATA[<400> 297]]>
          Tyr Pro Gly Asn Gly Ala 
          1               5       
          <![CDATA[<210> 298]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR1 (Chothia)]]>
          <![CDATA[<400> 298]]>
          Gly Tyr Thr Phe Thr Asp His 
          1               5           
          <![CDATA[<210> 299]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR2 (Chothia)]]>
          <![CDATA[<400> 299]]>
          Tyr Pro Arg Asp Gly Ser 
          1               5       
          <![CDATA[<210> 300]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223]]>> CDH17#8 HCDR1 (Chothia)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 300]]&gt;
          <br/><![CDATA[Gly Tyr Thr Phe Ser Asp His 
          1               5           
          <![CDATA[<210> 301]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR2 (Chothia)]]>
          <![CDATA[<400> 301]]>
          Tyr Pro Arg Leu Gly Ser 
          1               5       
          <![CDATA[<210> 302]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#15、#20、#23、#24 HCDR1 (Chothia)]]>
          <![CDATA[<400> 302]]>
          Gly Phe Thr Phe Asn Thr Tyr 
          1               5           
          <![CDATA[<210> 303]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#18、#20、#22、#23、#24 HCDR1 (Chothia)]]>
          <![CDATA[<400> 303]]>
          Arg Ser Lys Tyr Asn Asn Tyr Ala 
          1               5               
          <![CDATA[<210> 304]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220>]]> 
          <![CDATA[<223> CD3#16至#19、#21、#22 HCDR1 (Chothia)]]>
          <![CDATA[<400> 304]]>
          Gly Phe Thr Phe Ser Thr Tyr 
          1               5           
          <![CDATA[<210> 305]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19、#21、HCDR1 (Chothia)]]>
          <![CDATA[<400> 305]]>
          Arg Ser Ile Tyr Asn Asn Tyr Ala 
          1               5               
          <![CDATA[<210> 306]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25至#42 HCDR1 (Chothia)]]>
          <![CDATA[<400> 306]]>
          Gly Tyr Thr Phe Thr Ser Tyr 
          1               5           
          <![CDATA[<210> 307]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25、#26、#37至#42 HCDR1 (Chothia)]]>
          <![CDATA[<400> 307]]>
          Asn Ala Asp Thr Gly Ser 
          1               5       
          <![CDATA[<210> 308]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27至#36 HCDR1 (Chothia)]]>
          <![CDATA[<400> 308]]>
          Asn Ala Ser Thr Gly Ser 
          1               5       
          <![CDATA[<210> 309]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR1 (IMGT)]]>
          <![CDATA[<400> 309]]>
          Gly Tyr Thr Phe Thr Asp Tyr Thr 
          1               5               
          <![CDATA[<210> 310]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR2 (IMGT)]]>
          <![CDATA[<400> 310]]>
          Ile Tyr Pro Asn Tyr Gly Asp Thr 
          1               5               
          <![CDATA[<210> 311]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR3 (IMGT)]]>
          <![CDATA[<400> 311]]>
          Ser Arg Lys Thr Val Leu Leu Arg Leu Arg Tyr Phe Asp Val 
          1               5                   10                  
          <![CDATA[<210> 312]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR1 (IMGT)]]>
          <![CDATA[<400> 312]]>
          Gly Asn Ile His Asn Tyr 
          1               5       
          <![CDATA[<210> 313]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR1 (IMGT)]]>
          <![CDATA[<400> 313]]>
          Gly Asn Ile His Asn Tyr 
          1               5       
          <![CDATA[<210> 314]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR1 (IMGT)]]>
          <![CDATA[<400> 314]]>
          Gly Leu Ser Leu Ser Arg Tyr Ser 
          1               5               
          <![CDATA[<210> 315]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR2 (IMGT)]]>
          <![CDATA[<400> 315]]>
          Ile Trp Gly Gly Gly Ser Thr 
          1               5           
          <![CDATA[<210> 316]]>
          <![CDATA[<211> 15]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR3 (IMGT)]]>
          <![CDATA[<400> 316]]>
          Ala Arg Lys Gly Ser Tyr Tyr Thr Asn Tyr Gly Ala Met Asp Tyr 
          1               5                   10                  15  
          <![CDATA[<210>]]> 317
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR1 (IMGT)]]>
          <![CDATA[<400> 317]]>
          Gln Asp Ile Asn Lys Tyr 
          1               5       
          <![CDATA[<210> 318]]>
          <![CDATA[<211> 6]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR1 (IMGT)]]>
          <![CDATA[<400> 318]]>
          Gln Asp Ile Asn Lys Tyr 
          1               5       
          <![CDATA[<210> 319]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR1 (IMGT)]]>
          <![CDATA[<400> 319]]>
          Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr 
          1               5                   
          <![CDATA[<210> 320]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11HCDR2 (IMGT)]]>
          <![CDATA[<400> 320]]>
          Ile Ser Tyr Asp Gly Arg Asn 
          1               5           
          <![CDATA[<210> 321]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11至#18 HCDR3 (IMGT)]]>
          <![CDATA[<400> 321]]>
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr 
          1               5                   10  
          <![CDATA[<210> 322]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 LCDR1 (IMGT)]]>
          <![CDATA[<400> 322]]>
          Glu Ser Val Asp Ser Ser Val Asn Arg Phe 
          1               5                   10  
          <![CDATA[<210> 323]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 LCDR1 (IMGT)]]>
          <![CDATA[<400> 323]]>
          Glu Ser Val Asp Ser Ser Val Asn Arg Phe 
          1               5                   10  
          <![CDATA[<210> 324]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR1 (IMGT)]]>
          <![CDATA[<400> 324]]>
          Gly Tyr Ser Ile Ser Ser Gly Tyr Tyr 
          1               5                   
          <![CDATA[<210> 325]]>
          <![CDATA[<211> 7]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR2 (IMGT)]]>
          <![CDATA[<400> 325]]>
          Ile Ser Tyr Ser Gly Arg Asn 
          1               5           
          <![CDATA[<210> 326]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 LCDR1 (IMGT)]]>
          <![CDATA[<400> 326]]>
          Glu Ser Val Ser Ser Ser Val Asn Arg Phe 
          1               5                   10  
          <![CDATA[<210> 327]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR1 (IMGT)]]>
          <![CDATA[<400> 327]]>
          Gly Tyr Thr Phe Thr Asp Tyr Tyr 
          1               5               
          <![CDATA[<210> 328]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR2 (IMGT)]]>
          <![CDATA[<400> 328]]>
          Ile Tyr Pro Asn Asn Gly Ala Thr 
          1               5               
          <![CDATA[<210> 329]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR3 (IMGT)]]>
          <![CDATA[<400> 329]]>
          Ala Arg Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 330]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人]]>工序列
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 LCDR1 (IMGT)]]>
          <![CDATA[<400> 330]]>
          Gln Ser Leu Val His Ser Asn Gly Asn Thr Phe 
          1               5                   10      
          <![CDATA[<210> 331]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 LCDR1 (IMGT)]]>
          <![CDATA[<400> 331]]>
          Gln Ser Leu Val His Ser Asn Gly Asn Thr Phe 
          1               5                   10      
          <![CDATA[<210> 332]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR1 (IMGT)]]>
          <![CDATA[<400> 332]]>
          Gly Tyr Thr Phe Thr Asn Tyr Tyr 
          1               5               
          <![CDATA[<210> 333]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR2 (IMGT)]]>
          <![CDATA[<400> 333]]>
          Ile Tyr Pro Gly Asn Gly Ala Thr 
          1               5               
          <![CDATA[<210> 334]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR3 (IMGT)]]>
          <![CDATA[<400]]>> 334]]&gt;
          <br/><![CDATA[Ala Arg Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   10      
          <![CDATA[<210> 335]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 LCDR1 (IMGT)]]>
          <![CDATA[<400> 335]]>
          Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr 
          1               5                   10      
          <![CDATA[<210> 336]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR1 (IMGT)]]>
          <![CDATA[<400> 336]]>
          Gly Tyr Thr Phe Thr Asp His Thr 
          1               5               
          <![CDATA[<210> 337]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR2 (IMGT)]]>
          <![CDATA[<400> 337]]>
          Ile Tyr Pro Arg Asp Gly Ser Thr 
          1               5               
          <![CDATA[<210> 338]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1及#8 HCDR3 (IMGT)]]>
          <![CDATA[<400> 338]]>
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 339]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 LCDR1 (IMGT)]]>
          <![CDATA[<400> 339]]>
          Gln Ser Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr 
          1               5                   10          
          <![CDATA[<210> 340]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 LCDR1 (IMGT)]]>
          <![CDATA[<400> 340]]>
          Gln Ser Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr 
          1               5                   10          
          <![CDATA[<210> 341]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR1 (IMGT)]]>
          <![CDATA[<400> 341]]>
          Gly Tyr Thr Phe Ser Asp His Thr 
          1               5               
          <![CDATA[<210> 342]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR2 (IMGT)]]>
          <![CDATA[<400> 342]]>
          Ile Tyr Pro Arg Leu Gly Ser Thr 
          1               5               
          <![CDATA[<210> 343]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LCDR1 (IMGT)]]>
          <![CDATA[<400> 343]]>
          Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Gln Tyr 
          1               5                   10          
          <![CDATA[<210> 344]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LCDR1 (IMGT)]]>
          <![CDATA[<400> 344]]>
          Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Gln Tyr 
          1               5                   10          
          <![CDATA[<210> 345]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至# 15、#20、#23、#24 HCDR1 (IMGT)]]>
          <![CDATA[<400> 345]]>
          Gly Phe Thr Phe Asn Thr Tyr Ala 
          1               5               
          <![CDATA[<210> 346]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至# 18、#20、#22、#23、#24 HCDR2 (IMGT)]]>
          <![CDATA[<400> 346]]>
          Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr 
          1               5                   10  
          <![CDATA[<210> 347]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至# 10、#12、#13、#15、#20、#23、#24 HCDR3 (IMGT)]]>
          <![CDATA[<400> 347]]>
          Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 348]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至# 10、#12至#16、#18、#19、#21、#24 LCDR1 (IMGT)]]>
          <![CDATA[<400> 348]]>
          Thr Gly Ala Val Thr Thr Ser Asn Tyr 
          1               5                   
          <![CDATA[<210> 349]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至# 10、#12至#16、#18、#19、#21、#24 LCDR1 (IMGT)]]>
          <![CDATA[<400> 349]]>
          Thr Gly Ala Val Thr Thr Ser Asn Tyr 
          1               5                   
          <![CDATA[<210> 350]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#11、#14 HCDR3 (IMGT)]]>
          <![CDATA[<400> 350]]>
          Val Arg His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 351]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#11、#20、#23 LCDR1 (IMGT)]]>
          <![CDATA[<400> 351]]>
          Thr Gly Ala Val Thr Thr Ser Tyr Tyr 
          1               5                   
          <![CDATA[<210> 352]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16至# 19、#21、#22 HCDR1 (IMGT)]]>
          <![CDATA[<400> 352]]>
          Gly Phe Thr Phe Ser Thr Tyr Ala 
          1               5               
          <![CDATA[<210> 353]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16至# 18、#21、#22、HCDR2 (IMGT)]]>
          <![CDATA[<400> 353]]>
          Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 354]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#17及# 22]]>
          <![CDATA[<400> 354]]>
          Thr Gly Ala Val Thr Thr Ser Trp Tyr 
          1               5                   
          <![CDATA[<210> 355]]>
          <![CDATA[<211]]>> 10]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; CD3#19及#21 HCDR2 (IMGT)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 355]]&gt;
          <br/><![CDATA[Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr 
          1               5                   10  
          <![CDATA[<210> 356]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19 HCDR3 (IMGT)]]>
          <![CDATA[<400> 356]]>
          Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 357]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25至#42 HCDR1 (IMGT)]]>
          <![CDATA[<400> 357]]>
          Gly Tyr Thr Phe Thr Ser Tyr Trp 
          1               5               
          <![CDATA[<210> 358]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25、#26、#37至#42 HCDR2 (IMGT)]]>
          <![CDATA[<400> 358]]>
          Ile Asn Ala Asp Thr Gly Ser Thr 
          1               5               
          <![CDATA[<210> 359]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25、#28至#30、#39 HCDR3 (I]]>MGT)
          <![CDATA[<400> 359]]>
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 360]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25至#29、#32、#34、#36至#42 LCDR1 (IMGT)]]>
          <![CDATA[<400> 360]]>
          Gln Ser Leu Leu Asn Ser Arg Thr Arg Lys Asn Tyr 
          1               5                   10          
          <![CDATA[<210> 361]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26、#32至#37、#40 HCDR3 (IMGT)]]>
          <![CDATA[<400> 361]]>
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 362]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27至#36 HCDR2 (IMGT)]]>
          <![CDATA[<400> 362]]>
          Ile Asn Ala Ser Thr Gly Ser Thr 
          1               5               
          <![CDATA[<210> 363]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27、#31、#41 HCDR3 (IMGT)]]>
          <![CDATA[<400> 363]]>
          Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 364]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#30、#31、#33、#35 LCDR1 (IMGT)]]>
          <![CDATA[<400> 364]]>
          Gln Ser Leu Leu Asn Ala Arg Thr Arg Lys Asn Tyr 
          1               5                   10          
          <![CDATA[<210> 365]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38、#42 HCDR3 (IMGT)]]>
          <![CDATA[<400> 365]]>
          Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 366]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR1 (North)]]>
          <![CDATA[<400> 366]]>
          Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Thr Met His 
          1               5                   10              
          <![CDATA[<210> 367]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR2 (North)]]>
          <![CDATA[<400> 367]]>
          Gly Ile Tyr Pro Asn Tyr Gly Asp Thr Asn 
          1               5                   10  
          <![CDATA[<210> 368]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 HCDR3 (North)]]>
          <![CDATA[<400> 368]]>
          Ser Arg Lys Thr Val Leu Leu Arg Leu Arg Tyr Phe Asp Val 
          1               5                   10                  
          <![CDATA[<210> 369]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#1 LCDR2 (North]]>
          <![CDATA[<400> 369]]>
          Tyr Asn Ala Ile Thr Leu Ala Asp 
          1               5               
          <![CDATA[<210> 370]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR1 (North)]]>
          <![CDATA[<400> 370]]>
          Thr Val Ser Gly Leu Ser Leu Ser Arg Tyr Ser Val His 
          1               5                   10              
          <![CDATA[<210> 371]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR2 (North)]]>
          <![CDATA[<400> 371]]>
          Met Ile Trp Gly Gly Gly Ser Thr Asp 
          1               5                   
          <![CDATA[<210> 372]]>
          <![CDATA[<211> 15]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 HCDR3 (North)]]>
          <![CDATA[<400> 372]]>
          Ala Arg Lys Gly Ser Tyr Tyr Thr Asn Tyr Gly Ala Met Asp Tyr 
          1               5                   10                  15  
          <![CDATA[<210> 373]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#8 LCDR2 (North)]]>
          <![CDATA[<400> 373]]>
          His Tyr Thr Ser Thr Leu Gln Pro 
          1               5               
          <![CDATA[<210> 374]]>
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11 HCDR1 (North)]]>
          <![CDATA[<400> 374]]>
          Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr Trp Asn 
          1               5                   10                  
          <![CDATA[<210> 375]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11HCDR2 (North)]]>
          <![CDATA[<400> 375]]>
          Tyr Ile Ser Tyr Asp Gly Arg Asn Asn 
          1               5                   
          <![CDATA[<210> 376]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11至#18 HCDR3 (North)]]>
          <![CDATA[<400> 376]]>
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr 
          1               5                   10  
          <![CDATA[<210> 377]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#11至#18 LC]]>DR2 (North)
          <![CDATA[<400> 377]]>
          Tyr Arg Ala Ser Asn Leu Glu Ser 
          1               5               
          <![CDATA[<210> ]]>378
          <![CDATA[<211> 14]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR1 (North)]]>
          <![CDATA[<400> 378]]>
          Thr Val Ser Gly Tyr Ser Ile Ser Ser Gly Tyr Tyr Trp Asn 
          1               5                   10                  
          <![CDATA[<210> 379]]>
          <![CDATA[<211> 9]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#12至#18 HCDR2 (North)]]>
          <![CDATA[<400> 379]]>
          Tyr Ile Ser Tyr Ser Gly Arg Asn Leu 
          1               5                   
          <![CDATA[<210> 380]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR1 (North)]]>
          <![CDATA[<400> 380]]>
          Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Tyr Met Asn 
          1               5                   10              
          <![CDATA[<210> 381]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR2 (North)]]>
          <![CDATA[<400> 381]]>
          Tyr Ile Tyr Pro Asn Asn Gly Ala Thr Gly 
          1               5                   10  
          <![CDATA[<210> 382]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9 HCDR3 (North)]]>
          <![CDATA[<400> 382]]>
          Ala Arg Glu Asp Ser Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 383]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#9及#10 LCDR2 (North)]]>
          <![CDATA[<400> 383]]>
          Tyr Lys Val Ser Asn Arg Phe Ser 
          1               5               
          <![CDATA[<210> 384]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR1 (North)]]>
          <![CDATA[<400> 384]]>
          Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Ile His 
          1               5                   10              
          <![CDATA[<210> 385]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10]]>
          <![CDATA[<400> 385]]>
          Tyr Ile Tyr Pro Gly Asn Gly Ala Thr Ala 
          1               5                   10  
          <![CDATA[<210> 386]]>
          <![CDATA[<211> 11]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Trop2#10 HCDR3 (North)]]>
          <![CDATA[<400> 386]]>
          Ala Arg Glu Asp Tyr Tyr Tyr Ala Met Asp Tyr 
          1               5                   10      
          <![CDATA[<210> 387]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR1 (North)]]>
          <![CDATA[<400> 387]]>
          Lys Val Ser Gly Tyr Thr Phe Thr Asp His Thr Ile His 
          1               5                   10              
          <![CDATA[<210> 388]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 HCDR2 (North)]]>
          <![CDATA[<400> 388]]>
          Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys 
          1               5                   10  
          <![CDATA[<210> 389]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1及#8 HCDR3 (North)]]>
          <![CDATA[<400> 389]]>
          Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe Asp Tyr 
          1               5                   10                  15      
          <![CDATA[<210]]>> 390]]&gt;
          <br/>&lt;![CDATA[&lt;211&gt; 8]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; CDH17#1 LCDR2 (North)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 390]]&gt;
          <br/><![CDATA[Tyr Trp Ala Ser Thr Arg Glu Ser 
          1               5               
          <![CDATA[<210> 391]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR1 (North)]]>
          <![CDATA[<400> 391]]>
          Lys Ala Ser Gly Tyr Thr Phe Ser Asp His Thr Ile His 
          1               5                   10              
          <![CDATA[<210> 392]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 HCDR2 (North)]]>
          <![CDATA[<400> 392]]>
          Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys 
          1               5                   10  
          <![CDATA[<210> 393]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 LCDR2 (North)]]>
          <![CDATA[<400> 393]]>
          Tyr Gly Ala Ser Thr Arg Glu Thr 
          1               5               
          <![CDATA[<210> 394]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#15、#20、#23、#24 HCDR1 (North)]]>
          <![CDATA[<400> 394]]>
          Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn 
          1               5                   10              
          <![CDATA[<210> 395]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#18、#20、#22、#23、#24 HCDR2 (North)]]>
          <![CDATA[<400> 395]]>
          Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr 
          1               5                   10          
          <![CDATA[<210> 396]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#10、#12、#13、#15、#20、#23、#24 HCDR3 (North)]]>
          <![CDATA[<400> 396]]>
          Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 3]]>97
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#1至#12、#16、#18、#19、#21、#22、#23 LCDR2 (North)]]>
          <![CDATA[<400> 397]]>
          Gly Gly Thr Asn Lys Arg Ala Pro 
          1               5               
          <![CDATA[<210> 398]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#11及#14 HCDR3 (North)]]>
          <![CDATA[<400> 398]]>
          Val Arg His Gly Asn Phe Leu Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 399]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#13至#15、#17、#20、#24 LCDR2 (North)]]>
          <![CDATA[<400> 399]]>
          Gly Gly Thr Asn Ile Arg Ala Pro 
          1               5               
          <![CDATA[<210> 400]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16至#18、#21、#22 HCDR1 (North)]]>
          <![CDATA[<400> 400]]>
          Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr Ala Met Asn 
          1               5                   10              
          <![CDATA[<210> 401]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#16至#18、#21、#22 HCDR3 (North)]]>
          <![CDATA[<400> 401]]>
          Val Arg His Gly Asn Phe Ile Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 402]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<21]]>2> PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; CD3#19及#21 HCDR2 (North)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 402]]&gt;
          <br/><![CDATA[Arg Ile Arg Ser Ile Tyr Asn Asn Tyr Ala Thr Tyr 
          1               5                   10          
          <![CDATA[<210> 403]]>
          <![CDATA[<211> 16]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#19 HCDR3 (North)]]>
          <![CDATA[<400> 403]]>
          Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr 
          1               5                   10                  15      
          <![CDATA[<210> 404]]>
          <![CDATA[<211> 13]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25至#42 HCDR1 (North)]]>
          <![CDATA[<400> 404]]>
          Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His 
          1               5                   10              
          <![CDATA[<210> 405]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25、#26、#38、# 41、#42 HCDR2 (North)]]>
          <![CDATA[<400> 405]]>
          Asn Ile Asn Ala Asp Thr Gly Ser Thr Asn 
          1               5                   10  
          <![CDATA[<210> 406]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25、#28至#30、#39 HCDR3(North)]]>
          <![CDATA[<400> 406]]>
          Thr Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 407]]>
          <![CDATA[<211> 8]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#25至# 42 LCDR2 (North)]]>
          <![CDATA[<400> 407]]>
          Tyr Trp Ala Ser Thr Arg Lys Ser 
          1               5               
          <![CDATA[<210> 408]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#26、#32至#37、#40 HCDR3(North)]]>
          <![CDATA[<400> 408]]>
          Ala Arg Asp Gly Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 409]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27、#29至#31、#33、# 35 HCDR2 (North)]]>
          <![CDATA[<400> 409]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Asn 
          1               5                   10  
          <![CDATA[<210> 410]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#27、#31、#41 HCDR3(North)]]>
          <![CDATA[<400> 410]]>
          Thr Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 411]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#28、#32、#34、#36 HCDR2 (North)]]>
          <![CDATA[<400> 411]]>
          Asn Ile Asn Ala Ser Thr Gly Ser Thr Ser 
          1               5                   10  
          <![CDATA[<210> 412]]>
          <![CDATA[<211> 10]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#37、#39、#40 HCDR2 (North)]]>
          <![CDATA[<400> 412]]>
          Asn Ile Asn Ala Asp Thr Gly Ser Thr Lys 
          1               5                   10  
          <![CDATA[<210> 413]]>
          <![CDATA[<211> 12]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CD3#38 #42 HCDR3(North)]]>
          <![CDATA[<400> 413]]>
          Ala Arg Asp Ala Tyr Ser Phe Tyr Tyr Phe Asp Tyr 
          1               5                   10          
          <![CDATA[<210> 414]]>
          <![CDATA[<211> 330]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> IgG1野生型HC]]>
          <![CDATA[<400> 414]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
          1               5                   10                  15      
          Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
          65                  70                  75                  80  
          Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
                      100                 105                 110         
          Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                  115                 120                 125             
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
              130                 135                 140                 
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
          145                 150                 155                 160 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                          165                 170                 175     
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                      180                 185                 190         
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                  195                 200                 205             
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
              210                 215                 220                 
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
          225                 230                 235                 240 
          Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                          245                 250                 255     
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                      260                 265                 270         
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                  275                 280                 285             
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
              290                 295                 300                 
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
          305                 310                 315                 320 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                          325                 330 
          <![CDATA[<210> 415]]>
          <![CDATA[<211> 329]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> IgG1 KO HC]]>
          <![CDATA[<400> 415]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
          1               5                   10                  15      
          Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
          65                  70                  75                  80  
          Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
                      100                 105                 110         
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                  115                 120                 125             
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
              130                 135                 140                 
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
          145                 150                 155                 160 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                          165                 170                 175     
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                      180                 185                 190         
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                  195                 200                 205             
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
              210                 215                 220                 
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
          225                 230                 235                 240 
          Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                          245                 250                 255     
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                      260                 265                 270         
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                  275                 280                 285             
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
              290                 295                 300                 
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
          305                 310                 315                 320 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                          325                 
          <![CDATA[<210> 416]]>
          <![CDATA[<211> 327]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> IgG4 Pro野生型HC]]>
          <![CDATA[<400> 416]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
          1               5                   10                  15      
          Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
          65                  70                  75                  80  
          Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
                      100                 105                 110         
          Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                  115                 120                 125             
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
              130                 135                 140                 
          Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
          145                 150                 155                 160 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                          165                 170                 175     
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                      180                 185                 190         
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
                  195                 200                 205             
          Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
              210                 215                 220                 
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
          225                 230                 235                 240 
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                          245                 250                 255     
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                      260                 265                 270         
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                  275                 280                 285             
          Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
              290                 295                 300                 
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
          305                 310                 315                 320 
          Leu Ser Leu Ser Leu Gly Lys 
                          325         
          <![CDATA[<210> 417]]>
          <![CDATA[<211> 329]]>
          <![CDATA[<212>]]> PRT
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> IgG1 FcRnmut]]>
          <![CDATA[<400> 417]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
          1               5                   10                  15      
          Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
          65                  70                  75                  80  
          Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
                      100                 105                 110         
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                  115                 120                 125             
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
              130                 135                 140                 
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
          145                 150                 155                 160 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                          165                 170                 175     
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                      180                 185                 190         
          Ala Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                  195                 200                 205             
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
              210                 215                 220                 
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
          225                 230                 235                 240 
          Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                          245                 250                 255     
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                      260                 265                 270         
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                  275                 280                 285             
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
              290                 295                 300                 
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
          305                 310                 315                 320 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                          325                 
          <![CDATA[<210> 418]]>
          <![CDATA[<211> 107]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類輕鏈恆定域(κ)]]>
          <![CDATA[<400> 418]]>
          Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
          1               5                   10                  15      
          Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
                      20                  25                  30          
          Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
                  35                  40                  45              
          Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
              50                  55                  60                  
          Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
          65                  70                  75                  80  
          Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                          85                  90                  95      
          Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
                      100                 105         
          <![CDATA[<210> 419]]>
          <![CDATA[<211> 323]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類Trop2]]>
          <![CDATA[<400> 419]]>
          Met Ala Arg Gly Pro Gly Leu Ala Pro Pro Pro Leu Arg Leu Pro Leu 
          1               5                   10                  15      
          Leu Leu Leu Val Leu Ala Ala Val Thr Gly His Thr Ala Ala Gln Asp 
                      20                  25                  30          
          Asn Cys Thr Cys Pro Thr Asn Lys Met Thr Val Cys Ser Pro Asp Gly 
                  35                  40                  45              
          Pro Gly Gly Arg Cys Gln Cys Arg Ala Leu Gly Ser Gly Met Ala Val 
              50                  55                  60                  
          Asp Cys Ser Thr Leu Thr Ser Lys Cys Leu Leu Leu Lys Ala Arg Met 
          65                  70                  75                  80  
          Ser Ala Pro Lys Asn Ala Arg Thr Leu Val Arg Pro Ser Glu His Ala 
                          85                  90                  95      
          Leu Val Asp Asn Asp Gly Leu Tyr Asp Pro Asp Cys Asp Pro Glu Gly 
                      100                 105                 110         
          Arg Phe Lys Ala Arg Gln Cys Asn Gln Thr Ser Val Cys Trp Cys Val 
                  115                 120                 125             
          Asn Ser Val Gly Val Arg Arg Thr Asp Lys Gly Asp Leu Ser Leu Arg 
              130                 135                 140                 
          Cys Asp Glu Leu Val Arg Thr His His Ile Leu Ile Asp Leu Arg His 
          145                 150                 155                 160 
          Arg Pro Thr Ala Gly Ala Phe Asn His Ser Asp Leu Asp Ala Glu Leu 
                          165                 170                 175     
          Arg Arg Leu Phe Arg Glu Arg Tyr Arg Leu His Pro Lys Phe Val Ala 
                      180                 185                 190         
          Ala Val His Tyr Glu Gln Pro Thr Ile Gln Ile Glu Leu Arg Gln Asn 
                  195                 200                 205             
          Thr Ser Gln Lys Ala Ala Gly Asp Val Asp Ile Gly Asp Ala Ala Tyr 
              210                 215                 220                 
          Tyr Phe Glu Arg Asp Ile Lys Gly Glu Ser Leu Phe Gln Gly Arg Gly 
          225                 230                 235                 240 
          Gly Leu Asp Leu Arg Val Arg Gly Glu Pro Leu Gln Val Glu Arg Thr 
                          245                 250                 255     
          Leu Ile Tyr Tyr Leu Asp Glu Ile Pro Pro Lys Phe Ser Met Lys Arg 
                      260                 265                 270         
          Leu Thr Ala Gly Leu Ile Ala Val Ile Val Val Val Val Val Ala Leu 
                  275                 280                 285             
          Val Ala Gly Met Ala Val Leu Val Ile Thr Asn Arg Arg Lys Ser Gly 
              290                 295                 300                 
          Lys Tyr Lys Lys Val Glu Ile Lys Glu Leu Gly Glu Leu Arg Lys Glu 
          305                 310                 315                 320 
          Pro Ser Leu 
          <![CDATA[<210> 420]]>
          <![CDATA[<211> 832]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類CDH17]]>
          <![CDATA[<400> 420]]>
          Met Ile Leu Gln Ala His Leu His Ser Leu Cys Leu Leu Met Leu Tyr 
          1               5                   10                  15      
          Leu Ala Thr Gly Tyr Gly Gln Glu Gly Lys Phe Ser Gly Pro Leu Lys 
                      20                  25                  30          
          Pro Met Thr Phe Ser Ile Tyr Glu Gly Gln Glu Pro Ser Gln Ile Ile 
                  35                  40                  45              
          Phe Gln Phe Lys Ala Asn Pro Pro Ala Val Thr Phe Glu Leu Thr Gly 
              50                  55                  60                  
          Glu Thr Asp Asn Ile Phe Val Ile Glu Arg Glu Gly Leu Leu Tyr Tyr 
          65                  70                  75                  80  
          Asn Arg Ala Leu Asp Arg Glu Thr Arg Ser Thr His Asn Leu Gln Val 
                          85                  90                  95      
          Ala Ala Leu Asp Ala Asn Gly Ile Ile Val Glu Gly Pro Val Pro Ile 
                      100                 105                 110         
          Thr Ile Lys Val Lys Asp Ile Asn Asp Asn Arg Pro Thr Phe Leu Gln 
                  115                 120                 125             
          Ser Lys Tyr Glu Gly Ser Val Arg Gln Asn Ser Arg Pro Gly Lys Pro 
              130                 135                 140                 
          Phe Leu Tyr Val Asn Ala Thr Asp Leu Asp Asp Pro Ala Thr Pro Asn 
          145                 150                 155                 160 
          Gly Gln Leu Tyr Tyr Gln Ile Val Ile Gln Leu Pro Met Ile Asn Asn 
                          165                 170                 175     
          Val Met Tyr Phe Gln Ile Asn Asn Lys Thr Gly Ala Ile Ser Leu Thr 
                      180                 185                 190         
          Arg Glu Gly Ser Gln Glu Leu Asn Pro Ala Lys Asn Pro Ser Tyr Asn 
                  195                 200                 205             
          Leu Val Ile Ser Val Lys Asp Met Gly Gly Gln Ser Glu Asn Ser Phe 
              210                 215                 220                 
          Ser Asp Thr Thr Ser Val Asp Ile Ile Val Thr Glu Asn Ile Trp Lys 
          225                 230                 235                 240 
          Ala Pro Lys Pro Val Glu Met Val Glu Asn Ser Thr Asp Pro His Pro 
                          245                 250                 255     
          Ile Lys Ile Thr Gln Val Arg Trp Asn Asp Pro Gly Ala Gln Tyr Ser 
                      260                 265                 270         
          Leu Val Asp Lys Glu Lys Leu Pro Arg Phe Pro Phe Ser Ile Asp Gln 
                  275                 280                 285             
          Glu Gly Asp Ile Tyr Val Thr Gln Pro Leu Asp Arg Glu Glu Lys Asp 
              290                 295                 300                 
          Ala Tyr Val Phe Tyr Ala Val Ala Lys Asp Glu Tyr Gly Lys Pro Leu 
          305                 310                 315                 320 
          Ser Tyr Pro Leu Glu Ile His Val Lys Val Lys Asp Ile Asn Asp Asn 
                          325                 330                 335     
          Pro Pro Thr Cys Pro Ser Pro Val Thr Val Phe Glu Val Gln Glu Asn 
                      340                 345                 350         
          Glu Arg Leu Gly Asn Ser Ile Gly Thr Leu Thr Ala His Asp Arg Asp 
                  355                 360                 365             
          Glu Glu Asn Thr Ala Asn Ser Phe Leu Asn Tyr Arg Ile Val Glu Gln 
              370                 375                 380                 
          Thr Pro Lys Leu Pro Met Asp Gly Leu Phe Leu Ile Gln Thr Tyr Ala 
          385                 390                 395                 400 
          Gly Met Leu Gln Leu Ala Lys Gln Ser Leu Lys Lys Gln Asp Thr Pro 
                          405                 410                 415     
          Gln Tyr Asn Leu Thr Ile Glu Val Ser Asp Lys Asp Phe Lys Thr Leu 
                      420                 425                 430         
          Cys Phe Val Gln Ile Asn Val Ile Asp Ile Asn Asp Gln Ile Pro Ile 
                  435                 440                 445             
          Phe Glu Lys Ser Asp Tyr Gly Asn Leu Thr Leu Ala Glu Asp Thr Asn 
              450                 455                 460                 
          Ile Gly Ser Thr Ile Leu Thr Ile Gln Ala Thr Asp Ala Asp Glu Pro 
          465                 470                 475                 480 
          Phe Thr Gly Ser Ser Lys Ile Leu Tyr His Ile Ile Lys Gly Asp Ser 
                          485                 490                 495     
          Glu Gly Arg Leu Gly Val Asp Thr Asp Pro His Thr Asn Thr Gly Tyr 
                      500                 505                 510         
          Val Ile Ile Lys Lys Pro Leu Asp Phe Glu Thr Ala Ala Val Ser Asn 
                  515                 520                 525             
          Ile Val Phe Lys Ala Glu Asn Pro Glu Pro Leu Val Phe Gly Val Lys 
              530                 535                 540                 
          Tyr Asn Ala Ser Ser Phe Ala Lys Phe Thr Leu Ile Val Thr Asp Val 
          545                 550                 555                 560 
          Asn Glu Ala Pro Gln Phe Ser Gln His Val Phe Gln Ala Lys Val Ser 
                          565                 570                 575     
          Glu Asp Val Ala Ile Gly Thr Lys Val Gly Asn Val Thr Ala Lys Asp 
                      580                 585                 590         
          Pro Glu Gly Leu Asp Ile Ser Tyr Ser Leu Arg Gly Asp Thr Arg Gly 
                  595                 600                 605             
          Trp Leu Lys Ile Asp His Val Thr Gly Glu Ile Phe Ser Val Ala Pro 
              610                 615                 620                 
          Leu Asp Arg Glu Ala Gly Ser Pro Tyr Arg Val Gln Val Val Ala Thr 
          625                 630                 635                 640 
          Glu Val Gly Gly Ser Ser Leu Ser Ser Val Ser Glu Phe His Leu Ile 
                          645                 650                 655     
          Leu Met Asp Val Asn Asp Asn Pro Pro Arg Leu Ala Lys Asp Tyr Thr 
                      660                 665                 670         
          Gly Leu Phe Phe Cys His Pro Leu Ser Ala Pro Gly Ser Leu Ile Phe 
                  675                 680                 685             
          Glu Ala Thr Asp Asp Asp Gln His Leu Phe Arg Gly Pro His Phe Thr 
              690                 695                 700                 
          Phe Ser Leu Gly Ser Gly Ser Leu Gln Asn Asp Trp Glu Val Ser Lys 
          705                 710                 715                 720 
          Ile Asn Gly Thr His Ala Arg Leu Ser Thr Arg His Thr Glu Phe Glu 
                          725                 730                 735     
          Glu Arg Glu Tyr Val Val Leu Ile Arg Ile Asn Asp Gly Gly Arg Pro 
                      740                 745                 750         
          Pro Leu Glu Gly Ile Val Ser Leu Pro Val Thr Phe Cys Ser Cys Val 
                  755                 760                 765             
          Glu Gly Ser Cys Phe Arg Pro Ala Gly His Gln Thr Gly Ile Pro Thr 
              770                 775                 780                 
          Val Gly Met Ala Val Gly Ile Leu Leu Thr Thr Leu Leu Val Ile Gly 
          785                 790                 795                 800 
          Ile Ile Leu Ala Val Val Phe Ile Arg Ile Lys Lys Asp Lys Gly Lys 
                          805                 810                 815     
          Asp Asn Val Glu Ser Ala Gln Ala Ser Glu Val Lys Pro Leu Arg Ser 
                      820                 825                 830         
          <![CDATA[<210> 421]]>
          <![CDATA[<211>]]> 171
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類CD3 δ鏈]]>
          <![CDATA[<400> 421]]>
          Met Glu His Ser Thr Phe Leu Ser Gly Leu Val Leu Ala Thr Leu Leu 
          1               5                   10                  15      
          Ser Gln Val Ser Pro Phe Lys Ile Pro Ile Glu Glu Leu Glu Asp Arg 
                      20                  25                  30          
          Val Phe Val Asn Cys Asn Thr Ser Ile Thr Trp Val Glu Gly Thr Val 
                  35                  40                  45              
          Gly Thr Leu Leu Ser Asp Ile Thr Arg Leu Asp Leu Gly Lys Arg Ile 
              50                  55                  60                  
          Leu Asp Pro Arg Gly Ile Tyr Arg Cys Asn Gly Thr Asp Ile Tyr Lys 
          65                  70                  75                  80  
          Asp Lys Glu Ser Thr Val Gln Val His Tyr Arg Met Cys Gln Ser Cys 
                          85                  90                  95      
          Val Glu Leu Asp Pro Ala Thr Val Ala Gly Ile Ile Val Thr Asp Val 
                      100                 105                 110         
          Ile Ala Thr Leu Leu Leu Ala Leu Gly Val Phe Cys Phe Ala Gly His 
                  115                 120                 125             
          Glu Thr Gly Arg Leu Ser Gly Ala Ala Asp Thr Gln Ala Leu Leu Arg 
              130                 135                 140                 
          Asn Asp Gln Val Tyr Gln Pro Leu Arg Asp Arg Asp Asp Ala Gln Tyr 
          145                 150                 155                 160 
          Ser His Leu Gly Gly Asn Trp Ala Arg Asn Lys 
                          165                 170     
          <![CDATA[<210> 422]]>
          <![CDATA[<211> 207]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類CD3 ε鏈]]>
          <![CDATA[<400> 422]]>
          Met Gln Ser Gly Thr His Trp Arg Val Leu Gly Leu Cys Leu Leu Ser 
          1               5                   10                  15      
          Val Gly Val Trp Gly Gln Asp Gly Asn Glu Glu Met Gly Gly Ile Thr 
                      20                  25                  30          
          Gln Thr Pro Tyr Lys Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr 
                  35                  40                  45              
          Cys Pro Gln Tyr Pro Gly Ser Glu Ile Leu Trp Gln His Asn Asp Lys 
              50                  55                  60                  
          Asn Ile Gly Gly Asp Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp 
          65                  70                  75                  80  
          His Leu Ser Leu Lys Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr 
                          85                  90                  95      
          Val Cys Tyr Pro Arg Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu 
                      100                 105                 110         
          Tyr Leu Arg Ala Arg Val Cys Glu Asn Cys Met Glu Met Asp Val Met 
                  115                 120                 125             
          Ser Val Ala Thr Ile Val Ile Val Asp Ile Cys Ile Thr Gly Gly Leu 
              130                 135                 140                 
          Leu Leu Leu Val Tyr Tyr Trp Ser Lys Asn Arg Lys Ala Lys Ala Lys 
          145                 150                 155                 160 
          Pro Val Thr Arg Gly Ala Gly Ala Gly Gly Arg Gln Arg Gly Gln Asn 
                          165                 170                 175     
          Lys Glu Arg Pro Pro Pro Val Pro Asn Pro Asp Tyr Glu Pro Ile Arg 
                      180                 185                 190         
          Lys Gly Gln Arg Asp Leu Tyr Ser Gly Leu Asn Gln Arg Arg Ile 
                  195                 200                 205         
          <![CDATA[<210]]>> 423]]&gt;
          <br/>&lt;![CDATA[&lt;211&gt; 182]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; 人類CD3 γ鏈]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 423]]&gt;
          <br/><![CDATA[Met Glu Gln Gly Lys Gly Leu Ala Val Leu Ile Leu Ala Ile Ile Leu 
          1               5                   10                  15      
          Leu Gln Gly Thr Leu Ala Gln Ser Ile Lys Gly Asn His Leu Val Lys 
                      20                  25                  30          
          Val Tyr Asp Tyr Gln Glu Asp Gly Ser Val Leu Leu Thr Cys Asp Ala 
                  35                  40                  45              
          Glu Ala Lys Asn Ile Thr Trp Phe Lys Asp Gly Lys Met Ile Gly Phe 
              50                  55                  60                  
          Leu Thr Glu Asp Lys Lys Lys Trp Asn Leu Gly Ser Asn Ala Lys Asp 
          65                  70                  75                  80  
          Pro Arg Gly Met Tyr Gln Cys Lys Gly Ser Gln Asn Lys Ser Lys Pro 
                          85                  90                  95      
          Leu Gln Val Tyr Tyr Arg Met Cys Gln Asn Cys Ile Glu Leu Asn Ala 
                      100                 105                 110         
          Ala Thr Ile Ser Gly Phe Leu Phe Ala Glu Ile Val Ser Ile Phe Val 
                  115                 120                 125             
          Leu Ala Val Gly Val Tyr Phe Ile Ala Gly Gln Asp Gly Val Arg Gln 
              130                 135                 140                 
          Ser Arg Ala Ser Asp Lys Gln Thr Leu Leu Pro Asn Asp Gln Leu Tyr 
          145                 150                 155                 160 
          Gln Pro Leu Lys Asp Arg Glu Asp Asp Gln Tyr Ser His Leu Gln Gly 
                          165                 170                 175     
          Asn Gln Leu Arg Arg Asn 
                      180         
          <![CDATA[<210> 424]]>
          <![CDATA[<211> 164]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> 人類CD3 ζ鏈]]>
          <![CDATA[<400> 424]]>
          Met Lys Trp Lys Ala Leu Phe Thr Ala Ala Ile Leu Gln Ala Gln Leu 
          1               5                   10                  15      
          Pro Ile Thr Glu Ala Gln Ser Phe Gly Leu Leu Asp Pro Lys Leu Cys 
                      20                  25                  30          
          Tyr Leu Leu Asp Gly Ile Leu Phe Ile Tyr Gly Val Ile Leu Thr Ala 
                  35                  40                  45              
          Leu Phe Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr 
              50                  55                  60                  
          Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg 
          65                  70                  75                  80  
          Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met 
                          85                  90                  95      
          Gly Gly Lys Pro Gln Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn 
                      100                 105                 110         
          Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met 
                  115                 120                 125             
          Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly 
              130                 135                 140                 
          Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala 
          145                 150                 155                 160 
          Leu Pro Pro Arg 
          <![CDATA[<210> 425]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#5全長]]>
          <![CDATA[<400> 425]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 426]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#6全長]]>
          <![CDATA[<400> 426]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Cys 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 427]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (臼) / CD3#7全長]]>
          <![CDATA[<400> 427]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 428]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#2全長]]>
          <![CDATA[<400> 428]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Lys Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 429]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#3全長]]>
          <![CDATA[<400> 429]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 430]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#4全長]]>
          <![CDATA[<400> 430]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Cys 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 431]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#5全長]]>
          <![CDATA[<400> 431]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 432]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#6全長]]>
          <![CDATA[<400> 432]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Cys 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 433]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#8 (杵) / CD3#7全長]]>
          <![CDATA[<400> 433]]>
          Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
          1               5                   10                  15      
          Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Gln Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Thr Gly Ile 
              50                  55                  60                  
          Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                      260                 265                 270         
          Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser 
                  275                 280                 285             
          Asp His Thr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Met Gly Tyr Ile Tyr Pro Arg Leu Gly Ser Thr Lys Tyr Ala Glu 
          305                 310                 315                 320 
          Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                      340                 345                 350         
          Tyr Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Gln Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980                 
          <![CDATA[<210> 434]]>
          <![CDATA[<211> 329]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Fc域杵]]>
          <![CDATA[<400> 434]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
          1               5                   10                  15      
          Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
          65                  70                  75                  80  
          Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
                      100                 105                 110         
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                  115                 120                 125             
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
              130                 135                 140                 
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
          145                 150                 155                 160 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                          165                 170                 175     
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                      180                 185                 190         
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                  195                 200                 205             
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
              210                 215                 220                 
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
          225                 230                 235                 240 
          Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
                          245                 250                 255     
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                      260                 265                 270         
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                  275                 280                 285             
          Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
              290                 295                 300                 
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
          305                 310                 315                 320 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                          325                 
          <![CDATA[<210> 435]]>
          <![CDATA[<211> 329]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> Fc域臼]]>
          <![CDATA[<400> 435]]>
          Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
          1               5                   10                  15      
          Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
                      20                  25                  30          
          Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
                  35                  40                  45              
          Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
              50                  55                  60                  
          Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
          65                  70                  75                  80  
          Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                          85                  90                  95      
          Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
                      100                 105                 110         
          Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                  115                 120                 125             
          Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
              130                 135                 140                 
          Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
          145                 150                 155                 160 
          Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                          165                 170                 175     
          Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                      180                 185                 190         
          His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                  195                 200                 205             
          Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
              210                 215                 220                 
          Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
          225                 230                 235                 240 
          Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
                          245                 250                 255     
          Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                      260                 265                 270         
          Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                  275                 280                 285             
          Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
              290                 295                 300                 
          Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr 
          305                 310                 315                 320 
          Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                          325                 
          <![CDATA[<210]]>> 436]]&gt;
          <br/>&lt;![CDATA[&lt;211&gt; 702]]&gt;
          <br/>&lt;![CDATA[&lt;212&gt; PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt; 人工序列]]&gt;
          <br/>
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt; ]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt; Trop2#11全長(臼)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt; 436]]&gt;
          <br/><![CDATA[Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Val Ser Leu Gly 
          1               5                   10                  15      
          Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Ser Ser 
                      20                  25                  30          
          Val Asn Arg Phe Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
                  35                  40                  45              
          Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 
              50                  55                  60                  
          Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asn 
          65                  70                  75                  80  
          Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                          85                  90                  95      
          Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
                      100                 105                 110         
          Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                  115                 120                 125             
          Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
              130                 135                 140                 
          Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
          145                 150                 155                 160 
          Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                          165                 170                 175     
          Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
                      180                 185                 190         
          His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                  195                 200                 205             
          Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Glu 
              210                 215                 220                 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu Gly Lys 
          225                 230                 235                 240 
          Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly Gly Ser 
                          245                 250                 255     
          Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
                      260                 265                 270         
          Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly 
                  275                 280                 285             
          Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 
              290                 295                 300                 
          Met Gly Tyr Ile Ser Tyr Asp Gly Arg Asn Asn Tyr Asn Pro Ser Leu 
          305                 310                 315                 320 
          Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Glu Asn Gln Phe Phe 
                          325                 330                 335     
          Leu Lys Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Thr Tyr Tyr Cys 
                      340                 345                 350         
          Ala Arg Asp Thr Thr Ala Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr 
                  355                 360                 365             
          Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
              370                 375                 380                 
          Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
          385                 390                 395                 400 
          Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
                          405                 410                 415     
          Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                      420                 425                 430         
          Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
                  435                 440                 445             
          Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
              450                 455                 460                 
          Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
          465                 470                 475                 480 
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                          485                 490                 495     
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      500                 505                 510         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  515                 520                 525             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              530                 535                 540                 
          Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
          545                 550                 555                 560 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          565                 570                 575     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      580                 585                 590         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  595                 600                 605             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
              610                 615                 620                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          625                 630                 635                 640 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          645                 650                 655     
          Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      660                 665                 670         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  675                 680                 685             
          His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
              690                 695                 700         
          <![CDATA[<210> 437]]>
          <![CDATA[<211> 984]]>
          <![CDATA[<212> PRT]]>
          <![CDATA[<213> 人工序列]]>
          <![CDATA[<220> ]]>
          <![CDATA[<223> CDH17#1 (杵) / CD3#1全長]]>
          <![CDATA[<400> 437]]>
          Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
          1               5                   10                  15      
          Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
                      20                  25                  30          
          Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                  35                  40                  45              
          Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
              50                  55                  60                  
          Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
          65                  70                  75                  80  
          Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                          85                  90                  95      
          Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
                      100                 105                 110         
          Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
                  115                 120                 125             
          Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
              130                 135                 140                 
          Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
          145                 150                 155                 160 
          Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                          165                 170                 175     
          Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
                      180                 185                 190         
          Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
                  195                 200                 205             
          Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly 
              210                 215                 220                 
          Ser Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Glu 
          225                 230                 235                 240 
          Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Gly 
                          245                 250                 255     
          Gly Ser Gln Val Gln Leu Gln Gln Ser Asp Ala Glu Leu Val Lys Pro 
                      260                 265                 270         
          Gly Ala Ser Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr 
                  275                 280                 285             
          Asp His Thr Ile His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu Glu 
              290                 295                 300                 
          Trp Ile Gly Tyr Ile Tyr Pro Arg Asp Gly Ser Thr Lys Tyr Asn Glu 
          305                 310                 315                 320 
          Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr 
                          325                 330                 335     
          Ala Tyr Met Gln Leu Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr 
                      340                 345                 350         
          Phe Cys Ala Arg Trp Gly Tyr Tyr Tyr Gly Ser Ser Arg Tyr Tyr Phe 
                  355                 360                 365             
          Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr 
              370                 375                 380                 
          Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
          385                 390                 395                 400 
          Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                          405                 410                 415     
          Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
                      420                 425                 430         
          Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
                  435                 440                 445             
          Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
              450                 455                 460                 
          Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 
          465                 470                 475                 480 
          Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                          485                 490                 495     
          Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      500                 505                 510         
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  515                 520                 525             
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              530                 535                 540                 
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
          545                 550                 555                 560 
          Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                          565                 570                 575     
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      580                 585                 590         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  595                 600                 605             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              610                 615                 620                 
          Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          625                 630                 635                 640 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          645                 650                 655     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      660                 665                 670         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  675                 680                 685             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              690                 695                 700                 
          Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          705                 710                 715                 720 
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ala Val Val Thr Gln 
                          725                 730                 735     
          Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys 
                      740                 745                 750         
          Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val 
                  755                 760                 765             
          Gln Glu Lys Pro Gly Gln Leu Pro Arg Gly Leu Ile Gly Gly Thr Asn 
              770                 775                 780                 
          Lys Arg Ala Pro Trp Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly 
          785                 790                 795                 800 
          Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu Ala 
                          805                 810                 815     
          Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn Leu Trp Val Phe Gly Gly 
                      820                 825                 830         
          Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Glu Gly Lys Ser Ser Gly 
                  835                 840                 845             
          Ser Gly Ser Glu Ser Lys Ser Thr Gly Gly Ser Glu Val Gln Leu Val 
              850                 855                 860                 
          Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser 
          865                 870                 875                 880 
          Cys Ala Ala Ser Gly Phe Thr Phe Asn Thr Tyr Ala Met Asn Trp Val 
                          885                 890                 895     
          Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser 
                      900                 905                 910         
          Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg 
                  915                 920                 925             
          Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met 
              930                 935                 940                 
          Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
          945                 950                 955                 960 
          Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
                          965                 970                 975     
          Gly Thr Leu Val Thr Val Ser Ala 
                      980
Figure 12_A0101_SEQ_0001
Figure 12_A0101_SEQ_0002
Figure 12_A0101_SEQ_0003
Figure 12_A0101_SEQ_0004
Figure 12_A0101_SEQ_0005
Figure 12_A0101_SEQ_0006
Figure 12_A0101_SEQ_0007
Figure 12_A0101_SEQ_0008
Figure 12_A0101_SEQ_0009
Figure 12_A0101_SEQ_0010
Figure 12_A0101_SEQ_0011
Figure 12_A0101_SEQ_0012
Figure 12_A0101_SEQ_0013
Figure 12_A0101_SEQ_0014
Figure 12_A0101_SEQ_0015
Figure 12_A0101_SEQ_0016
Figure 12_A0101_SEQ_0017
Figure 12_A0101_SEQ_0018
Figure 12_A0101_SEQ_0019
Figure 12_A0101_SEQ_0020
Figure 12_A0101_SEQ_0021
Figure 12_A0101_SEQ_0022
Figure 12_A0101_SEQ_0023
Figure 12_A0101_SEQ_0024
Figure 12_A0101_SEQ_0025
Figure 12_A0101_SEQ_0026
Figure 12_A0101_SEQ_0027
Figure 12_A0101_SEQ_0028
Figure 12_A0101_SEQ_0029
Figure 12_A0101_SEQ_0030
Figure 12_A0101_SEQ_0031
Figure 12_A0101_SEQ_0032
Figure 12_A0101_SEQ_0033
Figure 12_A0101_SEQ_0034
Figure 12_A0101_SEQ_0035
Figure 12_A0101_SEQ_0036
Figure 12_A0101_SEQ_0037
Figure 12_A0101_SEQ_0038
Figure 12_A0101_SEQ_0039
Figure 12_A0101_SEQ_0040
Figure 12_A0101_SEQ_0041
Figure 12_A0101_SEQ_0042
Figure 12_A0101_SEQ_0043
Figure 12_A0101_SEQ_0044
Figure 12_A0101_SEQ_0045
Figure 12_A0101_SEQ_0046
Figure 12_A0101_SEQ_0047
Figure 12_A0101_SEQ_0048
Figure 12_A0101_SEQ_0049
Figure 12_A0101_SEQ_0050
Figure 12_A0101_SEQ_0051
Figure 12_A0101_SEQ_0052
Figure 12_A0101_SEQ_0053
Figure 12_A0101_SEQ_0054
Figure 12_A0101_SEQ_0055
Figure 12_A0101_SEQ_0056
Figure 12_A0101_SEQ_0057
Figure 12_A0101_SEQ_0058
Figure 12_A0101_SEQ_0059
Figure 12_A0101_SEQ_0060
Figure 12_A0101_SEQ_0061
Figure 12_A0101_SEQ_0062
Figure 12_A0101_SEQ_0063
Figure 12_A0101_SEQ_0064
Figure 12_A0101_SEQ_0065
Figure 12_A0101_SEQ_0066
Figure 12_A0101_SEQ_0067
Figure 12_A0101_SEQ_0068
Figure 12_A0101_SEQ_0069
Figure 12_A0101_SEQ_0070
Figure 12_A0101_SEQ_0071
Figure 12_A0101_SEQ_0072
Figure 12_A0101_SEQ_0073
Figure 12_A0101_SEQ_0074
Figure 12_A0101_SEQ_0075
Figure 12_A0101_SEQ_0076
Figure 12_A0101_SEQ_0077
Figure 12_A0101_SEQ_0078
Figure 12_A0101_SEQ_0079
Figure 12_A0101_SEQ_0080
Figure 12_A0101_SEQ_0081
Figure 12_A0101_SEQ_0082
Figure 12_A0101_SEQ_0083
Figure 12_A0101_SEQ_0084
Figure 12_A0101_SEQ_0085
Figure 12_A0101_SEQ_0086
Figure 12_A0101_SEQ_0087
Figure 12_A0101_SEQ_0088
Figure 12_A0101_SEQ_0089
Figure 12_A0101_SEQ_0090
Figure 12_A0101_SEQ_0091
Figure 12_A0101_SEQ_0092
Figure 12_A0101_SEQ_0093
Figure 12_A0101_SEQ_0094
Figure 12_A0101_SEQ_0095
Figure 12_A0101_SEQ_0096
Figure 12_A0101_SEQ_0097
Figure 12_A0101_SEQ_0098
Figure 12_A0101_SEQ_0099
Figure 12_A0101_SEQ_0100
Figure 12_A0101_SEQ_0101
Figure 12_A0101_SEQ_0102
Figure 12_A0101_SEQ_0103
Figure 12_A0101_SEQ_0104
Figure 12_A0101_SEQ_0105
Figure 12_A0101_SEQ_0106
Figure 12_A0101_SEQ_0107
Figure 12_A0101_SEQ_0108
Figure 12_A0101_SEQ_0109
Figure 12_A0101_SEQ_0110
Figure 12_A0101_SEQ_0111
Figure 12_A0101_SEQ_0112
Figure 12_A0101_SEQ_0113
Figure 12_A0101_SEQ_0114
Figure 12_A0101_SEQ_0115
Figure 12_A0101_SEQ_0116
Figure 12_A0101_SEQ_0117
Figure 12_A0101_SEQ_0118
Figure 12_A0101_SEQ_0119
Figure 12_A0101_SEQ_0120
Figure 12_A0101_SEQ_0121
Figure 12_A0101_SEQ_0122
Figure 12_A0101_SEQ_0123
Figure 12_A0101_SEQ_0124
Figure 12_A0101_SEQ_0125
Figure 12_A0101_SEQ_0126
Figure 12_A0101_SEQ_0127
Figure 12_A0101_SEQ_0128
Figure 12_A0101_SEQ_0129
Figure 12_A0101_SEQ_0130
Figure 12_A0101_SEQ_0131
Figure 12_A0101_SEQ_0132
Figure 12_A0101_SEQ_0133
Figure 12_A0101_SEQ_0134
Figure 12_A0101_SEQ_0135
Figure 12_A0101_SEQ_0136
Figure 12_A0101_SEQ_0137
Figure 12_A0101_SEQ_0138
Figure 12_A0101_SEQ_0139
Figure 12_A0101_SEQ_0140
Figure 12_A0101_SEQ_0141
Figure 12_A0101_SEQ_0142
Figure 12_A0101_SEQ_0143
Figure 12_A0101_SEQ_0144
Figure 12_A0101_SEQ_0145
Figure 12_A0101_SEQ_0146
Figure 12_A0101_SEQ_0147
Figure 12_A0101_SEQ_0148
Figure 12_A0101_SEQ_0149
Figure 12_A0101_SEQ_0150
Figure 12_A0101_SEQ_0151
Figure 12_A0101_SEQ_0152
Figure 12_A0101_SEQ_0153
Figure 12_A0101_SEQ_0154
Figure 12_A0101_SEQ_0155
Figure 12_A0101_SEQ_0156
Figure 12_A0101_SEQ_0157
Figure 12_A0101_SEQ_0158
Figure 12_A0101_SEQ_0159
Figure 12_A0101_SEQ_0160
Figure 12_A0101_SEQ_0161
Figure 12_A0101_SEQ_0162
Figure 12_A0101_SEQ_0163
Figure 12_A0101_SEQ_0164
Figure 12_A0101_SEQ_0165
Figure 12_A0101_SEQ_0166
Figure 12_A0101_SEQ_0167
Figure 12_A0101_SEQ_0168
Figure 12_A0101_SEQ_0169
Figure 12_A0101_SEQ_0170
Figure 12_A0101_SEQ_0171
Figure 12_A0101_SEQ_0172
Figure 12_A0101_SEQ_0173
Figure 12_A0101_SEQ_0174
Figure 12_A0101_SEQ_0175
Figure 12_A0101_SEQ_0176
Figure 12_A0101_SEQ_0177
Figure 12_A0101_SEQ_0178
Figure 12_A0101_SEQ_0179
Figure 12_A0101_SEQ_0180
Figure 12_A0101_SEQ_0181
Figure 12_A0101_SEQ_0182
Figure 12_A0101_SEQ_0183
Figure 12_A0101_SEQ_0184
Figure 12_A0101_SEQ_0185
Figure 12_A0101_SEQ_0186
Figure 12_A0101_SEQ_0187
Figure 12_A0101_SEQ_0188
Figure 12_A0101_SEQ_0189
Figure 12_A0101_SEQ_0190
Figure 12_A0101_SEQ_0191
Figure 12_A0101_SEQ_0192
Figure 12_A0101_SEQ_0193
Figure 12_A0101_SEQ_0194
Figure 12_A0101_SEQ_0195
Figure 12_A0101_SEQ_0196
Figure 12_A0101_SEQ_0197
Figure 12_A0101_SEQ_0198
Figure 12_A0101_SEQ_0199
Figure 12_A0101_SEQ_0200
Figure 12_A0101_SEQ_0201
Figure 12_A0101_SEQ_0202
Figure 12_A0101_SEQ_0203
Figure 12_A0101_SEQ_0204
Figure 12_A0101_SEQ_0205
Figure 12_A0101_SEQ_0206
Figure 12_A0101_SEQ_0207
Figure 12_A0101_SEQ_0208
Figure 12_A0101_SEQ_0209
Figure 12_A0101_SEQ_0210
Figure 12_A0101_SEQ_0211
Figure 12_A0101_SEQ_0212
Figure 12_A0101_SEQ_0213
Figure 12_A0101_SEQ_0214
Figure 12_A0101_SEQ_0215
Figure 12_A0101_SEQ_0216
Figure 12_A0101_SEQ_0217
Figure 12_A0101_SEQ_0218
Figure 12_A0101_SEQ_0219
Figure 12_A0101_SEQ_0220
Figure 12_A0101_SEQ_0221
Figure 12_A0101_SEQ_0222
Figure 12_A0101_SEQ_0223
Figure 12_A0101_SEQ_0224
Figure 12_A0101_SEQ_0225
Figure 12_A0101_SEQ_0226
Figure 12_A0101_SEQ_0227
Figure 12_A0101_SEQ_0228
Figure 12_A0101_SEQ_0229
Figure 12_A0101_SEQ_0230
Figure 12_A0101_SEQ_0231
Figure 12_A0101_SEQ_0232
Figure 12_A0101_SEQ_0233
Figure 12_A0101_SEQ_0234
Figure 12_A0101_SEQ_0235
Figure 12_A0101_SEQ_0236
Figure 12_A0101_SEQ_0237
Figure 12_A0101_SEQ_0238
Figure 12_A0101_SEQ_0239
Figure 12_A0101_SEQ_0240
Figure 12_A0101_SEQ_0241
Figure 12_A0101_SEQ_0242
Figure 12_A0101_SEQ_0243
Figure 12_A0101_SEQ_0244
Figure 12_A0101_SEQ_0245
Figure 12_A0101_SEQ_0246
Figure 12_A0101_SEQ_0247
Figure 12_A0101_SEQ_0248
Figure 12_A0101_SEQ_0249
Figure 12_A0101_SEQ_0250
Figure 12_A0101_SEQ_0251
Figure 12_A0101_SEQ_0252
Figure 12_A0101_SEQ_0253
Figure 12_A0101_SEQ_0254
Figure 12_A0101_SEQ_0255
Figure 12_A0101_SEQ_0256
Figure 12_A0101_SEQ_0257
Figure 12_A0101_SEQ_0258
Figure 12_A0101_SEQ_0259
Figure 12_A0101_SEQ_0260
Figure 12_A0101_SEQ_0261
Figure 12_A0101_SEQ_0262
Figure 12_A0101_SEQ_0263
Figure 12_A0101_SEQ_0264
Figure 12_A0101_SEQ_0265
Figure 12_A0101_SEQ_0266
Figure 12_A0101_SEQ_0267
Figure 12_A0101_SEQ_0268
Figure 12_A0101_SEQ_0269
Figure 12_A0101_SEQ_0270
Figure 12_A0101_SEQ_0271
Figure 12_A0101_SEQ_0272
Figure 12_A0101_SEQ_0273
Figure 12_A0101_SEQ_0274
Figure 12_A0101_SEQ_0275
Figure 12_A0101_SEQ_0276
Figure 12_A0101_SEQ_0277
Figure 12_A0101_SEQ_0278
Figure 12_A0101_SEQ_0279

Claims (18)

  1. 一種結合分子，其包含： (a)  至少一個以Kd ≥ 1 nM特異性結合於滋養層細胞表面抗原2 (TROP2)之抗原結合位點， (b)  至少一個特異性結合於鈣黏素-17 (CDH17)之抗原結合位點，其中該至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群： (i)  抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:33 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:35 (CDR1)、SEQ ID NO.:36 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR； 及 (ii) 抗原結合位點，其包括包含SEQ ID NO.:32 (CDR1)、SEQ ID NO.:38 (CDR2)及SEQ ID NO.:34 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:39 (CDR1)、SEQ ID NO.:40 (CDR2)及SEQ ID NO.:37 (CDR3)之胺基酸序列之輕鏈CDR，及 (c)  至少一個特異性結合於分化簇3 (CD3)之抗原結合位點。
  2. 如請求項1之結合分子，其中該至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(vi)組成之群： (i)   抗原結合位點，其包括包含SEQ ID NO.:1 (CDR1)、SEQ ID NO.:2 (CDR2)及SEQ ID NO.:3 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:4 (CDR1)、SEQ ID NO.:5 (CDR2)及SEQ ID NO.:6 (CDR3)之胺基酸序列之輕鏈CDR； (ii)  抗原結合位點，其包括包含SEQ ID NO.:7 (CDR1)、SEQ ID NO.:8 (CDR2)及SEQ ID NO.:9 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:10 (CDR1)、SEQ ID NO.:11 (CDR2)及SEQ ID NO.:12 (CDR3)之胺基酸序列之輕鏈CDRS； (iii) 抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:14 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:16 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (iv) 抗原結合位點，其包括包含SEQ ID NO.:13 (CDR1)、SEQ ID NO.:19 (CDR2)及SEQ ID NO.:15 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:20 (CDR1)、SEQ ID NO.:17 (CDR2)及SEQ ID NO.:18 (CDR3)之胺基酸序列之輕鏈CDR； (v)  抗原結合位點，其包括包含SEQ ID NO.:21 (CDR1)、SEQ ID NO.:22 (CDR2)及SEQ ID NO.:23 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:24 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:26 (CDR3)之胺基酸序列之輕鏈CDR； 及 (vi) 抗原結合位點，其包括包含SEQ ID NO.:27 (CDR1)、SEQ ID NO.:28 (CDR2)及SEQ ID NO.:29 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:30 (CDR1)、SEQ ID NO.:25 (CDR2)及SEQ ID NO.:31 (CDR3)之胺基酸序列之輕鏈CDR。
  3. 如請求項1之結合分子，其中該至少一個特異性結合於TROP2之抗原結合位點係選自由抗原結合位點(i)至(xii)組成之群： (i)   抗原結合位點，其包括包含SEQ ID NO:83之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:84之胺基酸序列之免疫球蛋白輕鏈可變域； (ii)  抗原結合位點，其包括包含SEQ ID NO:85之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:86之胺基酸序列之免疫球蛋白輕鏈可變域； (iii) 抗原結合位點，其包括包含SEQ ID NO:87之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:88之胺基酸序列之免疫球蛋白輕鏈可變域； (iv) 抗原結合位點，其包括包含SEQ ID NO:89之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:90之胺基酸序列之免疫球蛋白輕鏈可變域； (v)  抗原結合位點，其包括包含SEQ ID NO:91之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:92之胺基酸序列之免疫球蛋白輕鏈可變域； (vi) 抗原結合位點，其包括包含SEQ ID NO:93之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (vii) 抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:94之胺基酸序列之免疫球蛋白輕鏈可變域； (viii) 抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域； (ix) 抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (x)  抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:97之胺基酸序列之免疫球蛋白輕鏈可變域； (xi) 抗原結合位點，其包括包含SEQ ID NO:95之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:99之胺基酸序列之免疫球蛋白輕鏈可變域； 或 (xii) 抗原結合位點，其包括包含SEQ ID NO:98之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:96之胺基酸序列之免疫球蛋白輕鏈可變域。
  4. 如請求項1至3中任一項之結合分子，其中該至少一個特異性結合於CDH17之抗原結合位點係選自由抗原結合位點(i)至(ii)組成之群： (i)   抗原結合位點，其包括包含SEQ ID NO:100之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:101之胺基酸序列之免疫球蛋白輕鏈可變域； 及 (ii)  抗原結合位點，其包括包含SEQ ID NO:102之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:103之胺基酸序列之免疫球蛋白輕鏈可變域。
  5. 如請求項1至3中任一項之結合分子，其中該至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xxxi)組成之群： (i)   抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (ii)  抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:46 (CDR3)之胺基酸序列之輕鏈CDR； (iii) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (iv) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:50 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (v)  抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDRS及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vi) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:49 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:44 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (vii) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:53 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:47 (CDR3)之胺基酸序列之輕鏈CDR； (viii)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:55 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (ix) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (x)  抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:48 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xi) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:58 (CDR2)及SEQ ID NO.:59 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:60 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xii) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiii)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:62 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xiv)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:63 (CDR2)及SEQ ID NO.:54 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:56 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xv) 抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:61 (CDR1)、SEQ ID NO.:45 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvi)     抗原結合位點，其包括包含SEQ ID NO.:41 (CDR1)、SEQ ID NO.:42 (CDR2)及SEQ ID NO.:43 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:57 (CDR1)、SEQ ID NO.:52 (CDR2)及SEQ ID NO.:51 (CDR3)之胺基酸序列之輕鏈CDR； (xvii)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:64 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xviii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xix)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:72 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xx) 抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxi)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:74 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxii)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:73 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:75 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxiv)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:69 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxv)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:76 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvi)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:77 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:71 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxvii)   抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:78 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxviii)  抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxix)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； (xxx)     抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:79 (CDR2)及SEQ ID NO.:65 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:80 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR； 及 (xxxi)    抗原結合位點，其包括包含SEQ ID NO.:82 (CDR1)、SEQ ID NO.:81 (CDR2)及SEQ ID NO.:70 (CDR3)之胺基酸序列之重鏈CDR及包含SEQ ID NO.:66 (CDR1)、SEQ ID NO.:67 (CDR2)及SEQ ID NO.:68 (CDR3)之胺基酸序列之輕鏈CDR。
  6. 如請求項1至3中任一項之結合分子，其中該至少一個特異性結合於CD3之抗原結合位點係選自由抗原結合位點(i)至(xvi)組成之群： (i)   抗原結合位點，其包括包含SEQ ID NO:104之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:105、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:109、SEQ ID NO:114、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:123及SEQ ID NO:129組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (ii)  抗原結合位點，其包括包含SEQ ID NO:110之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:111之胺基酸序列之免疫球蛋白輕鏈可變域； (iii) 抗原結合位點，其包括包含SEQ ID NO:112之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:113之胺基酸序列之免疫球蛋白輕鏈可變域； (iv) 抗原結合位點，其包括包含SEQ ID NO:118之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:119及SEQ ID NO:122組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)  抗原結合位點，其包括包含SEQ ID NO:124之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:125、SEQ ID NO:126及SEQ ID NO:127組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (v)  抗原結合位點，其包括包含選自由SEQ ID NO:128及SEQ ID NO:130組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:127之胺基酸序列之免疫球蛋白輕鏈可變域； (vi) 抗原結合位點，其包括包含SEQ ID NO:131之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:132之胺基酸序列之免疫球蛋白輕鏈可變域； (vii) 抗原結合位點，其包括包含SEQ ID NO:133之胺基酸序列之免疫球蛋白重鏈可變域及包含選自由SEQ ID NO:134及SEQ ID NO:135組成之群之胺基酸序列的免疫球蛋白輕鏈可變域； (viii)  抗原結合位點，其包括包含SEQ ID NO:136之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:137之胺基酸序列之免疫球蛋白輕鏈可變域； (ix) 抗原結合位點，其包括包含選自由SEQ ID NO:138及SEQ ID NO：156組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:139之胺基酸序列之免疫球蛋白輕鏈可變域； (x)    抗原結合位點，其包括包含選自由SEQ ID NO:140、SEQ ID NO:142、SEQ ID NO:143及SEQ ID NO:161組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:141之胺基酸序列之免疫球蛋白輕鏈可變域； (xi)   抗原結合位點，其包括包含選自由SEQ ID NO:144及SEQ ID NO:146組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:145之胺基酸序列之免疫球蛋白輕鏈可變域； (xii)  抗原結合位點，其包括包含選自由SEQ ID NO:147、SEQ ID NO:151、SEQ ID NO:153及SEQ ID NO:162組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:148之胺基酸序列之免疫球蛋白輕鏈可變域； (xiii)  抗原結合位點，其包括包含選自由SEQ ID NO:149及SEQ ID NO:152組成之群之胺基酸序列的免疫球蛋白重鏈可變域及包含SEQ ID NO:150之胺基酸序列之免疫球蛋白輕鏈可變域； (xiv) 抗原結合位點，其包括包含SEQ ID NO:154之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:155之胺基酸序列之免疫球蛋白輕鏈可變域； (xv)  抗原結合位點，其包括包含SEQ ID NO:157之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:158之胺基酸序列之免疫球蛋白輕鏈可變域；及 (xvi) 抗原結合位點，其包括包含SEQ ID NO:159之胺基酸序列之免疫球蛋白重鏈可變域及包含SEQ ID NO:160之胺基酸序列之免疫球蛋白輕鏈可變域。
  7. 如請求項1至3中任一項之結合分子，其中該結合分子為經修飾之免疫球蛋白(Ig)分子，較佳經修飾之IgG分子，其中該至少一個特異性結合於TROP2之抗原結合位點及該至少一個特異性結合於CDH17之抗原結合位點存在於該Ig分子之可變區，且其中該至少一個特異性結合於CD3之抗原結合位點為與該TROP2-CDH17特異性Ig分子融合的scFv。
  8. 如請求項7之結合分子，其中該scFv與該Ig分子之重鏈之C端融合，較佳與包含該至少一個特異性結合於CDH17之抗原結合位點的該Ig分子之部分之重鏈融合。
  9. 如請求項1至3中任一項之結合分子，其中該結合分子包含： (a)選自(a-i)至(a-xii)之第一免疫球蛋白輕鏈及免疫球蛋白重鏈組合，較佳藉由肽連接子連接在一起： (a-i)     包含SEQ ID NO:169之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:170之胺基酸序列之免疫球蛋白重鏈； (a-ii)    包含SEQ ID NO:171之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:172之胺基酸序列之免疫球蛋白重鏈； (a-iii)   包含SEQ ID NO:173之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:174之胺基酸序列之免疫球蛋白重鏈； (a-iv)    包含SEQ ID NO:175之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:176之胺基酸序列之免疫球蛋白重鏈； (a-v)     包含SEQ ID NO:177之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:178之胺基酸序列之免疫球蛋白重鏈； (a-vi)    包含SEQ ID NO:179之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:180之胺基酸序列之免疫球蛋白重鏈； (a-vii)   包含SEQ ID NO:181之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:182之胺基酸序列之免疫球蛋白重鏈； (a-viii)  包含SEQ ID NO:183之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:184之胺基酸序列之免疫球蛋白重鏈； (a-ix)    包含SEQ ID NO:185之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:186之胺基酸序列之免疫球蛋白重鏈； (a-x)     包含SEQ ID NO:187之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:188之胺基酸序列之免疫球蛋白重鏈； (a-xi)    包含SEQ ID NO:189之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:190之胺基酸序列之免疫球蛋白重鏈；或 (a-xii)   包含SEQ ID NO:191之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:192之胺基酸序列之免疫球蛋白重鏈； 及 (b)  選自(b-i)至(b-ii)之第二免疫球蛋白重鏈及免疫球蛋白輕鏈組合，較佳藉由肽連接子連接在一起： (b-i)     包含SEQ ID NO:196之胺基酸序列之免疫球蛋白輕鏈及包含SEQ ID NO:197之胺基酸序列之免疫球蛋白重鏈；或 (b-ii)    包含SEQ ID NO:198之胺基酸序列之免疫球蛋白重鏈及包含SEQ ID NO:199之胺基酸序列之免疫球蛋白輕鏈； 及 (c)  包含選自由SEQ ID NO: 222至264組成之群之胺基酸序列的單鏈可變片段(scFv)，較佳連接於該第二免疫球蛋白重鏈及免疫球蛋白輕鏈組合之該免疫球蛋白重鏈的C端。
  10. 如請求項1至3中任一項之結合分子，其中該結合分子包含以下或由以下組成： (a-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (a-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:267之胺基酸序列； (b-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (b-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:268之胺基酸序列； (c-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (c-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:269之胺基酸序列； (d-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (d-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:270之胺基酸序列； (e-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (e-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:271之胺基酸序列； (f-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-iv)     SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-v)      SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vi)     SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-vii)    SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-viii)   SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-ix)     SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-x)      SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xi)     SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (f-xii)    SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:272之胺基酸序列； (g-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (g-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:424之胺基酸序列； (h-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-iv)    SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-v)     SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vi)    SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-vii)   SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-viii)  SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-ix)    SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-x)     SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xi)    SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (h-xii)   SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:425之胺基酸序列； (i-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-iv)     SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-v)      SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vi)     SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-vii)    SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-viii)   SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-ix)     SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-x)      SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xi)     SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (i-xii)    SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:426之胺基酸序列； (j-i)      SEQ ID NO.:200之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ii)     SEQ ID NO.:207之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iii)    SEQ ID NO.:208之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-iv)     SEQ ID NO.:209之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-v)      SEQ ID NO.:210之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vi)     SEQ ID NO.:211之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-vii)    SEQ ID NO.:212之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-viii)   SEQ ID NO.:213之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-ix)     SEQ ID NO.:214之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-x)      SEQ ID NO.:215之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xi)     SEQ ID NO.:216之胺基酸序列及SEQ ID NO.:427之胺基酸序列； (j-xii)    SEQ ID NO.:217之胺基酸序列及SEQ ID NO.:427之胺基酸序列；或 (k)        SEQ ID NO.:436之胺基酸序列及SEQ ID NO.:437之胺基酸序列。
  11. 一種核酸分子，其編碼如請求項1至10中任一項之結合分子或其一部分。
  12. 一種表現載體，其包含一或多種如請求項11之核酸分子。
  13. 一種宿主細胞，其經如請求項12之表現載體轉染。
  14. 一種產生如請求項1至10中任一項之結合分子之方法，該方法包含以下步驟： (a)  在允許如請求項1至10中任一項之結合分子表現之條件下培養如請求項13之宿主細胞； (b)  視情況回收該分子；及視情況， (c)  進一步純化及/或修飾及/或調配該結合分子。
  15. 一種醫藥組合物，其包含一或多種如請求項1至10中任一項之結合分子及視情況選用之醫藥學上可接受之載劑或由其組成。
  16. 一種如請求項1至10中任一項之結合分子或如請求項15之醫藥組合物的用途，其用於製備供治療、預防或改善癌症之醫藥組合物。
  17. 如請求項16之用途，其中該癌症為大腸直腸癌(CRC)、胃癌(GC)或胰臟癌(PAC)。
  18. 如請求項16之用途，其中該結合分子將與免疫檢查點抑制劑、較佳抗PD-1或抗PD-1-L1抗體組合使用。
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